LISTADO DE SECUENCIAS +ADw-110+AD4- F. Hoffmann-La Roche AG +ADw-120+AD4- NUEVAS MOLÉCULAS DE UNIÓN A ANTÍGENO BIESPECÍFICAS CAPACES DE UNIRSE ESPECÍFICAMENTE A CD40 Y A FAP +ADw-130+AD4- P34214-WO +ADw-150+AD4- EP17164725.8 +ADw-151+AD4- 04-04-2017 +ADw-150+AD4- EP18158751.0 +ADw-151+AD4- 27-02-2018 +ADw-160+AD4- 269 +ADw-170+AD4- PatentIn versión 3.5 +ADw-210+AD4- 1 +ADw-211+AD4- 277 +ADw-212+AD4- PRT +ADw-213+AD4- Homo sapiens +ADw-400+AD4- 1 Met Val Arg Leu Pro Leu Gln Cys Val Leu Trp Gly Cys Leu Leu Thr 1 5 10 15 Ala Val His Pro Glu Pro Pro Thr Ala Cys Arg Glu Lys Gln Tyr Leu 20 25 30 Ile Asn Ser Gln Cys Cys Ser Leu Cys Gln Pro Gly Gln Lys Leu Val 35 40 45 Ser Asp Cys Thr Glu Phe Thr Glu Thr Glu Cys Leu Pro Cys Gly Glu 50 55 60 Ser Glu Phe Leu Asp Thr Trp Asn Arg Glu Thr His Cys His Gln His 65 70 75 80 Lys Tyr Cys Asp Pro Asn Leu Gly Leu Arg Val Gln Gln Lys Gly Thr 85 90 95 Ser Glu Thr Asp Thr Ile Cys Thr Cys Glu Glu Gly Trp His Cys Thr 100 105 110 Ser Glu Ala Cys Glu Ser Cys Val Leu His Arg Ser Cys Ser Pro Gly 115 120 125 Phe Gly Val Lys Gln Ile Ala Thr Gly Val Ser Asp Thr Ile Cys Glu 130 135 140 Pro Cys Pro Val Gly Phe Phe Ser Asn Val Ser Ser Ala Phe Glu Lys 145 150 155 160 Cys His Pro Trp Thr Ser Cys Glu Thr Lys Asp Leu Val Val Gln Gln 165 170 175 Ala Gly Thr Asn Lys Thr Asp Val Val Cys Gly Pro Gln Asp Arg Leu 180 185 190 Arg Ala Leu Val Val Ile Pro Ile Ile Phe Gly Ile Leu Phe Ala Ile 195 200 205 Leu Leu Val Leu Val Phe Ile Lys Lys Val Ala Lys Lys Pro Thr Asn 210 215 220 Lys Ala Pro His Pro Lys Gln Glu Pro Gln Glu Ile Asn Phe Pro Asp 225 230 235 240 Asp Leu Pro Gly Ser Asn Thr Ala Ala Pro Val Gln Glu Thr Leu His 245 250 255 Gly Cys Gln Pro Val Thr Gln Glu Asp Gly Lys Glu Ser Arg Ile Ser 260 265 270 Val Gln Glu Arg Gln 275 +ADw-210+AD4- 2 +ADw-211+AD4- 760 +ADw-212+AD4- PRT +ADw-213+AD4- Homo sapiens +ADw-400+AD4- 2 Met Lys Thr Trp Val Lys Ile Val Phe Gly Val Ala Thr Ser Ala Val 1 5 10 15 Leu Ala Leu Leu Val Met Cys Ile Val Leu Arg Pro Ser Arg Val His 20 25 30 Asn Ser Glu Glu Asn Thr Met Arg Ala Leu Thr Leu Lys Asp Ile Leu 35 40 45 Asn Gly Thr Phe Ser Tyr Lys Thr Phe Phe Pro Asn Trp Ile Ser Gly 50 55 60 Gln Glu Tyr Leu His Gln Ser Ala Asp Asn Asn Ile Val Leu Tyr Asn 65 70 75 80 Ile Glu Thr Gly Gln Ser Tyr Thr Ile Leu Ser Asn Arg Thr Met Lys 85 90 95 Ser Val Asn Ala Ser Asn Tyr Gly Leu Ser Pro Asp Arg Gln Phe Val 100 105 110 Tyr Leu Glu Ser Asp Tyr Ser Lys Leu Trp Arg Tyr Ser Tyr Thr Ala 115 120 125 Thr Tyr Tyr Ile Tyr Asp Leu Ser Asn Gly Glu Phe Val Arg Gly Asn 130 135 140 Glu Leu Pro Arg Pro Ile Gln Tyr Leu Cys Trp Ser Pro Val Gly Ser 145 150 155 160 Lys Leu Ala Tyr Val Tyr Gln Asn Asn Ile Tyr Leu Lys Gln Arg Pro 165 170 175 Gly Asp Pro Pro Phe Gln Ile Thr Phe Asn Gly Arg Glu Asn Lys Ile 180 185 190 Phe Asn Gly Ile Pro Asp Trp Val Tyr Glu Glu Glu Met Leu Ala Thr 195 200 205 Lys Tyr Ala Leu Trp Trp Ser Pro Asn Gly Lys Phe Leu Ala Tyr Ala 210 215 220 Glu Phe Asn Asp Thr Asp Ile Pro Val Ile Ala Tyr Ser Tyr Tyr Gly 225 230 235 240 Asp Glu Gln Tyr Pro Arg Thr Ile Asn Ile Pro Tyr Pro Lys Ala Gly 245 250 255 Ala Lys Asn Pro Val Val Arg Ile Phe Ile Ile Asp Thr Thr Tyr Pro 260 265 270 Ala Tyr Val Gly Pro Gln Glu Val Pro Val Pro Ala Met Ile Ala Ser 275 280 285 Ser Asp Tyr Tyr Phe Ser Trp Leu Thr Trp Val Thr Asp Glu Arg Val 290 295 300 Cys Leu Gln Trp Leu Lys Arg Val Gln Asn Val Ser Val Leu Ser Ile 305 310 315 320 Cys Asp Phe Arg Glu Asp Trp Gln Thr Trp Asp Cys Pro Lys Thr Gln 325 330 335 Glu His Ile Glu Glu Ser Arg Thr Gly Trp Ala Gly Gly Phe Phe Val 340 345 350 Ser Thr Pro Val Phe Ser Tyr Asp Ala Ile Ser Tyr Tyr Lys Ile Phe 355 360 365 Ser Asp Lys Asp Gly Tyr Lys His Ile His Tyr Ile Lys Asp Thr Val 370 375 380 Glu Asn Ala Ile Gln Ile Thr Ser Gly Lys Trp Glu Ala Ile Asn Ile 385 390 395 400 Phe Arg Val Thr Gln Asp Ser Leu Phe Tyr Ser Ser Asn Glu Phe Glu 405 410 415 Glu Tyr Pro Gly Arg Arg Asn Ile Tyr Arg Ile Ser Ile Gly Ser Tyr 420 425 430 Pro Pro Ser Lys Lys Cys Val Thr Cys His Leu Arg Lys Glu Arg Cys 435 440 445 Gln Tyr Tyr Thr Ala Ser Phe Ser Asp Tyr Ala Lys Tyr Tyr Ala Leu 450 455 460 Val Cys Tyr Gly Pro Gly Ile Pro Ile Ser Thr Leu His Asp Gly Arg 465 470 475 480 Thr Asp Gln Glu Ile Lys Ile Leu Glu Glu Asn Lys Glu Leu Glu Asn 485 490 495 Ala Leu Lys Asn Ile Gln Leu Pro Lys Glu Glu Ile Lys Lys Leu Glu 500 505 510 Val Asp Glu Ile Thr Leu Trp Tyr Lys Met Ile Leu Pro Pro Gln Phe 515 520 525 Asp Arg Ser Lys Lys Tyr Pro Leu Leu Ile Gln Val Tyr Gly Gly Pro 530 535 540 Cys Ser Gln Ser Val Arg Ser Val Phe Ala Val Asn Trp Ile Ser Tyr 545 550 555 560 Leu Ala Ser Lys Glu Gly Met Val Ile Ala Leu Val Asp Gly Arg Gly 565 570 575 Thr Ala Phe Gln Gly Asp Lys Leu Leu Tyr Ala Val Tyr Arg Lys Leu 580 585 590 Gly Val Tyr Glu Val Glu Asp Gln Ile Thr Ala Val Arg Lys Phe Ile 595 600 605 Glu Met Gly Phe Ile Asp Glu Lys Arg Ile Ala Ile Trp Gly Trp Ser 610 615 620 Tyr Gly Gly Tyr Val Ser Ser Leu Ala Leu Ala Ser Gly Thr Gly Leu 625 630 635 640 Phe Lys Cys Gly Ile Ala Val Ala Pro Val Ser Ser Trp Glu Tyr Tyr 645 650 655 Ala Ser Val Tyr Thr Glu Arg Phe Met Gly Leu Pro Thr Lys Asp Asp 660 665 670 Asn Leu Glu His Tyr Lys Asn Ser Thr Val Met Ala Arg Ala Glu Tyr 675 680 685 Phe Arg Asn Val Asp Tyr Leu Leu Ile His Gly Thr Ala Asp Asp Asn 690 695 700 Val His Phe Gln Asn Ser Ala Gln Ile Ala Lys Ala Leu Val Asn Ala 705 710 715 720 Gln Val Asp Phe Gln Ala Met Trp Tyr Ser Asp Gln Asn His Gly Leu 725 730 735 Ser Gly Leu Ser Thr Asn His Leu Tyr Thr His Met Thr His Phe Leu 740 745 750 Lys Gln Cys Phe Ser Leu Ser Asp 755 760 +ADw-210+AD4- 3 +ADw-211+AD4- 5 +ADw-212+AD4- PRT +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- CDR-H1 de FAP(28H1) +ADw-400+AD4- 3 Ser His Ala Met Ser 1 5 +ADw-210+AD4- 4 +ADw-211+AD4- 16 +ADw-212+AD4- PRT +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- CDR-H2 de FAP(28H1) +ADw-400+AD4- 4 Ala Ile Trp Ala Ser Gly Glu Gln Tyr Tyr Ala Asp Ser Val Lys Gly 1 5 10 15 +ADw-210+AD4- 5 +ADw-211+AD4- 8 +ADw-212+AD4- PRT +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- CDR-H3 de FAP(28H1) +ADw-400+AD4- 5 Gly Trp Leu Gly Asn Phe Asp Tyr 1 5 +ADw-210+AD4- 6 +ADw-211+AD4- 12 +ADw-212+AD4- PRT +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- CDR-L1 de FAP(28H1) +ADw-400+AD4- 6 Arg Ala Ser Gln Ser Val Ser Arg Ser Tyr Leu Ala 1 5 10 +ADw-210+AD4- 7 +ADw-211+AD4- 7 +ADw-212+AD4- PRT +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- CDR-L2 de FAP(28H1) +ADw-400+AD4- 7 Gly Ala Ser Thr Arg Ala Thr 1 5 +ADw-210+AD4- 8 +ADw-211+AD4- 9 +ADw-212+AD4- PRT +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- CDR-L3 de FAP(28H1) +ADw-400+AD4- 8 Gln Gln Gly Gln Val Ile Pro Pro Thr 1 5 +ADw-210+AD4- 9 +ADw-211+AD4- 116 +ADw-212+AD4- PRT +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- VH de FAP(28H1) +ADw-400+AD4- 9 Glu Val Gln Leu Leu Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 1 5 10 15 Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Ser His 20 25 30 Ala Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45 Ser Ala Ile Trp Ala Ser Gly Glu Gln Tyr Tyr Ala Asp Ser Val Lys 50 55 60 Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr Leu 65 70 75 80 Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala 85 90 95 Lys Gly Trp Leu Gly Asn Phe Asp Tyr Trp Gly Gln Gly Thr Leu Val 100 105 110 Thr Val Ser Ser 115 +ADw-210+AD4- 10 +ADw-211+AD4- 108 +ADw-212+AD4- PRT +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- VL de FAP(28H1) +ADw-400+AD4- 10 Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly 1 5 10 15 Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Arg Ser 20 25 30 Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu 35 40 45 Ile Ile Gly Ala Ser Thr Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser 50 55 60 Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu 65 70 75 80 Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Gly Gln Val Ile Pro 85 90 95 Pro Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys 100 105 +ADw-210+AD4- 11 +ADw-211+AD4- 5 +ADw-212+AD4- PRT +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- CDR-H1 de FAP(4B9) +ADw-400+AD4- 11 Ser Tyr Ala Met Ser 1 5 +ADw-210+AD4- 12 +ADw-211+AD4- 17 +ADw-212+AD4- PRT +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- CDR-H2 de FAP(4B9) +ADw-400+AD4- 12 Ala Ile Ile Gly Ser Gly Ala Ser Thr Tyr Tyr Ala Asp Ser Val Lys 1 5 10 15 Gly +ADw-210+AD4- 13 +ADw-211+AD4- 8 +ADw-212+AD4- PRT +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- CDR-H3 de FAP(4B9) +ADw-400+AD4- 13 Gly Trp Phe Gly Gly Phe Asn Tyr 1 5 +ADw-210+AD4- 14 +ADw-211+AD4- 12 +ADw-212+AD4- PRT +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- CDR-L1 de FAP(4B9) +ADw-400+AD4- 14 Arg Ala Ser Gln Ser Val Ser Arg Ser Tyr Leu Ala 1 5 10 +ADw-210+AD4- 15 +ADw-211+AD4- 7 +ADw-212+AD4- PRT +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- CDR-L2 de FAP(4B9) +ADw-400+AD4- 15 Val Gly Ser Arg Arg Ala Thr 1 5 +ADw-210+AD4- 16 +ADw-211+AD4- 9 +ADw-212+AD4- PRT +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- CDR-L3 de FAP(4B9) +ADw-400+AD4- 16 Gln Gln Gly Ile Met Leu Pro Pro Thr 1 5 +ADw-210+AD4- 17 +ADw-211+AD4- 117 +ADw-212+AD4- PRT +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- VH de FAP(4B9) +ADw-400+AD4- 17 Glu Val Gln Leu Leu Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 1 5 10 15 Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Ser Tyr 20 25 30 Ala Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45 Ser Ala Ile Ile Gly Ser Gly Ala Ser Thr Tyr Tyr Ala Asp Ser Val 50 55 60 Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 65 70 75 80 Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Ala Lys Gly Trp Phe Gly Gly Phe Asn Tyr Trp Gly Gln Gly Thr Leu 100 105 110 Val Thr Val Ser Ser 115 +ADw-210+AD4- 18 +ADw-211+AD4- 108 +ADw-212+AD4- PRT +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- VL de FAP(4B9) +ADw-400+AD4- 18 Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly 1 5 10 15 Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Thr Ser Ser 20 25 30 Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu 35 40 45 Ile Asn Val Gly Ser Arg Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser 50 55 60 Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu 65 70 75 80 Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Gly Ile Met Leu Pro 85 90 95 Pro Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys 100 105 +ADw-210+AD4- 19 +ADw-211+AD4- 5 +ADw-212+AD4- PRT +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- hu CD40 CDR-H1 +ADw-400+AD4- 19 Gly Tyr Tyr Ile His 1 5 +ADw-210+AD4- 20 +ADw-211+AD4- 17 +ADw-212+AD4- PRT +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- hu CD40 CDR-H2 +ADw-400+AD4- 20 Arg Val Ile Pro Asn Ala Gly Gly Thr Ser Tyr Asn Gln Lys Phe Lys 1 5 10 15 Gly +ADw-210+AD4- 21 +ADw-211+AD4- 5 +ADw-212+AD4- PRT +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- hu CD40 CDR-H3 +ADw-400+AD4- 21 Glu Gly Ile Tyr Trp 1 5 +ADw-210+AD4- 22 +ADw-211+AD4- 16 +ADw-212+AD4- PRT +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- hu CD40 CDR-L1 +ADw-400+AD4- 22 Arg Ser Ser Gln Ser Leu Val His Ser Asn Gly Asn Thr Phe Leu His 1 5 10 15 +ADw-210+AD4- 23 +ADw-211+AD4- 7 +ADw-212+AD4- PRT +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- hu CD40 CDR-L2 +ADw-400+AD4- 23 Thr Val Ser Asn Arg Phe Ser 1 5 +ADw-210+AD4- 24 +ADw-211+AD4- 9 +ADw-212+AD4- PRT +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- hu CD40 CDR-L3 +ADw-400+AD4- 24 Ser Gln Thr Thr His Val Pro Trp Thr 1 5 +ADw-210+AD4- 25 +ADw-211+AD4- 114 +ADw-212+AD4- PRT +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- hu CD40 VH +ADw-400+AD4- 25 Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 1 5 10 15 Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Tyr Ser Phe Thr Gly Tyr 20 25 30 Tyr Ile His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45 Ala Arg Val Ile Pro Asn Ala Gly Gly Thr Ser Tyr Asn Gln Lys Phe 50 55 60 Lys Gly Arg Phe Thr Leu Ser Val Asp Asn Ser Lys Asn Thr Ala Tyr 65 70 75 80 Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Ala Arg Glu Gly Ile Tyr Trp Trp Gly Gln Gly Thr Leu Val Thr Val 100 105 110 Ser Ser +ADw-210+AD4- 26 +ADw-211+AD4- 112 +ADw-212+AD4- PRT +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- hu CD40 VL +ADw-400+AD4- 26 Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 1 5 10 15 Asp Arg Val Thr Ile Thr Cys Arg Ser Ser Gln Ser Leu Val His Ser 20 25 30 Asn Gly Asn Thr Phe Leu His Trp Tyr Gln Gln Lys Pro Gly Lys Ala 35 40 45 Pro Lys Leu Leu Ile Tyr Thr Val Ser Asn Arg Phe Ser Gly Val Pro 50 55 60 Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile 65 70 75 80 Ser Ser Leu Gln Pro Glu Asp Phe Ala Thr Tyr Phe Cys Ser Gln Thr 85 90 95 Thr His Val Pro Trp Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys 100 105 110 +ADw-210+AD4- 27 +ADw-211+AD4- 5 +ADw-212+AD4- PRT +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- mu CD40 CDR-H1 +ADw-400+AD4- 27 Asp Tyr Tyr Met Ala 1 5 +ADw-210+AD4- 28 +ADw-211+AD4- 17 +ADw-212+AD4- PRT +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- mu CD40 CDR-H2 +ADw-400+AD4- 28 Ser Ile Ser Tyr Asp Gly Ser Ser Thr Tyr Tyr Arg Asp Ser Val Lys 1 5 10 15 Gly +ADw-210+AD4- 29 +ADw-211+AD4- 7 +ADw-212+AD4- PRT +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- mu CD40 CDR-H3 +ADw-400+AD4- 29 His Ser Ser Tyr Phe Asp Tyr 1 5 +ADw-210+AD4- 30 +ADw-211+AD4- 10 +ADw-212+AD4- PRT +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- mu CD40 CDR-L1 +ADw-400+AD4- 30 Ala Ser Asp Ser Val Ser Thr Leu Met His 1 5 10 +ADw-210+AD4- 31 +ADw-211+AD4- 7 +ADw-212+AD4- PRT +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- mu CD40 CDR-L2 +ADw-400+AD4- 31 Leu Ala Ser His Leu Glu Ser 1 5 +ADw-210+AD4- 32 +ADw-211+AD4- 9 +ADw-212+AD4- PRT +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- mu CD40 CDR-L3 +ADw-400+AD4- 32 Gln Gln Ser Trp Asn Asp Pro Trp Thr 1 5 +ADw-210+AD4- 33 +ADw-211+AD4- 116 +ADw-212+AD4- PRT +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- mu CD40 VH +ADw-400+AD4- 33 Glu Val Gln Leu Val Glu Ser Asp Gly Gly Leu Val Gln Pro Gly Arg 1 5 10 15 Ser Leu Lys Leu Pro Cys Ala Ala Ser Gly Phe Thr Phe Ser Asp Tyr 20 25 30 Tyr Met Ala Trp Val Arg Gln Ala Pro Thr Lys Gly Leu Glu Trp Val 35 40 45 Ala Ser Ile Ser Tyr Asp Gly Ser Ser Thr Tyr Tyr Arg Asp Ser Val 50 55 60 Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Ser Thr Leu Tyr 65 70 75 80 Leu Gln Met Asp Ser Leu Arg Ser Glu Asp Thr Ala Thr Tyr Tyr Cys 85 90 95 Gly Arg His Ser Ser Tyr Phe Asp Tyr Trp Gly Gln Gly Val Met Val 100 105 110 Thr Val Ser Ser 115 +ADw-210+AD4- 34 +ADw-211+AD4- 106 +ADw-212+AD4- PRT +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- mu CD40 VL +ADw-400+AD4- 34 Asp Thr Val Leu Thr Gln Ser Pro Ala Leu Ala Val Ser Pro Gly Glu 1 5 10 15 Arg Val Thr Ile Ser Cys Arg Ala Ser Asp Ser Val Ser Thr Leu Met 20 25 30 His Trp Tyr Gln Gln Lys Pro Gly Gln Gln Pro Lys Leu Leu Ile Tyr 35 40 45 Leu Ala Ser His Leu Glu Ser Gly Val Pro Ala Arg Phe Ser Gly Ser 50 55 60 Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Asp Pro Val Glu Ala Asp 65 70 75 80 Asp Thr Ala Thr Tyr Tyr Cys Gln Gln Ser Trp Asn Asp Pro Trp Thr 85 90 95 Phe Gly Gly Gly Thr Lys Leu Glu Leu Lys 100 105 +ADw-210+AD4- 35 +ADw-211+AD4- 10 +ADw-212+AD4- PRT +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- hu CD40 CDR-H1 larga +ADw-400+AD4- 35 Gly Tyr Ser Phe Thr Gly Tyr Tyr Ile His 1 5 10 +ADw-210+AD4- 36 +ADw-211+AD4- 17 +ADw-212+AD4- PRT +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- hu CD40 CDR-H2 (hVH+AF8-1, hVH+AF8-2) +ADw-400+AD4- 36 Arg Val Ile Pro Asn Asn Gly Gly Thr Ser Tyr Asn Gln Lys Phe Lys 1 5 10 15 Gly +ADw-210+AD4- 37 +ADw-211+AD4- 17 +ADw-212+AD4- PRT +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- hu CD40 CDR-H2 (hVH+AF8-3) +ADw-400+AD4- 37 Arg Val Ile Pro Asn Ala Gly Gly Thr Ser Tyr Asn Gln Lys Phe Lys 1 5 10 15 Gly +ADw-210+AD4- 38 +ADw-211+AD4- 17 +ADw-212+AD4- PRT +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- hu CD40 CDR-H2 (hVH+AF8-4) +ADw-400+AD4- 38 Arg Val Ile Pro Gln Ala Gly Gly Thr Ser Tyr Asn Gln Lys Phe Lys 1 5 10 15 Gly +ADw-210+AD4- 39 +ADw-211+AD4- 17 +ADw-212+AD4- PRT +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- hu CD40 CDR-H2 (hVH+AF8-5) +ADw-400+AD4- 39 Arg Val Ile Pro Asn Asn Gly Gly Thr Ser Tyr Asn Gln Lys Phe Gln 1 5 10 15 Gly +ADw-210+AD4- 40 +ADw-211+AD4- 17 +ADw-212+AD4- PRT +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- hu CD40 CDR-H2 (hVH+AF8-6) +ADw-400+AD4- 40 Arg Val Ile Pro Asn Asn Gly Gly Thr Ser Tyr Ala Gln Lys Phe Lys 1 5 10 15 Gly +ADw-210+AD4- 41 +ADw-211+AD4- 17 +ADw-212+AD4- PRT +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- hu CD40 CDR-H2 (hVH+AF8-7) +ADw-400+AD4- 41 Arg Val Ile Pro Asn Asn Gly Gly Thr Ser Tyr Ala Gln Lys Phe Gln 1 5 10 15 Gly +ADw-210+AD4- 42 +ADw-211+AD4- 17 +ADw-212+AD4- PRT +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- hu CD40 CDR-H2 (hVH+AF8-5+AF8-N288A) +ADw-400+AD4- 42 Arg Val Ile Pro Asn Ala Gly Gly Thr Ser Tyr Asn Gln Lys Phe Gln 1 5 10 15 Gly +ADw-210+AD4- 43 +ADw-211+AD4- 17 +ADw-212+AD4- PRT +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- hu CD40 CDR-H2 (hVH+AF8-6+AF8-N288A) +ADw-400+AD4- 43 Arg Val Ile Pro Asn Ala Gly Gly Thr Ser Tyr Ala Gln Lys Phe Lys 1 5 10 15 Gly +ADw-210+AD4- 44 +ADw-211+AD4- 17 +ADw-212+AD4- PRT +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- hu CD40 CDR-H2 (hVH+AF8-7+AF8-N288A) +ADw-400+AD4- 44 Arg Val Ile Pro Asn Ala Gly Gly Thr Ser Tyr Ala Gln Lys Phe Gln 1 5 10 15 Gly +ADw-210+AD4- 45 +ADw-211+AD4- 114 +ADw-212+AD4- PRT +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- hu CD40 hVH+AF8-1 +ADw-400+AD4- 45 Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala 1 5 10 15 Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Ser Phe Thr Gly Tyr 20 25 30 Tyr Ile His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met 35 40 45 Gly Arg Val Ile Pro Asn Asn Gly Gly Thr Ser Tyr Asn Gln Lys Phe 50 55 60 Lys Gly Arg Val Thr Ser Thr Arg Asp Thr Ser Ile Ser Thr Ala Tyr 65 70 75 80 Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Val Val Tyr Tyr Cys 85 90 95 Ala Arg Glu Gly Ile Tyr Trp Trp Gly Gln Gly Thr Thr Val Thr Val 100 105 110 Ser Ser +ADw-210+AD4- 46 +ADw-211+AD4- 114 +ADw-212+AD4- PRT +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- hu CD40 hVH+AF8-2 +ADw-400+AD4- 46 Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala 1 5 10 15 Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Ser Phe Thr Gly Tyr 20 25 30 Tyr Ile His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Ile 35 40 45 Gly Arg Val Ile Pro Asn Asn Gly Gly Thr Ser Tyr Asn Gln Lys Phe 50 55 60 Lys Gly Arg Val Thr Ser Thr Val Asp Thr Ser Ile Ser Thr Ala Tyr 65 70 75 80 Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Val Val Tyr Tyr Cys 85 90 95 Ala Arg Glu Gly Ile Tyr Trp Trp Gly Gln Gly Thr Thr Val Thr Val 100 105 110 Ser Ser +ADw-210+AD4- 47 +ADw-211+AD4- 114 +ADw-212+AD4- PRT +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- hu CD40 hVH+AF8-3 +ADw-400+AD4- 47 Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala 1 5 10 15 Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Ser Phe Thr Gly Tyr 20 25 30 Tyr Ile His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Ile 35 40 45 Gly Arg Val Ile Pro Asn Ala Gly Gly Thr Ser Tyr Asn Gln Lys Phe 50 55 60 Lys Gly Arg Val Thr Ser Thr Val Asp Thr Ser Ile Ser Thr Ala Tyr 65 70 75 80 Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Val Val Tyr Tyr Cys 85 90 95 Ala Arg Glu Gly Ile Tyr Trp Trp Gly Gln Gly Thr Thr Val Thr Val 100 105 110 Ser Ser +ADw-210+AD4- 48 +ADw-211+AD4- 114 +ADw-212+AD4- PRT +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- hu CD40 hVH+AF8-4 +ADw-400+AD4- 48 Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala 1 5 10 15 Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Ser Phe Thr Gly Tyr 20 25 30 Tyr Ile His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Ile 35 40 45 Gly Arg Val Ile Pro Gln Ala Gly Gly Thr Ser Tyr Asn Gln Lys Phe 50 55 60 Lys Gly Arg Val Thr Ser Thr Val Asp Thr Ser Ile Ser Thr Ala Tyr 65 70 75 80 Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Val Val Tyr Tyr Cys 85 90 95 Ala Arg Glu Gly Ile Tyr Trp Trp Gly Gln Gly Thr Thr Val Thr Val 100 105 110 Ser Ser +ADw-210+AD4- 49 +ADw-211+AD4- 114 +ADw-212+AD4- PRT +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- hu CD40 hVH+AF8-5 +ADw-400+AD4- 49 Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala 1 5 10 15 Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Ser Phe Thr Gly Tyr 20 25 30 Tyr Ile His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Ile 35 40 45 Gly Arg Val Ile Pro Asn Asn Gly Gly Thr Ser Tyr Asn Gln Lys Phe 50 55 60 Gln Gly Arg Val Thr Ser Thr Val Asp Thr Ser Ile Ser Thr Ala Tyr 65 70 75 80 Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Val Val Tyr Tyr Cys 85 90 95 Ala Arg Glu Gly Ile Tyr Trp Trp Gly Gln Gly Thr Thr Val Thr Val 100 105 110 Ser Ser +ADw-210+AD4- 50 +ADw-211+AD4- 114 +ADw-212+AD4- PRT +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- hu CD40 hVH+AF8-6 +ADw-400+AD4- 50 Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala 1 5 10 15 Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Ser Phe Thr Gly Tyr 20 25 30 Tyr Ile His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Ile 35 40 45 Gly Arg Val Ile Pro Asn Asn Gly Gly Thr Ser Tyr Ala Gln Lys Phe 50 55 60 Lys Gly Arg Val Thr Ser Thr Val Asp Thr Ser Ile Ser Thr Ala Tyr 65 70 75 80 Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Val Val Tyr Tyr Cys 85 90 95 Ala Arg Glu Gly Ile Tyr Trp Trp Gly Gln Gly Thr Thr Val Thr Val 100 105 110 Ser Ser +ADw-210+AD4- 51 +ADw-211+AD4- 114 +ADw-212+AD4- PRT +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- hu CD40 hVH+AF8-7 +ADw-400+AD4- 51 Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala 1 5 10 15 Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Ser Phe Thr Gly Tyr 20 25 30 Tyr Ile His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Ile 35 40 45 Gly Arg Val Ile Pro Asn Asn Gly Gly Thr Ser Tyr Ala Gln Lys Phe 50 55 60 Gln Gly Arg Val Thr Ser Thr Val Asp Thr Ser Ile Ser Thr Ala Tyr 65 70 75 80 Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Val Val Tyr Tyr Cys 85 90 95 Ala Arg Glu Gly Ile Tyr Trp Trp Gly Gln Gly Thr Thr Val Thr Val 100 105 110 Ser Ser +ADw-210+AD4- 52 +ADw-211+AD4- 114 +ADw-212+AD4- PRT +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- hu CD40 hVH+AF8-2+AF8-N288A +ADw-400+AD4- 52 Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala 1 5 10 15 Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Ser Phe Thr Gly Tyr 20 25 30 Tyr Ile His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Ile 35 40 45 Gly Arg Val Ile Pro Asn Ala Gly Gly Thr Ser Tyr Asn Gln Lys Phe 50 55 60 Lys Gly Arg Val Thr Ser Thr Val Asp Thr Ser Ile Ser Thr Ala Tyr 65 70 75 80 Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Val Val Tyr Tyr Cys 85 90 95 Ala Arg Glu Gly Ile Tyr Trp Trp Gly Gln Gly Thr Thr Val Thr Val 100 105 110 Ser Ser +ADw-210+AD4- 53 +ADw-211+AD4- 114 +ADw-212+AD4- PRT +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- hu CD40 hVH+AF8-5+AF8-N288A +ADw-400+AD4- 53 Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala 1 5 10 15 Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Ser Phe Thr Gly Tyr 20 25 30 Tyr Ile His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Ile 35 40 45 Gly Arg Val Ile Pro Asn Ala Gly Gly Thr Ser Tyr Asn Gln Lys Phe 50 55 60 Gln Gly Arg Val Thr Ser Thr Val Asp Thr Ser Ile Ser Thr Ala Tyr 65 70 75 80 Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Val Val Tyr Tyr Cys 85 90 95 Ala Arg Glu Gly Ile Tyr Trp Trp Gly Gln Gly Thr Thr Val Thr Val 100 105 110 Ser Ser +ADw-210+AD4- 54 +ADw-211+AD4- 114 +ADw-212+AD4- PRT +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- hu CD40 hVH+AF8-6+AF8-N288A +ADw-400+AD4- 54 Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala 1 5 10 15 Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Ser Phe Thr Gly Tyr 20 25 30 Tyr Ile His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Ile 35 40 45 Gly Arg Val Ile Pro Asn Ala Gly Gly Thr Ser Tyr Ala Gln Lys Phe 50 55 60 Lys Gly Arg Val Thr Ser Thr Val Asp Thr Ser Ile Ser Thr Ala Tyr 65 70 75 80 Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Val Val Tyr Tyr Cys 85 90 95 Ala Arg Glu Gly Ile Tyr Trp Trp Gly Gln Gly Thr Thr Val Thr Val 100 105 110 Ser Ser +ADw-210+AD4- 55 +ADw-211+AD4- 114 +ADw-212+AD4- PRT +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- hu CD40 hVH+AF8-7+AF8-N288A +ADw-400+AD4- 55 Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala 1 5 10 15 Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Ser Phe Thr Gly Tyr 20 25 30 Tyr Ile His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Ile 35 40 45 Gly Arg Val Ile Pro Asn Ala Gly Gly Thr Ser Tyr Ala Gln Lys Phe 50 55 60 Gln Gly Arg Val Thr Ser Thr Val Asp Thr Ser Ile Ser Thr Ala Tyr 65 70 75 80 Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Val Val Tyr Tyr Cys 85 90 95 Ala Arg Glu Gly Ile Tyr Trp Trp Gly Gln Gly Thr Thr Val Thr Val 100 105 110 Ser Ser +ADw-210+AD4- 56 +ADw-211+AD4- 112 +ADw-212+AD4- PRT +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- hu CD40 hVK+AF8-1 +ADw-400+AD4- 56 Asp Val Val Met Thr Gln Ser Pro Leu Ser Leu Pro Val Thr Leu Gly 1 5 10 15 Gln Pro Ala Ser Ile Ser Cys Arg Ser Ser Gln Ser Leu Val His Ser 20 25 30 Asn Gly Asn Thr Phe Leu His Trp Phe Gln Gln Arg Pro Gly Gln Ser 35 40 45 Pro Arg Arg Leu Ile Tyr Thr Val Ser Asn Arg Phe Ser Gly Val Pro 50 55 60 Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile 65 70 75 80 Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Tyr Cys Ser Gln Thr 85 90 95 Thr His Val Pro Trp Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys 100 105 110 +ADw-210+AD4- 57 +ADw-211+AD4- 112 +ADw-212+AD4- PRT +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- hu CD40 hVK+AF8-2 +ADw-400+AD4- 57 Asp Val Val Met Thr Gln Ser Pro Leu Ser Leu Pro Val Thr Leu Gly 1 5 10 15 Gln Pro Ala Ser Ile Ser Cys Arg Ser Ser Gln Ser Leu Val His Ser 20 25 30 Asn Gly Asn Thr Phe Leu His Trp Tyr Gln Gln Arg Pro Gly Gln Ser 35 40 45 Pro Arg Leu Leu Ile Tyr Thr Val Ser Asn Arg Phe Ser Gly Val Pro 50 55 60 Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile 65 70 75 80 Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Tyr Cys Ser Gln Thr 85 90 95 Thr His Val Pro Trp Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys 100 105 110 +ADw-210+AD4- 58 +ADw-211+AD4- 112 +ADw-212+AD4- PRT +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- hu CD40 hVK+AF8-3 +ADw-400+AD4- 58 Asp Val Val Met Thr Gln Ser Pro Leu Ser Leu Pro Val Thr Leu Gly 1 5 10 15 Gln Pro Ala Ser Ile Ser Cys Arg Ser Ser Gln Ser Leu Val His Ser 20 25 30 Asn Gly Asn Thr Phe Leu His Trp Tyr Gln Gln Arg Pro Gly Gln Ser 35 40 45 Pro Arg Leu Leu Ile Tyr Thr Val Ser Asn Arg Phe Ser Gly Val Pro 50 55 60 Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile 65 70 75 80 Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Phe Cys Ser Gln Thr 85 90 95 Thr His Val Pro Trp Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys 100 105 110 +ADw-210+AD4- 59 +ADw-211+AD4- 112 +ADw-212+AD4- PRT +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- hu CD40 hVK+AF8-4 +ADw-400+AD4- 59 Asp Val Val Met Thr Gln Ser Pro Leu Ser Leu Pro Val Thr Leu Gly 1 5 10 15 Gln Pro Ala Ser Ile Ser Cys Arg Ser Ser Gln Ser Leu Val His Ser 20 25 30 Asn Pro Asn Thr Phe Leu His Trp Tyr Gln Gln Arg Pro Gly Gln Ser 35 40 45 Pro Arg Leu Leu Ile Tyr Thr Val Ser Asn Arg Phe Ser Gly Val Pro 50 55 60 Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile 65 70 75 80 Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Phe Cys Ser Gln Thr 85 90 95 Thr His Val Pro Trp Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys 100 105 110 +ADw-210+AD4- 60 +ADw-211+AD4- 112 +ADw-212+AD4- PRT +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- hu CD40 hVK+AF8-5 +ADw-400+AD4- 60 Asp Val Val Met Thr Gln Ser Pro Leu Ser Leu Pro Val Thr Leu Gly 1 5 10 15 Gln Pro Ala Ser Ile Ser Cys Arg Ser Ser Gln Ser Leu Val His Ser 20 25 30 Asn Gly Asn Ile Phe Leu His Trp Tyr Gln Gln Arg Pro Gly Gln Ser 35 40 45 Pro Arg Leu Leu Ile Tyr Thr Val Ser Asn Arg Phe Ser Gly Val Pro 50 55 60 Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile 65 70 75 80 Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Phe Cys Ser Gln Thr 85 90 95 Thr His Val Pro Trp Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys 100 105 110 +ADw-210+AD4- 61 +ADw-211+AD4- 112 +ADw-212+AD4- PRT +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- hu CD40 hVK+AF8-6 +ADw-400+AD4- 61 Asp Val Val Met Thr Gln Ser Pro Leu Ser Leu Pro Val Thr Leu Gly 1 5 10 15 Gln Pro Ala Ser Ile Ser Cys Arg Ser Ser Gln Ser Leu Val His Ser 20 25 30 Asn Pro Asn Ile Phe Leu His Trp Tyr Gln Gln Arg Pro Gly Gln Ser 35 40 45 Pro Arg Leu Leu Ile Tyr Thr Val Ser Asn Arg Phe Ser Gly Val Pro 50 55 60 Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile 65 70 75 80 Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Phe Cys Ser Gln Thr 85 90 95 Thr His Val Pro Trp Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys 100 105 110 +ADw-210+AD4- 62 +ADw-211+AD4- 112 +ADw-212+AD4- PRT +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- hu CD40 hVK+AF8-7 +ADw-400+AD4- 62 Asp Val Val Met Thr Gln Ser Pro Leu Ser Leu Pro Val Thr Leu Gly 1 5 10 15 Gln Pro Ala Ser Ile Ser Cys Arg Ser Ser Gln Ser Leu Val His Ser 20 25 30 Gln Gly Asn Thr Phe Leu His Trp Tyr Gln Gln Arg Pro Gly Gln Ser 35 40 45 Pro Arg Leu Leu Ile Tyr Thr Val Ser Asn Arg Phe Ser Gly Val Pro 50 55 60 Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile 65 70 75 80 Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Phe Cys Ser Gln Thr 85 90 95 Thr His Val Pro Trp Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys 100 105 110 +ADw-210+AD4- 63 +ADw-211+AD4- 112 +ADw-212+AD4- PRT +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- hu CD40 hVK+AF8-8 +ADw-400+AD4- 63 Asp Val Val Met Thr Gln Ser Pro Leu Ser Leu Pro Val Thr Leu Gly 1 5 10 15 Gln Pro Ala Ser Ile Ser Cys Arg Ser Ser Gln Ser Leu Val His Ser 20 25 30 Asn Gly Gln Thr Phe Leu His Trp Tyr Gln Gln Arg Pro Gly Gln Ser 35 40 45 Pro Arg Leu Leu Ile Tyr Thr Val Ser Asn Arg Phe Ser Gly Val Pro 50 55 60 Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile 65 70 75 80 Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Phe Cys Ser Gln Thr 85 90 95 Thr His Val Pro Trp Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys 100 105 110 +ADw-210+AD4- 64 +ADw-211+AD4- 112 +ADw-212+AD4- PRT +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- hu CD40 hVK+AF8-9 +ADw-400+AD4- 64 Asp Val Val Met Thr Gln Ser Pro Leu Ser Leu Pro Val Thr Leu Gly 1 5 10 15 Gln Pro Ala Ser Ile Ser Cys Arg Ser Ser Gln Ser Leu Val His Ser 20 25 30 Gln Gly Gln Thr Phe Leu His Trp Tyr Gln Gln Arg Pro Gly Gln Ser 35 40 45 Pro Arg Leu Leu Ile Tyr Thr Val Ser Asn Arg Phe Ser Gly Val Pro 50 55 60 Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile 65 70 75 80 Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Phe Cys Ser Gln Thr 85 90 95 Thr His Val Pro Trp Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys 100 105 110 +ADw-210+AD4- 65 +ADw-211+AD4- 5 +ADw-212+AD4- PRT +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- DP47-CDR H1 +ADw-400+AD4- 65 Ser Tyr Ala Met Ser 1 5 +ADw-210+AD4- 66 +ADw-211+AD4- 17 +ADw-212+AD4- PRT +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- DP47-CDR H2 +ADw-400+AD4- 66 Ala Ile Ser Gly Ser Gly Gly Ser Thr Tyr Tyr Ala Asp Ser Val Lys 1 5 10 15 Gly +ADw-210+AD4- 67 +ADw-211+AD4- 6 +ADw-212+AD4- PRT +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- DP47-CDR H3 +ADw-400+AD4- 67 Gly Ser Gly Phe Asp Tyr 1 5 +ADw-210+AD4- 68 +ADw-211+AD4- 12 +ADw-212+AD4- PRT +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- DP47-CDR L1 +ADw-400+AD4- 68 Arg Ala Ser Gln Ser Val Ser Ser Ser Tyr Leu Ala 1 5 10 +ADw-210+AD4- 69 +ADw-211+AD4- 7 +ADw-212+AD4- PRT +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- DP47-CDR L2 +ADw-400+AD4- 69 Gly Ala Ser Ser Arg Ala Thr 1 5 +ADw-210+AD4- 70 +ADw-211+AD4- 9 +ADw-212+AD4- PRT +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- DP47-CDR L3 +ADw-400+AD4- 70 Gln Gln Tyr Gly Ser Ser Pro Leu Thr 1 5 +ADw-210+AD4- 71 +ADw-211+AD4- 115 +ADw-212+AD4- PRT +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- DP47 VH +ADw-400+AD4- 71 Glu Val Gln Leu Leu Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 1 5 10 15 Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Ser Tyr 20 25 30 Ala Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45 Ser Ala Ile Ser Gly Ser Gly Gly Ser Thr Tyr Tyr Ala Asp Ser Val 50 55 60 Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 65 70 75 80 Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Ala Lys Gly Ser Gly Phe Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr 100 105 110 Val Ser Ser 115 +ADw-210+AD4- 72 +ADw-211+AD4- 108 +ADw-212+AD4- PRT +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- DP47 VL +ADw-400+AD4- 72 Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly 1 5 10 15 Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Ser Ser 20 25 30 Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu 35 40 45 Ile Tyr Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser 50 55 60 Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu 65 70 75 80 Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Gly Ser Ser Pro 85 90 95 Leu Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys 100 105 +ADw-210+AD4- 73 +ADw-211+AD4- 342 +ADw-212+AD4- ADN +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- hu CD40 VH (secuencia de nucle+APM-tidos) +ADw-400+AD4- 73 gaggtgcagc tggtggaatc tggcggcgga ctggtgcagc ctggcggatc tctgagactg 60 agctgtgccg ccagcggcta cagcttcacc ggctactaca tccactgggt gcgccaggcc 120 cctggcaagg gactggaatg ggtggccaga gtgatcccca atgccggcgg aaccagctac 180 aaccagaagt tcaagggccg gttcaccctg agcgtggaca acagcaagaa caccgcctac 240 ctgcagatga acagcctgcg ggccgaggac accgccgtgt actattgtgc ccgcgagggc 300 atctattggt ggggccaggg aacactcgtg accgtgtcca gc 342 +ADw-210+AD4- 74 +ADw-211+AD4- 336 +ADw-212+AD4- ADN +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- hu CD40 VL (secuencia de nucle+APM-tidos) +ADw-400+AD4- 74 gacatccaga tgacccagag ccccagcagc ctgtctgcca gcgtgggcga cagagtgacc 60 atcacctgtc ggagcagcca gagcctggtg cacagcaacg gcaacacctt cctgcactgg 120 tatcagcaga agcccggcaa ggcccccaag ctgctgatct acaccgtgtc caaccggttc 180 agcggcgtgc ccagcagatt ttctggcagc ggctccggca ccgacttcac cctgacaatc 240 agctccctgc agcccgagga cttcgccacc tatttctgca gccagaccac ccacgtgccc 300 tggacatttg gacagggcac caaggtggaa atcaag 336 +ADw-210+AD4- 75 +ADw-211+AD4- 348 +ADw-212+AD4- ADN +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- FAP 28H1 VH (secuencia de nucle+APM-tidos) +ADw-400+AD4- 75 gaggtgcagc tgctggaatc cggcggaggc ctggtgcagc ctggcggatc tctgagactg 60 tcctgcgccg cctccggctt caccttctcc tcccacgcca tgtcctgggt ccgacaggct 120 cctggcaaag gcctggaatg ggtgtccgcc atctgggcct ccggcgagca gtactacgcc 180 gactctgtga agggccggtt caccatctcc cgggacaact ccaagaacac cctgtacctg 240 cagatgaact ccctgcgggc cgaggacacc gccgtgtact actgtgccaa gggctggctg 300 ggcaacttcg actactgggg ccagggcacc ctggtcaccg tgtccagc 348 +ADw-210+AD4- 76 +ADw-211+AD4- 324 +ADw-212+AD4- ADN +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- FAP 28H1 VL (secuencia de nucle+APM-tidos) +ADw-400+AD4- 76 gagatcgtgc tgacccagtc tcccggcacc ctgagcctga gccctggcga gagagccacc 60 ctgagctgca gagccagcca gagcgtgagc cggagctacc tggcctggta tcagcagaag 120 cccggccagg cccccagact gctgatcatc ggcgccagca cccgggccac cggcatcccc 180 gatagattca gcggcagcgg ctccggcacc gacttcaccc tgaccatcag ccggctggaa 240 cccgaggact tcgccgtgta ctactgccag cagggccagg tgatcccccc caccttcggc 300 cagggcacca aggtggaaat caag 324 +ADw-210+AD4- 77 +ADw-211+AD4- 345 +ADw-212+AD4- ADN +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- DP47 VH (secuencia de nucle+APM-tidos) +ADw-400+AD4- 77 gaggtgcaat tgttggagtc tgggggaggc ttggtacagc ctggggggtc cctgagactc 60 tcctgtgcag ccagcggatt cacctttagc agttatgcca tgagctgggt ccgccaggct 120 ccagggaagg ggctggagtg ggtctcagct attagtggta gtggtggtag cacatactac 180 gcagactccg tgaagggccg gttcaccatc tccagagaca attccaagaa cacgctgtat 240 ctgcagatga acagcctgag agccgaggac acggccgtat attactgtgc gaaaggcagc 300 ggatttgact actggggcca aggaaccctg gtcaccgtct cgagc 345 +ADw-210+AD4- 78 +ADw-211+AD4- 324 +ADw-212+AD4- ADN +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- DP47 VL(secuencia de nucle+APM-tidos) +ADw-400+AD4- 78 gaaattgtgc tgacccagag ccccggcacc ctgtcactgt ctccaggcga aagagccacc 60 ctgagctgca gagccagcca gagcgtgtcc agctcttacc tggcctggta tcagcagaag 120 cccggacagg cccccagact gctgatctac ggcgcctctt ctagagccac cggcatcccc 180 gatagattca gcggcagcgg ctccggcacc gacttcaccc tgacaatcag cagactggaa 240 cccgaggact ttgccgtgta ttactgccag cagtacggca gcagccccct gacctttggc 300 cagggcacca aggtggaaat caaa 324 +ADw-210+AD4- 79 +ADw-211+AD4- 348 +ADw-212+AD4- ADN +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- mu CD40 VH (secuencia de nucle+APM-tidos) +ADw-400+AD4- 79 gaagtgcagc tggtggaatc cgacggcgga ctggtgcagc ctggcagatc tctgaagctg 60 ccttgtgccg cctccggctt caccttctcc gactactaca tggcctgggt gcgacaggcc 120 cctaccaagg gactggaatg ggtggcctcc atctcctacg acggctcctc cacctactac 180 cgggactctg tgaagggccg gttcaccatc tctcgggaca acgccaagtc caccctgtac 240 ctgcagatgg actccctgcg gagcgaggac accgctacct actactgcgg cagacactcc 300 tcctacttcg actactgggg ccagggcgtg atggtcaccg tgtcctct 348 +ADw-210+AD4- 80 +ADw-211+AD4- 318 +ADw-212+AD4- ADN +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- mu CD40 VL (secuencia de nucle+APM-tidos) +ADw-400+AD4- 80 gacactgtac tgacccagtc tcctgctttg gctgtgtctc caggagagag ggttaccatc 60 tcctgtaggg ccagtgacag tgtcagtaca cttatgcact ggtaccaaca gaaaccagga 120 cagcaaccca aactcctcat ctatctagca tcacacctag aatctggggt ccctgccagg 180 ttcagtggca gtgggtctgg gacagacttc accctcacca ttgatcctgt ggaggctgat 240 gacactgcaa cctattactg tcagcagagt tggaatgatc cgtggacgtt cggtggaggc 300 accaagctgg aattgaaa 318 +ADw-210+AD4- 81 +ADw-211+AD4- 443 +ADw-212+AD4- PRT +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- CD40 IgG cadena pesada +ADw-400+AD4- 81 Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 1 5 10 15 Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Tyr Ser Phe Thr Gly Tyr 20 25 30 Tyr Ile His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45 Ala Arg Val Ile Pro Asn Ala Gly Gly Thr Ser Tyr Asn Gln Lys Phe 50 55 60 Lys Gly Arg Phe Thr Leu Ser Val Asp Asn Ser Lys Asn Thr Ala Tyr 65 70 75 80 Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Ala Arg Glu Gly Ile Tyr Trp Trp Gly Gln Gly Thr Leu Val Thr Val 100 105 110 Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser 115 120 125 Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Lys 130 135 140 Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu 145 150 155 160 Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu 165 170 175 Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr 180 185 190 Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys Val 195 200 205 Asp Lys Lys Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro 210 215 220 Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe 225 230 235 240 Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val 245 250 255 Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe 260 265 270 Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro 275 280 285 Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr 290 295 300 Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val 305 310 315 320 Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala 325 330 335 Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg 340 345 350 Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly 355 360 365 Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro 370 375 380 Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser 385 390 395 400 Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln 405 410 415 Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His 420 425 430 Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly 435 440 +ADw-210+AD4- 82 +ADw-211+AD4- 219 +ADw-212+AD4- PRT +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- CD40 cadena ligera +ADw-400+AD4- 82 Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 1 5 10 15 Asp Arg Val Thr Ile Thr Cys Arg Ser Ser Gln Ser Leu Val His Ser 20 25 30 Asn Gly Asn Thr Phe Leu His Trp Tyr Gln Gln Lys Pro Gly Lys Ala 35 40 45 Pro Lys Leu Leu Ile Tyr Thr Val Ser Asn Arg Phe Ser Gly Val Pro 50 55 60 Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile 65 70 75 80 Ser Ser Leu Gln Pro Glu Asp Phe Ala Thr Tyr Phe Cys Ser Gln Thr 85 90 95 Thr His Val Pro Trp Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys 100 105 110 Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu 115 120 125 Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe 130 135 140 Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln 145 150 155 160 Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser 165 170 175 Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu 180 185 190 Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser 195 200 205 Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys 210 215 +ADw-210+AD4- 83 +ADw-211+AD4- 807 +ADw-212+AD4- PRT +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- CD40 VHCH1-CD40 VHCH1-Fcpomo+AF8-PGLALA -28H1 VH +ADw-400+AD4- 83 Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 1 5 10 15 Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Tyr Ser Phe Thr Gly Tyr 20 25 30 Tyr Ile His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45 Ala Arg Val Ile Pro Asn Ala Gly Gly Thr Ser Tyr Asn Gln Lys Phe 50 55 60 Lys Gly Arg Phe Thr Leu Ser Val Asp Asn Ser Lys Asn Thr Ala Tyr 65 70 75 80 Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Ala Arg Glu Gly Ile Tyr Trp Trp Gly Gln Gly Thr Leu Val Thr Val 100 105 110 Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser 115 120 125 Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Lys 130 135 140 Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu 145 150 155 160 Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu 165 170 175 Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr 180 185 190 Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys Val 195 200 205 Asp Lys Lys Val Glu Pro Lys Ser Cys Asp Gly Gly Gly Gly Ser Gly 210 215 220 Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val 225 230 235 240 Gln Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Tyr Ser 245 250 255 Phe Thr Gly Tyr Tyr Ile His Trp Val Arg Gln Ala Pro Gly Lys Gly 260 265 270 Leu Glu Trp Val Ala Arg Val Ile Pro Asn Ala Gly Gly Thr Ser Tyr 275 280 285 Asn Gln Lys Phe Lys Gly Arg Phe Thr Leu Ser Val Asp Asn Ser Lys 290 295 300 Asn Thr Ala Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala 305 310 315 320 Val Tyr Tyr Cys Ala Arg Glu Gly Ile Tyr Trp Trp Gly Gln Gly Thr 325 330 335 Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro 340 345 350 Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly 355 360 365 Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn 370 375 380 Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln 385 390 395 400 Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser 405 410 415 Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser 420 425 430 Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp Lys Thr 435 440 445 His Thr Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly Gly Pro Ser 450 455 460 Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg 465 470 475 480 Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro 485 490 495 Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala 500 505 510 Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val 515 520 525 Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr 530 535 540 Lys Cys Lys Val Ser Asn Lys Ala Leu Gly Ala Pro Ile Glu Lys Thr 545 550 555 560 Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu 565 570 575 Pro Pro Cys Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Trp Cys 580 585 590 Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser 595 600 605 Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp 610 615 620 Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser 625 630 635 640 Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala 645 650 655 Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Gly 660 665 670 Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly 675 680 685 Gly Gly Ser Glu Val Gln Leu Leu Glu Ser Gly Gly Gly Leu Val Gln 690 695 700 Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe 705 710 715 720 Ser Ser His Ala Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu 725 730 735 Glu Trp Val Ser Ala Ile Trp Ala Ser Gly Glu Gln Tyr Tyr Ala Asp 740 745 750 Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr 755 760 765 Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr 770 775 780 Tyr Cys Ala Lys Gly Trp Leu Gly Asn Phe Asp Tyr Trp Gly Gln Gly 785 790 795 800 Thr Leu Val Thr Val Ser Ser 805 +ADw-210+AD4- 84 +ADw-211+AD4- 799 +ADw-212+AD4- PRT +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- CD40 VHCH1-CD40 VHCH1-Fcagujero+AF8-PGLALA-28H1 VL +ADw-400+AD4- 84 Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 1 5 10 15 Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Tyr Ser Phe Thr Gly Tyr 20 25 30 Tyr Ile His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45 Ala Arg Val Ile Pro Asn Ala Gly Gly Thr Ser Tyr Asn Gln Lys Phe 50 55 60 Lys Gly Arg Phe Thr Leu Ser Val Asp Asn Ser Lys Asn Thr Ala Tyr 65 70 75 80 Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Ala Arg Glu Gly Ile Tyr Trp Trp Gly Gln Gly Thr Leu Val Thr Val 100 105 110 Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser 115 120 125 Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Lys 130 135 140 Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu 145 150 155 160 Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu 165 170 175 Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr 180 185 190 Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys Val 195 200 205 Asp Lys Lys Val Glu Pro Lys Ser Cys Asp Gly Gly Gly Gly Ser Gly 210 215 220 Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val 225 230 235 240 Gln Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Tyr Ser 245 250 255 Phe Thr Gly Tyr Tyr Ile His Trp Val Arg Gln Ala Pro Gly Lys Gly 260 265 270 Leu Glu Trp Val Ala Arg Val Ile Pro Asn Ala Gly Gly Thr Ser Tyr 275 280 285 Asn Gln Lys Phe Lys Gly Arg Phe Thr Leu Ser Val Asp Asn Ser Lys 290 295 300 Asn Thr Ala Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala 305 310 315 320 Val Tyr Tyr Cys Ala Arg Glu Gly Ile Tyr Trp Trp Gly Gln Gly Thr 325 330 335 Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro 340 345 350 Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly 355 360 365 Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn 370 375 380 Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln 385 390 395 400 Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser 405 410 415 Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser 420 425 430 Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp Lys Thr 435 440 445 His Thr Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly Gly Pro Ser 450 455 460 Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg 465 470 475 480 Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro 485 490 495 Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala 500 505 510 Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val 515 520 525 Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr 530 535 540 Lys Cys Lys Val Ser Asn Lys Ala Leu Gly Ala Pro Ile Glu Lys Thr 545 550 555 560 Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Cys Thr Leu 565 570 575 Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Ser Cys 580 585 590 Ala Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser 595 600 605 Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp 610 615 620 Ser Asp Gly Ser Phe Phe Leu Val Ser Lys Leu Thr Val Asp Lys Ser 625 630 635 640 Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala 645 650 655 Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Gly 660 665 670 Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly 675 680 685 Gly Gly Ser Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu 690 695 700 Ser Pro Gly Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val 705 710 715 720 Ser Arg Ser Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro 725 730 735 Arg Leu Leu Ile Ile Gly Ala Ser Thr Arg Ala Thr Gly Ile Pro Asp 740 745 750 Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser 755 760 765 Arg Leu Glu Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Gly Gln 770 775 780 Val Ile Pro Pro Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys 785 790 795 +ADw-210+AD4- 85 +ADw-211+AD4- 904 +ADw-212+AD4- PRT +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- CD40 VHCH1-CD40 VHCH1-Fc+AF8-PGLALA-28H1 VLCH1 EE +ADw-400+AD4- 85 Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 1 5 10 15 Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Tyr Ser Phe Thr Gly Tyr 20 25 30 Tyr Ile His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45 Ala Arg Val Ile Pro Asn Ala Gly Gly Thr Ser Tyr Asn Gln Lys Phe 50 55 60 Lys Gly Arg Phe Thr Leu Ser Val Asp Asn Ser Lys Asn Thr Ala Tyr 65 70 75 80 Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Ala Arg Glu Gly Ile Tyr Trp Trp Gly Gln Gly Thr Leu Val Thr Val 100 105 110 Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser 115 120 125 Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Glu 130 135 140 Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu 145 150 155 160 Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu 165 170 175 Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr 180 185 190 Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys Val 195 200 205 Asp Glu Lys Val Glu Pro Lys Ser Cys Asp Gly Gly Gly Gly Ser Gly 210 215 220 Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val 225 230 235 240 Gln Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Tyr Ser 245 250 255 Phe Thr Gly Tyr Tyr Ile His Trp Val Arg Gln Ala Pro Gly Lys Gly 260 265 270 Leu Glu Trp Val Ala Arg Val Ile Pro Asn Ala Gly Gly Thr Ser Tyr 275 280 285 Asn Gln Lys Phe Lys Gly Arg Phe Thr Leu Ser Val Asp Asn Ser Lys 290 295 300 Asn Thr Ala Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala 305 310 315 320 Val Tyr Tyr Cys Ala Arg Glu Gly Ile Tyr Trp Trp Gly Gln Gly Thr 325 330 335 Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro 340 345 350 Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly 355 360 365 Cys Leu Val Glu Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn 370 375 380 Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln 385 390 395 400 Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser 405 410 415 Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser 420 425 430 Asn Thr Lys Val Asp Glu Lys Val Glu Pro Lys Ser Cys Asp Lys Thr 435 440 445 His Thr Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly Gly Pro Ser 450 455 460 Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg 465 470 475 480 Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro 485 490 495 Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala 500 505 510 Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val 515 520 525 Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr 530 535 540 Lys Cys Lys Val Ser Asn Lys Ala Leu Gly Ala Pro Ile Glu Lys Thr 545 550 555 560 Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu 565 570 575 Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Thr Cys 580 585 590 Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser 595 600 605 Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp 610 615 620 Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser 625 630 635 640 Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala 645 650 655 Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Gly 660 665 670 Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly 675 680 685 Gly Gly Ser Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu 690 695 700 Ser Pro Gly Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val 705 710 715 720 Ser Arg Ser Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro 725 730 735 Arg Leu Leu Ile Ile Gly Ala Ser Thr Arg Ala Thr Gly Ile Pro Asp 740 745 750 Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser 755 760 765 Arg Leu Glu Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Gly Gln 770 775 780 Val Ile Pro Pro Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Ser 785 790 795 800 Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser Ser 805 810 815 Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Lys Asp 820 825 830 Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr 835 840 845 Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr 850 855 860 Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Gln 865 870 875 880 Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys Val Asp 885 890 895 Lys Lys Val Glu Pro Lys Ser Cys 900 +ADw-210+AD4- 86 +ADw-211+AD4- 219 +ADw-212+AD4- PRT +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- CD40 cadena ligera RK +ADw-400+AD4- 86 Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 1 5 10 15 Asp Arg Val Thr Ile Thr Cys Arg Ser Ser Gln Ser Leu Val His Ser 20 25 30 Asn Gly Asn Thr Phe Leu His Trp Tyr Gln Gln Lys Pro Gly Lys Ala 35 40 45 Pro Lys Leu Leu Ile Tyr Thr Val Ser Asn Arg Phe Ser Gly Val Pro 50 55 60 Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile 65 70 75 80 Ser Ser Leu Gln Pro Glu Asp Phe Ala Thr Tyr Phe Cys Ser Gln Thr 85 90 95 Thr His Val Pro Trp Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys 100 105 110 Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Arg 115 120 125 Lys Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe 130 135 140 Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln 145 150 155 160 Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser 165 170 175 Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu 180 185 190 Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser 195 200 205 Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys 210 215 +ADw-210+AD4- 87 +ADw-211+AD4- 223 +ADw-212+AD4- PRT +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- 28H1 VHCL +ADw-400+AD4- 87 Glu Val Gln Leu Leu Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 1 5 10 15 Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Ser His 20 25 30 Ala Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45 Ser Ala Ile Trp Ala Ser Gly Glu Gln Tyr Tyr Ala Asp Ser Val Lys 50 55 60 Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr Leu 65 70 75 80 Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala 85 90 95 Lys Gly Trp Leu Gly Asn Phe Asp Tyr Trp Gly Gln Gly Thr Leu Val 100 105 110 Thr Val Ser Ser Ala Ser Val Ala Ala Pro Ser Val Phe Ile Phe Pro 115 120 125 Pro Ser Asp Glu Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu 130 135 140 Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp 145 150 155 160 Asn Ala Leu Gln Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp 165 170 175 Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys 180 185 190 Ala Asp Tyr Glu Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln 195 200 205 Gly Leu Ser Ser Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys 210 215 220 +ADw-210+AD4- 88 +ADw-211+AD4- 571 +ADw-212+AD4- PRT +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- huCD40+AF8-Fcagujero+AF8-PGLALA+AF8-28H1 VL +ADw-400+AD4- 88 Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 1 5 10 15 Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Tyr Ser Phe Thr Gly Tyr 20 25 30 Tyr Ile His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45 Ala Arg Val Ile Pro Asn Ala Gly Gly Thr Ser Tyr Asn Gln Lys Phe 50 55 60 Lys Gly Arg Phe Thr Leu Ser Val Asp Asn Ser Lys Asn Thr Ala Tyr 65 70 75 80 Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Ala Arg Glu Gly Ile Tyr Trp Trp Gly Gln Gly Thr Leu Val Thr Val 100 105 110 Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser 115 120 125 Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Lys 130 135 140 Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu 145 150 155 160 Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu 165 170 175 Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr 180 185 190 Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys Val 195 200 205 Asp Lys Lys Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro 210 215 220 Pro Cys Pro Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe 225 230 235 240 Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val 245 250 255 Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe 260 265 270 Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro 275 280 285 Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr 290 295 300 Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val 305 310 315 320 Ser Asn Lys Ala Leu Gly Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala 325 330 335 Lys Gly Gln Pro Arg Glu Pro Gln Val Cys Thr Leu Pro Pro Ser Arg 340 345 350 Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Ser Cys Ala Val Lys Gly 355 360 365 Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro 370 375 380 Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser 385 390 395 400 Phe Phe Leu Val Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln 405 410 415 Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His 420 425 430 Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Gly Gly Gly Gly Ser 435 440 445 Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Glu 450 455 460 Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly Glu 465 470 475 480 Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Arg Ser Tyr 485 490 495 Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile 500 505 510 Ile Gly Ala Ser Thr Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser Gly 515 520 525 Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu Pro 530 535 540 Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Gly Gln Val Ile Pro Pro 545 550 555 560 Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys 565 570 +ADw-210+AD4- 89 +ADw-211+AD4- 579 +ADw-212+AD4- PRT +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- huCD40+AF8-Fcpomo+AF8-PGLALA+AF8-28H1 VH +ADw-400+AD4- 89 Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 1 5 10 15 Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Tyr Ser Phe Thr Gly Tyr 20 25 30 Tyr Ile His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45 Ala Arg Val Ile Pro Asn Ala Gly Gly Thr Ser Tyr Asn Gln Lys Phe 50 55 60 Lys Gly Arg Phe Thr Leu Ser Val Asp Asn Ser Lys Asn Thr Ala Tyr 65 70 75 80 Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Ala Arg Glu Gly Ile Tyr Trp Trp Gly Gln Gly Thr Leu Val Thr Val 100 105 110 Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser 115 120 125 Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Lys 130 135 140 Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu 145 150 155 160 Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu 165 170 175 Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr 180 185 190 Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys Val 195 200 205 Asp Lys Lys Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro 210 215 220 Pro Cys Pro Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe 225 230 235 240 Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val 245 250 255 Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe 260 265 270 Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro 275 280 285 Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr 290 295 300 Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val 305 310 315 320 Ser Asn Lys Ala Leu Gly Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala 325 330 335 Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Cys Arg 340 345 350 Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Trp Cys Leu Val Lys Gly 355 360 365 Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro 370 375 380 Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser 385 390 395 400 Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln 405 410 415 Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His 420 425 430 Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Gly Gly Gly Gly Ser 435 440 445 Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Glu 450 455 460 Val Gln Leu Leu Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser 465 470 475 480 Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Ser His Ala 485 490 495 Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ser 500 505 510 Ala Ile Trp Ala Ser Gly Glu Gln Tyr Tyr Ala Asp Ser Val Lys Gly 515 520 525 Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr Leu Gln 530 535 540 Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Lys 545 550 555 560 Gly Trp Leu Gly Asn Phe Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr 565 570 575 Val Ser Ser +ADw-210+AD4- 90 +ADw-211+AD4- 676 +ADw-212+AD4- PRT +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- huCD40-Fc+AF8-PGLALA+AF8-28H1+AF8-VLCH1 EE +ADw-400+AD4- 90 Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 1 5 10 15 Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Tyr Ser Phe Thr Gly Tyr 20 25 30 Tyr Ile His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45 Ala Arg Val Ile Pro Asn Ala Gly Gly Thr Ser Tyr Asn Gln Lys Phe 50 55 60 Lys Gly Arg Phe Thr Leu Ser Val Asp Asn Ser Lys Asn Thr Ala Tyr 65 70 75 80 Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Ala Arg Glu Gly Ile Tyr Trp Trp Gly Gln Gly Thr Leu Val Thr Val 100 105 110 Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser 115 120 125 Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Glu 130 135 140 Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu 145 150 155 160 Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu 165 170 175 Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr 180 185 190 Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys Val 195 200 205 Asp Glu Lys Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro 210 215 220 Pro Cys Pro Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe 225 230 235 240 Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val 245 250 255 Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe 260 265 270 Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro 275 280 285 Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr 290 295 300 Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val 305 310 315 320 Ser Asn Lys Ala Leu Gly Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala 325 330 335 Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg 340 345 350 Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly 355 360 365 Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro 370 375 380 Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser 385 390 395 400 Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln 405 410 415 Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His 420 425 430 Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Gly Gly Gly Gly Ser 435 440 445 Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Glu 450 455 460 Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly Glu 465 470 475 480 Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Arg Ser Tyr 485 490 495 Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile 500 505 510 Ile Gly Ala Ser Thr Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser Gly 515 520 525 Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu Pro 530 535 540 Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Gly Gln Val Ile Pro Pro 545 550 555 560 Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Ser Ser Ala Ser Thr 565 570 575 Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser 580 585 590 Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu 595 600 605 Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His 610 615 620 Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser 625 630 635 640 Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys 645 650 655 Asn Val Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Lys Val Glu 660 665 670 Pro Lys Ser Cys 675 +ADw-210+AD4- 91 +ADw-211+AD4- 806 +ADw-212+AD4- PRT +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- CD40 VHCH1-CD40 VHCH1-Fcpomo+AF8-PGLALA-DP47 VH +ADw-400+AD4- 91 Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 1 5 10 15 Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Tyr Ser Phe Thr Gly Tyr 20 25 30 Tyr Ile His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45 Ala Arg Val Ile Pro Asn Ala Gly Gly Thr Ser Tyr Asn Gln Lys Phe 50 55 60 Lys Gly Arg Phe Thr Leu Ser Val Asp Asn Ser Lys Asn Thr Ala Tyr 65 70 75 80 Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Ala Arg Glu Gly Ile Tyr Trp Trp Gly Gln Gly Thr Leu Val Thr Val 100 105 110 Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser 115 120 125 Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Lys 130 135 140 Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu 145 150 155 160 Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu 165 170 175 Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr 180 185 190 Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys Val 195 200 205 Asp Lys Lys Val Glu Pro Lys Ser Cys Asp Gly Gly Gly Gly Ser Gly 210 215 220 Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val 225 230 235 240 Gln Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Tyr Ser 245 250 255 Phe Thr Gly Tyr Tyr Ile His Trp Val Arg Gln Ala Pro Gly Lys Gly 260 265 270 Leu Glu Trp Val Ala Arg Val Ile Pro Asn Ala Gly Gly Thr Ser Tyr 275 280 285 Asn Gln Lys Phe Lys Gly Arg Phe Thr Leu Ser Val Asp Asn Ser Lys 290 295 300 Asn Thr Ala Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala 305 310 315 320 Val Tyr Tyr Cys Ala Arg Glu Gly Ile Tyr Trp Trp Gly Gln Gly Thr 325 330 335 Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro 340 345 350 Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly 355 360 365 Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn 370 375 380 Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln 385 390 395 400 Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser 405 410 415 Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser 420 425 430 Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp Lys Thr 435 440 445 His Thr Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly Gly Pro Ser 450 455 460 Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg 465 470 475 480 Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro 485 490 495 Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala 500 505 510 Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val 515 520 525 Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr 530 535 540 Lys Cys Lys Val Ser Asn Lys Ala Leu Gly Ala Pro Ile Glu Lys Thr 545 550 555 560 Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu 565 570 575 Pro Pro Cys Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Trp Cys 580 585 590 Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser 595 600 605 Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp 610 615 620 Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser 625 630 635 640 Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala 645 650 655 Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Gly 660 665 670 Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly 675 680 685 Gly Gly Ser Glu Val Gln Leu Leu Glu Ser Gly Gly Gly Leu Val Gln 690 695 700 Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe 705 710 715 720 Ser Ser Tyr Ala Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu 725 730 735 Glu Trp Val Ser Ala Ile Ser Gly Ser Gly Gly Ser Thr Tyr Tyr Ala 740 745 750 Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn 755 760 765 Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val 770 775 780 Tyr Tyr Cys Ala Lys Gly Ser Gly Phe Asp Tyr Trp Gly Gln Gly Thr 785 790 795 800 Leu Val Thr Val Ser Ser 805 +ADw-210+AD4- 92 +ADw-211+AD4- 799 +ADw-212+AD4- PRT +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- CD40 VHCH1-CD40 VHCH1-Fagujero+AF8-PGLALA-DP47 VL +ADw-400+AD4- 92 Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 1 5 10 15 Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Tyr Ser Phe Thr Gly Tyr 20 25 30 Tyr Ile His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45 Ala Arg Val Ile Pro Asn Ala Gly Gly Thr Ser Tyr Asn Gln Lys Phe 50 55 60 Lys Gly Arg Phe Thr Leu Ser Val Asp Asn Ser Lys Asn Thr Ala Tyr 65 70 75 80 Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Ala Arg Glu Gly Ile Tyr Trp Trp Gly Gln Gly Thr Leu Val Thr Val 100 105 110 Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser 115 120 125 Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Lys 130 135 140 Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu 145 150 155 160 Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu 165 170 175 Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr 180 185 190 Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys Val 195 200 205 Asp Lys Lys Val Glu Pro Lys Ser Cys Asp Gly Gly Gly Gly Ser Gly 210 215 220 Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val 225 230 235 240 Gln Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Tyr Ser 245 250 255 Phe Thr Gly Tyr Tyr Ile His Trp Val Arg Gln Ala Pro Gly Lys Gly 260 265 270 Leu Glu Trp Val Ala Arg Val Ile Pro Asn Ala Gly Gly Thr Ser Tyr 275 280 285 Asn Gln Lys Phe Lys Gly Arg Phe Thr Leu Ser Val Asp Asn Ser Lys 290 295 300 Asn Thr Ala Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala 305 310 315 320 Val Tyr Tyr Cys Ala Arg Glu Gly Ile Tyr Trp Trp Gly Gln Gly Thr 325 330 335 Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro 340 345 350 Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly 355 360 365 Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn 370 375 380 Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln 385 390 395 400 Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser 405 410 415 Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser 420 425 430 Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp Lys Thr 435 440 445 His Thr Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly Gly Pro Ser 450 455 460 Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg 465 470 475 480 Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro 485 490 495 Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala 500 505 510 Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val 515 520 525 Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr 530 535 540 Lys Cys Lys Val Ser Asn Lys Ala Leu Gly Ala Pro Ile Glu Lys Thr 545 550 555 560 Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Cys Thr Leu 565 570 575 Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Ser Cys 580 585 590 Ala Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser 595 600 605 Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp 610 615 620 Ser Asp Gly Ser Phe Phe Leu Val Ser Lys Leu Thr Val Asp Lys Ser 625 630 635 640 Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala 645 650 655 Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Gly 660 665 670 Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly 675 680 685 Gly Gly Ser Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu 690 695 700 Ser Pro Gly Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val 705 710 715 720 Ser Ser Ser Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro 725 730 735 Arg Leu Leu Ile Tyr Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro Asp 740 745 750 Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser 755 760 765 Arg Leu Glu Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Gly 770 775 780 Ser Ser Pro Leu Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys 785 790 795 +ADw-210+AD4- 93 +ADw-211+AD4- 904 +ADw-212+AD4- PRT +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- CD40 VHCH1-CD40 VHCH1-Fc+AF8-PGLALA-DP47 VLCH1 EE +ADw-400+AD4- 93 Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 1 5 10 15 Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Tyr Ser Phe Thr Gly Tyr 20 25 30 Tyr Ile His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45 Ala Arg Val Ile Pro Asn Ala Gly Gly Thr Ser Tyr Asn Gln Lys Phe 50 55 60 Lys Gly Arg Phe Thr Leu Ser Val Asp Asn Ser Lys Asn Thr Ala Tyr 65 70 75 80 Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Ala Arg Glu Gly Ile Tyr Trp Trp Gly Gln Gly Thr Leu Val Thr Val 100 105 110 Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser 115 120 125 Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Glu 130 135 140 Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu 145 150 155 160 Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu 165 170 175 Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr 180 185 190 Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys Val 195 200 205 Asp Glu Lys Val Glu Pro Lys Ser Cys Asp Gly Gly Gly Gly Ser Gly 210 215 220 Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val 225 230 235 240 Gln Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Tyr Ser 245 250 255 Phe Thr Gly Tyr Tyr Ile His Trp Val Arg Gln Ala Pro Gly Lys Gly 260 265 270 Leu Glu Trp Val Ala Arg Val Ile Pro Asn Ala Gly Gly Thr Ser Tyr 275 280 285 Asn Gln Lys Phe Lys Gly Arg Phe Thr Leu Ser Val Asp Asn Ser Lys 290 295 300 Asn Thr Ala Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala 305 310 315 320 Val Tyr Tyr Cys Ala Arg Glu Gly Ile Tyr Trp Trp Gly Gln Gly Thr 325 330 335 Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro 340 345 350 Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly 355 360 365 Cys Leu Val Glu Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn 370 375 380 Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln 385 390 395 400 Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser 405 410 415 Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser 420 425 430 Asn Thr Lys Val Asp Glu Lys Val Glu Pro Lys Ser Cys Asp Lys Thr 435 440 445 His Thr Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly Gly Pro Ser 450 455 460 Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg 465 470 475 480 Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro 485 490 495 Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala 500 505 510 Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val 515 520 525 Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr 530 535 540 Lys Cys Lys Val Ser Asn Lys Ala Leu Gly Ala Pro Ile Glu Lys Thr 545 550 555 560 Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu 565 570 575 Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Thr Cys 580 585 590 Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser 595 600 605 Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp 610 615 620 Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser 625 630 635 640 Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala 645 650 655 Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Gly 660 665 670 Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly 675 680 685 Gly Gly Ser Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu 690 695 700 Ser Pro Gly Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val 705 710 715 720 Ser Ser Ser Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro 725 730 735 Arg Leu Leu Ile Tyr Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro Asp 740 745 750 Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser 755 760 765 Arg Leu Glu Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Gly 770 775 780 Ser Ser Pro Leu Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Ser 785 790 795 800 Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser Ser 805 810 815 Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Lys Asp 820 825 830 Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr 835 840 845 Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr 850 855 860 Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Gln 865 870 875 880 Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys Val Asp 885 890 895 Lys Lys Val Glu Pro Lys Ser Cys 900 +ADw-210+AD4- 94 +ADw-211+AD4- 222 +ADw-212+AD4- PRT +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- DP47VHCL +ADw-400+AD4- 94 Glu Val Gln Leu Leu Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 1 5 10 15 Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Ser Tyr 20 25 30 Ala Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45 Ser Ala Ile Ser Gly Ser Gly Gly Ser Thr Tyr Tyr Ala Asp Ser Val 50 55 60 Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 65 70 75 80 Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Ala Lys Gly Ser Gly Phe Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr 100 105 110 Val Ser Ser Ala Ser Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro 115 120 125 Ser Asp Glu Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu 130 135 140 Asn Asn Phe Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn 145 150 155 160 Ala Leu Gln Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser 165 170 175 Lys Asp Ser Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala 180 185 190 Asp Tyr Glu Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly 195 200 205 Leu Ser Ser Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys 210 215 220 +ADw-210+AD4- 95 +ADw-211+AD4- 803 +ADw-212+AD4- PRT +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- muCD40 VHCH1-muCD40 VHCH1-FcKK+AF8-DAPG -28H1 VH +ADw-400+AD4- 95 Glu Val Gln Leu Val Glu Ser Asp Gly Gly Leu Val Gln Pro Gly Arg 1 5 10 15 Ser Leu Lys Leu Pro Cys Ala Ala Ser Gly Phe Thr Phe Ser Asp Tyr 20 25 30 Tyr Met Ala Trp Val Arg Gln Ala Pro Thr Lys Gly Leu Glu Trp Val 35 40 45 Ala Ser Ile Ser Tyr Asp Gly Ser Ser Thr Tyr Tyr Arg Asp Ser Val 50 55 60 Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Ser Thr Leu Tyr 65 70 75 80 Leu Gln Met Asp Ser Leu Arg Ser Glu Asp Thr Ala Thr Tyr Tyr Cys 85 90 95 Gly Arg His Ser Ser Tyr Phe Asp Tyr Trp Gly Gln Gly Val Met Val 100 105 110 Thr Val Ser Ser Ala Lys Thr Thr Pro Pro Ser Val Tyr Pro Leu Ala 115 120 125 Pro Gly Ser Ala Ala Gln Thr Asn Ser Met Val Thr Leu Gly Cys Leu 130 135 140 Val Lys Gly Tyr Phe Pro Glu Pro Val Thr Val Thr Trp Asn Ser Gly 145 150 155 160 Ser Leu Ser Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Asp 165 170 175 Leu Tyr Thr Leu Ser Ser Ser Val Thr Val Pro Ser Ser Thr Trp Pro 180 185 190 Ser Gln Thr Val Thr Cys Asn Val Ala His Pro Ala Ser Ser Thr Lys 195 200 205 Val Asp Lys Lys Ile Val Pro Arg Asp Cys Gly Gly Gly Gly Ser Gly 210 215 220 Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Asp Gly Gly Leu Val 225 230 235 240 Gln Pro Gly Arg Ser Leu Lys Leu Pro Cys Ala Ala Ser Gly Phe Thr 245 250 255 Phe Ser Asp Tyr Tyr Met Ala Trp Val Arg Gln Ala Pro Thr Lys Gly 260 265 270 Leu Glu Trp Val Ala Ser Ile Ser Tyr Asp Gly Ser Ser Thr Tyr Tyr 275 280 285 Arg Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys 290 295 300 Ser Thr Leu Tyr Leu Gln Met Asp Ser Leu Arg Ser Glu Asp Thr Ala 305 310 315 320 Thr Tyr Tyr Cys Gly Arg His Ser Ser Tyr Phe Asp Tyr Trp Gly Gln 325 330 335 Gly Val Met Val Thr Val Ser Ser Ala Lys Thr Thr Pro Pro Ser Val 340 345 350 Tyr Pro Leu Ala Pro Gly Ser Ala Ala Gln Thr Asn Ser Met Val Thr 355 360 365 Leu Gly Cys Leu Val Lys Gly Tyr Phe Pro Glu Pro Val Thr Val Thr 370 375 380 Trp Asn Ser Gly Ser Leu Ser Ser Gly Val His Thr Phe Pro Ala Val 385 390 395 400 Leu Gln Ser Asp Leu Tyr Thr Leu Ser Ser Ser Val Thr Val Pro Ser 405 410 415 Ser Thr Trp Pro Ser Gln Thr Val Thr Cys Asn Val Ala His Pro Ala 420 425 430 Ser Ser Thr Lys Val Asp Lys Lys Ile Val Pro Arg Asp Cys Gly Cys 435 440 445 Lys Pro Cys Ile Cys Thr Val Pro Glu Val Ser Ser Val Phe Ile Phe 450 455 460 Pro Pro Lys Pro Lys Asp Val Leu Thr Ile Thr Leu Thr Pro Lys Val 465 470 475 480 Thr Cys Val Val Val Ala Ile Ser Lys Asp Asp Pro Glu Val Gln Phe 485 490 495 Ser Trp Phe Val Asp Asp Val Glu Val His Thr Ala Gln Thr Lys Pro 500 505 510 Arg Glu Glu Gln Ile Asn Ser Thr Phe Arg Ser Val Ser Glu Leu Pro 515 520 525 Ile Met His Gln Asp Trp Leu Asn Gly Lys Glu Phe Lys Cys Arg Val 530 535 540 Asn Ser Ala Ala Phe Gly Ala Pro Ile Glu Lys Thr Ile Ser Lys Thr 545 550 555 560 Lys Gly Arg Pro Lys Ala Pro Gln Val Tyr Thr Ile Pro Pro Pro Lys 565 570 575 Lys Gln Met Ala Lys Asp Lys Val Ser Leu Thr Cys Met Ile Thr Asn 580 585 590 Phe Phe Pro Glu Asp Ile Thr Val Glu Trp Gln Trp Asn Gly Gln Pro 595 600 605 Ala Glu Asn Tyr Lys Asn Thr Gln Pro Ile Met Lys Thr Asp Gly Ser 610 615 620 Tyr Phe Val Tyr Ser Lys Leu Asn Val Gln Lys Ser Asn Trp Glu Ala 625 630 635 640 Gly Asn Thr Phe Thr Cys Ser Val Leu His Glu Gly Leu His Asn His 645 650 655 His Thr Glu Lys Ser Leu Ser His Ser Pro Gly Gly Gly Gly Gly Ser 660 665 670 Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Glu 675 680 685 Val Gln Leu Leu Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser 690 695 700 Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Ser His Ala 705 710 715 720 Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ser 725 730 735 Ala Ile Trp Ala Ser Gly Glu Gln Tyr Tyr Ala Asp Ser Val Lys Gly 740 745 750 Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr Leu Gln 755 760 765 Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Lys 770 775 780 Gly Trp Leu Gly Asn Phe Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr 785 790 795 800 Val Ser Ser +ADw-210+AD4- 96 +ADw-211+AD4- 795 +ADw-212+AD4- PRT +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- muCD40 VHCH1-muCD40 VHCH1-FcDD+AF8-DAPG -28H1 VL +ADw-400+AD4- 96 Glu Val Gln Leu Val Glu Ser Asp Gly Gly Leu Val Gln Pro Gly Arg 1 5 10 15 Ser Leu Lys Leu Pro Cys Ala Ala Ser Gly Phe Thr Phe Ser Asp Tyr 20 25 30 Tyr Met Ala Trp Val Arg Gln Ala Pro Thr Lys Gly Leu Glu Trp Val 35 40 45 Ala Ser Ile Ser Tyr Asp Gly Ser Ser Thr Tyr Tyr Arg Asp Ser Val 50 55 60 Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Ser Thr Leu Tyr 65 70 75 80 Leu Gln Met Asp Ser Leu Arg Ser Glu Asp Thr Ala Thr Tyr Tyr Cys 85 90 95 Gly Arg His Ser Ser Tyr Phe Asp Tyr Trp Gly Gln Gly Val Met Val 100 105 110 Thr Val Ser Ser Ala Lys Thr Thr Pro Pro Ser Val Tyr Pro Leu Ala 115 120 125 Pro Gly Ser Ala Ala Gln Thr Asn Ser Met Val Thr Leu Gly Cys Leu 130 135 140 Val Lys Gly Tyr Phe Pro Glu Pro Val Thr Val Thr Trp Asn Ser Gly 145 150 155 160 Ser Leu Ser Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Asp 165 170 175 Leu Tyr Thr Leu Ser Ser Ser Val Thr Val Pro Ser Ser Thr Trp Pro 180 185 190 Ser Gln Thr Val Thr Cys Asn Val Ala His Pro Ala Ser Ser Thr Lys 195 200 205 Val Asp Lys Lys Ile Val Pro Arg Asp Cys Gly Gly Gly Gly Ser Gly 210 215 220 Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Asp Gly Gly Leu Val 225 230 235 240 Gln Pro Gly Arg Ser Leu Lys Leu Pro Cys Ala Ala Ser Gly Phe Thr 245 250 255 Phe Ser Asp Tyr Tyr Met Ala Trp Val Arg Gln Ala Pro Thr Lys Gly 260 265 270 Leu Glu Trp Val Ala Ser Ile Ser Tyr Asp Gly Ser Ser Thr Tyr Tyr 275 280 285 Arg Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys 290 295 300 Ser Thr Leu Tyr Leu Gln Met Asp Ser Leu Arg Ser Glu Asp Thr Ala 305 310 315 320 Thr Tyr Tyr Cys Gly Arg His Ser Ser Tyr Phe Asp Tyr Trp Gly Gln 325 330 335 Gly Val Met Val Thr Val Ser Ser Ala Lys Thr Thr Pro Pro Ser Val 340 345 350 Tyr Pro Leu Ala Pro Gly Ser Ala Ala Gln Thr Asn Ser Met Val Thr 355 360 365 Leu Gly Cys Leu Val Lys Gly Tyr Phe Pro Glu Pro Val Thr Val Thr 370 375 380 Trp Asn Ser Gly Ser Leu Ser Ser Gly Val His Thr Phe Pro Ala Val 385 390 395 400 Leu Gln Ser Asp Leu Tyr Thr Leu Ser Ser Ser Val Thr Val Pro Ser 405 410 415 Ser Thr Trp Pro Ser Gln Thr Val Thr Cys Asn Val Ala His Pro Ala 420 425 430 Ser Ser Thr Lys Val Asp Lys Lys Ile Val Pro Arg Asp Cys Gly Cys 435 440 445 Lys Pro Cys Ile Cys Thr Val Pro Glu Val Ser Ser Val Phe Ile Phe 450 455 460 Pro Pro Lys Pro Lys Asp Val Leu Thr Ile Thr Leu Thr Pro Lys Val 465 470 475 480 Thr Cys Val Val Val Ala Ile Ser Lys Asp Asp Pro Glu Val Gln Phe 485 490 495 Ser Trp Phe Val Asp Asp Val Glu Val His Thr Ala Gln Thr Lys Pro 500 505 510 Arg Glu Glu Gln Ile Asn Ser Thr Phe Arg Ser Val Ser Glu Leu Pro 515 520 525 Ile Met His Gln Asp Trp Leu Asn Gly Lys Glu Phe Lys Cys Arg Val 530 535 540 Asn Ser Ala Ala Phe Gly Ala Pro Ile Glu Lys Thr Ile Ser Lys Thr 545 550 555 560 Lys Gly Arg Pro Lys Ala Pro Gln Val Tyr Thr Ile Pro Pro Pro Lys 565 570 575 Glu Gln Met Ala Lys Asp Lys Val Ser Leu Thr Cys Met Ile Thr Asn 580 585 590 Phe Phe Pro Glu Asp Ile Thr Val Glu Trp Gln Trp Asn Gly Gln Pro 595 600 605 Ala Glu Asn Tyr Asp Asn Thr Gln Pro Ile Met Asp Thr Asp Gly Ser 610 615 620 Tyr Phe Val Tyr Ser Asp Leu Asn Val Gln Lys Ser Asn Trp Glu Ala 625 630 635 640 Gly Asn Thr Phe Thr Cys Ser Val Leu His Glu Gly Leu His Asn His 645 650 655 His Thr Glu Lys Ser Leu Ser His Ser Pro Gly Gly Gly Gly Gly Ser 660 665 670 Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Glu 675 680 685 Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly Glu 690 695 700 Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Arg Ser Tyr 705 710 715 720 Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile 725 730 735 Ile Gly Ala Ser Thr Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser Gly 740 745 750 Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu Pro 755 760 765 Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Gly Gln Val Ile Pro Pro 770 775 780 Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys 785 790 795 +ADw-210+AD4- 97 +ADw-211+AD4- 213 +ADw-212+AD4- PRT +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- mu CD40 cadena ligera +ADw-400+AD4- 97 Asp Thr Val Leu Thr Gln Ser Pro Ala Leu Ala Val Ser Pro Gly Glu 1 5 10 15 Arg Val Thr Ile Ser Cys Arg Ala Ser Asp Ser Val Ser Thr Leu Met 20 25 30 His Trp Tyr Gln Gln Lys Pro Gly Gln Gln Pro Lys Leu Leu Ile Tyr 35 40 45 Leu Ala Ser His Leu Glu Ser Gly Val Pro Ala Arg Phe Ser Gly Ser 50 55 60 Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Asp Pro Val Glu Ala Asp 65 70 75 80 Asp Thr Ala Thr Tyr Tyr Cys Gln Gln Ser Trp Asn Asp Pro Trp Thr 85 90 95 Phe Gly Gly Gly Thr Lys Leu Glu Leu Lys Arg Ala Asp Ala Ala Pro 100 105 110 Thr Val Ser Ile Phe Pro Pro Ser Ser Glu Gln Leu Thr Ser Gly Gly 115 120 125 Ala Ser Val Val Cys Phe Leu Asn Asn Phe Tyr Pro Lys Asp Ile Asn 130 135 140 Val Lys Trp Lys Ile Asp Gly Ser Glu Arg Gln Asn Gly Val Leu Asn 145 150 155 160 Ser Trp Thr Asp Gln Asp Ser Lys Asp Ser Thr Tyr Ser Met Ser Ser 165 170 175 Thr Leu Thr Leu Thr Lys Asp Glu Tyr Glu Arg His Asn Ser Tyr Thr 180 185 190 Cys Glu Ala Thr His Lys Thr Ser Thr Ser Pro Ile Val Lys Ser Phe 195 200 205 Asn Arg Asn Glu Cys 210 +ADw-210+AD4- 98 +ADw-211+AD4- 900 +ADw-212+AD4- PRT +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- muCD40 VHCH1-muCD40 VHCH1-Fc+AF8-DAPG-28H1 VLCH1 +ADw-400+AD4- 98 Glu Val Gln Leu Val Glu Ser Asp Gly Gly Leu Val Gln Pro Gly Arg 1 5 10 15 Ser Leu Lys Leu Pro Cys Ala Ala Ser Gly Phe Thr Phe Ser Asp Tyr 20 25 30 Tyr Met Ala Trp Val Arg Gln Ala Pro Thr Lys Gly Leu Glu Trp Val 35 40 45 Ala Ser Ile Ser Tyr Asp Gly Ser Ser Thr Tyr Tyr Arg Asp Ser Val 50 55 60 Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Ser Thr Leu Tyr 65 70 75 80 Leu Gln Met Asp Ser Leu Arg Ser Glu Asp Thr Ala Thr Tyr Tyr Cys 85 90 95 Gly Arg His Ser Ser Tyr Phe Asp Tyr Trp Gly Gln Gly Val Met Val 100 105 110 Thr Val Ser Ser Ala Lys Thr Thr Pro Pro Ser Val Tyr Pro Leu Ala 115 120 125 Pro Gly Ser Ala Ala Gln Thr Asn Ser Met Val Thr Leu Gly Cys Leu 130 135 140 Val Glu Gly Tyr Phe Pro Glu Pro Val Thr Val Thr Trp Asn Ser Gly 145 150 155 160 Ser Leu Ser Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Asp 165 170 175 Leu Tyr Thr Leu Ser Ser Ser Val Thr Val Pro Ser Ser Thr Trp Pro 180 185 190 Ser Gln Thr Val Thr Cys Asn Val Ala His Pro Ala Ser Ser Thr Lys 195 200 205 Val Asp Glu Lys Ile Val Pro Arg Asp Cys Gly Gly Gly Gly Ser Gly 210 215 220 Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Asp Gly Gly Leu Val 225 230 235 240 Gln Pro Gly Arg Ser Leu Lys Leu Pro Cys Ala Ala Ser Gly Phe Thr 245 250 255 Phe Ser Asp Tyr Tyr Met Ala Trp Val Arg Gln Ala Pro Thr Lys Gly 260 265 270 Leu Glu Trp Val Ala Ser Ile Ser Tyr Asp Gly Ser Ser Thr Tyr Tyr 275 280 285 Arg Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys 290 295 300 Ser Thr Leu Tyr Leu Gln Met Asp Ser Leu Arg Ser Glu Asp Thr Ala 305 310 315 320 Thr Tyr Tyr Cys Gly Arg His Ser Ser Tyr Phe Asp Tyr Trp Gly Gln 325 330 335 Gly Val Met Val Thr Val Ser Ser Ala Lys Thr Thr Pro Pro Ser Val 340 345 350 Tyr Pro Leu Ala Pro Gly Ser Ala Ala Gln Thr Asn Ser Met Val Thr 355 360 365 Leu Gly Cys Leu Val Glu Gly Tyr Phe Pro Glu Pro Val Thr Val Thr 370 375 380 Trp Asn Ser Gly Ser Leu Ser Ser Gly Val His Thr Phe Pro Ala Val 385 390 395 400 Leu Gln Ser Asp Leu Tyr Thr Leu Ser Ser Ser Val Thr Val Pro Ser 405 410 415 Ser Thr Trp Pro Ser Gln Thr Val Thr Cys Asn Val Ala His Pro Ala 420 425 430 Ser Ser Thr Lys Val Asp Glu Lys Ile Val Pro Arg Asp Cys Gly Cys 435 440 445 Lys Pro Cys Ile Cys Thr Val Pro Glu Val Ser Ser Val Phe Ile Phe 450 455 460 Pro Pro Lys Pro Lys Asp Val Leu Thr Ile Thr Leu Thr Pro Lys Val 465 470 475 480 Thr Cys Val Val Val Ala Ile Ser Lys Asp Asp Pro Glu Val Gln Phe 485 490 495 Ser Trp Phe Val Asp Asp Val Glu Val His Thr Ala Gln Thr Lys Pro 500 505 510 Arg Glu Glu Gln Ile Asn Ser Thr Phe Arg Ser Val Ser Glu Leu Pro 515 520 525 Ile Met His Gln Asp Trp Leu Asn Gly Lys Glu Phe Lys Cys Arg Val 530 535 540 Asn Ser Ala Ala Phe Gly Ala Pro Ile Glu Lys Thr Ile Ser Lys Thr 545 550 555 560 Lys Gly Arg Pro Lys Ala Pro Gln Val Tyr Thr Ile Pro Pro Pro Lys 565 570 575 Glu Gln Met Ala Lys Asp Lys Val Ser Leu Thr Cys Met Ile Thr Asn 580 585 590 Phe Phe Pro Glu Asp Ile Thr Val Glu Trp Gln Trp Asn Gly Gln Pro 595 600 605 Ala Glu Asn Tyr Lys Asn Thr Gln Pro Ile Met Asp Thr Asp Gly Ser 610 615 620 Tyr Phe Val Tyr Ser Lys Leu Asn Val Gln Lys Ser Asn Trp Glu Ala 625 630 635 640 Gly Asn Thr Phe Thr Cys Ser Val Leu His Glu Gly Leu His Asn His 645 650 655 His Thr Glu Lys Ser Leu Ser His Ser Pro Gly Lys Gly Gly Gly Gly 660 665 670 Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser 675 680 685 Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly 690 695 700 Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Arg Ser 705 710 715 720 Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu 725 730 735 Ile Ile Gly Ala Ser Thr Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser 740 745 750 Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu 755 760 765 Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Gly Gln Val Ile Pro 770 775 780 Pro Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Ser Ser Ala Lys 785 790 795 800 Thr Thr Pro Pro Ser Val Tyr Pro Leu Ala Pro Gly Ser Ala Ala Gln 805 810 815 Thr Asn Ser Met Val Thr Leu Gly Cys Leu Val Lys Gly Tyr Phe Pro 820 825 830 Glu Pro Val Thr Val Thr Trp Asn Ser Gly Ser Leu Ser Ser Gly Val 835 840 845 His Thr Phe Pro Ala Val Leu Gln Ser Asp Leu Tyr Thr Leu Ser Ser 850 855 860 Ser Val Thr Val Pro Ser Ser Thr Trp Pro Ser Gln Thr Val Thr Cys 865 870 875 880 Asn Val Ala His Pro Ala Ser Ser Thr Lys Val Asp Lys Lys Ile Val 885 890 895 Pro Arg Asp Cys 900 +ADw-210+AD4- 99 +ADw-211+AD4- 223 +ADw-212+AD4- PRT +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- 28H1 VHCL (mu) +ADw-400+AD4- 99 Glu Val Gln Leu Leu Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 1 5 10 15 Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Ser His 20 25 30 Ala Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45 Ser Ala Ile Trp Ala Ser Gly Glu Gln Tyr Tyr Ala Asp Ser Val Lys 50 55 60 Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr Leu 65 70 75 80 Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala 85 90 95 Lys Gly Trp Leu Gly Asn Phe Asp Tyr Trp Gly Gln Gly Thr Leu Val 100 105 110 Thr Val Ser Ser Ala Ser Asp Ala Ala Pro Thr Val Ser Ile Phe Pro 115 120 125 Pro Ser Ser Glu Gln Leu Thr Ser Gly Gly Ala Ser Val Val Cys Phe 130 135 140 Leu Asn Asn Phe Tyr Pro Lys Asp Ile Asn Val Lys Trp Lys Ile Asp 145 150 155 160 Gly Ser Glu Arg Gln Asn Gly Val Leu Asn Ser Trp Thr Asp Gln Asp 165 170 175 Ser Lys Asp Ser Thr Tyr Ser Met Ser Ser Thr Leu Thr Leu Thr Lys 180 185 190 Asp Glu Tyr Glu Arg His Asn Ser Tyr Thr Cys Glu Ala Thr His Lys 195 200 205 Thr Ser Thr Ser Pro Ile Val Lys Ser Phe Asn Arg Asn Glu Cys 210 215 220 +ADw-210+AD4- 100 +ADw-211+AD4- 213 +ADw-212+AD4- PRT +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- mu CD40 cadena ligera+ADs- 'RK' +ADw-400+AD4- 100 Asp Thr Val Leu Thr Gln Ser Pro Ala Leu Ala Val Ser Pro Gly Glu 1 5 10 15 Arg Val Thr Ile Ser Cys Arg Ala Ser Asp Ser Val Ser Thr Leu Met 20 25 30 His Trp Tyr Gln Gln Lys Pro Gly Gln Gln Pro Lys Leu Leu Ile Tyr 35 40 45 Leu Ala Ser His Leu Glu Ser Gly Val Pro Ala Arg Phe Ser Gly Ser 50 55 60 Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Asp Pro Val Glu Ala Asp 65 70 75 80 Asp Thr Ala Thr Tyr Tyr Cys Gln Gln Ser Trp Asn Asp Pro Trp Thr 85 90 95 Phe Gly Gly Gly Thr Lys Leu Glu Leu Lys Arg Ala Asp Ala Ala Pro 100 105 110 Thr Val Ser Ile Phe Pro Pro Ser Ser Arg Lys Leu Thr Ser Gly Gly 115 120 125 Ala Ser Val Val Cys Phe Leu Asn Asn Phe Tyr Pro Lys Asp Ile Asn 130 135 140 Val Lys Trp Lys Ile Asp Gly Ser Glu Arg Gln Asn Gly Val Leu Asn 145 150 155 160 Ser Trp Thr Asp Gln Asp Ser Lys Asp Ser Thr Tyr Ser Met Ser Ser 165 170 175 Thr Leu Thr Leu Thr Lys Asp Glu Tyr Glu Arg His Asn Ser Tyr Thr 180 185 190 Cys Glu Ala Thr His Lys Thr Ser Thr Ser Pro Ile Val Lys Ser Phe 195 200 205 Asn Arg Asn Glu Cys 210 +ADw-210+AD4- 101 +ADw-211+AD4- 802 +ADw-212+AD4- PRT +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- muCD40 VHCH1-muCD40 VHCH1-FcKK+AF8-DAPG-DP47 VH +ADw-400+AD4- 101 Glu Val Gln Leu Val Glu Ser Asp Gly Gly Leu Val Gln Pro Gly Arg 1 5 10 15 Ser Leu Lys Leu Pro Cys Ala Ala Ser Gly Phe Thr Phe Ser Asp Tyr 20 25 30 Tyr Met Ala Trp Val Arg Gln Ala Pro Thr Lys Gly Leu Glu Trp Val 35 40 45 Ala Ser Ile Ser Tyr Asp Gly Ser Ser Thr Tyr Tyr Arg Asp Ser Val 50 55 60 Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Ser Thr Leu Tyr 65 70 75 80 Leu Gln Met Asp Ser Leu Arg Ser Glu Asp Thr Ala Thr Tyr Tyr Cys 85 90 95 Gly Arg His Ser Ser Tyr Phe Asp Tyr Trp Gly Gln Gly Val Met Val 100 105 110 Thr Val Ser Ser Ala Lys Thr Thr Pro Pro Ser Val Tyr Pro Leu Ala 115 120 125 Pro Gly Ser Ala Ala Gln Thr Asn Ser Met Val Thr Leu Gly Cys Leu 130 135 140 Val Lys Gly Tyr Phe Pro Glu Pro Val Thr Val Thr Trp Asn Ser Gly 145 150 155 160 Ser Leu Ser Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Asp 165 170 175 Leu Tyr Thr Leu Ser Ser Ser Val Thr Val Pro Ser Ser Thr Trp Pro 180 185 190 Ser Gln Thr Val Thr Cys Asn Val Ala His Pro Ala Ser Ser Thr Lys 195 200 205 Val Asp Lys Lys Ile Val Pro Arg Asp Cys Gly Gly Gly Gly Ser Gly 210 215 220 Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Asp Gly Gly Leu Val 225 230 235 240 Gln Pro Gly Arg Ser Leu Lys Leu Pro Cys Ala Ala Ser Gly Phe Thr 245 250 255 Phe Ser Asp Tyr Tyr Met Ala Trp Val Arg Gln Ala Pro Thr Lys Gly 260 265 270 Leu Glu Trp Val Ala Ser Ile Ser Tyr Asp Gly Ser Ser Thr Tyr Tyr 275 280 285 Arg Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys 290 295 300 Ser Thr Leu Tyr Leu Gln Met Asp Ser Leu Arg Ser Glu Asp Thr Ala 305 310 315 320 Thr Tyr Tyr Cys Gly Arg His Ser Ser Tyr Phe Asp Tyr Trp Gly Gln 325 330 335 Gly Val Met Val Thr Val Ser Ser Ala Lys Thr Thr Pro Pro Ser Val 340 345 350 Tyr Pro Leu Ala Pro Gly Ser Ala Ala Gln Thr Asn Ser Met Val Thr 355 360 365 Leu Gly Cys Leu Val Lys Gly Tyr Phe Pro Glu Pro Val Thr Val Thr 370 375 380 Trp Asn Ser Gly Ser Leu Ser Ser Gly Val His Thr Phe Pro Ala Val 385 390 395 400 Leu Gln Ser Asp Leu Tyr Thr Leu Ser Ser Ser Val Thr Val Pro Ser 405 410 415 Ser Thr Trp Pro Ser Gln Thr Val Thr Cys Asn Val Ala His Pro Ala 420 425 430 Ser Ser Thr Lys Val Asp Lys Lys Ile Val Pro Arg Asp Cys Gly Cys 435 440 445 Lys Pro Cys Ile Cys Thr Val Pro Glu Val Ser Ser Val Phe Ile Phe 450 455 460 Pro Pro Lys Pro Lys Asp Val Leu Thr Ile Thr Leu Thr Pro Lys Val 465 470 475 480 Thr Cys Val Val Val Ala Ile Ser Lys Asp Asp Pro Glu Val Gln Phe 485 490 495 Ser Trp Phe Val Asp Asp Val Glu Val His Thr Ala Gln Thr Lys Pro 500 505 510 Arg Glu Glu Gln Ile Asn Ser Thr Phe Arg Ser Val Ser Glu Leu Pro 515 520 525 Ile Met His Gln Asp Trp Leu Asn Gly Lys Glu Phe Lys Cys Arg Val 530 535 540 Asn Ser Ala Ala Phe Gly Ala Pro Ile Glu Lys Thr Ile Ser Lys Thr 545 550 555 560 Lys Gly Arg Pro Lys Ala Pro Gln Val Tyr Thr Ile Pro Pro Pro Lys 565 570 575 Lys Gln Met Ala Lys Asp Lys Val Ser Leu Thr Cys Met Ile Thr Asn 580 585 590 Phe Phe Pro Glu Asp Ile Thr Val Glu Trp Gln Trp Asn Gly Gln Pro 595 600 605 Ala Glu Asn Tyr Lys Asn Thr Gln Pro Ile Met Lys Thr Asp Gly Ser 610 615 620 Tyr Phe Val Tyr Ser Lys Leu Asn Val Gln Lys Ser Asn Trp Glu Ala 625 630 635 640 Gly Asn Thr Phe Thr Cys Ser Val Leu His Glu Gly Leu His Asn His 645 650 655 His Thr Glu Lys Ser Leu Ser His Ser Pro Gly Gly Gly Gly Gly Ser 660 665 670 Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Glu 675 680 685 Val Gln Leu Leu Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser 690 695 700 Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Ser Tyr Ala 705 710 715 720 Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ser 725 730 735 Ala Ile Ser Gly Ser Gly Gly Ser Thr Tyr Tyr Ala Asp Ser Val Lys 740 745 750 Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr Leu 755 760 765 Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala 770 775 780 Lys Gly Ser Gly Phe Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val 785 790 795 800 Ser Ser +ADw-210+AD4- 102 +ADw-211+AD4- 795 +ADw-212+AD4- PRT +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- muCD40 VHCH1-mu CD40 VHCH1-FcDD+AF8-DAPG-DP47 VL +ADw-400+AD4- 102 Glu Val Gln Leu Val Glu Ser Asp Gly Gly Leu Val Gln Pro Gly Arg 1 5 10 15 Ser Leu Lys Leu Pro Cys Ala Ala Ser Gly Phe Thr Phe Ser Asp Tyr 20 25 30 Tyr Met Ala Trp Val Arg Gln Ala Pro Thr Lys Gly Leu Glu Trp Val 35 40 45 Ala Ser Ile Ser Tyr Asp Gly Ser Ser Thr Tyr Tyr Arg Asp Ser Val 50 55 60 Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Ser Thr Leu Tyr 65 70 75 80 Leu Gln Met Asp Ser Leu Arg Ser Glu Asp Thr Ala Thr Tyr Tyr Cys 85 90 95 Gly Arg His Ser Ser Tyr Phe Asp Tyr Trp Gly Gln Gly Val Met Val 100 105 110 Thr Val Ser Ser Ala Lys Thr Thr Pro Pro Ser Val Tyr Pro Leu Ala 115 120 125 Pro Gly Ser Ala Ala Gln Thr Asn Ser Met Val Thr Leu Gly Cys Leu 130 135 140 Val Lys Gly Tyr Phe Pro Glu Pro Val Thr Val Thr Trp Asn Ser Gly 145 150 155 160 Ser Leu Ser Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Asp 165 170 175 Leu Tyr Thr Leu Ser Ser Ser Val Thr Val Pro Ser Ser Thr Trp Pro 180 185 190 Ser Gln Thr Val Thr Cys Asn Val Ala His Pro Ala Ser Ser Thr Lys 195 200 205 Val Asp Lys Lys Ile Val Pro Arg Asp Cys Gly Gly Gly Gly Ser Gly 210 215 220 Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Asp Gly Gly Leu Val 225 230 235 240 Gln Pro Gly Arg Ser Leu Lys Leu Pro Cys Ala Ala Ser Gly Phe Thr 245 250 255 Phe Ser Asp Tyr Tyr Met Ala Trp Val Arg Gln Ala Pro Thr Lys Gly 260 265 270 Leu Glu Trp Val Ala Ser Ile Ser Tyr Asp Gly Ser Ser Thr Tyr Tyr 275 280 285 Arg Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys 290 295 300 Ser Thr Leu Tyr Leu Gln Met Asp Ser Leu Arg Ser Glu Asp Thr Ala 305 310 315 320 Thr Tyr Tyr Cys Gly Arg His Ser Ser Tyr Phe Asp Tyr Trp Gly Gln 325 330 335 Gly Val Met Val Thr Val Ser Ser Ala Lys Thr Thr Pro Pro Ser Val 340 345 350 Tyr Pro Leu Ala Pro Gly Ser Ala Ala Gln Thr Asn Ser Met Val Thr 355 360 365 Leu Gly Cys Leu Val Lys Gly Tyr Phe Pro Glu Pro Val Thr Val Thr 370 375 380 Trp Asn Ser Gly Ser Leu Ser Ser Gly Val His Thr Phe Pro Ala Val 385 390 395 400 Leu Gln Ser Asp Leu Tyr Thr Leu Ser Ser Ser Val Thr Val Pro Ser 405 410 415 Ser Thr Trp Pro Ser Gln Thr Val Thr Cys Asn Val Ala His Pro Ala 420 425 430 Ser Ser Thr Lys Val Asp Lys Lys Ile Val Pro Arg Asp Cys Gly Cys 435 440 445 Lys Pro Cys Ile Cys Thr Val Pro Glu Val Ser Ser Val Phe Ile Phe 450 455 460 Pro Pro Lys Pro Lys Asp Val Leu Thr Ile Thr Leu Thr Pro Lys Val 465 470 475 480 Thr Cys Val Val Val Ala Ile Ser Lys Asp Asp Pro Glu Val Gln Phe 485 490 495 Ser Trp Phe Val Asp Asp Val Glu Val His Thr Ala Gln Thr Lys Pro 500 505 510 Arg Glu Glu Gln Ile Asn Ser Thr Phe Arg Ser Val Ser Glu Leu Pro 515 520 525 Ile Met His Gln Asp Trp Leu Asn Gly Lys Glu Phe Lys Cys Arg Val 530 535 540 Asn Ser Ala Ala Phe Gly Ala Pro Ile Glu Lys Thr Ile Ser Lys Thr 545 550 555 560 Lys Gly Arg Pro Lys Ala Pro Gln Val Tyr Thr Ile Pro Pro Pro Lys 565 570 575 Glu Gln Met Ala Lys Asp Lys Val Ser Leu Thr Cys Met Ile Thr Asn 580 585 590 Phe Phe Pro Glu Asp Ile Thr Val Glu Trp Gln Trp Asn Gly Gln Pro 595 600 605 Ala Glu Asn Tyr Asp Asn Thr Gln Pro Ile Met Asp Thr Asp Gly Ser 610 615 620 Tyr Phe Val Tyr Ser Asp Leu Asn Val Gln Lys Ser Asn Trp Glu Ala 625 630 635 640 Gly Asn Thr Phe Thr Cys Ser Val Leu His Glu Gly Leu His Asn His 645 650 655 His Thr Glu Lys Ser Leu Ser His Ser Pro Gly Gly Gly Gly Gly Ser 660 665 670 Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Glu 675 680 685 Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly Glu 690 695 700 Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Ser Ser Tyr 705 710 715 720 Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile 725 730 735 Tyr Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser Gly 740 745 750 Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu Pro 755 760 765 Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Gly Ser Ser Pro Leu 770 775 780 Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys 785 790 795 +ADw-210+AD4- 103 +ADw-211+AD4- 900 +ADw-212+AD4- PRT +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- muCD40 VHCH1-muCD40 VHCH1-Fc+AF8-DAPG-28H1 VLCH1 +ADw-400+AD4- 103 Glu Val Gln Leu Val Glu Ser Asp Gly Gly Leu Val Gln Pro Gly Arg 1 5 10 15 Ser Leu Lys Leu Pro Cys Ala Ala Ser Gly Phe Thr Phe Ser Asp Tyr 20 25 30 Tyr Met Ala Trp Val Arg Gln Ala Pro Thr Lys Gly Leu Glu Trp Val 35 40 45 Ala Ser Ile Ser Tyr Asp Gly Ser Ser Thr Tyr Tyr Arg Asp Ser Val 50 55 60 Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Ser Thr Leu Tyr 65 70 75 80 Leu Gln Met Asp Ser Leu Arg Ser Glu Asp Thr Ala Thr Tyr Tyr Cys 85 90 95 Gly Arg His Ser Ser Tyr Phe Asp Tyr Trp Gly Gln Gly Val Met Val 100 105 110 Thr Val Ser Ser Ala Lys Thr Thr Pro Pro Ser Val Tyr Pro Leu Ala 115 120 125 Pro Gly Ser Ala Ala Gln Thr Asn Ser Met Val Thr Leu Gly Cys Leu 130 135 140 Val Glu Gly Tyr Phe Pro Glu Pro Val Thr Val Thr Trp Asn Ser Gly 145 150 155 160 Ser Leu Ser Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Asp 165 170 175 Leu Tyr Thr Leu Ser Ser Ser Val Thr Val Pro Ser Ser Thr Trp Pro 180 185 190 Ser Gln Thr Val Thr Cys Asn Val Ala His Pro Ala Ser Ser Thr Lys 195 200 205 Val Asp Glu Lys Ile Val Pro Arg Asp Cys Gly Gly Gly Gly Ser Gly 210 215 220 Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Asp Gly Gly Leu Val 225 230 235 240 Gln Pro Gly Arg Ser Leu Lys Leu Pro Cys Ala Ala Ser Gly Phe Thr 245 250 255 Phe Ser Asp Tyr Tyr Met Ala Trp Val Arg Gln Ala Pro Thr Lys Gly 260 265 270 Leu Glu Trp Val Ala Ser Ile Ser Tyr Asp Gly Ser Ser Thr Tyr Tyr 275 280 285 Arg Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys 290 295 300 Ser Thr Leu Tyr Leu Gln Met Asp Ser Leu Arg Ser Glu Asp Thr Ala 305 310 315 320 Thr Tyr Tyr Cys Gly Arg His Ser Ser Tyr Phe Asp Tyr Trp Gly Gln 325 330 335 Gly Val Met Val Thr Val Ser Ser Ala Lys Thr Thr Pro Pro Ser Val 340 345 350 Tyr Pro Leu Ala Pro Gly Ser Ala Ala Gln Thr Asn Ser Met Val Thr 355 360 365 Leu Gly Cys Leu Val Glu Gly Tyr Phe Pro Glu Pro Val Thr Val Thr 370 375 380 Trp Asn Ser Gly Ser Leu Ser Ser Gly Val His Thr Phe Pro Ala Val 385 390 395 400 Leu Gln Ser Asp Leu Tyr Thr Leu Ser Ser Ser Val Thr Val Pro Ser 405 410 415 Ser Thr Trp Pro Ser Gln Thr Val Thr Cys Asn Val Ala His Pro Ala 420 425 430 Ser Ser Thr Lys Val Asp Glu Lys Ile Val Pro Arg Asp Cys Gly Cys 435 440 445 Lys Pro Cys Ile Cys Thr Val Pro Glu Val Ser Ser Val Phe Ile Phe 450 455 460 Pro Pro Lys Pro Lys Asp Val Leu Thr Ile Thr Leu Thr Pro Lys Val 465 470 475 480 Thr Cys Val Val Val Ala Ile Ser Lys Asp Asp Pro Glu Val Gln Phe 485 490 495 Ser Trp Phe Val Asp Asp Val Glu Val His Thr Ala Gln Thr Lys Pro 500 505 510 Arg Glu Glu Gln Ile Asn Ser Thr Phe Arg Ser Val Ser Glu Leu Pro 515 520 525 Ile Met His Gln Asp Trp Leu Asn Gly Lys Glu Phe Lys Cys Arg Val 530 535 540 Asn Ser Ala Ala Phe Gly Ala Pro Ile Glu Lys Thr Ile Ser Lys Thr 545 550 555 560 Lys Gly Arg Pro Lys Ala Pro Gln Val Tyr Thr Ile Pro Pro Pro Lys 565 570 575 Glu Gln Met Ala Lys Asp Lys Val Ser Leu Thr Cys Met Ile Thr Asn 580 585 590 Phe Phe Pro Glu Asp Ile Thr Val Glu Trp Gln Trp Asn Gly Gln Pro 595 600 605 Ala Glu Asn Tyr Lys Asn Thr Gln Pro Ile Met Asp Thr Asp Gly Ser 610 615 620 Tyr Phe Val Tyr Ser Lys Leu Asn Val Gln Lys Ser Asn Trp Glu Ala 625 630 635 640 Gly Asn Thr Phe Thr Cys Ser Val Leu His Glu Gly Leu His Asn His 645 650 655 His Thr Glu Lys Ser Leu Ser His Ser Pro Gly Lys Gly Gly Gly Gly 660 665 670 Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser 675 680 685 Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly 690 695 700 Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Ser Ser 705 710 715 720 Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu 725 730 735 Ile Tyr Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser 740 745 750 Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu 755 760 765 Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Gly Ser Ser Pro 770 775 780 Leu Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Ser Ser Ala Lys 785 790 795 800 Thr Thr Pro Pro Ser Val Tyr Pro Leu Ala Pro Gly Ser Ala Ala Gln 805 810 815 Thr Asn Ser Met Val Thr Leu Gly Cys Leu Val Lys Gly Tyr Phe Pro 820 825 830 Glu Pro Val Thr Val Thr Trp Asn Ser Gly Ser Leu Ser Ser Gly Val 835 840 845 His Thr Phe Pro Ala Val Leu Gln Ser Asp Leu Tyr Thr Leu Ser Ser 850 855 860 Ser Val Thr Val Pro Ser Ser Thr Trp Pro Ser Gln Thr Val Thr Cys 865 870 875 880 Asn Val Ala His Pro Ala Ser Ser Thr Lys Val Asp Lys Lys Ile Val 885 890 895 Pro Arg Asp Cys 900 +ADw-210+AD4- 104 +ADw-211+AD4- 222 +ADw-212+AD4- PRT +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- DP47 VHCL (mu) +ADw-400+AD4- 104 Glu Val Gln Leu Leu Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 1 5 10 15 Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Ser Tyr 20 25 30 Ala Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45 Ser Ala Ile Ser Gly Ser Gly Gly Ser Thr Tyr Tyr Ala Asp Ser Val 50 55 60 Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 65 70 75 80 Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Ala Lys Gly Ser Gly Phe Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr 100 105 110 Val Ser Ser Ala Ser Asp Ala Ala Pro Thr Val Ser Ile Phe Pro Pro 115 120 125 Ser Ser Glu Gln Leu Thr Ser Gly Gly Ala Ser Val Val Cys Phe Leu 130 135 140 Asn Asn Phe Tyr Pro Lys Asp Ile Asn Val Lys Trp Lys Ile Asp Gly 145 150 155 160 Ser Glu Arg Gln Asn Gly Val Leu Asn Ser Trp Thr Asp Gln Asp Ser 165 170 175 Lys Asp Ser Thr Tyr Ser Met Ser Ser Thr Leu Thr Leu Thr Lys Asp 180 185 190 Glu Tyr Glu Arg His Asn Ser Tyr Thr Cys Glu Ala Thr His Lys Thr 195 200 205 Ser Thr Ser Pro Ile Val Lys Ser Phe Asn Arg Asn Glu Cys 210 215 220 +ADw-210+AD4- 105 +ADw-211+AD4- 1332 +ADw-212+AD4- ADN +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- CD40 IgG cadena pesada (secuencia de nucle+APM-tidos) +ADw-400+AD4- 105 gaggtgcagc tggtggaatc tggcggcgga ctggtgcagc ctggcggatc tctgagactg 60 agctgtgccg ccagcggcta cagcttcacc ggctactaca tccactgggt gcgccaggcc 120 cctggcaagg gactggaatg ggtggccaga gtgatcccca atgccggcgg aaccagctac 180 aaccagaagt tcaagggccg gttcaccctg agcgtggaca acagcaagaa caccgcctac 240 ctgcagatga acagcctgcg ggccgaggac accgccgtgt actattgtgc ccgcgagggc 300 atctattggt ggggccaggg aacactcgtg accgtgtcca gcgctagcac caagggccca 360 agcgtgttcc cactggcccc aagcagcaag tctaccagcg gaggaacagc cgccctggga 420 tgtctggtga aggactactt ccccgagcca gtgacagtga gctggaactc tggcgccctg 480 acatctggcg tgcacacatt cccagccgtg ctgcagtcta gcggcctgta cagcctgtcc 540 agcgtggtga cagtgccaag cagctctctg ggcacccaga cctacatctg caacgtgaac 600 cacaagccca gcaacaccaa ggtggacaag aaggtggagc ccaagagctg cgacaagacc 660 cacacctgcc caccatgtcc agccccagag ctgctgggag gacctagcgt gttcctgttc 720 ccccccaagc caaaggacac cctgatgatc agcagaaccc ccgaggtgac atgtgtggtg 780 gtggacgtgt ctcacgagga cccagaggtg aagttcaact ggtacgtgga cggagtggag 840 gtgcacaacg ccaagaccaa gcccagagag gagcagtaca acagcaccta ccgcgtggtg 900 tctgtgctga cagtgctgca ccaggactgg ctgaacggca aagaatacaa gtgcaaggtc 960 tccaacaagg ccctgccagc cccaatcgaa aagaccatca gcaaggccaa gggccagcca 1020 agggagccac aggtgtacac cctgccccca tctagggagg agatgaccaa gaaccaggtc 1080 agcctgacct gcctggtcaa aggcttctat cccagcgaca tcgccgtgga gtgggagagc 1140 aatgggcagc cggagaacaa ctacaagacc acgcctcccg tgctggactc cgacggctcc 1200 ttcttcctct acagcaagct caccgtggac aagagcaggt ggcagcaggg gaacgtcttc 1260 tcatgctccg tgatgcatga ggctctgcac aaccactaca cgcagaagag cctctccctg 1320 tctccgggta aa 1332 +ADw-210+AD4- 106 +ADw-211+AD4- 657 +ADw-212+AD4- ADN +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- CD40 cadena ligera (secuencia de nucle+APM-tidos) +ADw-400+AD4- 106 gacatccaga tgacccagag ccccagcagc ctgtctgcca gcgtgggcga cagagtgacc 60 atcacctgtc ggagcagcca gagcctggtg cacagcaacg gcaacacctt cctgcactgg 120 tatcagcaga agcccggcaa ggcccccaag ctgctgatct acaccgtgtc caaccggttc 180 agcggcgtgc ccagcagatt ttctggcagc ggctccggca ccgacttcac cctgacaatc 240 agctccctgc agcccgagga cttcgccacc tatttctgca gccagaccac ccacgtgccc 300 tggacatttg gacagggcac caaggtggaa atcaagcgta cggtggctgc accatctgtc 360 ttcatcttcc cgccatctga tgagcagttg aaatctggaa ctgcctctgt tgtgtgcctg 420 ctgaataact tctatcccag agaggccaaa gtacagtgga aggtggataa cgccctccaa 480 tcgggtaact cccaggagag tgtcacagag caggacagca aggacagcac ctacagcctc 540 agcagcaccc tgacgctgag caaagcagac tacgagaaac acaaagtcta cgcctgcgaa 600 gtcacccatc agggcctgag ctcgcccgtc acaaagagct tcaacagggg agagtgt 657 +ADw-210+AD4- 107 +ADw-211+AD4- 2421 +ADw-212+AD4- ADN +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- CD40 VHCH1-CD40 VHCH1-Fcpomo+AF8-PGLALA -28H1 VH +ADw-400+AD4- 107 gaggtgcagc tggtggaatc tggcggcgga ctggtgcagc ctggcggatc tctgagactg 60 agctgtgccg ccagcggcta cagcttcacc ggctactaca tccactgggt gcgccaggcc 120 cctggcaagg gactggaatg ggtggccaga gtgatcccca atgccggcgg aaccagctac 180 aaccagaagt tcaagggccg gttcaccctg agcgtggaca acagcaagaa caccgcctac 240 ctgcagatga acagcctgcg ggccgaggac accgccgtgt actattgtgc ccgcgagggc 300 atctattggt ggggccaggg aacactcgtg accgtgtcca gcgcttccac caagggccct 360 agcgtgttcc ctctggcccc tagcagcaag tctaccagcg gaggaacagc cgccctgggc 420 tgcctcgtga aggactactt tcccgagccc gtgacagtgt cctggaactc tggcgccctg 480 acaagcggcg tgcacacctt tccagccgtg ctgcagagca gcggcctgta ctctctgagc 540 agcgtcgtga ctgtgcccag cagcagcctg ggaacccaga cctacatctg caacgtgaac 600 cacaagccca gcaacaccaa ggtggacaag aaggtggaac ccaagagctg cgacggcgga 660 ggcggatcag gcggcggagg atccgaagtg cagctggtgg aaagtggggg aggcctggtg 720 cagccagggg gaagcctgag actgtcttgt gccgcttccg gctactcttt taccgggtat 780 tatatccatt gggtgcggca ggctccaggg aaaggcctgg aatgggtggc acgcgtgatc 840 cctaacgcag gcggcacctc ttataatcag aagtttaaag ggcgctttac cctgtccgtg 900 gacaattcca agaatactgc ttacctgcag atgaattccc tgcgcgccga agatacagct 960 gtgtattact gcgccagaga agggatctat tggtggggac agggcaccct cgtgacagtg 1020 tcatccgcta gcaccaaggg cccatcggtc ttccccctgg caccctcctc caagagcacc 1080 tctgggggca cagcggccct gggctgcctg gtcaaggact acttccccga accggtgacg 1140 gtgtcgtgga actcaggcgc cctgaccagc ggcgtgcaca ccttcccggc tgtcctacag 1200 tcctcaggac tctactccct cagcagcgtg gtgaccgtgc cctccagcag cttgggcacc 1260 cagacctaca tctgcaacgt gaatcacaag cccagcaaca ccaaggtgga caagaaagtt 1320 gagcccaaat cttgtgacaa aactcacaca tgcccaccgt gcccagcacc tgaagctgca 1380 gggggaccgt cagtcttcct cttcccccca aaacccaagg acaccctcat gatctcccgg 1440 acccctgagg tcacatgcgt ggtggtggac gtgagccacg aagaccctga ggtcaagttc 1500 aactggtacg tggacggcgt ggaggtgcat aatgccaaga caaagccgcg ggaggagcag 1560 tacaacagca cgtaccgtgt ggtcagcgtc ctcaccgtcc tgcaccagga ctggctgaat 1620 ggcaaggagt acaagtgcaa ggtctccaac aaagccctcg gcgcccccat cgagaaaacc 1680 atctccaaag ccaaagggca gccccgagaa ccacaggtgt acaccctgcc cccctgcaga 1740 gatgagctga ccaagaacca ggtgtccctg tggtgtctgg tcaagggctt ctaccccagc 1800 gatatcgccg tggagtggga gagcaacggc cagcctgaga acaactacaa gaccaccccc 1860 cctgtgctgg acagcgacgg cagcttcttc ctgtactcca aactgaccgt ggacaagagc 1920 cggtggcagc agggcaacgt gttcagctgc agcgtgatgc acgaggccct gcacaaccac 1980 tacacccaga agtccctgag cctgagcccc ggcggaggcg gcggaagcgg aggaggagga 2040 tccggaggag ggggaagtgg cggcggagga tctgaggtgc agctgctgga atccggcgga 2100 ggcctggtgc agcctggcgg atctctgaga ctgtcctgcg ccgcctccgg cttcaccttc 2160 tcctcccacg ccatgtcctg ggtccgacag gctcctggca aaggcctgga atgggtgtcc 2220 gccatctggg cctccggcga gcagtactac gccgactctg tgaagggccg gttcaccatc 2280 tcccgggaca actccaagaa caccctgtac ctgcagatga actccctgcg ggccgaggac 2340 accgccgtgt actactgtgc caagggctgg ctgggcaact tcgactactg gggccagggc 2400 accctggtca ccgtgtccag c 2421 +ADw-210+AD4- 108 +ADw-211+AD4- 2397 +ADw-212+AD4- ADN +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- CD40 VHCH1-CD40 VHCH1-Fcagujero+AF8-PGLALA-28H1 VL +ADw-400+AD4- 108 gaggtgcagc tggtggaatc tggcggcgga ctggtgcagc ctggcggatc tctgagactg 60 agctgtgccg ccagcggcta cagcttcacc ggctactaca tccactgggt gcgccaggcc 120 cctggcaagg gactggaatg ggtggccaga gtgatcccca atgccggcgg aaccagctac 180 aaccagaagt tcaagggccg gttcaccctg agcgtggaca acagcaagaa caccgcctac 240 ctgcagatga acagcctgcg ggccgaggac accgccgtgt actattgtgc ccgcgagggc 300 atctattggt ggggccaggg aacactcgtg accgtgtcca gcgcttccac caagggccct 360 agcgtgttcc ctctggcccc tagcagcaag tctaccagcg gaggaacagc cgccctgggc 420 tgcctcgtga aggactactt tcccgagccc gtgacagtgt cctggaactc tggcgccctg 480 acaagcggcg tgcacacctt tccagccgtg ctgcagagca gcggcctgta ctctctgagc 540 agcgtcgtga ctgtgcccag cagcagcctg ggaacccaga cctacatctg caacgtgaac 600 cacaagccca gcaacaccaa ggtggacaag aaggtggaac ccaagagctg cgacggcgga 660 ggcggatcag gcggcggagg atccgaagtg cagctggtgg aaagtggggg aggcctggtg 720 cagccagggg gaagcctgag actgtcttgt gccgcttccg gctactcttt taccgggtat 780 tatatccatt gggtgcggca ggctccaggg aaaggcctgg aatgggtggc acgcgtgatc 840 cctaacgcag gcggcacctc ttataatcag aagtttaaag ggcgctttac cctgtccgtg 900 gacaattcca agaatactgc ttacctgcag atgaattccc tgcgcgccga agatacagct 960 gtgtattact gcgccagaga agggatctat tggtggggac agggcaccct cgtgacagtg 1020 tcatccgcta gcaccaaggg cccatcggtc ttccccctgg caccctcctc caagagcacc 1080 tctgggggca cagcggccct gggctgcctg gtcaaggact acttccccga accggtgacg 1140 gtgtcgtgga actcaggcgc cctgaccagc ggcgtgcaca ccttcccggc tgtcctacag 1200 tcctcaggac tctactccct cagcagcgtg gtgaccgtgc cctccagcag cttgggcacc 1260 cagacctaca tctgcaacgt gaatcacaag cccagcaaca ccaaggtgga caagaaagtt 1320 gagcccaaat cttgtgacaa aactcacaca tgcccaccgt gcccagcacc tgaagctgca 1380 gggggaccgt cagtcttcct cttcccccca aaacccaagg acaccctcat gatctcccgg 1440 acccctgagg tcacatgcgt ggtggtggac gtgagccacg aagaccctga ggtcaagttc 1500 aactggtacg tggacggcgt ggaggtgcat aatgccaaga caaagccgcg ggaggagcag 1560 tacaacagca cgtaccgtgt ggtcagcgtc ctcaccgtcc tgcaccagga ctggctgaat 1620 ggcaaggagt acaagtgcaa ggtctccaac aaagccctcg gcgcccccat cgagaaaacc 1680 atctccaaag ccaaagggca gccccgagaa ccacaggtgt gcaccctgcc cccatcccgg 1740 gatgagctga ccaagaacca ggtcagcctc tcgtgcgcag tcaaaggctt ctatcccagc 1800 gacatcgccg tggagtggga gagcaatggg cagccggaga acaactacaa gaccacgcct 1860 cccgtgctgg actccgacgg ctccttcttc ctcgtgagca agctcaccgt ggacaagagc 1920 aggtggcagc aggggaacgt cttctcatgc tccgtgatgc atgaggctct gcacaaccac 1980 tacacgcaga agagcctctc cctgtctccg ggtggaggcg gcggaagcgg aggaggagga 2040 tccggtggtg gcggatctgg gggcggtgga tctgagatcg tgctgaccca gtctcccggc 2100 accctgagcc tgagccctgg cgagagagcc accctgagct gcagagccag ccagagcgtg 2160 agccggagct acctggcctg gtatcagcag aagcccggcc aggcccccag actgctgatc 2220 atcggcgcca gcacccgggc caccggcatc cccgatagat tcagcggcag cggctccggc 2280 accgacttca ccctgaccat cagccggctg gaacccgagg acttcgccgt gtactactgc 2340 cagcagggcc aggtgatccc ccccaccttc ggccagggca ccaaggtgga aatcaag 2397 +ADw-210+AD4- 109 +ADw-211+AD4- 2712 +ADw-212+AD4- ADN +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- CD40 VHCH1-CD40 VHCH1-Fc+AF8-PGLALA-28H1 VLCH1 EE +ADw-400+AD4- 109 gaggtgcagc tggtggaatc tggcggcgga ctggtgcagc ctggcggatc tctgagactg 60 agctgtgccg ccagcggcta cagcttcacc ggctactaca tccactgggt gcgccaggcc 120 cctggcaagg gactggaatg ggtggccaga gtgatcccca atgccggcgg aaccagctac 180 aaccagaagt tcaagggccg gttcaccctg agcgtggaca acagcaagaa caccgcctac 240 ctgcagatga acagcctgcg ggccgaggac accgccgtgt actattgtgc ccgcgagggc 300 atctattggt ggggccaggg aacactcgtg accgtgtcca gcgcttctac caagggcccc 360 agcgtgttcc ctctggcccc tagcagcaag agcacatctg gcggaacagc cgccctgggc 420 tgcctcgtgg aggactactt tcccgagccc gtgacagtgt cctggaactc tggcgccctg 480 acaagcggcg tgcacacctt tccagccgtg ctccagagca gcggcctgta ctctctgagc 540 agcgtcgtga ctgtgcccag cagcagcctg ggaacccaga cctacatctg caacgtgaac 600 cacaagccca gcaacaccaa ggtggacgag aaggtggaac ccaagagctg cgacggcgga 660 ggcggatctg gcggcggagg atccgaagtg cagctggtgg aaagtggggg aggcctggtg 720 cagccagggg gaagcctgag actgtcttgt gccgcttccg gctactcttt taccgggtat 780 tatatccatt gggtgcggca ggctccaggg aaaggcctgg aatgggtggc acgcgtgatc 840 cctaacgcag gcggcacctc ttataatcag aagtttaaag ggcgctttac cctgtccgtg 900 gacaattcca agaatactgc ttacctgcag atgaattccc tgcgcgccga agatacagct 960 gtgtattact gcgccagaga agggatctat tggtggggac agggcaccct cgtgacagtg 1020 tcatccgcta gcaccaaggg accttccgtg tttcccctgg ctcccagctc caagtctacc 1080 tctgggggca cagctgctct gggatgtctg gtggaagatt attttcctga acctgtgacc 1140 gtgtcatgga acagcggagc cctgacctcc ggggtgcaca cattccctgc tgtgctgcag 1200 tcctccggcc tgtatagcct gagcagcgtc gtgaccgtgc cttccagctc tctgggcaca 1260 cagacatata tctgtaatgt gaatcacaaa ccctctaata ccaaagtgga tgagaaagtg 1320 gaacctaagt cctgcgacaa gacccacacc tgtccccctt gtcctgcccc tgaagctgct 1380 ggcggcccat ctgtgtttct gttcccccca aagcccaagg acaccctgat gatcagccgg 1440 acccccgaag tgacctgcgt ggtggtggat gtgtcccacg aggacccaga agtgaagttc 1500 aattggtacg tggacggcgt ggaagtgcac aacgccaaga ccaagccgcg ggaagaacag 1560 tacaacagca cctaccgggt ggtgtccgtg ctgacagtgc tgcaccagga ctggctgaac 1620 ggcaaagagt acaagtgcaa ggtgtccaac aaggccctgg gagcccccat cgagaaaacc 1680 atcagcaagg ccaagggcca gccccgcgaa cctcaggtgt acaccctgcc cccaagcagg 1740 gacgagctga ccaagaacca ggtgtccctg acctgtctcg tgaagggctt ctacccctcc 1800 gatatcgccg tggaatggga gagcaacggc cagcccgaga acaactacaa gaccaccccc 1860 cctgtgctgg acagcgacgg ctcattcttc ctgtactcca agctgaccgt ggacaagagc 1920 cggtggcagc agggcaacgt gttcagctgc agcgtgatgc acgaggccct gcacaaccac 1980 tacacacaga agtctctgag cctgagccct ggcggagggg gaggatctgg gggaggcgga 2040 agtgggggag ggggttccgg aggcggcgga tcagaaattg tgctgaccca gtcccccggc 2100 accctgtcac tgtctccagg cgaaagagcc accctgagct gtagggcctc ccagagcgtg 2160 tccagaagct atctggcctg gtatcagcag aagcccggac aggcccccag actgctgatc 2220 attggcgcct ctaccagagc caccggcatc cccgatagat tcagcggctc tggcagcggc 2280 accgacttca ccctgaccat ctccagactg gaacccgagg actttgccgt gtactattgc 2340 cagcagggcc aagtgatccc ccccaccttt ggccagggaa caaaggtgga aatcaagtcc 2400 agcgcttcca ccaagggccc ctcagtgttc ccactggcac catccagcaa gtccacaagc 2460 ggaggaaccg ccgctctggg ctgtctcgtg aaagactact ttccagagcc agtgaccgtg 2520 tcctggaata gtggcgctct gacttctggc gtgcacactt tccccgcagt gctgcagagt 2580 tctggcctgt actccctgag tagcgtcgtg acagtgccct cctctagcct gggcactcag 2640 acttacatct gcaatgtgaa tcataagcct tccaacacaa aagtggacaa aaaagtggaa 2700 cccaaatctt gc 2712 +ADw-210+AD4- 110 +ADw-211+AD4- 657 +ADw-212+AD4- ADN +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- CD40 cadena ligera RK +ADw-400+AD4- 110 gacatccaga tgacccagag ccccagcagc ctgtctgcca gcgtgggcga cagagtgacc 60 atcacctgtc ggagcagcca gagcctggtg cacagcaacg gcaacacctt cctgcactgg 120 tatcagcaga agcccggcaa ggcccccaag ctgctgatct acaccgtgtc caaccggttc 180 agcggcgtgc ccagcagatt ttctggcagc ggctccggca ccgacttcac cctgacaatc 240 agctccctgc agcccgagga cttcgccacc tatttctgca gccagaccac ccacgtgccc 300 tggacatttg gacagggcac caaggtggaa atcaagcgta cggtggctgc accatctgtc 360 ttcatcttcc cgccatctga tcggaagttg aaatctggaa ctgcctctgt tgtgtgcctg 420 ctgaataact tctatcccag agaggccaaa gtacagtgga aggtggataa cgccctccaa 480 tcgggtaact cccaggagag tgtcacagag caggacagca aggacagcac ctacagcctc 540 agcagcaccc tgacgctgag caaagcagac tacgagaaac acaaagtcta cgcctgcgaa 600 gtcacccatc agggcctgag ctcgcccgtc acaaagagct tcaacagggg agagtgt 657 +ADw-210+AD4- 111 +ADw-211+AD4- 669 +ADw-212+AD4- ADN +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- 28H1 VHCL +ADw-400+AD4- 111 gaagtgcagc tgctggaatc cggcggaggc ctggtgcagc ctggcggatc tctgagactg 60 tcctgcgccg cctccggctt caccttctcc tcccacgcca tgtcctgggt ccgacaggct 120 cctggcaaag gcctggaatg ggtgtccgcc atctgggcct ccggcgagca gtactacgcc 180 gactctgtga agggccggtt caccatctcc cgggacaact ccaagaacac cctgtacctg 240 cagatgaact ccctgcgggc cgaggacacc gccgtgtact actgtgccaa gggctggctg 300 ggcaacttcg actactgggg acagggcacc ctggtcaccg tgtccagcgc tagcgtggcc 360 gctccctccg tgttcatctt cccaccttcc gacgagcagc tgaagtccgg caccgcttct 420 gtcgtgtgcc tgctgaacaa cttctacccc cgcgaggcca aggtgcagtg gaaggtggac 480 aacgccctgc agtccggcaa cagccaggaa tccgtgaccg agcaggactc caaggacagc 540 acctactccc tgtcctccac cctgaccctg tccaaggccg actacgagaa gcacaaggtg 600 tacgcctgcg aagtgaccca ccagggcctg tctagccccg tgaccaagtc tttcaaccgg 660 ggcgagtgc 669 +ADw-210+AD4- 112 +ADw-211+AD4- 1716 +ADw-212+AD4- ADN +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- huCD40+AF8-Fcagujero+AF8-PGLALA+AF8-28H1 VL +ADw-400+AD4- 112 gaggtgcagc tggtggaatc tggcggcgga ctggtgcagc ctggcggatc tctgagactg 60 agctgtgccg ccagcggcta cagcttcacc ggctactaca tccactgggt gcgccaggcc 120 cctggcaagg gactggaatg ggtggccaga gtgatcccca atgccggcgg aaccagctac 180 aaccagaagt tcaagggccg gttcaccctg agcgtggaca acagcaagaa caccgcctac 240 ctgcagatga acagcctgcg ggccgaggac accgccgtgt actattgtgc ccgcgagggc 300 atctattggt ggggccaggg aacactcgtg accgtgtcca gcgctagcac caagggccca 360 tcggtcttcc ccctggcacc ctcctccaag agcacctctg ggggcacagc ggccctgggc 420 tgcctggtca aggactactt ccccgaaccg gtgacggtgt cgtggaactc aggcgccctg 480 accagcggcg tgcacacctt cccggctgtc ctacagtcct caggactcta ctccctcagc 540 agcgtggtga ccgtgccctc cagcagcttg ggcacccaga cctacatctg caacgtgaat 600 cacaagccca gcaacaccaa ggtggacaag aaagttgagc ccaaatcttg tgacaaaact 660 cacacatgcc caccgtgccc agcacctgaa gctgcagggg gaccgtcagt cttcctcttc 720 cccccaaaac ccaaggacac cctcatgatc tcccggaccc ctgaggtcac atgcgtggtg 780 gtggacgtga gccacgaaga ccctgaggtc aagttcaact ggtacgtgga cggcgtggag 840 gtgcataatg ccaagacaaa gccgcgggag gagcagtaca acagcacgta ccgtgtggtc 900 agcgtcctca ccgtcctgca ccaggactgg ctgaatggca aggagtacaa gtgcaaggtc 960 tccaacaaag ccctcggcgc ccccatcgag aaaaccatct ccaaagccaa agggcagccc 1020 cgagaaccac aggtgtgcac cctgccccca tcccgggatg agctgaccaa gaaccaggtc 1080 agcctctcgt gcgcagtcaa aggcttctat cccagcgaca tcgccgtgga gtgggagagc 1140 aatgggcagc cggagaacaa ctacaagacc acgcctcccg tgctggactc cgacggctcc 1200 ttcttcctcg tgagcaagct caccgtggac aagagcaggt ggcagcaggg gaacgtcttc 1260 tcatgctccg tgatgcatga ggctctgcac aaccactaca cgcagaagag cctctccctg 1320 tctccgggtg gaggcggcgg aagcggagga ggaggatccg gtggtggcgg atctgggggc 1380 ggtggatctg agatcgtgct gacccagtct cccggcaccc tgagcctgag ccctggcgag 1440 agagccaccc tgagctgcag agccagccag agcgtgagcc ggagctacct ggcctggtat 1500 cagcagaagc ccggccaggc ccccagactg ctgatcatcg gcgccagcac ccgggccacc 1560 ggcatccccg atagattcag cggcagcggc tccggcaccg acttcaccct gaccatcagc 1620 cggctggaac ccgaggactt cgccgtgtac tactgccagc agggccaggt gatccccccc 1680 accttcggcc agggcaccaa ggtggaaatc aagtga 1716 +ADw-210+AD4- 113 +ADw-211+AD4- 1740 +ADw-212+AD4- ADN +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- huCD40+AF8-Fcpomo+AF8-PGLALA+AF8-28H1 VH +ADw-400+AD4- 113 gaggtgcagc tggtggaatc tggcggcgga ctggtgcagc ctggcggatc tctgagactg 60 agctgtgccg ccagcggcta cagcttcacc ggctactaca tccactgggt gcgccaggcc 120 cctggcaagg gactggaatg ggtggccaga gtgatcccca atgccggcgg aaccagctac 180 aaccagaagt tcaagggccg gttcaccctg agcgtggaca acagcaagaa caccgcctac 240 ctgcagatga acagcctgcg ggccgaggac accgccgtgt actattgtgc ccgcgagggc 300 atctattggt ggggccaggg aacactcgtg accgtgtcca gcgctagcac caagggccca 360 tcggtcttcc ccctggcacc ctcctccaag agcacctctg ggggcacagc ggccctgggc 420 tgcctggtca aggactactt ccccgaaccg gtgacggtgt cgtggaactc aggcgccctg 480 accagcggcg tgcacacctt cccggctgtc ctacagtcct caggactcta ctccctcagc 540 agcgtggtga ccgtgccctc cagcagcttg ggcacccaga cctacatctg caacgtgaat 600 cacaagccca gcaacaccaa ggtggacaag aaagttgagc ccaaatcttg tgacaaaact 660 cacacatgcc caccgtgccc agcacctgaa gctgcagggg gaccgtcagt cttcctcttc 720 cccccaaaac ccaaggacac cctcatgatc tcccggaccc ctgaggtcac atgcgtggtg 780 gtggacgtga gccacgaaga ccctgaggtc aagttcaact ggtacgtgga cggcgtggag 840 gtgcataatg ccaagacaaa gccgcgggag gagcagtaca acagcacgta ccgtgtggtc 900 agcgtcctca ccgtcctgca ccaggactgg ctgaatggca aggagtacaa gtgcaaggtc 960 tccaacaaag ccctcggcgc ccccatcgag aaaaccatct ccaaagccaa agggcagccc 1020 cgagaaccac aggtgtacac cctgcccccc tgcagagatg agctgaccaa gaaccaggtg 1080 tccctgtggt gtctggtcaa gggcttctac cccagcgata tcgccgtgga gtgggagagc 1140 aacggccagc ctgagaacaa ctacaagacc accccccctg tgctggacag cgacggcagc 1200 ttcttcctgt actccaaact gaccgtggac aagagccggt ggcagcaggg caacgtgttc 1260 agctgcagcg tgatgcacga ggccctgcac aaccactaca cccagaagtc cctgagcctg 1320 agccccggcg gaggcggcgg aagcggagga ggaggatccg gaggaggggg aagtggcggc 1380 ggaggatctg aggtgcagct gctggaatcc ggcggaggcc tggtgcagcc tggcggatct 1440 ctgagactgt cctgcgccgc ctccggcttc accttctcct cccacgccat gtcctgggtc 1500 cgacaggctc ctggcaaagg cctggaatgg gtgtccgcca tctgggcctc cggcgagcag 1560 tactacgccg actctgtgaa gggccggttc accatctccc gggacaactc caagaacacc 1620 ctgtacctgc agatgaactc cctgcgggcc gaggacaccg ccgtgtacta ctgtgccaag 1680 ggctggctgg gcaacttcga ctactggggc cagggcaccc tggtcaccgt gtccagctga 1740 +ADw-210+AD4- 114 +ADw-211+AD4- 2031 +ADw-212+AD4- ADN +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- huCD40-Fc+AF8-PGLALA+AF8-28H1+AF8-VLCH1 EE +ADw-400+AD4- 114 gaggtgcagc tggtggaatc tggcggcgga ctggtgcagc ctggcggatc tctgagactg 60 agctgtgccg ccagcggcta cagcttcacc ggctactaca tccactgggt gcgccaggcc 120 cctggcaagg gactggaatg ggtggccaga gtgatcccca atgccggcgg aaccagctac 180 aaccagaagt tcaagggccg gttcaccctg agcgtggaca acagcaagaa caccgcctac 240 ctgcagatga acagcctgcg ggccgaggac accgccgtgt actattgtgc ccgcgagggc 300 atctattggt ggggccaggg aacactcgtg accgtgtcca gcgctagcac caagggacct 360 tccgtgtttc ccctggctcc cagctccaag tctacctctg ggggcacagc tgctctggga 420 tgtctggtgg aagattattt tcctgaacct gtgaccgtgt catggaacag cggagccctg 480 acctccgggg tgcacacatt ccctgctgtg ctgcagtcct ccggcctgta tagcctgagc 540 agcgtcgtga ccgtgccttc cagctctctg ggcacacaga catatatctg taatgtgaat 600 cacaaaccct ctaataccaa agtggatgag aaagtggaac ctaagtcctg cgacaagacc 660 cacacctgtc ccccttgtcc tgcccctgaa gctgctggcg gcccatctgt gtttctgttc 720 cccccaaagc ccaaggacac cctgatgatc agccggaccc ccgaagtgac ctgcgtggtg 780 gtggatgtgt cccacgagga cccagaagtg aagttcaatt ggtacgtgga cggcgtggaa 840 gtgcacaacg ccaagaccaa gccgcgggaa gaacagtaca acagcaccta ccgggtggtg 900 tccgtgctga cagtgctgca ccaggactgg ctgaacggca aagagtacaa gtgcaaggtg 960 tccaacaagg ccctgggagc ccccatcgag aaaaccatca gcaaggccaa gggccagccc 1020 cgcgaacctc aggtgtacac cctgccccca agcagggacg agctgaccaa gaaccaggtg 1080 tccctgacct gtctcgtgaa gggcttctac ccctccgata tcgccgtgga atgggagagc 1140 aacggccagc ccgagaacaa ctacaagacc accccccctg tgctggacag cgacggctca 1200 ttcttcctgt actccaagct gaccgtggac aagagccggt ggcagcaggg caacgtgttc 1260 agctgcagcg tgatgcacga ggccctgcac aaccactaca cacagaagtc tctgagcctg 1320 agccctggcg gagggggagg atctggggga ggcggaagtg ggggaggggg ttccggaggc 1380 ggcggatcag aaattgtgct gacccagtcc cccggcaccc tgtcactgtc tccaggcgaa 1440 agagccaccc tgagctgtag ggcctcccag agcgtgtcca gaagctatct ggcctggtat 1500 cagcagaagc ccggacaggc ccccagactg ctgatcattg gcgcctctac cagagccacc 1560 ggcatccccg atagattcag cggctctggc agcggcaccg acttcaccct gaccatctcc 1620 agactggaac ccgaggactt tgccgtgtac tattgccagc agggccaagt gatccccccc 1680 acctttggcc agggaacaaa ggtggaaatc aagtccagcg cttccaccaa gggcccctca 1740 gtgttcccac tggcaccatc cagcaagtcc acaagcggag gaaccgccgc tctgggctgt 1800 ctcgtgaaag actactttcc agagccagtg accgtgtcct ggaatagtgg cgctctgact 1860 tctggcgtgc acactttccc cgcagtgctg cagagttctg gcctgtactc cctgagtagc 1920 gtcgtgacag tgccctcctc tagcctgggc actcagactt acatctgcaa tgtgaatcat 1980 aagccttcca acacaaaagt ggacaaaaaa gtggaaccca aatcttgctg a 2031 +ADw-210+AD4- 115 +ADw-211+AD4- 2418 +ADw-212+AD4- ADN +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- CD40 VHCH1-CD40 VHCH1-Fcpomo+AF8-PGLALA-DP47 VH +ADw-400+AD4- 115 gaggtgcagc tggtggaatc tggcggcgga ctggtgcagc ctggcggatc tctgagactg 60 agctgtgccg ccagcggcta cagcttcacc ggctactaca tccactgggt gcgccaggcc 120 cctggcaagg gactggaatg ggtggccaga gtgatcccca atgccggcgg aaccagctac 180 aaccagaagt tcaagggccg gttcaccctg agcgtggaca acagcaagaa caccgcctac 240 ctgcagatga acagcctgcg ggccgaggac accgccgtgt actattgtgc ccgcgagggc 300 atctattggt ggggccaggg aacactcgtg accgtgtcca gcgcttccac caagggccct 360 agcgtgttcc ctctggcccc tagcagcaag tctaccagcg gaggaacagc cgccctgggc 420 tgcctcgtga aggactactt tcccgagccc gtgacagtgt cctggaactc tggcgccctg 480 acaagcggcg tgcacacctt tccagccgtg ctgcagagca gcggcctgta ctctctgagc 540 agcgtcgtga ctgtgcccag cagcagcctg ggaacccaga cctacatctg caacgtgaac 600 cacaagccca gcaacaccaa ggtggacaag aaggtggaac ccaagagctg cgacggcgga 660 ggcggatcag gcggcggagg atccgaagtg cagctggtgg aaagtggggg aggcctggtg 720 cagccagggg gaagcctgag actgtcttgt gccgcttccg gctactcttt taccgggtat 780 tatatccatt gggtgcggca ggctccaggg aaaggcctgg aatgggtggc acgcgtgatc 840 cctaacgcag gcggcacctc ttataatcag aagtttaaag ggcgctttac cctgtccgtg 900 gacaattcca agaatactgc ttacctgcag atgaattccc tgcgcgccga agatacagct 960 gtgtattact gcgccagaga agggatctat tggtggggac agggcaccct cgtgacagtg 1020 tcatccgcta gcaccaaggg cccatcggtc ttccccctgg caccctcctc caagagcacc 1080 tctgggggca cagcggccct gggctgcctg gtcaaggact acttccccga accggtgacg 1140 gtgtcgtgga actcaggcgc cctgaccagc ggcgtgcaca ccttcccggc tgtcctacag 1200 tcctcaggac tctactccct cagcagcgtg gtgaccgtgc cctccagcag cttgggcacc 1260 cagacctaca tctgcaacgt gaatcacaag cccagcaaca ccaaggtgga caagaaagtt 1320 gagcccaaat cttgtgacaa aactcacaca tgcccaccgt gcccagcacc tgaagctgca 1380 gggggaccgt cagtcttcct cttcccccca aaacccaagg acaccctcat gatctcccgg 1440 acccctgagg tcacatgcgt ggtggtggac gtgagccacg aagaccctga ggtcaagttc 1500 aactggtacg tggacggcgt ggaggtgcat aatgccaaga caaagccgcg ggaggagcag 1560 tacaacagca cgtaccgtgt ggtcagcgtc ctcaccgtcc tgcaccagga ctggctgaat 1620 ggcaaggagt acaagtgcaa ggtctccaac aaagccctcg gcgcccccat cgagaaaacc 1680 atctccaaag ccaaagggca gccccgagaa ccacaggtgt acaccctgcc cccctgcaga 1740 gatgagctga ccaagaacca ggtgtccctg tggtgtctgg tcaagggctt ctaccccagc 1800 gatatcgccg tggagtggga gagcaacggc cagcctgaga acaactacaa gaccaccccc 1860 cctgtgctgg acagcgacgg cagcttcttc ctgtactcca aactgaccgt ggacaagagc 1920 cggtggcagc agggcaacgt gttcagctgc agcgtgatgc acgaggccct gcacaaccac 1980 tacacccaga agtccctgag cctgagcccc ggcggaggcg gcggaagcgg aggaggagga 2040 tccggaggag ggggaagtgg cggcggagga tctgaggtgc aattgttgga gtctggggga 2100 ggcttggtac agcctggggg gtccctgaga ctctcctgtg cagccagcgg attcaccttt 2160 agcagttatg ccatgagctg ggtccgccag gctccaggga aggggctgga gtgggtctca 2220 gctattagtg gtagtggtgg tagcacatac tacgcagact ccgtgaaggg ccggttcacc 2280 atctccagag acaattccaa gaacacgctg tatctgcaga tgaacagcct gagagccgag 2340 gacacggccg tatattactg tgcgaaaggc agcggatttg actactgggg ccaaggaacc 2400 ctggtcaccg tctcgagc 2418 +ADw-210+AD4- 116 +ADw-211+AD4- 2397 +ADw-212+AD4- ADN +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- CD40 VHCH1-CD40 VHCH1-Fc agujero+AF8-PGLALA-DP47 VL DNA +ADw-400+AD4- 116 gaggtgcagc tggtggagag cggcggcggc ctggtgcagc ccggcggcag cctgaggctg 60 agctgcgccg ccagcggcta cagcttcacc ggctactaca tccactgggt gaggcaggcc 120 cccggcaagg gcctggagtg ggtggccagg gtgatcccca acgccggcgg caccagctac 180 aaccagaagt tcaagggcag gttcaccctg agcgtggaca acagcaagaa caccgcctac 240 ctgcagatga acagcctgag ggccgaggac accgccgtgt actactgcgc cagggagggc 300 atctactggt ggggccaggg caccctggtg accgtgagca gcgccagcac caagggcccc 360 agcgtgttcc ccctggcccc cagcagcaag agcaccagcg gcggcaccgc cgccctgggc 420 tgcctggtga aggactactt ccccgagccc gtgaccgtga gctggaacag cggcgccctg 480 accagcggcg tgcacacctt ccccgccgtg ctgcagagca gcggcctgta cagcctgagc 540 agcgtggtga ccgtgcccag cagcagcctg ggcacccaga cctacatctg caacgtgaac 600 cacaagccca gcaacaccaa ggtggacaag aaggtggagc ccaagagctg cgacggcggc 660 ggcggcagcg gcggcggcgg cagcgaggtg cagctggtgg agagcggcgg cggcctggtg 720 cagcccggcg gcagcctgag gctgagctgc gccgccagcg gctacagctt caccggctac 780 tacatccact gggtgaggca ggcccccggc aagggcctgg agtgggtggc cagggtgatc 840 cccaacgccg gcggcaccag ctacaaccag aagttcaagg gcaggttcac cctgagcgtg 900 gacaacagca agaacaccgc ctacctgcag atgaacagcc tgagggccga ggacaccgcc 960 gtgtactact gcgccaggga gggcatctac tggtggggcc agggcaccct ggtgaccgtg 1020 agcagcgcca gcaccaaggg ccccagcgtg ttccccctgg cccccagcag caagagcacc 1080 agcggcggca ccgccgccct gggctgcctg gtgaaggact acttccccga gcccgtgacc 1140 gtgagctgga acagcggcgc cctgaccagc ggcgtgcaca ccttccccgc cgtgctgcag 1200 agcagcggcc tgtacagcct gagcagcgtg gtgaccgtgc ccagcagcag cctgggcacc 1260 cagacctaca tctgcaacgt gaaccacaag cccagcaaca ccaaggtgga caagaaggtg 1320 gagcccaaga gctgcgacaa gacccacacc tgccccccct gccccgcccc cgaggccgcc 1380 ggcggcccca gcgtgttcct gttccccccc aagcccaagg acaccctgat gatcagcagg 1440 acccccgagg tgacctgcgt ggtggtggac gtgagccacg aggaccccga ggtgaagttc 1500 aactggtacg tggacggcgt ggaggtgcac aacgccaaga ccaagcccag ggaggagcag 1560 tacaacagca cctacagggt ggtgagcgtg ctgaccgtgc tgcaccagga ctggctgaac 1620 ggcaaggagt acaagtgcaa ggtgagcaac aaggccctgg gcgcccccat cgagaagacc 1680 atcagcaagg ccaagggcca gcccagggag ccccaggtgt gcaccctgcc ccccagcagg 1740 gacgagctga ccaagaacca ggtgagcctg agctgcgccg tgaagggctt ctaccccagc 1800 gacatcgccg tggagtggga gagcaacggc cagcccgaga acaactacaa gaccaccccc 1860 cccgtgctgg acagcgacgg cagcttcttc ctggtgagca agctgaccgt ggacaagagc 1920 aggtggcagc agggcaacgt gttcagctgc agcgtgatgc acgaggccct gcacaaccac 1980 tacacccaga agagcctgag cctgagcccc ggcggcggcg gcggcagcgg cggcggcggc 2040 agcggcggcg gcggcagcgg cggcggcggc agcgagatcg tgctgaccca gagccccggc 2100 accctgagcc tgagccccgg cgagagggcc accctgagct gcagggccag ccagagcgtg 2160 agcagcagct acctggcctg gtaccagcag aagcccggcc aggcccccag gctgctgatc 2220 tacggcgcca gcagcagggc caccggcatc cccgacaggt tcagcggcag cggcagcggc 2280 accgacttca ccctgaccat cagcaggctg gagcccgagg acttcgccgt gtactactgc 2340 cagcagtacg gcagcagccc cctgaccttc ggccagggca ccaaggtgga gatcaag 2397 +ADw-210+AD4- 117 +ADw-211+AD4- 2712 +ADw-212+AD4- ADN +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- CD40 VHCH1-CD40 VHCH1-Fc+AF8-PGLALA-DP47 VLCH1 EE +ADw-400+AD4- 117 gaggtgcagc tggtggaatc tggcggcgga ctggtgcagc ctggcggatc tctgagactg 60 agctgtgccg ccagcggcta cagcttcacc ggctactaca tccactgggt gcgccaggcc 120 cctggcaagg gactggaatg ggtggccaga gtgatcccca atgccggcgg aaccagctac 180 aaccagaagt tcaagggccg gttcaccctg agcgtggaca acagcaagaa caccgcctac 240 ctgcagatga acagcctgcg ggccgaggac accgccgtgt actattgtgc ccgcgagggc 300 atctattggt ggggccaggg aacactcgtg accgtgtcca gcgcttctac caagggcccc 360 agcgtgttcc ctctggcccc tagcagcaag agcacatctg gcggaacagc cgccctgggc 420 tgcctcgtgg aggactactt tcccgagccc gtgacagtgt cctggaactc tggcgccctg 480 acaagcggcg tgcacacctt tccagccgtg ctccagagca gcggcctgta ctctctgagc 540 agcgtcgtga ctgtgcccag cagcagcctg ggaacccaga cctacatctg caacgtgaac 600 cacaagccca gcaacaccaa ggtggacgag aaggtggaac ccaagagctg cgacggcgga 660 ggcggatctg gcggcggagg atccgaagtg cagctggtgg aaagtggggg aggcctggtg 720 cagccagggg gaagcctgag actgtcttgt gccgcttccg gctactcttt taccgggtat 780 tatatccatt gggtgcggca ggctccaggg aaaggcctgg aatgggtggc acgcgtgatc 840 cctaacgcag gcggcacctc ttataatcag aagtttaaag ggcgctttac cctgtccgtg 900 gacaattcca agaatactgc ttacctgcag atgaattccc tgcgcgccga agatacagct 960 gtgtattact gcgccagaga agggatctat tggtggggac agggcaccct cgtgacagtg 1020 tcatccgcta gcaccaaggg accttccgtg tttcccctgg ctcccagctc caagtctacc 1080 tctgggggca cagctgctct gggatgtctg gtggaagatt attttcctga acctgtgacc 1140 gtgtcatgga acagcggagc cctgacctcc ggggtgcaca cattccctgc tgtgctgcag 1200 tcctccggcc tgtatagcct gagcagcgtc gtgaccgtgc cttccagctc tctgggcaca 1260 cagacatata tctgtaatgt gaatcacaaa ccctctaata ccaaagtgga tgagaaagtg 1320 gaacctaagt cctgcgacaa gacccacacc tgtccccctt gtcctgcccc tgaagctgct 1380 ggcggcccat ctgtgtttct gttcccccca aagcccaagg acaccctgat gatcagccgg 1440 acccccgaag tgacctgcgt ggtggtggat gtgtcccacg aggacccaga agtgaagttc 1500 aattggtacg tggacggcgt ggaagtgcac aacgccaaga ccaagccgcg ggaagaacag 1560 tacaacagca cctaccgggt ggtgtccgtg ctgacagtgc tgcaccagga ctggctgaac 1620 ggcaaagagt acaagtgcaa ggtgtccaac aaggccctgg gagcccccat cgagaaaacc 1680 atcagcaagg ccaagggcca gccccgcgaa cctcaggtgt acaccctgcc cccaagcagg 1740 gacgagctga ccaagaacca ggtgtccctg acctgtctcg tgaagggctt ctacccctcc 1800 gatatcgccg tggaatggga gagcaacggc cagcccgaga acaactacaa gaccaccccc 1860 cctgtgctgg acagcgacgg ctcattcttc ctgtactcca agctgaccgt ggacaagagc 1920 cggtggcagc agggcaacgt gttcagctgc agcgtgatgc acgaggccct gcacaaccac 1980 tacacacaga agtctctgag cctgagccct ggcggagggg gaggatctgg gggaggcgga 2040 agtgggggag ggggttccgg aggcggagga tccgaaatcg tgttaacgca gtctccaggc 2100 accctgtctt tgtctccagg ggaaagagcc accctctctt gcagggccag tcagagtgtt 2160 agcagcagct acttagcctg gtaccagcag aaacctggcc aggctcccag gctcctcatc 2220 tatggagcat ccagcagggc cactggcatc ccagacaggt tcagtggcag tggatccggg 2280 acagacttca ctctcaccat cagcagactg gagcctgaag attttgcagt gtattactgt 2340 cagcagtatg gtagctcacc gctgacgttc ggccagggga ccaaagtgga aatcaaaagc 2400 agcgcttcca ccaagggccc ctcagtgttc ccactggcac catccagcaa gtccacaagc 2460 ggaggaaccg ccgctctggg ctgtctcgtg aaagactact ttccagagcc agtgaccgtg 2520 tcctggaata gtggcgctct gacttctggc gtgcacactt tccccgcagt gctgcagagt 2580 tctggcctgt actccctgag tagcgtcgtg acagtgccct cctctagcct gggcactcag 2640 acttacatct gcaatgtgaa tcataagcct tccaacacaa aagtggacaa aaaagtggaa 2700 cccaaatctt gc 2712 +ADw-210+AD4- 118 +ADw-211+AD4- 666 +ADw-212+AD4- ADN +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- DP47 VHCL +ADw-400+AD4- 118 gaggtgcaat tgttggagtc tgggggaggc ttggtacagc ctggggggtc cctgagactc 60 tcctgtgcag cctccggatt cacctttagc agttatgcca tgagctgggt ccgccaggct 120 ccagggaagg ggctggagtg ggtctcagct attagtggta gtggtggtag cacatactac 180 gcagactccg tgaagggccg gttcaccatc tccagagaca attccaagaa cacgctgtat 240 ctgcagatga acagcctgag agccgaggac acggccgtat attactgtgc gaaaggcagc 300 ggatttgact actggggcca aggaaccctg gtcaccgtct cgagtgctag cgtggccgct 360 ccctccgtgt tcatcttccc accttccgac gagcagctga agtccggcac cgcttctgtc 420 gtgtgcctgc tgaacaactt ctacccccgc gaggccaagg tgcagtggaa ggtggacaac 480 gccctgcagt ccggcaacag ccaggaatcc gtgaccgagc aggactccaa ggacagcacc 540 tactccctgt cctccaccct gaccctgtcc aaggccgact acgagaagca caaggtgtac 600 gcctgcgaag tgacccacca gggcctgtct agccccgtga ccaagtcttt caaccggggc 660 gagtgc 666 +ADw-210+AD4- 119 +ADw-211+AD4- 2409 +ADw-212+AD4- ADN +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- muCD40 VHCH1-muCD40 VHCH1-FcKK+AF8-DAPG -28H1 VH +ADw-400+AD4- 119 gaagtgcagc tggtggaaag cgacggcgga ctggtgcagc ctggcagatc tctgaagctg 60 ccttgtgccg ccagcggctt caccttcagc gactactaca tggcctgggt gcgacaggcc 120 cctaccaagg gactggaatg ggtggccagc atcagctacg acggcagcag cacctactac 180 agagacagcg tgaagggcag attcaccatc agcagagaca acgccaagag caccctgtac 240 ctgcagatgg acagcctgag aagcgaggac accgctacct actactgcgg cagacacagc 300 agctacttcg actactgggg ccagggcgtg atggtcaccg tgtctagcgc caagaccaca 360 ccccccagcg tgtaccctct ggctcctgga tctgccgccc agaccaacag catggtcaca 420 ctgggctgcc tggtgaaggg ctacttcccc gagcctgtga ccgtgacctg gaacagcggc 480 tctctgtcta gcggcgtgca caccttccct gccgtgctgc agagcgacct gtacaccctg 540 tcctccagcg tgaccgtgcc ttcctccacc tggccttccc agaccgtgac atgcaacgtg 600 gcccaccctg ccagctccac caaggtggac aagaaaatcg tgccccggga ctgcggaggg 660 ggcggttccg gcggaggagg atccgaggtg cagctggtgg aatctgatgg gggcctggtg 720 cagcccggaa gaagcctgaa actgccctgt gctgcctctg gcttcacatt ctctgattac 780 tatatggctt gggtgcgcca ggctccaaca aaaggcctgg aatgggtggc atccatctct 840 tacgacggct cctccactta ctacagggac tctgtgaagg gccggttcac aatctcccgg 900 gataacgcca agtctacact gtacctgcag atggattccc tgcgctccga ggacacagcc 960 acatattact gtggcaggca ctcctcctac tttgattatt ggggacaggg cgtgatggtc 1020 acagtgtcca gcgctaagac caccccccct agcgtgtacc ctctggcccc tggatctgcc 1080 gcccagacca acagcatggt gaccctgggc tgcctggtga agggctactt ccccgagcct 1140 gtgaccgtga cctggaacag cggcagcctg agcagcggcg tgcacacctt tccagccgtg 1200 ctgcagagcg acctgtacac cctgagcagc tccgtgaccg tgcctagcag cacctggccc 1260 agccagacag tgacctgcaa cgtggcccac cctgccagca gcaccaaggt ggacaagaaa 1320 atcgtgcccc gggactgcgg ctgcaagccc tgcatctgca ccgtgcccga ggtgtccagc 1380 gtgttcatct tcccacccaa gcccaaggac gtgctgacca tcaccctgac ccccaaagtg 1440 acctgcgtgg tggtggccat cagcaaggac gaccccgagg tgcagttctc ttggtttgtg 1500 gacgacgtgg aggtgcacac agcccagaca aagccccggg aggaacagat caacagcacc 1560 ttcagaagcg tgtccgagct gcccatcatg caccaggact ggctgaacgg caaagaattc 1620 aagtgcagag tgaacagcgc cgccttcggc gcccccatcg agaaaaccat cagcaagacc 1680 aagggcagac ccaaggcccc ccaggtgtac accatccccc cacccaaaaa acagatggcc 1740 aaggacaagg tgtccctgac ctgcatgatc accaactttt tccccgagga catcaccgtg 1800 gagtggcagt ggaatggcca gcccgccgag aactacaaga acacccagcc catcatgaag 1860 accgacggca gctacttcgt gtacagcaag ctgaacgtgc agaagtccaa ctgggaggcc 1920 ggcaacacct tcacctgtag cgtgctgcac gagggcctgc acaaccacca caccgagaag 1980 tccctgagcc actcccccgg cggcggaggc ggttccggag gaggaggatc cggaggaggg 2040 ggaagtggcg gcggaggatc tgaggtgcag ctgctggaat ccggcggagg cctggtgcag 2100 cctggcggat ctctgagact gtcctgcgcc gcctccggct tcaccttctc ctcccacgcc 2160 atgtcctggg tccgacaggc tcctggcaaa ggcctggaat gggtgtccgc catctgggcc 2220 tccggcgagc agtactacgc cgactctgtg aagggccggt tcaccatctc ccgggacaac 2280 tccaagaaca ccctgtacct gcagatgaac tccctgcggg ccgaggacac cgccgtgtac 2340 tactgtgcca agggctggct gggcaacttc gactactggg gccagggcac cctggtcacc 2400 gtgtccagc 2409 +ADw-210+AD4- 120 +ADw-211+AD4- 2385 +ADw-212+AD4- ADN +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- muCD40 VHCH1-muCD40 VHCH1-FcDD+AF8-DAPG -28H1 VL +ADw-400+AD4- 120 gaagtgcagc tggtggaaag cgacggcgga ctggtgcagc ctggcagatc tctgaagctg 60 ccttgtgccg ccagcggctt caccttcagc gactactaca tggcctgggt gcgacaggcc 120 cctaccaagg gactggaatg ggtggccagc atcagctacg acggcagcag cacctactac 180 agagacagcg tgaagggcag attcaccatc agcagagaca acgccaagag caccctgtac 240 ctgcagatgg acagcctgag aagcgaggac accgctacct actactgcgg cagacacagc 300 agctacttcg actactgggg ccagggcgtg atggtcaccg tgtctagcgc caagaccaca 360 ccccccagcg tgtaccctct ggctcctgga tctgccgccc agaccaacag catggtcaca 420 ctgggctgcc tggtgaaggg ctacttcccc gagcctgtga ccgtgacctg gaacagcggc 480 tctctgtcta gcggcgtgca caccttccct gccgtgctgc agagcgacct gtacaccctg 540 tcctccagcg tgaccgtgcc ttcctccacc tggccttccc agaccgtgac atgcaacgtg 600 gcccaccctg ccagctccac caaggtggac aagaaaatcg tgccccggga ctgcggaggg 660 ggcggttccg gcggaggagg atccgaggtg cagctggtgg aatctgatgg gggcctggtg 720 cagcccggaa gaagcctgaa actgccctgt gctgcctctg gcttcacatt ctctgattac 780 tatatggctt gggtgcgcca ggctccaaca aaaggcctgg aatgggtggc atccatctct 840 tacgacggct cctccactta ctacagggac tctgtgaagg gccggttcac aatctcccgg 900 gataacgcca agtctacact gtacctgcag atggattccc tgcgctccga ggacacagcc 960 acatattact gtggcaggca ctcctcctac tttgattatt ggggacaggg cgtgatggtc 1020 acagtgtcca gcgctaagac caccccccct agcgtgtacc ctctggcccc tggatctgcc 1080 gcccagacca acagcatggt gaccctgggc tgcctggtga agggctactt ccccgagcct 1140 gtgaccgtga cctggaacag cggcagcctg agcagcggcg tgcacacctt tccagccgtg 1200 ctgcagagcg acctgtacac cctgagcagc tccgtgaccg tgcctagcag cacctggccc 1260 agccagacag tgacctgcaa cgtggcccac cctgccagca gcaccaaggt ggacaagaaa 1320 atcgtgcccc gggactgcgg ctgcaagccc tgcatctgca ccgtgcccga ggtgtccagc 1380 gtgttcatct tcccacccaa gcccaaggac gtgctgacca tcaccctgac ccccaaagtg 1440 acctgcgtgg tggtggccat cagcaaggac gaccccgagg tgcagttctc ttggtttgtg 1500 gacgacgtgg aggtgcacac agcccagaca aagccccggg aggaacagat caacagcacc 1560 ttcagaagcg tgtccgagct gcccatcatg caccaggact ggctgaacgg caaagaattc 1620 aagtgcagag tgaacagcgc cgccttcggc gcccccatcg agaaaaccat cagcaagacc 1680 aagggcagac ccaaggcccc ccaggtgtac accatccccc cacccaaaga acagatggcc 1740 aaggacaagg tgtccctgac ctgcatgatc accaactttt tccccgagga catcaccgtg 1800 gagtggcagt ggaatggcca gcccgccgag aactacgaca acacccagcc catcatggac 1860 accgacggca gctacttcgt gtacagcgac ctgaacgtgc agaagtccaa ctgggaggcc 1920 ggcaacacct tcacctgtag cgtgctgcac gagggcctgc acaaccacca caccgagaag 1980 tccctgagcc acagcccagg cggcggaggc ggatctggcg gaggaggttc cggaggtggc 2040 ggatctgggg gcggtggatc tgagatcgtg ctgacccagt ctcccggcac cctgagcctg 2100 agccctggcg agagagccac cctgagctgc agagccagcc agagcgtgag ccggagctac 2160 ctggcctggt atcagcagaa gcccggccag gcccccagac tgctgatcat cggcgccagc 2220 acccgggcca ccggcatccc cgatagattc agcggcagcg gctccggcac cgacttcacc 2280 ctgaccatca gccggctgga acccgaggac ttcgccgtgt actactgcca gcagggccag 2340 gtgatccccc ccaccttcgg ccagggcacc aaggtggaaa tcaag 2385 +ADw-210+AD4- 121 +ADw-211+AD4- 639 +ADw-212+AD4- ADN +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- mu CD40 cadena ligera +ADw-400+AD4- 121 gacactgtac tgacccagtc tcctgctttg gctgtgtctc caggagagag ggttaccatc 60 tcctgtaggg ccagtgacag tgtcagtaca cttatgcact ggtaccaaca gaaaccagga 120 cagcaaccca aactcctcat ctatctagca tcacacctag aatctggggt ccctgccagg 180 ttcagtggca gtgggtctgg gacagacttc accctcacca ttgatcctgt ggaggctgat 240 gacactgcaa cctattactg tcagcagagt tggaatgatc cgtggacgtt cggtggaggc 300 accaagctgg aattgaaacg tgccgatgct gcaccaactg tatcgatttt cccaccatcc 360 agtgagcagt taacatctgg aggtgcctca gtcgtgtgct tcttgaacaa cttctacccc 420 aaagacatca atgtcaagtg gaagattgat ggcagtgaac gacaaaatgg cgtcctgaac 480 agttggactg atcaggacag caaagacagc acctacagca tgagcagcac cctcacgttg 540 accaaggacg agtatgaacg acataacagc tatacctgtg aggccactca caagacatca 600 acttcaccca ttgtcaagag cttcaacagg aatgagtgt 639 +ADw-210+AD4- 122 +ADw-211+AD4- 2700 +ADw-212+AD4- ADN +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- muCD40 VHCH1-muCD40 VHCH1-Fc+AF8-DAPG-28H1 VLCH1 +ADw-400+AD4- 122 gaagtgcagc tggtggaatc cgacggcgga ctggtgcagc ctggcagatc tctgaagctg 60 ccttgtgccg cctccggctt caccttctcc gactactaca tggcctgggt gcgacaggcc 120 cctaccaagg gactggaatg ggtggcctcc atctcctacg acggctcctc cacctactac 180 cgggactctg tgaagggccg gttcaccatc tctcgggaca acgccaagtc caccctgtac 240 ctgcagatgg actccctgcg gagcgaggac accgctacct actactgcgg cagacactcc 300 tcctacttcg actactgggg ccagggcgtg atggtcaccg tgtcctctgc taagaccacc 360 cccccctccg tgtaccctct ggctcctgga tctgccgccc agaccaactc catggtcacc 420 ctgggctgtc tggtggaagg ctacttcccc gagcctgtga ccgtgacctg gaactccggc 480 tctctgtcct ctggcgtgca caccttccct gccgtgctgc agtccgacct gtacaccctg 540 agcagctccg tgaccgtgcc tagcagcacc tggcccagcc agacagtgac ctgcaacgtg 600 gcccaccctg ccagcagcac caaggtggac gagaaaatcg tgccccggga ctgcggcggt 660 ggaggttccg gaggcggcgg atccgaggtg cagctggtgg aaagtgatgg gggcctggtg 720 cagcccggaa gaagcctgaa actgccctgc gccgcttctg gctttacctt tagcgattac 780 tatatggctt gggtgcgcca ggctccaaca aaaggcctgg aatgggtggc atctatcagc 840 tacgatggca gcagcaccta ctatagagac agcgtgaagg ggagattcac catcagcaga 900 gataacgcta agagcacact gtacctgcag atggatagcc tgagatccga ggataccgcc 960 acatattact gtggccggca cagcagctac tttgattatt ggggacaggg cgtgatggtc 1020 acagtgtcta gcgctaagac tacccctcct agcgtgtacc ccctggcacc aggttccgct 1080 gctcagacca acagcatggt cacactggga tgcctggtgg aaggatattt tcctgaaccc 1140 gtgacagtga catggaatag cggctccctg tctagcggag tgcatacctt tccagctgtg 1200 ctgcagagcg atctgtatac actgagcagc tctgtgacag tgccttccag cacctggccc 1260 agccagacag tgacctgtaa tgtggctcat cccgcctcta gcaccaaagt ggatgagaaa 1320 atcgtgcccc gggactgcgg ctgcaagccc tgtatctgta ccgtgcccga ggtgtcctcc 1380 gtgttcatct tcccacctaa gcccaaggac gtgctgacaa tcaccctgac ccccaaagtg 1440 acctgcgtgg tggtggccat ctccaaggac gatcccgagg tgcagttcag ttggttcgtg 1500 gacgacgtgg aagtgcacac agcccagaca aagcccagag aggaacagat caactccacc 1560 ttcagaagcg tgtccgagct gcccatcatg caccaggact ggctgaacgg caaagaattc 1620 aagtgcagag tgaactccgc cgcctttggc gcccctatcg aaaagaccat ctccaagacc 1680 aagggcagac ccaaggcccc ccaggtgtac acaatccccc cacccaaaga acagatggcc 1740 aaggacaagg tgtccctgac ctgcatgatc accaactttt tcccagagga catcaccgtg 1800 gaatggcagt ggaacggcca gcccgccgag aactacaaga acacccagcc catcatggac 1860 accgacggct cctacttcgt gtactccaag ctgaacgtgc agaagtccaa ctgggaggcc 1920 ggcaacacct tcacctgttc cgtgctgcac gagggcctgc acaaccacca caccgagaag 1980 tccctgtccc actcccctgg aaaaggcgga ggcggatctg gtggcggagg atctggcggt 2040 ggtggttccg gaggcggtgg atctgagatc gtgctgaccc agtctcccgg caccctgtca 2100 ctgtctccag gcgagagagc caccctgtcc tgcagagcct ctcagtccgt gtcccggtct 2160 tacctggcct ggtatcagca gaagcccggc caggctcccc ggctgctgat catcggagct 2220 tctaccagag ccaccggcat ccccgacaga ttctccggct ctggctctgg caccgacttc 2280 accctgacca tctctcggct ggaacccgag gacttcgccg tgtactactg ccagcagggc 2340 caagtgatcc cccccacctt tggccagggc accaaggtgg aaatcaagtc cagcgctaag 2400 accacccccc cctccgtgta tcctctggcc cctggatctg ccgcccagac caactccatg 2460 gtcaccctgg gctgcctcgt gaagggctac ttccctgagc ctgtgaccgt gacctggaac 2520 tccggctccc tgtctagcgg cgtgcacacc tttccagctg tgctgcagtc cgacctgtac 2580 accctgagca gctccgtgac cgtgccttcc tccacctggc cttcccagac cgtgacatgc 2640 aacgtggccc accctgccag ctccacaaag gtggacaaga aaatcgtgcc ccgggactgc 2700 +ADw-210+AD4- 123 +ADw-211+AD4- 669 +ADw-212+AD4- ADN +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- 28H1 VHCL (mu) +ADw-400+AD4- 123 gaagtgcagc tgctggaatc cggcggaggc ctggtgcagc ctggcggatc tctgagactg 60 tcctgcgccg cctccggctt caccttctcc tcccacgcca tgtcctgggt ccgacaggct 120 cctggcaaag gcctggaatg ggtgtccgcc atctgggcct ccggcgagca gtactacgcc 180 gactctgtga agggccggtt caccatctcc cgggacaact ccaagaacac cctgtacctg 240 cagatgaact ccctgcgggc cgaggacacc gccgtgtact actgtgccaa gggctggctg 300 ggcaacttcg actactgggg acagggcacc ctggtcaccg tgtccagcgc ttctgatgcc 360 gcccctaccg tatcgatttt cccaccctcc agcgagcagc tgacaagcgg cggagctagc 420 gtcgtgtgct tcctgaacaa cttctacccc aaggacatca acgtgaagtg gaagatcgac 480 ggcagcgagc ggcagaacgg cgtgctgaat agctggaccg accaggacag caaggactcc 540 acctacagca tgagcagcac cctgaccctg accaaggacg agtacgagcg gcacaacagc 600 tacacatgcg aggccaccca caagaccagc accagcccca tcgtgaagtc cttcaaccgg 660 aacgagtgc 669 +ADw-210+AD4- 124 +ADw-211+AD4- 639 +ADw-212+AD4- ADN +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- mu CD40 cadena ligera+ADs- 'RK' +ADw-400+AD4- 124 gacactgtac tgacccagtc tcctgctttg gctgtgtctc caggagagag ggttaccatc 60 tcctgtaggg ccagtgacag tgtcagtaca cttatgcact ggtaccaaca gaaaccagga 120 cagcaaccca aactcctcat ctatctagca tcacacctag aatctggggt ccctgccagg 180 ttcagtggca gtgggtctgg gacagacttc accctcacca ttgatcctgt ggaggctgat 240 gacactgcaa cctattactg tcagcagagt tggaatgatc cgtggacgtt cggtggaggc 300 accaagctgg aattgaaacg tgccgatgct gcaccaactg tatcgatttt cccaccatcc 360 agtcggaagt taacatctgg aggtgcctca gtcgtgtgct tcttgaacaa cttctacccc 420 aaagacatca atgtcaagtg gaagattgat ggcagtgaac gacaaaatgg cgtcctgaac 480 agttggactg atcaggacag caaagacagc acctacagca tgagcagcac cctcacgttg 540 accaaggacg agtatgaacg acataacagc tatacctgtg aggccactca caagacatca 600 acttcaccca ttgtcaagag cttcaacagg aatgagtgt 639 +ADw-210+AD4- 125 +ADw-211+AD4- 2406 +ADw-212+AD4- ADN +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- muCD40 VHCH1-muCD40 VHCH1-FcKK+AF8-DAPG-DP47 VH +ADw-400+AD4- 125 gaagtgcagc tggtggaaag cgacggcgga ctggtgcagc ctggcagatc tctgaagctg 60 ccttgtgccg ccagcggctt caccttcagc gactactaca tggcctgggt gcgacaggcc 120 cctaccaagg gactggaatg ggtggccagc atcagctacg acggcagcag cacctactac 180 agagacagcg tgaagggcag attcaccatc agcagagaca acgccaagag caccctgtac 240 ctgcagatgg acagcctgag aagcgaggac accgctacct actactgcgg cagacacagc 300 agctacttcg actactgggg ccagggcgtg atggtcaccg tgtctagcgc caagaccaca 360 ccccccagcg tgtaccctct ggctcctgga tctgccgccc agaccaacag catggtcaca 420 ctgggctgcc tggtgaaggg ctacttcccc gagcctgtga ccgtgacctg gaacagcggc 480 tctctgtcta gcggcgtgca caccttccct gccgtgctgc agagcgacct gtacaccctg 540 tcctccagcg tgaccgtgcc ttcctccacc tggccttccc agaccgtgac atgcaacgtg 600 gcccaccctg ccagctccac caaggtggac aagaaaatcg tgccccggga ctgcggaggg 660 ggcggttccg gcggaggagg atccgaggtg cagctggtgg aatctgatgg gggcctggtg 720 cagcccggaa gaagcctgaa actgccctgt gctgcctctg gcttcacatt ctctgattac 780 tatatggctt gggtgcgcca ggctccaaca aaaggcctgg aatgggtggc atccatctct 840 tacgacggct cctccactta ctacagggac tctgtgaagg gccggttcac aatctcccgg 900 gataacgcca agtctacact gtacctgcag atggattccc tgcgctccga ggacacagcc 960 acatattact gtggcaggca ctcctcctac tttgattatt ggggacaggg cgtgatggtc 1020 acagtgtcca gcgctaagac caccccccct agcgtgtacc ctctggcccc tggatctgcc 1080 gcccagacca acagcatggt gaccctgggc tgcctggtga agggctactt ccccgagcct 1140 gtgaccgtga cctggaacag cggcagcctg agcagcggcg tgcacacctt tccagccgtg 1200 ctgcagagcg acctgtacac cctgagcagc tccgtgaccg tgcctagcag cacctggccc 1260 agccagacag tgacctgcaa cgtggcccac cctgccagca gcaccaaggt ggacaagaaa 1320 atcgtgcccc gggactgcgg ctgcaagccc tgcatctgca ccgtgcccga ggtgtccagc 1380 gtgttcatct tcccacccaa gcccaaggac gtgctgacca tcaccctgac ccccaaagtg 1440 acctgcgtgg tggtggccat cagcaaggac gaccccgagg tgcagttctc ttggtttgtg 1500 gacgacgtgg aggtgcacac agcccagaca aagccccggg aggaacagat caacagcacc 1560 ttcagaagcg tgtccgagct gcccatcatg caccaggact ggctgaacgg caaagaattc 1620 aagtgcagag tgaacagcgc cgccttcggc gcccccatcg agaaaaccat cagcaagacc 1680 aagggcagac ccaaggcccc ccaggtgtac accatccccc cacccaaaaa acagatggcc 1740 aaggacaagg tgtccctgac ctgcatgatc accaactttt tccccgagga catcaccgtg 1800 gagtggcagt ggaatggcca gcccgccgag aactacaaga acacccagcc catcatgaag 1860 accgacggca gctacttcgt gtacagcaag ctgaacgtgc agaagtccaa ctgggaggcc 1920 ggcaacacct tcacctgtag cgtgctgcac gagggcctgc acaaccacca caccgagaag 1980 tccctgagcc actcccccgg cggcggaggc ggttccggag gaggaggatc cggaggaggg 2040 ggaagtggcg gcggaggatc tgaggtgcaa ttgttggagt ctgggggagg cttggtacag 2100 cctggggggt ccctgagact ctcctgtgca gccagcggat tcacctttag cagttatgcc 2160 atgagctggg tccgccaggc tccagggaag gggctggagt gggtctcagc tattagtggt 2220 agtggtggta gcacatacta cgcagactcc gtgaagggcc ggttcaccat ctccagagac 2280 aattccaaga acacgctgta tctgcagatg aacagcctga gagccgagga cacggccgta 2340 tattactgtg cgaaaggcag cggatttgac tactggggcc aaggaaccct ggtcaccgtc 2400 tcgagc 2406 +ADw-210+AD4- 126 +ADw-211+AD4- 2385 +ADw-212+AD4- ADN +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- muCD40 VHCH1-mu CD40 VHCH1-FcDD+AF8-DAPG-DP47 VL +ADw-400+AD4- 126 gaagtgcagc tggtggaaag cgacggcgga ctggtgcagc ctggcagatc tctgaagctg 60 ccttgtgccg ccagcggctt caccttcagc gactactaca tggcctgggt gcgacaggcc 120 cctaccaagg gactggaatg ggtggccagc atcagctacg acggcagcag cacctactac 180 agagacagcg tgaagggcag attcaccatc agcagagaca acgccaagag caccctgtac 240 ctgcagatgg acagcctgag aagcgaggac accgctacct actactgcgg cagacacagc 300 agctacttcg actactgggg ccagggcgtg atggtcaccg tgtctagcgc caagaccaca 360 ccccccagcg tgtaccctct ggctcctgga tctgccgccc agaccaacag catggtcaca 420 ctgggctgcc tggtgaaggg ctacttcccc gagcctgtga ccgtgacctg gaacagcggc 480 tctctgtcta gcggcgtgca caccttccct gccgtgctgc agagcgacct gtacaccctg 540 tcctccagcg tgaccgtgcc ttcctccacc tggccttccc agaccgtgac atgcaacgtg 600 gcccaccctg ccagctccac caaggtggac aagaaaatcg tgccccggga ctgcggaggg 660 ggcggttccg gcggaggagg atccgaggtg cagctggtgg aatctgatgg gggcctggtg 720 cagcccggaa gaagcctgaa actgccctgt gctgcctctg gcttcacatt ctctgattac 780 tatatggctt gggtgcgcca ggctccaaca aaaggcctgg aatgggtggc atccatctct 840 tacgacggct cctccactta ctacagggac tctgtgaagg gccggttcac aatctcccgg 900 gataacgcca agtctacact gtacctgcag atggattccc tgcgctccga ggacacagcc 960 acatattact gtggcaggca ctcctcctac tttgattatt ggggacaggg cgtgatggtc 1020 acagtgtcca gcgctaagac caccccccct agcgtgtacc ctctggcccc tggatctgcc 1080 gcccagacca acagcatggt gaccctgggc tgcctggtga agggctactt ccccgagcct 1140 gtgaccgtga cctggaacag cggcagcctg agcagcggcg tgcacacctt tccagccgtg 1200 ctgcagagcg acctgtacac cctgagcagc tccgtgaccg tgcctagcag cacctggccc 1260 agccagacag tgacctgcaa cgtggcccac cctgccagca gcaccaaggt ggacaagaaa 1320 atcgtgcccc gggactgcgg ctgcaagccc tgcatctgca ccgtgcccga ggtgtccagc 1380 gtgttcatct tcccacccaa gcccaaggac gtgctgacca tcaccctgac ccccaaagtg 1440 acctgcgtgg tggtggccat cagcaaggac gaccccgagg tgcagttctc ttggtttgtg 1500 gacgacgtgg aggtgcacac agcccagaca aagccccggg aggaacagat caacagcacc 1560 ttcagaagcg tgtccgagct gcccatcatg caccaggact ggctgaacgg caaagaattc 1620 aagtgcagag tgaacagcgc cgccttcggc gcccccatcg agaaaaccat cagcaagacc 1680 aagggcagac ccaaggcccc ccaggtgtac accatccccc cacccaaaga acagatggcc 1740 aaggacaagg tgtccctgac ctgcatgatc accaactttt tccccgagga catcaccgtg 1800 gagtggcagt ggaatggcca gcccgccgag aactacgaca acacccagcc catcatggac 1860 accgacggca gctacttcgt gtacagcgac ctgaacgtgc agaagtccaa ctgggaggcc 1920 ggcaacacct tcacctgtag cgtgctgcac gagggcctgc acaaccacca caccgagaag 1980 tccctgagcc acagcccagg cggcggaggc ggatctggcg gaggaggttc cggaggcggc 2040 ggaagcggag ggggaggctc tgaaattgtg ctgacccaga gccccggcac cctgtcactg 2100 tctccaggcg aaagagccac cctgagctgc agagccagcc agagcgtgtc cagctcttac 2160 ctggcctggt atcagcagaa gcccggacag gcccccagac tgctgatcta cggcgcctct 2220 tctagagcca ccggcatccc cgatagattc agcggcagcg gctccggcac cgacttcacc 2280 ctgacaatca gcagactgga acccgaggac tttgccgtgt attactgcca gcagtacggc 2340 agcagccccc tgacctttgg ccagggcacc aaggtggaaa tcaaa 2385 +ADw-210+AD4- 127 +ADw-211+AD4- 2700 +ADw-212+AD4- ADN +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- muCD40 VHCH1-muCD40 VHCH1-Fc+AF8-DAPG-28H1 VLCH1 +ADw-400+AD4- 127 gaagtgcagc tggtggaatc cgacggcgga ctggtgcagc ctggcagatc tctgaagctg 60 ccttgtgccg cctccggctt caccttctcc gactactaca tggcctgggt gcgacaggcc 120 cctaccaagg gactggaatg ggtggcctcc atctcctacg acggctcctc cacctactac 180 cgggactctg tgaagggccg gttcaccatc tctcgggaca acgccaagtc caccctgtac 240 ctgcagatgg actccctgcg gagcgaggac accgctacct actactgcgg cagacactcc 300 tcctacttcg actactgggg ccagggcgtg atggtcaccg tgtcctctgc taagaccacc 360 cccccctccg tgtaccctct ggctcctgga tctgccgccc agaccaactc catggtcacc 420 ctgggctgtc tggtggaagg ctacttcccc gagcctgtga ccgtgacctg gaactccggc 480 tctctgtcct ctggcgtgca caccttccct gccgtgctgc agtccgacct gtacaccctg 540 agcagctccg tgaccgtgcc tagcagcacc tggcccagcc agacagtgac ctgcaacgtg 600 gcccaccctg ccagcagcac caaggtggac gagaaaatcg tgccccggga ctgcggcggt 660 ggaggttccg gaggcggcgg atccgaggtg cagctggtgg aaagtgatgg gggcctggtg 720 cagcccggaa gaagcctgaa actgccctgc gccgcttctg gctttacctt tagcgattac 780 tatatggctt gggtgcgcca ggctccaaca aaaggcctgg aatgggtggc atctatcagc 840 tacgatggca gcagcaccta ctatagagac agcgtgaagg ggagattcac catcagcaga 900 gataacgcta agagcacact gtacctgcag atggatagcc tgagatccga ggataccgcc 960 acatattact gtggccggca cagcagctac tttgattatt ggggacaggg cgtgatggtc 1020 acagtgtcta gcgctaagac tacccctcct agcgtgtacc ccctggcacc aggttccgct 1080 gctcagacca acagcatggt cacactggga tgcctggtgg aaggatattt tcctgaaccc 1140 gtgacagtga catggaatag cggctccctg tctagcggag tgcatacctt tccagctgtg 1200 ctgcagagcg atctgtatac actgagcagc tctgtgacag tgccttccag cacctggccc 1260 agccagacag tgacctgtaa tgtggctcat cccgcctcta gcaccaaagt ggatgagaaa 1320 atcgtgcccc gggactgcgg ctgcaagccc tgtatctgta ccgtgcccga ggtgtcctcc 1380 gtgttcatct tcccacctaa gcccaaggac gtgctgacaa tcaccctgac ccccaaagtg 1440 acctgcgtgg tggtggccat ctccaaggac gatcccgagg tgcagttcag ttggttcgtg 1500 gacgacgtgg aagtgcacac agcccagaca aagcccagag aggaacagat caactccacc 1560 ttcagaagcg tgtccgagct gcccatcatg caccaggact ggctgaacgg caaagaattc 1620 aagtgcagag tgaactccgc cgcctttggc gcccctatcg aaaagaccat ctccaagacc 1680 aagggcagac ccaaggcccc ccaggtgtac acaatccccc cacccaaaga acagatggcc 1740 aaggacaagg tgtccctgac ctgcatgatc accaactttt tcccagagga catcaccgtg 1800 gaatggcagt ggaacggcca gcccgccgag aactacaaga acacccagcc catcatggac 1860 accgacggct cctacttcgt gtactccaag ctgaacgtgc agaagtccaa ctgggaggcc 1920 ggcaacacct tcacctgttc cgtgctgcac gagggcctgc acaaccacca caccgagaag 1980 tccctgtccc actcccctgg aaaaggcgga ggcggatctg gtggcggagg atctggcggt 2040 ggtggttccg gaggcggagg atccgaaatc gtgttaacgc agtctccagg caccctgtct 2100 ttgtctccag gggaaagagc caccctctct tgcagggcca gtcagagtgt tagcagcagc 2160 tacttagcct ggtaccagca gaaacctggc caggctccca ggctcctcat ctatggagca 2220 tccagcaggg ccactggcat cccagacagg ttcagtggca gtggatccgg gacagacttc 2280 actctcacca tcagcagact ggagcctgaa gattttgcag tgtattactg tcagcagtat 2340 ggtagctcac cgctgacgtt cggccagggg accaaagtgg aaatcaaaag cagcgctaag 2400 accacccccc cctccgtgta tcctctggcc cctggatctg ccgcccagac caactccatg 2460 gtcaccctgg gctgcctcgt gaagggctac ttccctgagc ctgtgaccgt gacctggaac 2520 tccggctccc tgtctagcgg cgtgcacacc tttccagctg tgctgcagtc cgacctgtac 2580 accctgagca gctccgtgac cgtgccttcc tccacctggc cttcccagac cgtgacatgc 2640 aacgtggccc accctgccag ctccacaaag gtggacaaga aaatcgtgcc ccgggactgc 2700 +ADw-210+AD4- 128 +ADw-211+AD4- 666 +ADw-212+AD4- ADN +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- DP47 VHCL (mu) +ADw-400+AD4- 128 gaggtgcaat tgttggagtc tgggggaggc ttggtacagc ctggggggtc cctgagactc 60 tcctgtgcag cctccggatt cacctttagc agttatgcca tgagctgggt ccgccaggct 120 ccagggaagg ggctggagtg ggtctcagct attagtggta gtggtggtag cacatactac 180 gcagactccg tgaagggccg gttcaccatc tccagagaca attccaagaa cacgctgtat 240 ctgcagatga acagcctgag agccgaggac acggccgtat attactgtgc gaaaggcagc 300 ggatttgact actggggcca aggaaccctg gtcaccgtct cgagcgcttc tgatgccgcc 360 cctaccgtat cgattttccc accctccagc gagcagctga caagcggcgg agctagcgtc 420 gtgtgcttcc tgaacaactt ctaccccaag gacatcaacg tgaagtggaa gatcgacggc 480 agcgagcggc agaacggcgt gctgaatagc tggaccgacc aggacagcaa ggactccacc 540 tacagcatga gcagcaccct gaccctgacc aaggacgagt acgagcggca caacagctac 600 acatgcgagg ccacccacaa gaccagcacc agccccatcg tgaagtcctt caaccggaac 660 gagtgc 666 +ADw-210+AD4- 129 +ADw-211+AD4- 114 +ADw-212+AD4- PRT +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- CD40 (S2C6) VH +ADw-400+AD4- 129 Glu Val Gln Leu Gln Gln Ser Gly Pro Asp Leu Val Lys Pro Gly Ala 1 5 10 15 Ser Val Lys Ile Ser Cys Lys Ala Ser Gly Tyr Ser Phe Thr Gly Tyr 20 25 30 Tyr Ile His Trp Val Lys Gln Ser His Gly Lys Ser Leu Glu Trp Ile 35 40 45 Gly Arg Val Ile Pro Asn Asn Gly Gly Thr Ser Tyr Asn Gln Lys Phe 50 55 60 Lys Gly Lys Ala Ile Leu Thr Val Asp Lys Ser Ser Ser Thr Ala Tyr 65 70 75 80 Met Glu Leu Arg Ser Leu Thr Ser Glu Asp Ser Ala Val Tyr Tyr Cys 85 90 95 Ala Arg Glu Gly Ile Tyr Trp Trp Gly His Gly Thr Thr Leu Thr Val 100 105 110 Ser Ser +ADw-210+AD4- 130 +ADw-211+AD4- 112 +ADw-212+AD4- PRT +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- CD40 (S2C6) VL +ADw-400+AD4- 130 Asp Val Val Val Thr Gln Thr Pro Leu Ser Leu Pro Val Ser Leu Gly 1 5 10 15 Ala Gln Ala Ser Ile Ser Cys Arg Ser Ser Gln Ser Leu Val His Ser 20 25 30 Asn Gly Asn Thr Phe Leu His Trp Tyr Leu Gln Lys Pro Gly Gln Ser 35 40 45 Pro Lys Leu Leu Ile Tyr Thr Val Ser Asn Arg Phe Ser Gly Val Pro 50 55 60 Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile 65 70 75 80 Ser Arg Val Glu Ala Glu Asp Leu Gly Val Tyr Phe Cys Ser Gln Thr 85 90 95 Thr His Val Pro Trp Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Gln 100 105 110 +ADw-210+AD4- 131 +ADw-211+AD4- 808 +ADw-212+AD4- PRT +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- hVH3+AF8-CD40 VHCH1-VHCH1-Fc pomo+AF8-PGLALA -4B9 VH +ADw-400+AD4- 131 Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala 1 5 10 15 Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Ser Phe Thr Gly Tyr 20 25 30 Tyr Ile His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Ile 35 40 45 Gly Arg Val Ile Pro Asn Ala Gly Gly Thr Ser Tyr Asn Gln Lys Phe 50 55 60 Lys Gly Arg Val Thr Ser Thr Val Asp Thr Ser Ile Ser Thr Ala Tyr 65 70 75 80 Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Val Val Tyr Tyr Cys 85 90 95 Ala Arg Glu Gly Ile Tyr Trp Trp Gly Gln Gly Thr Thr Val Thr Val 100 105 110 Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser 115 120 125 Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Lys 130 135 140 Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu 145 150 155 160 Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu 165 170 175 Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr 180 185 190 Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys Val 195 200 205 Asp Lys Lys Val Glu Pro Lys Ser Cys Asp Gly Gly Gly Gly Ser Gly 210 215 220 Gly Gly Gly Ser Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys 225 230 235 240 Lys Pro Gly Ala Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Ser 245 250 255 Phe Thr Gly Tyr Tyr Ile His Trp Val Arg Gln Ala Pro Gly Gln Gly 260 265 270 Leu Glu Trp Ile Gly Arg Val Ile Pro Asn Ala Gly Gly Thr Ser Tyr 275 280 285 Asn Gln Lys Phe Lys Gly Arg Val Thr Ser Thr Val Asp Thr Ser Ile 290 295 300 Ser Thr Ala Tyr Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Val 305 310 315 320 Val Tyr Tyr Cys Ala Arg Glu Gly Ile Tyr Trp Trp Gly Gln Gly Thr 325 330 335 Thr Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro 340 345 350 Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly 355 360 365 Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn 370 375 380 Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln 385 390 395 400 Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser 405 410 415 Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser 420 425 430 Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp Lys Thr 435 440 445 His Thr Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly Gly Pro Ser 450 455 460 Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg 465 470 475 480 Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro 485 490 495 Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala 500 505 510 Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val 515 520 525 Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr 530 535 540 Lys Cys Lys Val Ser Asn Lys Ala Leu Gly Ala Pro Ile Glu Lys Thr 545 550 555 560 Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu 565 570 575 Pro Pro Cys Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Trp Cys 580 585 590 Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser 595 600 605 Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp 610 615 620 Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser 625 630 635 640 Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala 645 650 655 Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Gly 660 665 670 Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly 675 680 685 Gly Gly Ser Glu Val Gln Leu Leu Glu Ser Gly Gly Gly Leu Val Gln 690 695 700 Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe 705 710 715 720 Ser Ser Tyr Ala Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu 725 730 735 Glu Trp Val Ser Ala Ile Ile Gly Ser Gly Ala Ser Thr Tyr Tyr Ala 740 745 750 Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn 755 760 765 Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val 770 775 780 Tyr Tyr Cys Ala Lys Gly Trp Phe Gly Gly Phe Asn Tyr Trp Gly Gln 785 790 795 800 Gly Thr Leu Val Thr Val Ser Ser 805 +ADw-210+AD4- 132 +ADw-211+AD4- 799 +ADw-212+AD4- PRT +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- hVH3+AF8-CD40 VHCH1- VHCH1-Fc agujero+AF8-PGLALA-4B9 VL +ADw-400+AD4- 132 Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala 1 5 10 15 Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Ser Phe Thr Gly Tyr 20 25 30 Tyr Ile His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Ile 35 40 45 Gly Arg Val Ile Pro Asn Ala Gly Gly Thr Ser Tyr Asn Gln Lys Phe 50 55 60 Lys Gly Arg Val Thr Ser Thr Val Asp Thr Ser Ile Ser Thr Ala Tyr 65 70 75 80 Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Val Val Tyr Tyr Cys 85 90 95 Ala Arg Glu Gly Ile Tyr Trp Trp Gly Gln Gly Thr Thr Val Thr Val 100 105 110 Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser 115 120 125 Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Lys 130 135 140 Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu 145 150 155 160 Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu 165 170 175 Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr 180 185 190 Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys Val 195 200 205 Asp Lys Lys Val Glu Pro Lys Ser Cys Asp Gly Gly Gly Gly Ser Gly 210 215 220 Gly Gly Gly Ser Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys 225 230 235 240 Lys Pro Gly Ala Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Ser 245 250 255 Phe Thr Gly Tyr Tyr Ile His Trp Val Arg Gln Ala Pro Gly Gln Gly 260 265 270 Leu Glu Trp Ile Gly Arg Val Ile Pro Asn Ala Gly Gly Thr Ser Tyr 275 280 285 Asn Gln Lys Phe Lys Gly Arg Val Thr Ser Thr Val Asp Thr Ser Ile 290 295 300 Ser Thr Ala Tyr Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Val 305 310 315 320 Val Tyr Tyr Cys Ala Arg Glu Gly Ile Tyr Trp Trp Gly Gln Gly Thr 325 330 335 Thr Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro 340 345 350 Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly 355 360 365 Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn 370 375 380 Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln 385 390 395 400 Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser 405 410 415 Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser 420 425 430 Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp Lys Thr 435 440 445 His Thr Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly Gly Pro Ser 450 455 460 Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg 465 470 475 480 Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro 485 490 495 Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala 500 505 510 Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val 515 520 525 Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr 530 535 540 Lys Cys Lys Val Ser Asn Lys Ala Leu Gly Ala Pro Ile Glu Lys Thr 545 550 555 560 Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Cys Thr Leu 565 570 575 Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Ser Cys 580 585 590 Ala Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser 595 600 605 Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp 610 615 620 Ser Asp Gly Ser Phe Phe Leu Val Ser Lys Leu Thr Val Asp Lys Ser 625 630 635 640 Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala 645 650 655 Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Gly 660 665 670 Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly 675 680 685 Gly Gly Ser Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu 690 695 700 Ser Pro Gly Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val 705 710 715 720 Thr Ser Ser Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro 725 730 735 Arg Leu Leu Ile Asn Val Gly Ser Arg Arg Ala Thr Gly Ile Pro Asp 740 745 750 Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser 755 760 765 Arg Leu Glu Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Gly Ile 770 775 780 Met Leu Pro Pro Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys 785 790 795 +ADw-210+AD4- 133 +ADw-211+AD4- 219 +ADw-212+AD4- PRT +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- hVK2+AF8-CD40 cadena ligera +ADw-400+AD4- 133 Asp Val Val Met Thr Gln Ser Pro Leu Ser Leu Pro Val Thr Leu Gly 1 5 10 15 Gln Pro Ala Ser Ile Ser Cys Arg Ser Ser Gln Ser Leu Val His Ser 20 25 30 Asn Gly Asn Thr Phe Leu His Trp Tyr Gln Gln Arg Pro Gly Gln Ser 35 40 45 Pro Arg Leu Leu Ile Tyr Thr Val Ser Asn Arg Phe Ser Gly Val Pro 50 55 60 Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile 65 70 75 80 Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Tyr Cys Ser Gln Thr 85 90 95 Thr His Val Pro Trp Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys 100 105 110 Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu 115 120 125 Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe 130 135 140 Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln 145 150 155 160 Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser 165 170 175 Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu 180 185 190 Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser 195 200 205 Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys 210 215 +ADw-210+AD4- 134 +ADw-211+AD4- 580 +ADw-212+AD4- PRT +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- hVH3+AF8-CD40 VHCH1- Fc pomo+AF8-PGLALA -4B9 VH +ADw-400+AD4- 134 Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala 1 5 10 15 Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Ser Phe Thr Gly Tyr 20 25 30 Tyr Ile His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Ile 35 40 45 Gly Arg Val Ile Pro Asn Ala Gly Gly Thr Ser Tyr Asn Gln Lys Phe 50 55 60 Lys Gly Arg Val Thr Ser Thr Val Asp Thr Ser Ile Ser Thr Ala Tyr 65 70 75 80 Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Val Val Tyr Tyr Cys 85 90 95 Ala Arg Glu Gly Ile Tyr Trp Trp Gly Gln Gly Thr Thr Val Thr Val 100 105 110 Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser 115 120 125 Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Lys 130 135 140 Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu 145 150 155 160 Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu 165 170 175 Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr 180 185 190 Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys Val 195 200 205 Asp Lys Lys Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro 210 215 220 Pro Cys Pro Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe 225 230 235 240 Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val 245 250 255 Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe 260 265 270 Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro 275 280 285 Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr 290 295 300 Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val 305 310 315 320 Ser Asn Lys Ala Leu Gly Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala 325 330 335 Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Cys Arg 340 345 350 Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Trp Cys Leu Val Lys Gly 355 360 365 Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro 370 375 380 Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser 385 390 395 400 Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln 405 410 415 Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His 420 425 430 Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Gly Gly Gly Gly Ser 435 440 445 Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Glu 450 455 460 Val Gln Leu Leu Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser 465 470 475 480 Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Ser Tyr Ala 485 490 495 Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ser 500 505 510 Ala Ile Ile Gly Ser Gly Ala Ser Thr Tyr Tyr Ala Asp Ser Val Lys 515 520 525 Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr Leu 530 535 540 Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala 545 550 555 560 Lys Gly Trp Phe Gly Gly Phe Asn Tyr Trp Gly Gln Gly Thr Leu Val 565 570 575 Thr Val Ser Ser 580 +ADw-210+AD4- 135 +ADw-211+AD4- 571 +ADw-212+AD4- PRT +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- hVH3+AF8-CD40 VHCH1- Fc agujero+AF8-PGLALA -4B9 VL +ADw-400+AD4- 135 Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala 1 5 10 15 Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Ser Phe Thr Gly Tyr 20 25 30 Tyr Ile His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Ile 35 40 45 Gly Arg Val Ile Pro Asn Ala Gly Gly Thr Ser Tyr Asn Gln Lys Phe 50 55 60 Lys Gly Arg Val Thr Ser Thr Val Asp Thr Ser Ile Ser Thr Ala Tyr 65 70 75 80 Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Val Val Tyr Tyr Cys 85 90 95 Ala Arg Glu Gly Ile Tyr Trp Trp Gly Gln Gly Thr Thr Val Thr Val 100 105 110 Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser 115 120 125 Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Lys 130 135 140 Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu 145 150 155 160 Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu 165 170 175 Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr 180 185 190 Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys Val 195 200 205 Asp Lys Lys Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro 210 215 220 Pro Cys Pro Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe 225 230 235 240 Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val 245 250 255 Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe 260 265 270 Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro 275 280 285 Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr 290 295 300 Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val 305 310 315 320 Ser Asn Lys Ala Leu Gly Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala 325 330 335 Lys Gly Gln Pro Arg Glu Pro Gln Val Cys Thr Leu Pro Pro Ser Arg 340 345 350 Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Ser Cys Ala Val Lys Gly 355 360 365 Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro 370 375 380 Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser 385 390 395 400 Phe Phe Leu Val Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln 405 410 415 Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His 420 425 430 Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Gly Gly Gly Gly Ser 435 440 445 Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Glu 450 455 460 Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly Glu 465 470 475 480 Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Thr Ser Ser Tyr 485 490 495 Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile 500 505 510 Asn Val Gly Ser Arg Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser Gly 515 520 525 Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu Pro 530 535 540 Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Gly Ile Met Leu Pro Pro 545 550 555 560 Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys 565 570 +ADw-210+AD4- 136 +ADw-211+AD4- 676 +ADw-212+AD4- PRT +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- hVH3+AF8-CD40-Fc pomo+AF8-PGLALA+AF8-4B9+AF8-VLCH1 'EE' +ADw-400+AD4- 136 Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala 1 5 10 15 Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Ser Phe Thr Gly Tyr 20 25 30 Tyr Ile His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Ile 35 40 45 Gly Arg Val Ile Pro Asn Ala Gly Gly Thr Ser Tyr Asn Gln Lys Phe 50 55 60 Lys Gly Arg Val Thr Ser Thr Val Asp Thr Ser Ile Ser Thr Ala Tyr 65 70 75 80 Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Val Val Tyr Tyr Cys 85 90 95 Ala Arg Glu Gly Ile Tyr Trp Trp Gly Gln Gly Thr Thr Val Thr Val 100 105 110 Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser 115 120 125 Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Glu 130 135 140 Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu 145 150 155 160 Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu 165 170 175 Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr 180 185 190 Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys Val 195 200 205 Asp Glu Lys Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro 210 215 220 Pro Cys Pro Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe 225 230 235 240 Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val 245 250 255 Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe 260 265 270 Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro 275 280 285 Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr 290 295 300 Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val 305 310 315 320 Ser Asn Lys Ala Leu Gly Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala 325 330 335 Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg 340 345 350 Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly 355 360 365 Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro 370 375 380 Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser 385 390 395 400 Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln 405 410 415 Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His 420 425 430 Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Gly Gly Gly Gly Ser 435 440 445 Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Glu 450 455 460 Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly Glu 465 470 475 480 Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Thr Ser Ser Tyr 485 490 495 Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile 500 505 510 Asn Val Gly Ser Arg Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser Gly 515 520 525 Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu Pro 530 535 540 Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Gly Ile Met Leu Pro Pro 545 550 555 560 Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Ser Ser Ala Ser Thr 565 570 575 Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser 580 585 590 Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu 595 600 605 Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His 610 615 620 Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser 625 630 635 640 Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys 645 650 655 Asn Val Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Lys Val Glu 660 665 670 Pro Lys Ser Cys 675 +ADw-210+AD4- 137 +ADw-211+AD4- 219 +ADw-212+AD4- PRT +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- hVK2+AF8-CD40 LC,RK' +ADw-400+AD4- 137 Asp Val Val Met Thr Gln Ser Pro Leu Ser Leu Pro Val Thr Leu Gly 1 5 10 15 Gln Pro Ala Ser Ile Ser Cys Arg Ser Ser Gln Ser Leu Val His Ser 20 25 30 Asn Gly Asn Thr Phe Leu His Trp Tyr Gln Gln Arg Pro Gly Gln Ser 35 40 45 Pro Arg Leu Leu Ile Tyr Thr Val Ser Asn Arg Phe Ser Gly Val Pro 50 55 60 Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile 65 70 75 80 Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Tyr Cys Ser Gln Thr 85 90 95 Thr His Val Pro Trp Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys 100 105 110 Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Arg 115 120 125 Lys Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe 130 135 140 Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln 145 150 155 160 Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser 165 170 175 Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu 180 185 190 Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser 195 200 205 Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys 210 215 +ADw-210+AD4- 138 +ADw-211+AD4- 224 +ADw-212+AD4- PRT +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- 4B9 VHCL +ADw-400+AD4- 138 Glu Val Gln Leu Leu Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 1 5 10 15 Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Ser Tyr 20 25 30 Ala Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45 Ser Ala Ile Ile Gly Ser Gly Ala Ser Thr Tyr Tyr Ala Asp Ser Val 50 55 60 Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 65 70 75 80 Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Ala Lys Gly Trp Phe Gly Gly Phe Asn Tyr Trp Gly Gln Gly Thr Leu 100 105 110 Val Thr Val Ser Ser Ala Ser Val Ala Ala Pro Ser Val Phe Ile Phe 115 120 125 Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys 130 135 140 Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val 145 150 155 160 Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln 165 170 175 Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser 180 185 190 Lys Ala Asp Tyr Glu Lys His Lys Val Tyr Ala Cys Glu Val Thr His 195 200 205 Gln Gly Leu Ser Ser Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys 210 215 220 +ADw-210+AD4- 139 +ADw-211+AD4- 676 +ADw-212+AD4- PRT +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- hVH3+AF8-CD40-Fc agujero+AF8-PGLALA 'EE' +ADw-400+AD4- 139 Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala 1 5 10 15 Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Ser Phe Thr Gly Tyr 20 25 30 Tyr Ile His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Ile 35 40 45 Gly Arg Val Ile Pro Asn Ala Gly Gly Thr Ser Tyr Asn Gln Lys Phe 50 55 60 Lys Gly Arg Val Thr Ser Thr Val Asp Thr Ser Ile Ser Thr Ala Tyr 65 70 75 80 Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Val Val Tyr Tyr Cys 85 90 95 Ala Arg Glu Gly Ile Tyr Trp Trp Gly Gln Gly Thr Thr Val Thr Val 100 105 110 Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser 115 120 125 Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Glu 130 135 140 Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu 145 150 155 160 Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu 165 170 175 Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr 180 185 190 Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys Val 195 200 205 Asp Glu Lys Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro 210 215 220 Pro Cys Pro Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe 225 230 235 240 Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val 245 250 255 Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe 260 265 270 Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro 275 280 285 Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr 290 295 300 Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val 305 310 315 320 Ser Asn Lys Ala Leu Gly Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala 325 330 335 Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Cys Arg 340 345 350 Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Trp Cys Leu Val Lys Gly 355 360 365 Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro 370 375 380 Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser 385 390 395 400 Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln 405 410 415 Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His 420 425 430 Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Gly Gly Gly Gly Ser 435 440 445 Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Glu 450 455 460 Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly Glu 465 470 475 480 Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Thr Ser Ser Tyr 485 490 495 Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile 500 505 510 Asn Val Gly Ser Arg Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser Gly 515 520 525 Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu Pro 530 535 540 Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Gly Ile Met Leu Pro Pro 545 550 555 560 Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Ser Ser Ala Ser Thr 565 570 575 Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser 580 585 590 Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu 595 600 605 Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His 610 615 620 Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser 625 630 635 640 Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys 645 650 655 Asn Val Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Lys Val Glu 660 665 670 Pro Lys Ser Cys 675 +ADw-210+AD4- 140 +ADw-211+AD4- 443 +ADw-212+AD4- PRT +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- hVH3+AF8-CD40-Fc agujero+AF8-PGLALA 'EE' +ADw-400+AD4- 140 Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala 1 5 10 15 Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Ser Phe Thr Gly Tyr 20 25 30 Tyr Ile His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Ile 35 40 45 Gly Arg Val Ile Pro Asn Ala Gly Gly Thr Ser Tyr Asn Gln Lys Phe 50 55 60 Lys Gly Arg Val Thr Ser Thr Val Asp Thr Ser Ile Ser Thr Ala Tyr 65 70 75 80 Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Val Val Tyr Tyr Cys 85 90 95 Ala Arg Glu Gly Ile Tyr Trp Trp Gly Gln Gly Thr Thr Val Thr Val 100 105 110 Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser 115 120 125 Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Glu 130 135 140 Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu 145 150 155 160 Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu 165 170 175 Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr 180 185 190 Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys Val 195 200 205 Asp Glu Lys Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro 210 215 220 Pro Cys Pro Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe 225 230 235 240 Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val 245 250 255 Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe 260 265 270 Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro 275 280 285 Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr 290 295 300 Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val 305 310 315 320 Ser Asn Lys Ala Leu Gly Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala 325 330 335 Lys Gly Gln Pro Arg Glu Pro Gln Val Cys Thr Leu Pro Pro Ser Arg 340 345 350 Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Ser Cys Ala Val Lys Gly 355 360 365 Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro 370 375 380 Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser 385 390 395 400 Phe Phe Leu Val Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln 405 410 415 Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His 420 425 430 Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly 435 440 +ADw-210+AD4- 141 +ADw-211+AD4- 439 +ADw-212+AD4- PRT +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- 4B9-Fc pomo+AF8-PGLALA +ADw-400+AD4- 141 Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly 1 5 10 15 Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Thr Ser Ser 20 25 30 Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu 35 40 45 Ile Asn Val Gly Ser Arg Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser 50 55 60 Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu 65 70 75 80 Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Gly Ile Met Leu Pro 85 90 95 Pro Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Ser Ser Ala Ser 100 105 110 Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr 115 120 125 Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro 130 135 140 Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val 145 150 155 160 His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser 165 170 175 Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile 180 185 190 Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Lys Val 195 200 205 Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala 210 215 220 Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro 225 230 235 240 Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val 245 250 255 Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val 260 265 270 Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln 275 280 285 Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln 290 295 300 Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala 305 310 315 320 Leu Gly Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro 325 330 335 Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Cys Arg Asp Glu Leu Thr 340 345 350 Lys Asn Gln Val Ser Leu Trp Cys Leu Val Lys Gly Phe Tyr Pro Ser 355 360 365 Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr 370 375 380 Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr 385 390 395 400 Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe 405 410 415 Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys 420 425 430 Ser Leu Ser Leu Ser Pro Gly 435 +ADw-210+AD4- 142 +ADw-211+AD4- 748 +ADw-212+AD4- PRT +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- ectodominio de hu FAP marcador Lys marcador avi +ADw-400+AD4- 142 Arg Pro Ser Arg Val His Asn Ser Glu Glu Asn Thr Met Arg Ala Leu 1 5 10 15 Thr Leu Lys Asp Ile Leu Asn Gly Thr Phe Ser Tyr Lys Thr Phe Phe 20 25 30 Pro Asn Trp Ile Ser Gly Gln Glu Tyr Leu His Gln Ser Ala Asp Asn 35 40 45 Asn Ile Val Leu Tyr Asn Ile Glu Thr Gly Gln Ser Tyr Thr Ile Leu 50 55 60 Ser Asn Arg Thr Met Lys Ser Val Asn Ala Ser Asn Tyr Gly Leu Ser 65 70 75 80 Pro Asp Arg Gln Phe Val Tyr Leu Glu Ser Asp Tyr Ser Lys Leu Trp 85 90 95 Arg Tyr Ser Tyr Thr Ala Thr Tyr Tyr Ile Tyr Asp Leu Ser Asn Gly 100 105 110 Glu Phe Val Arg Gly Asn Glu Leu Pro Arg Pro Ile Gln Tyr Leu Cys 115 120 125 Trp Ser Pro Val Gly Ser Lys Leu Ala Tyr Val Tyr Gln Asn Asn Ile 130 135 140 Tyr Leu Lys Gln Arg Pro Gly Asp Pro Pro Phe Gln Ile Thr Phe Asn 145 150 155 160 Gly Arg Glu Asn Lys Ile Phe Asn Gly Ile Pro Asp Trp Val Tyr Glu 165 170 175 Glu Glu Met Leu Ala Thr Lys Tyr Ala Leu Trp Trp Ser Pro Asn Gly 180 185 190 Lys Phe Leu Ala Tyr Ala Glu Phe Asn Asp Thr Asp Ile Pro Val Ile 195 200 205 Ala Tyr Ser Tyr Tyr Gly Asp Glu Gln Tyr Pro Arg Thr Ile Asn Ile 210 215 220 Pro Tyr Pro Lys Ala Gly Ala Lys Asn Pro Val Val Arg Ile Phe Ile 225 230 235 240 Ile Asp Thr Thr Tyr Pro Ala Tyr Val Gly Pro Gln Glu Val Pro Val 245 250 255 Pro Ala Met Ile Ala Ser Ser Asp Tyr Tyr Phe Ser Trp Leu Thr Trp 260 265 270 Val Thr Asp Glu Arg Val Cys Leu Gln Trp Leu Lys Arg Val Gln Asn 275 280 285 Val Ser Val Leu Ser Ile Cys Asp Phe Arg Glu Asp Trp Gln Thr Trp 290 295 300 Asp Cys Pro Lys Thr Gln Glu His Ile Glu Glu Ser Arg Thr Gly Trp 305 310 315 320 Ala Gly Gly Phe Phe Val Ser Thr Pro Val Phe Ser Tyr Asp Ala Ile 325 330 335 Ser Tyr Tyr Lys Ile Phe Ser Asp Lys Asp Gly Tyr Lys His Ile His 340 345 350 Tyr Ile Lys Asp Thr Val Glu Asn Ala Ile Gln Ile Thr Ser Gly Lys 355 360 365 Trp Glu Ala Ile Asn Ile Phe Arg Val Thr Gln Asp Ser Leu Phe Tyr 370 375 380 Ser Ser Asn Glu Phe Glu Glu Tyr Pro Gly Arg Arg Asn Ile Tyr Arg 385 390 395 400 Ile Ser Ile Gly Ser Tyr Pro Pro Ser Lys Lys Cys Val Thr Cys His 405 410 415 Leu Arg Lys Glu Arg Cys Gln Tyr Tyr Thr Ala Ser Phe Ser Asp Tyr 420 425 430 Ala Lys Tyr Tyr Ala Leu Val Cys Tyr Gly Pro Gly Ile Pro Ile Ser 435 440 445 Thr Leu His Asp Gly Arg Thr Asp Gln Glu Ile Lys Ile Leu Glu Glu 450 455 460 Asn Lys Glu Leu Glu Asn Ala Leu Lys Asn Ile Gln Leu Pro Lys Glu 465 470 475 480 Glu Ile Lys Lys Leu Glu Val Asp Glu Ile Thr Leu Trp Tyr Lys Met 485 490 495 Ile Leu Pro Pro Gln Phe Asp Arg Ser Lys Lys Tyr Pro Leu Leu Ile 500 505 510 Gln Val Tyr Gly Gly Pro Cys Ser Gln Ser Val Arg Ser Val Phe Ala 515 520 525 Val Asn Trp Ile Ser Tyr Leu Ala Ser Lys Glu Gly Met Val Ile Ala 530 535 540 Leu Val Asp Gly Arg Gly Thr Ala Phe Gln Gly Asp Lys Leu Leu Tyr 545 550 555 560 Ala Val Tyr Arg Lys Leu Gly Val Tyr Glu Val Glu Asp Gln Ile Thr 565 570 575 Ala Val Arg Lys Phe Ile Glu Met Gly Phe Ile Asp Glu Lys Arg Ile 580 585 590 Ala Ile Trp Gly Trp Ser Tyr Gly Gly Tyr Val Ser Ser Leu Ala Leu 595 600 605 Ala Ser Gly Thr Gly Leu Phe Lys Cys Gly Ile Ala Val Ala Pro Val 610 615 620 Ser Ser Trp Glu Tyr Tyr Ala Ser Val Tyr Thr Glu Arg Phe Met Gly 625 630 635 640 Leu Pro Thr Lys Asp Asp Asn Leu Glu His Tyr Lys Asn Ser Thr Val 645 650 655 Met Ala Arg Ala Glu Tyr Phe Arg Asn Val Asp Tyr Leu Leu Ile His 660 665 670 Gly Thr Ala Asp Asp Asn Val His Phe Gln Asn Ser Ala Gln Ile Ala 675 680 685 Lys Ala Leu Val Asn Ala Gln Val Asp Phe Gln Ala Met Trp Tyr Ser 690 695 700 Asp Gln Asn His Gly Leu Ser Gly Leu Ser Thr Asn His Leu Tyr Thr 705 710 715 720 His Met Thr His Phe Leu Lys Gln Cys Phe Ser Leu Ser Asp Gly Lys 725 730 735 Lys Lys Lys Lys Lys Gly His His His His His His 740 745 +ADw-210+AD4- 143 +ADw-211+AD4- 761 +ADw-212+AD4- PRT +ADw-213+AD4- murino +ADw-400+AD4- 143 Met Lys Thr Trp Leu Lys Thr Val Phe Gly Val Thr Thr Leu Ala Ala 1 5 10 15 Leu Ala Leu Val Val Ile Cys Ile Val Leu Arg Pro Ser Arg Val Tyr 20 25 30 Lys Pro Glu Gly Asn Thr Lys Arg Ala Leu Thr Leu Lys Asp Ile Leu 35 40 45 Asn Gly Thr Phe Ser Tyr Lys Thr Tyr Phe Pro Asn Trp Ile Ser Glu 50 55 60 Gln Glu Tyr Leu His Gln Ser Glu Asp Asp Asn Ile Val Phe Tyr Asn 65 70 75 80 Ile Glu Thr Arg Glu Ser Tyr Ile Ile Leu Ser Asn Ser Thr Met Lys 85 90 95 Ser Val Asn Ala Thr Asp Tyr Gly Leu Ser Pro Asp Arg Gln Phe Val 100 105 110 Tyr Leu Glu Ser Asp Tyr Ser Lys Leu Trp Arg Tyr Ser Tyr Thr Ala 115 120 125 Thr Tyr Tyr Ile Tyr Asp Leu Gln Asn Gly Glu Phe Val Arg Gly Tyr 130 135 140 Glu Leu Pro Arg Pro Ile Gln Tyr Leu Cys Trp Ser Pro Val Gly Ser 145 150 155 160 Lys Leu Ala Tyr Val Tyr Gln Asn Asn Ile Tyr Leu Lys Gln Arg Pro 165 170 175 Gly Asp Pro Pro Phe Gln Ile Thr Tyr Thr Gly Arg Glu Asn Arg Ile 180 185 190 Phe Asn Gly Ile Pro Asp Trp Val Tyr Glu Glu Glu Met Leu Ala Thr 195 200 205 Lys Tyr Ala Leu Trp Trp Ser Pro Asp Gly Lys Phe Leu Ala Tyr Val 210 215 220 Glu Phe Asn Asp Ser Asp Ile Pro Ile Ile Ala Tyr Ser Tyr Tyr Gly 225 230 235 240 Asp Gly Gln Tyr Pro Arg Thr Ile Asn Ile Pro Tyr Pro Lys Ala Gly 245 250 255 Ala Lys Asn Pro Val Val Arg Val Phe Ile Val Asp Thr Thr Tyr Pro 260 265 270 His His Val Gly Pro Met Glu Val Pro Val Pro Glu Met Ile Ala Ser 275 280 285 Ser Asp Tyr Tyr Phe Ser Trp Leu Thr Trp Val Ser Ser Glu Arg Val 290 295 300 Cys Leu Gln Trp Leu Lys Arg Val Gln Asn Val Ser Val Leu Ser Ile 305 310 315 320 Cys Asp Phe Arg Glu Asp Trp His Ala Trp Glu Cys Pro Lys Asn Gln 325 330 335 Glu His Val Glu Glu Ser Arg Thr Gly Trp Ala Gly Gly Phe Phe Val 340 345 350 Ser Thr Pro Ala Phe Ser Gln Asp Ala Thr Ser Tyr Tyr Lys Ile Phe 355 360 365 Ser Asp Lys Asp Gly Tyr Lys His Ile His Tyr Ile Lys Asp Thr Val 370 375 380 Glu Asn Ala Ile Gln Ile Thr Ser Gly Lys Trp Glu Ala Ile Tyr Ile 385 390 395 400 Phe Arg Val Thr Gln Asp Ser Leu Phe Tyr Ser Ser Asn Glu Phe Glu 405 410 415 Gly Tyr Pro Gly Arg Arg Asn Ile Tyr Arg Ile Ser Ile Gly Asn Ser 420 425 430 Pro Pro Ser Lys Lys Cys Val Thr Cys His Leu Arg Lys Glu Arg Cys 435 440 445 Gln Tyr Tyr Thr Ala Ser Phe Ser Tyr Lys Ala Lys Tyr Tyr Ala Leu 450 455 460 Val Cys Tyr Gly Pro Gly Leu Pro Ile Ser Thr Leu His Asp Gly Arg 465 470 475 480 Thr Asp Gln Glu Ile Gln Val Leu Glu Glu Asn Lys Glu Leu Glu Asn 485 490 495 Ser Leu Arg Asn Ile Gln Leu Pro Lys Val Glu Ile Lys Lys Leu Lys 500 505 510 Asp Gly Gly Leu Thr Phe Trp Tyr Lys Met Ile Leu Pro Pro Gln Phe 515 520 525 Asp Arg Ser Lys Lys Tyr Pro Leu Leu Ile Gln Val Tyr Gly Gly Pro 530 535 540 Cys Ser Gln Ser Val Lys Ser Val Phe Ala Val Asn Trp Ile Thr Tyr 545 550 555 560 Leu Ala Ser Lys Glu Gly Ile Val Ile Ala Leu Val Asp Gly Arg Gly 565 570 575 Thr Ala Phe Gln Gly Asp Lys Phe Leu His Ala Val Tyr Arg Lys Leu 580 585 590 Gly Val Tyr Glu Val Glu Asp Gln Leu Thr Ala Val Arg Lys Phe Ile 595 600 605 Glu Met Gly Phe Ile Asp Glu Glu Arg Ile Ala Ile Trp Gly Trp Ser 610 615 620 Tyr Gly Gly Tyr Val Ser Ser Leu Ala Leu Ala Ser Gly Thr Gly Leu 625 630 635 640 Phe Lys Cys Gly Ile Ala Val Ala Pro Val Ser Ser Trp Glu Tyr Tyr 645 650 655 Ala Ser Ile Tyr Ser Glu Arg Phe Met Gly Leu Pro Thr Lys Asp Asp 660 665 670 Asn Leu Glu His Tyr Lys Asn Ser Thr Val Met Ala Arg Ala Glu Tyr 675 680 685 Phe Arg Asn Val Asp Tyr Leu Leu Ile His Gly Thr Ala Asp Asp Asn 690 695 700 Val His Phe Gln Asn Ser Ala Gln Ile Ala Lys Ala Leu Val Asn Ala 705 710 715 720 Gln Val Asp Phe Gln Ala Met Trp Tyr Ser Asp Gln Asn His Gly Ile 725 730 735 Ser Ser Gly Arg Ser Gln Asn His Leu Tyr Thr His Met Thr His Phe 740 745 750 Leu Lys Gln Cys Phe Ser Leu Ser Asp 755 760 +ADw-210+AD4- 144 +ADw-211+AD4- 749 +ADw-212+AD4- PRT +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- ectodominio de FAP murino marcador Lys marcador avi +ADw-400+AD4- 144 Arg Pro Ser Arg Val Tyr Lys Pro Glu Gly Asn Thr Lys Arg Ala Leu 1 5 10 15 Thr Leu Lys Asp Ile Leu Asn Gly Thr Phe Ser Tyr Lys Thr Tyr Phe 20 25 30 Pro Asn Trp Ile Ser Glu Gln Glu Tyr Leu His Gln Ser Glu Asp Asp 35 40 45 Asn Ile Val Phe Tyr Asn Ile Glu Thr Arg Glu Ser Tyr Ile Ile Leu 50 55 60 Ser Asn Ser Thr Met Lys Ser Val Asn Ala Thr Asp Tyr Gly Leu Ser 65 70 75 80 Pro Asp Arg Gln Phe Val Tyr Leu Glu Ser Asp Tyr Ser Lys Leu Trp 85 90 95 Arg Tyr Ser Tyr Thr Ala Thr Tyr Tyr Ile Tyr Asp Leu Gln Asn Gly 100 105 110 Glu Phe Val Arg Gly Tyr Glu Leu Pro Arg Pro Ile Gln Tyr Leu Cys 115 120 125 Trp Ser Pro Val Gly Ser Lys Leu Ala Tyr Val Tyr Gln Asn Asn Ile 130 135 140 Tyr Leu Lys Gln Arg Pro Gly Asp Pro Pro Phe Gln Ile Thr Tyr Thr 145 150 155 160 Gly Arg Glu Asn Arg Ile Phe Asn Gly Ile Pro Asp Trp Val Tyr Glu 165 170 175 Glu Glu Met Leu Ala Thr Lys Tyr Ala Leu Trp Trp Ser Pro Asp Gly 180 185 190 Lys Phe Leu Ala Tyr Val Glu Phe Asn Asp Ser Asp Ile Pro Ile Ile 195 200 205 Ala Tyr Ser Tyr Tyr Gly Asp Gly Gln Tyr Pro Arg Thr Ile Asn Ile 210 215 220 Pro Tyr Pro Lys Ala Gly Ala Lys Asn Pro Val Val Arg Val Phe Ile 225 230 235 240 Val Asp Thr Thr Tyr Pro His His Val Gly Pro Met Glu Val Pro Val 245 250 255 Pro Glu Met Ile Ala Ser Ser Asp Tyr Tyr Phe Ser Trp Leu Thr Trp 260 265 270 Val Ser Ser Glu Arg Val Cys Leu Gln Trp Leu Lys Arg Val Gln Asn 275 280 285 Val Ser Val Leu Ser Ile Cys Asp Phe Arg Glu Asp Trp His Ala Trp 290 295 300 Glu Cys Pro Lys Asn Gln Glu His Val Glu Glu Ser Arg Thr Gly Trp 305 310 315 320 Ala Gly Gly Phe Phe Val Ser Thr Pro Ala Phe Ser Gln Asp Ala Thr 325 330 335 Ser Tyr Tyr Lys Ile Phe Ser Asp Lys Asp Gly Tyr Lys His Ile His 340 345 350 Tyr Ile Lys Asp Thr Val Glu Asn Ala Ile Gln Ile Thr Ser Gly Lys 355 360 365 Trp Glu Ala Ile Tyr Ile Phe Arg Val Thr Gln Asp Ser Leu Phe Tyr 370 375 380 Ser Ser Asn Glu Phe Glu Gly Tyr Pro Gly Arg Arg Asn Ile Tyr Arg 385 390 395 400 Ile Ser Ile Gly Asn Ser Pro Pro Ser Lys Lys Cys Val Thr Cys His 405 410 415 Leu Arg Lys Glu Arg Cys Gln Tyr Tyr Thr Ala Ser Phe Ser Tyr Lys 420 425 430 Ala Lys Tyr Tyr Ala Leu Val Cys Tyr Gly Pro Gly Leu Pro Ile Ser 435 440 445 Thr Leu His Asp Gly Arg Thr Asp Gln Glu Ile Gln Val Leu Glu Glu 450 455 460 Asn Lys Glu Leu Glu Asn Ser Leu Arg Asn Ile Gln Leu Pro Lys Val 465 470 475 480 Glu Ile Lys Lys Leu Lys Asp Gly Gly Leu Thr Phe Trp Tyr Lys Met 485 490 495 Ile Leu Pro Pro Gln Phe Asp Arg Ser Lys Lys Tyr Pro Leu Leu Ile 500 505 510 Gln Val Tyr Gly Gly Pro Cys Ser Gln Ser Val Lys Ser Val Phe Ala 515 520 525 Val Asn Trp Ile Thr Tyr Leu Ala Ser Lys Glu Gly Ile Val Ile Ala 530 535 540 Leu Val Asp Gly Arg Gly Thr Ala Phe Gln Gly Asp Lys Phe Leu His 545 550 555 560 Ala Val Tyr Arg Lys Leu Gly Val Tyr Glu Val Glu Asp Gln Leu Thr 565 570 575 Ala Val Arg Lys Phe Ile Glu Met Gly Phe Ile Asp Glu Glu Arg Ile 580 585 590 Ala Ile Trp Gly Trp Ser Tyr Gly Gly Tyr Val Ser Ser Leu Ala Leu 595 600 605 Ala Ser Gly Thr Gly Leu Phe Lys Cys Gly Ile Ala Val Ala Pro Val 610 615 620 Ser Ser Trp Glu Tyr Tyr Ala Ser Ile Tyr Ser Glu Arg Phe Met Gly 625 630 635 640 Leu Pro Thr Lys Asp Asp Asn Leu Glu His Tyr Lys Asn Ser Thr Val 645 650 655 Met Ala Arg Ala Glu Tyr Phe Arg Asn Val Asp Tyr Leu Leu Ile His 660 665 670 Gly Thr Ala Asp Asp Asn Val His Phe Gln Asn Ser Ala Gln Ile Ala 675 680 685 Lys Ala Leu Val Asn Ala Gln Val Asp Phe Gln Ala Met Trp Tyr Ser 690 695 700 Asp Gln Asn His Gly Ile Leu Ser Gly Arg Ser Gln Asn His Leu Tyr 705 710 715 720 Thr His Met Thr His Phe Leu Lys Gln Cys Phe Ser Leu Ser Asp Gly 725 730 735 Lys Lys Lys Lys Lys Lys Gly His His His His His His 740 745 +ADw-210+AD4- 145 +ADw-211+AD4- 748 +ADw-212+AD4- PRT +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- ectodominio de FAP de cinomolgo marcador Lys marcador avi +ADw-400+AD4- 145 Arg Pro Pro Arg Val His Asn Ser Glu Glu Asn Thr Met Arg Ala Leu 1 5 10 15 Thr Leu Lys Asp Ile Leu Asn Gly Thr Phe Ser Tyr Lys Thr Phe Phe 20 25 30 Pro Asn Trp Ile Ser Gly Gln Glu Tyr Leu His Gln Ser Ala Asp Asn 35 40 45 Asn Ile Val Leu Tyr Asn Ile Glu Thr Gly Gln Ser Tyr Thr Ile Leu 50 55 60 Ser Asn Arg Thr Met Lys Ser Val Asn Ala Ser Asn Tyr Gly Leu Ser 65 70 75 80 Pro Asp Arg Gln Phe Val Tyr Leu Glu Ser Asp Tyr Ser Lys Leu Trp 85 90 95 Arg Tyr Ser Tyr Thr Ala Thr Tyr Tyr Ile Tyr Asp Leu Ser Asn Gly 100 105 110 Glu Phe Val Arg Gly Asn Glu Leu Pro Arg Pro Ile Gln Tyr Leu Cys 115 120 125 Trp Ser Pro Val Gly Ser Lys Leu Ala Tyr Val Tyr Gln Asn Asn Ile 130 135 140 Tyr Leu Lys Gln Arg Pro Gly Asp Pro Pro Phe Gln Ile Thr Phe Asn 145 150 155 160 Gly Arg Glu Asn Lys Ile Phe Asn Gly Ile Pro Asp Trp Val Tyr Glu 165 170 175 Glu Glu Met Leu Ala Thr Lys Tyr Ala Leu Trp Trp Ser Pro Asn Gly 180 185 190 Lys Phe Leu Ala Tyr Ala Glu Phe Asn Asp Thr Asp Ile Pro Val Ile 195 200 205 Ala Tyr Ser Tyr Tyr Gly Asp Glu Gln Tyr Pro Arg Thr Ile Asn Ile 210 215 220 Pro Tyr Pro Lys Ala Gly Ala Lys Asn Pro Phe Val Arg Ile Phe Ile 225 230 235 240 Ile Asp Thr Thr Tyr Pro Ala Tyr Val Gly Pro Gln Glu Val Pro Val 245 250 255 Pro Ala Met Ile Ala Ser Ser Asp Tyr Tyr Phe Ser Trp Leu Thr Trp 260 265 270 Val Thr Asp Glu Arg Val Cys Leu Gln Trp Leu Lys Arg Val Gln Asn 275 280 285 Val Ser Val Leu Ser Ile Cys Asp Phe Arg Glu Asp Trp Gln Thr Trp 290 295 300 Asp Cys Pro Lys Thr Gln Glu His Ile Glu Glu Ser Arg Thr Gly Trp 305 310 315 320 Ala Gly Gly Phe Phe Val Ser Thr Pro Val Phe Ser Tyr Asp Ala Ile 325 330 335 Ser Tyr Tyr Lys Ile Phe Ser Asp Lys Asp Gly Tyr Lys His Ile His 340 345 350 Tyr Ile Lys Asp Thr Val Glu Asn Ala Ile Gln Ile Thr Ser Gly Lys 355 360 365 Trp Glu Ala Ile Asn Ile Phe Arg Val Thr Gln Asp Ser Leu Phe Tyr 370 375 380 Ser Ser Asn Glu Phe Glu Asp Tyr Pro Gly Arg Arg Asn Ile Tyr Arg 385 390 395 400 Ile Ser Ile Gly Ser Tyr Pro Pro Ser Lys Lys Cys Val Thr Cys His 405 410 415 Leu Arg Lys Glu Arg Cys Gln Tyr Tyr Thr Ala Ser Phe Ser Asp Tyr 420 425 430 Ala Lys Tyr Tyr Ala Leu Val Cys Tyr Gly Pro Gly Ile Pro Ile Ser 435 440 445 Thr Leu His Asp Gly Arg Thr Asp Gln Glu Ile Lys Ile Leu Glu Glu 450 455 460 Asn Lys Glu Leu Glu Asn Ala Leu Lys Asn Ile Gln Leu Pro Lys Glu 465 470 475 480 Glu Ile Lys Lys Leu Glu Val Asp Glu Ile Thr Leu Trp Tyr Lys Met 485 490 495 Ile Leu Pro Pro Gln Phe Asp Arg Ser Lys Lys Tyr Pro Leu Leu Ile 500 505 510 Gln Val Tyr Gly Gly Pro Cys Ser Gln Ser Val Arg Ser Val Phe Ala 515 520 525 Val Asn Trp Ile Ser Tyr Leu Ala Ser Lys Glu Gly Met Val Ile Ala 530 535 540 Leu Val Asp Gly Arg Gly Thr Ala Phe Gln Gly Asp Lys Leu Leu Tyr 545 550 555 560 Ala Val Tyr Arg Lys Leu Gly Val Tyr Glu Val Glu Asp Gln Ile Thr 565 570 575 Ala Val Arg Lys Phe Ile Glu Met Gly Phe Ile Asp Glu Lys Arg Ile 580 585 590 Ala Ile Trp Gly Trp Ser Tyr Gly Gly Tyr Val Ser Ser Leu Ala Leu 595 600 605 Ala Ser Gly Thr Gly Leu Phe Lys Cys Gly Ile Ala Val Ala Pro Val 610 615 620 Ser Ser Trp Glu Tyr Tyr Ala Ser Val Tyr Thr Glu Arg Phe Met Gly 625 630 635 640 Leu Pro Thr Lys Asp Asp Asn Leu Glu His Tyr Lys Asn Ser Thr Val 645 650 655 Met Ala Arg Ala Glu Tyr Phe Arg Asn Val Asp Tyr Leu Leu Ile His 660 665 670 Gly Thr Ala Asp Asp Asn Val His Phe Gln Asn Ser Ala Gln Ile Ala 675 680 685 Lys Ala Leu Val Asn Ala Gln Val Asp Phe Gln Ala Met Trp Tyr Ser 690 695 700 Asp Gln Asn His Gly Leu Ser Gly Leu Ser Thr Asn His Leu Tyr Thr 705 710 715 720 His Met Thr His Phe Leu Lys Gln Cys Phe Ser Leu Ser Asp Gly Lys 725 730 735 Lys Lys Lys Lys Lys Gly His His His His His His 740 745 +ADw-210+AD4- 146 +ADw-211+AD4- 289 +ADw-212+AD4- PRT +ADw-213+AD4- Mus musculus +ADw-400+AD4- 146 Met Val Ser Leu Pro Arg Leu Cys Ala Leu Trp Gly Cys Leu Leu Thr 1 5 10 15 Ala Val His Leu Gly Gln Cys Val Thr Cys Ser Asp Lys Gln Tyr Leu 20 25 30 His Asp Gly Gln Cys Cys Asp Leu Cys Gln Pro Gly Ser Arg Leu Thr 35 40 45 Ser His Cys Thr Ala Leu Glu Lys Thr Gln Cys His Pro Cys Asp Ser 50 55 60 Gly Glu Phe Ser Ala Gln Trp Asn Arg Glu Ile Arg Cys His Gln His 65 70 75 80 Arg His Cys Glu Pro Asn Gln Gly Leu Arg Val Lys Lys Glu Gly Thr 85 90 95 Ala Glu Ser Asp Thr Val Cys Thr Cys Lys Glu Gly Gln His Cys Thr 100 105 110 Ser Lys Asp Cys Glu Ala Cys Ala Gln His Thr Pro Cys Ile Pro Gly 115 120 125 Phe Gly Val Met Glu Met Ala Thr Glu Thr Thr Asp Thr Val Cys His 130 135 140 Pro Cys Pro Val Gly Phe Phe Ser Asn Gln Ser Ser Leu Phe Glu Lys 145 150 155 160 Cys Tyr Pro Trp Thr Ser Cys Glu Asp Lys Asn Leu Glu Val Leu Gln 165 170 175 Lys Gly Thr Ser Gln Thr Asn Val Ile Cys Gly Leu Lys Ser Arg Met 180 185 190 Arg Ala Leu Leu Val Ile Pro Val Val Met Gly Ile Leu Ile Thr Ile 195 200 205 Phe Gly Val Phe Leu Tyr Ile Lys Lys Val Val Lys Lys Pro Lys Asp 210 215 220 Asn Glu Ile Leu Pro Pro Ala Ala Arg Arg Gln Asp Pro Gln Glu Met 225 230 235 240 Glu Asp Tyr Pro Gly His Asn Thr Ala Ala Pro Val Gln Glu Thr Leu 245 250 255 His Gly Cys Gln Pro Val Thr Gln Glu Asp Gly Lys Glu Ser Arg Ile 260 265 270 Ser Val Gln Glu Arg Gln Val Thr Asp Ser Ile Ala Leu Arg Pro Leu 275 280 285 Val +ADw-210+AD4- 147 +ADw-211+AD4- 5 +ADw-212+AD4- PRT +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- Enlazador pept+AO0-dico G4S +ADw-400+AD4- 147 Gly Gly Gly Gly Ser 1 5 +ADw-210+AD4- 148 +ADw-211+AD4- 10 +ADw-212+AD4- PRT +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- Enlazador pept+AO0-dico (G4S)2 +ADw-400+AD4- 148 Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser 1 5 10 +ADw-210+AD4- 149 +ADw-211+AD4- 10 +ADw-212+AD4- PRT +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- Enlazador pept+AO0-dico (SG4)2 +ADw-400+AD4- 149 Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly 1 5 10 +ADw-210+AD4- 150 +ADw-211+AD4- 14 +ADw-212+AD4- PRT +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- Enlazador pept+AO0-dico G4(SG4)2 +ADw-400+AD4- 150 Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly 1 5 10 +ADw-210+AD4- 151 +ADw-211+AD4- 10 +ADw-212+AD4- PRT +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- Enlazador pept+AO0-dico +ADw-400+AD4- 151 Gly Ser Pro Gly Ser Ser Ser Ser Gly Ser 1 5 10 +ADw-210+AD4- 152 +ADw-211+AD4- 15 +ADw-212+AD4- PRT +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- Enlazador pept+AO0-dico (G4S)3 +ADw-400+AD4- 152 Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser 1 5 10 15 +ADw-210+AD4- 153 +ADw-211+AD4- 20 +ADw-212+AD4- PRT +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- Enlazador pept+AO0-dico (G4S)4 +ADw-400+AD4- 153 Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly 1 5 10 15 Gly Gly Gly Ser 20 +ADw-210+AD4- 154 +ADw-211+AD4- 8 +ADw-212+AD4- PRT +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- Enlazador pept+AO0-dico +ADw-400+AD4- 154 Gly Ser Gly Ser Gly Ser Gly Ser 1 5 +ADw-210+AD4- 155 +ADw-211+AD4- 8 +ADw-212+AD4- PRT +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- Enlazador pept+AO0-dico +ADw-400+AD4- 155 Gly Ser Gly Ser Gly Asn Gly Ser 1 5 +ADw-210+AD4- 156 +ADw-211+AD4- 8 +ADw-212+AD4- PRT +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- Enlazador pept+AO0-dico +ADw-400+AD4- 156 Gly Gly Ser Gly Ser Gly Ser Gly 1 5 +ADw-210+AD4- 157 +ADw-211+AD4- 6 +ADw-212+AD4- PRT +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- Enlazador pept+AO0-dico +ADw-400+AD4- 157 Gly Gly Ser Gly Ser Gly 1 5 +ADw-210+AD4- 158 +ADw-211+AD4- 4 +ADw-212+AD4- PRT +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- Enlazador pept+AO0-dico +ADw-400+AD4- 158 Gly Gly Ser Gly 1 +ADw-210+AD4- 159 +ADw-211+AD4- 8 +ADw-212+AD4- PRT +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- Enlazador pept+AO0-dico +ADw-400+AD4- 159 Gly Gly Ser Gly Asn Gly Ser Gly 1 5 +ADw-210+AD4- 160 +ADw-211+AD4- 8 +ADw-212+AD4- PRT +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- Enlazador pept+AO0-dico +ADw-400+AD4- 160 Gly Gly Asn Gly Ser Gly Ser Gly 1 5 +ADw-210+AD4- 161 +ADw-211+AD4- 6 +ADw-212+AD4- PRT +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- Enlazador pept+AO0-dico +ADw-400+AD4- 161 Gly Gly Asn Gly Ser Gly 1 5 +ADw-210+AD4- 162 +ADw-211+AD4- 223 +ADw-212+AD4- PRT +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- 28H1 cadena ligera cruzada VHCL +ADw-400+AD4- 162 Glu Val Gln Leu Leu Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 1 5 10 15 Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Ser His 20 25 30 Ala Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45 Ser Ala Ile Trp Ala Ser Gly Glu Gln Tyr Tyr Ala Asp Ser Val Lys 50 55 60 Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr Leu 65 70 75 80 Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala 85 90 95 Lys Gly Trp Leu Gly Asn Phe Asp Tyr Trp Gly Gln Gly Thr Leu Val 100 105 110 Thr Val Ser Ser Ala Ser Val Ala Ala Pro Ser Val Phe Ile Phe Pro 115 120 125 Pro Ser Asp Glu Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu 130 135 140 Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp 145 150 155 160 Asn Ala Leu Gln Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp 165 170 175 Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys 180 185 190 Ala Asp Tyr Glu Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln 195 200 205 Gly Leu Ser Ser Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys 210 215 220 +ADw-210+AD4- 163 +ADw-211+AD4- 439 +ADw-212+AD4- PRT +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- 28H1 (VLCH1)+AF8-FC pomo+AF8- PGLALA +ADw-400+AD4- 163 Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly 1 5 10 15 Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Arg Ser 20 25 30 Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu 35 40 45 Ile Ile Gly Ala Ser Thr Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser 50 55 60 Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu 65 70 75 80 Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Gly Gln Val Ile Pro 85 90 95 Pro Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Ser Ser Ala Ser 100 105 110 Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr 115 120 125 Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro 130 135 140 Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val 145 150 155 160 His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser 165 170 175 Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile 180 185 190 Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Lys Val 195 200 205 Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala 210 215 220 Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro 225 230 235 240 Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val 245 250 255 Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val 260 265 270 Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln 275 280 285 Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln 290 295 300 Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala 305 310 315 320 Leu Gly Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro 325 330 335 Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Cys Arg Asp Glu Leu Thr 340 345 350 Lys Asn Gln Val Ser Leu Trp Cys Leu Val Lys Gly Phe Tyr Pro Ser 355 360 365 Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr 370 375 380 Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr 385 390 395 400 Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe 405 410 415 Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys 420 425 430 Ser Leu Ser Leu Ser Pro Gly 435 +ADw-210+AD4- 164 +ADw-211+AD4- 444 +ADw-212+AD4- PRT +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- CD40 (VHCH1 cargado)+AF8-Fc agujero+AF8-PGLALA +ADw-400+AD4- 164 Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 1 5 10 15 Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Tyr Ser Phe Thr Gly Tyr 20 25 30 Tyr Ile His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45 Ala Arg Val Ile Pro Asn Ala Gly Gly Thr Ser Tyr Asn Gln Lys Phe 50 55 60 Lys Gly Arg Phe Thr Leu Ser Val Asp Asn Ser Lys Asn Thr Ala Tyr 65 70 75 80 Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Ala Arg Glu Gly Ile Tyr Trp Trp Gly Gln Gly Thr Leu Val Thr Val 100 105 110 Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser 115 120 125 Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Glu 130 135 140 Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu 145 150 155 160 Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu 165 170 175 Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr 180 185 190 Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys Val 195 200 205 Asp Glu Lys Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro 210 215 220 Pro Cys Pro Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe 225 230 235 240 Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val 245 250 255 Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe 260 265 270 Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro 275 280 285 Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr 290 295 300 Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val 305 310 315 320 Ser Asn Lys Ala Leu Gly Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala 325 330 335 Lys Gly Gln Pro Arg Glu Pro Gln Val Cys Thr Leu Pro Pro Ser Arg 340 345 350 Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Ser Cys Ala Val Lys Gly 355 360 365 Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro 370 375 380 Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser 385 390 395 400 Phe Phe Leu Val Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln 405 410 415 Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn Arg 420 425 430 Phe Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys 435 440 +ADw-210+AD4- 165 +ADw-211+AD4- 219 +ADw-212+AD4- PRT +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- CD40 cadena ligera (cargado) +ADw-400+AD4- 165 Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 1 5 10 15 Asp Arg Val Thr Ile Thr Cys Arg Ser Ser Gln Ser Leu Val His Ser 20 25 30 Asn Gly Asn Thr Phe Leu His Trp Tyr Gln Gln Lys Pro Gly Lys Ala 35 40 45 Pro Lys Leu Leu Ile Tyr Thr Val Ser Asn Arg Phe Ser Gly Val Pro 50 55 60 Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile 65 70 75 80 Ser Ser Leu Gln Pro Glu Asp Phe Ala Thr Tyr Phe Cys Ser Gln Thr 85 90 95 Thr His Val Pro Trp Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys 100 105 110 Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Arg 115 120 125 Lys Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe 130 135 140 Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln 145 150 155 160 Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser 165 170 175 Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu 180 185 190 Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser 195 200 205 Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys 210 215 +ADw-210+AD4- 166 +ADw-211+AD4- 667 +ADw-212+AD4- PRT +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- CD40 (VHCH1 cargado)+AF8-28H1 (VLCH1)+AF8-FC pomo+AF8- PGLALA +ADw-400+AD4- 166 Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 1 5 10 15 Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Tyr Ser Phe Thr Gly Tyr 20 25 30 Tyr Ile His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45 Ala Arg Val Ile Pro Asn Ala Gly Gly Thr Ser Tyr Asn Gln Lys Phe 50 55 60 Lys Gly Arg Phe Thr Leu Ser Val Asp Asn Ser Lys Asn Thr Ala Tyr 65 70 75 80 Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Ala Arg Glu Gly Ile Tyr Trp Trp Gly Gln Gly Thr Leu Val Thr Val 100 105 110 Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser 115 120 125 Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Glu 130 135 140 Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu 145 150 155 160 Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu 165 170 175 Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr 180 185 190 Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys Val 195 200 205 Asp Glu Lys Val Glu Pro Lys Ser Cys Asp Gly Gly Gly Gly Ser Gly 210 215 220 Gly Gly Gly Ser Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser 225 230 235 240 Leu Ser Pro Gly Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser 245 250 255 Val Ser Arg Ser Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala 260 265 270 Pro Arg Leu Leu Ile Ile Gly Ala Ser Thr Arg Ala Thr Gly Ile Pro 275 280 285 Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile 290 295 300 Ser Arg Leu Glu Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Gly 305 310 315 320 Gln Val Ile Pro Pro Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys 325 330 335 Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser 340 345 350 Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Lys 355 360 365 Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu 370 375 380 Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu 385 390 395 400 Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr 405 410 415 Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys Val 420 425 430 Asp Lys Lys Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro 435 440 445 Pro Cys Pro Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe 450 455 460 Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val 465 470 475 480 Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe 485 490 495 Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro 500 505 510 Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr 515 520 525 Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val 530 535 540 Ser Asn Lys Ala Leu Gly Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala 545 550 555 560 Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Cys Arg 565 570 575 Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Trp Cys Leu Val Lys Gly 580 585 590 Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro 595 600 605 Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser 610 615 620 Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln 625 630 635 640 Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His 645 650 655 Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly 660 665 +ADw-210+AD4- 167 +ADw-211+AD4- 676 +ADw-212+AD4- PRT +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- CD40 (VHCH1 cargado)+AF8-Fc pomo+AF8-PGLALA+AF8-28H1 (VLCH1) +ADw-400+AD4- 167 Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 1 5 10 15 Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Tyr Ser Phe Thr Gly Tyr 20 25 30 Tyr Ile His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45 Ala Arg Val Ile Pro Asn Ala Gly Gly Thr Ser Tyr Asn Gln Lys Phe 50 55 60 Lys Gly Arg Phe Thr Leu Ser Val Asp Asn Ser Lys Asn Thr Ala Tyr 65 70 75 80 Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Ala Arg Glu Gly Ile Tyr Trp Trp Gly Gln Gly Thr Leu Val Thr Val 100 105 110 Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser 115 120 125 Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Glu 130 135 140 Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu 145 150 155 160 Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu 165 170 175 Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr 180 185 190 Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys Val 195 200 205 Asp Glu Lys Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro 210 215 220 Pro Cys Pro Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe 225 230 235 240 Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val 245 250 255 Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe 260 265 270 Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro 275 280 285 Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr 290 295 300 Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val 305 310 315 320 Ser Asn Lys Ala Leu Gly Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala 325 330 335 Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Cys Arg 340 345 350 Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Trp Cys Leu Val Lys Gly 355 360 365 Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro 370 375 380 Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser 385 390 395 400 Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln 405 410 415 Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His 420 425 430 Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Gly Gly Gly Gly Ser 435 440 445 Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Glu 450 455 460 Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly Glu 465 470 475 480 Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Arg Ser Tyr 485 490 495 Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile 500 505 510 Ile Gly Ala Ser Thr Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser Gly 515 520 525 Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu Pro 530 535 540 Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Gly Gln Val Ile Pro Pro 545 550 555 560 Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Ser Ser Ala Ser Thr 565 570 575 Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser 580 585 590 Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu 595 600 605 Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His 610 615 620 Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser 625 630 635 640 Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys 645 650 655 Asn Val Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Lys Val Glu 660 665 670 Pro Lys Ser Cys 675 +ADw-210+AD4- 168 +ADw-211+AD4- 443 +ADw-212+AD4- PRT +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- CD40 (VHCH1 cargado)+AF8-Fc pomo+AF8-PGLALA sin lisina C-terminal +ADw-400+AD4- 168 Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 1 5 10 15 Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Tyr Ser Phe Thr Gly Tyr 20 25 30 Tyr Ile His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45 Ala Arg Val Ile Pro Asn Ala Gly Gly Thr Ser Tyr Asn Gln Lys Phe 50 55 60 Lys Gly Arg Phe Thr Leu Ser Val Asp Asn Ser Lys Asn Thr Ala Tyr 65 70 75 80 Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Ala Arg Glu Gly Ile Tyr Trp Trp Gly Gln Gly Thr Leu Val Thr Val 100 105 110 Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser 115 120 125 Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Glu 130 135 140 Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu 145 150 155 160 Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu 165 170 175 Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr 180 185 190 Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys Val 195 200 205 Asp Glu Lys Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro 210 215 220 Pro Cys Pro Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe 225 230 235 240 Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val 245 250 255 Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe 260 265 270 Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro 275 280 285 Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr 290 295 300 Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val 305 310 315 320 Ser Asn Lys Ala Leu Gly Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala 325 330 335 Lys Gly Gln Pro Arg Glu Pro Gln Val Cys Thr Leu Pro Pro Ser Arg 340 345 350 Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Ser Cys Ala Val Lys Gly 355 360 365 Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro 370 375 380 Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser 385 390 395 400 Phe Phe Leu Val Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln 405 410 415 Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His 420 425 430 Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly 435 440 +ADw-210+AD4- 169 +ADw-211+AD4- 904 +ADw-212+AD4- PRT +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- CD40 (VHCH1 cargado+AF8-CD40 (VHCH1 cargado)-Fc pomo+AF8-PGLALA+AF8-28H1 (VLCH1) +ADw-400+AD4- 169 Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 1 5 10 15 Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Tyr Ser Phe Thr Gly Tyr 20 25 30 Tyr Ile His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45 Ala Arg Val Ile Pro Asn Ala Gly Gly Thr Ser Tyr Asn Gln Lys Phe 50 55 60 Lys Gly Arg Phe Thr Leu Ser Val Asp Asn Ser Lys Asn Thr Ala Tyr 65 70 75 80 Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Ala Arg Glu Gly Ile Tyr Trp Trp Gly Gln Gly Thr Leu Val Thr Val 100 105 110 Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser 115 120 125 Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Glu 130 135 140 Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu 145 150 155 160 Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu 165 170 175 Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr 180 185 190 Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys Val 195 200 205 Asp Glu Lys Val Glu Pro Lys Ser Cys Asp Gly Gly Gly Gly Ser Gly 210 215 220 Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val 225 230 235 240 Gln Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Tyr Ser 245 250 255 Phe Thr Gly Tyr Tyr Ile His Trp Val Arg Gln Ala Pro Gly Lys Gly 260 265 270 Leu Glu Trp Val Ala Arg Val Ile Pro Asn Ala Gly Gly Thr Ser Tyr 275 280 285 Asn Gln Lys Phe Lys Gly Arg Phe Thr Leu Ser Val Asp Asn Ser Lys 290 295 300 Asn Thr Ala Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala 305 310 315 320 Val Tyr Tyr Cys Ala Arg Glu Gly Ile Tyr Trp Trp Gly Gln Gly Thr 325 330 335 Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro 340 345 350 Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly 355 360 365 Cys Leu Val Glu Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn 370 375 380 Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln 385 390 395 400 Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser 405 410 415 Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser 420 425 430 Asn Thr Lys Val Asp Glu Lys Val Glu Pro Lys Ser Cys Asp Lys Thr 435 440 445 His Thr Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly Gly Pro Ser 450 455 460 Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg 465 470 475 480 Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro 485 490 495 Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala 500 505 510 Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val 515 520 525 Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr 530 535 540 Lys Cys Lys Val Ser Asn Lys Ala Leu Gly Ala Pro Ile Glu Lys Thr 545 550 555 560 Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu 565 570 575 Pro Pro Cys Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Trp Cys 580 585 590 Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser 595 600 605 Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp 610 615 620 Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser 625 630 635 640 Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala 645 650 655 Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Gly 660 665 670 Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly 675 680 685 Gly Gly Ser Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu 690 695 700 Ser Pro Gly Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val 705 710 715 720 Ser Arg Ser Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro 725 730 735 Arg Leu Leu Ile Ile Gly Ala Ser Thr Arg Ala Thr Gly Ile Pro Asp 740 745 750 Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser 755 760 765 Arg Leu Glu Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Gly Gln 770 775 780 Val Ile Pro Pro Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Ser 785 790 795 800 Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser Ser 805 810 815 Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Lys Asp 820 825 830 Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr 835 840 845 Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr 850 855 860 Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Gln 865 870 875 880 Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys Val Asp 885 890 895 Lys Lys Val Glu Pro Lys Ser Cys 900 +ADw-210+AD4- 170 +ADw-211+AD4- 671 +ADw-212+AD4- PRT +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- CD40 (VHCH1 cargado+AF8-CD40 (VHCH1 cargado)-Fc agujero+AF8-PGLALA +ADw-400+AD4- 170 Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 1 5 10 15 Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Tyr Ser Phe Thr Gly Tyr 20 25 30 Tyr Ile His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45 Ala Arg Val Ile Pro Asn Ala Gly Gly Thr Ser Tyr Asn Gln Lys Phe 50 55 60 Lys Gly Arg Phe Thr Leu Ser Val Asp Asn Ser Lys Asn Thr Ala Tyr 65 70 75 80 Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Ala Arg Glu Gly Ile Tyr Trp Trp Gly Gln Gly Thr Leu Val Thr Val 100 105 110 Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser 115 120 125 Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Glu 130 135 140 Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu 145 150 155 160 Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu 165 170 175 Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr 180 185 190 Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys Val 195 200 205 Asp Glu Lys Val Glu Pro Lys Ser Cys Asp Gly Gly Gly Gly Ser Gly 210 215 220 Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val 225 230 235 240 Gln Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Tyr Ser 245 250 255 Phe Thr Gly Tyr Tyr Ile His Trp Val Arg Gln Ala Pro Gly Lys Gly 260 265 270 Leu Glu Trp Val Ala Arg Val Ile Pro Asn Ala Gly Gly Thr Ser Tyr 275 280 285 Asn Gln Lys Phe Lys Gly Arg Phe Thr Leu Ser Val Asp Asn Ser Lys 290 295 300 Asn Thr Ala Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala 305 310 315 320 Val Tyr Tyr Cys Ala Arg Glu Gly Ile Tyr Trp Trp Gly Gln Gly Thr 325 330 335 Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro 340 345 350 Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly 355 360 365 Cys Leu Val Glu Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn 370 375 380 Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln 385 390 395 400 Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser 405 410 415 Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser 420 425 430 Asn Thr Lys Val Asp Glu Lys Val Glu Pro Lys Ser Cys Asp Lys Thr 435 440 445 His Thr Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly Gly Pro Ser 450 455 460 Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg 465 470 475 480 Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro 485 490 495 Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala 500 505 510 Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val 515 520 525 Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr 530 535 540 Lys Cys Lys Val Ser Asn Lys Ala Leu Gly Ala Pro Ile Glu Lys Thr 545 550 555 560 Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Cys Thr Leu 565 570 575 Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Ser Cys 580 585 590 Ala Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser 595 600 605 Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp 610 615 620 Ser Asp Gly Ser Phe Phe Leu Val Ser Lys Leu Thr Val Asp Lys Ser 625 630 635 640 Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala 645 650 655 Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly 660 665 670 +ADw-210+AD4- 171 +ADw-211+AD4- 114 +ADw-212+AD4- PRT +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- VH1a (CD40) +ADw-400+AD4- 171 Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala 1 5 10 15 Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Ser Phe Thr Gly Tyr 20 25 30 Tyr Ile His Trp Val Arg Gln Ala Pro Gly Gln Ser Leu Glu Trp Met 35 40 45 Gly Arg Val Ile Pro Asn Ala Gly Gly Thr Ser Tyr Asn Gln Lys Phe 50 55 60 Lys Gly Arg Val Thr Leu Thr Val Asp Lys Ser Ile Ser Thr Ala Tyr 65 70 75 80 Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Ala Arg Glu Gly Ile Tyr Trp Trp Gly Gln Gly Thr Thr Val Thr Val 100 105 110 Ser Ser +ADw-210+AD4- 172 +ADw-211+AD4- 114 +ADw-212+AD4- PRT +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- VH1b (CD40) +ADw-400+AD4- 172 Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala 1 5 10 15 Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Ser Phe Thr Gly Tyr 20 25 30 Tyr Ile His Trp Val Arg Gln Ala Pro Gly Lys Ser Leu Glu Trp Met 35 40 45 Gly Arg Val Ile Pro Asn Ala Gly Gly Thr Ser Tyr Asn Gln Lys Phe 50 55 60 Lys Gly Arg Val Thr Leu Thr Val Asp Lys Ser Ile Ser Thr Ala Tyr 65 70 75 80 Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Ala Arg Glu Gly Ile Tyr Trp Trp Gly Gln Gly Thr Thr Val Thr Val 100 105 110 Ser Ser +ADw-210+AD4- 173 +ADw-211+AD4- 114 +ADw-212+AD4- PRT +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- VH1c (CD40) +ADw-400+AD4- 173 Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala 1 5 10 15 Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Ser Phe Thr Gly Tyr 20 25 30 Tyr Ile His Trp Val Arg Gln Ala Pro Gly Gln Ser Leu Glu Trp Met 35 40 45 Gly Arg Val Ile Pro Asn Ala Gly Gly Thr Ser Tyr Asn Gln Lys Phe 50 55 60 Lys Gly Arg Val Thr Leu Thr Val Asp Lys Ser Ile Ser Thr Ala Tyr 65 70 75 80 Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Ala Arg Glu Gly Ile Tyr Trp Trp Gly His Gly Thr Thr Val Thr Val 100 105 110 Ser Ser +ADw-210+AD4- 174 +ADw-211+AD4- 114 +ADw-212+AD4- PRT +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- VH1d (CD40) +ADw-400+AD4- 174 Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala 1 5 10 15 Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Ser Phe Thr Gly Tyr 20 25 30 Tyr Ile His Trp Val Arg Gln Ala Pro Gly Gln Ser Leu Glu Trp Met 35 40 45 Gly Arg Val Ile Pro Asn Ala Gly Gly Thr Ser Tyr Asn Gln Lys Phe 50 55 60 Lys Gly Arg Val Thr Leu Ser Val Asp Lys Ser Ile Ser Thr Ala Tyr 65 70 75 80 Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Ala Arg Glu Gly Ile Tyr Trp Trp Gly Gln Gly Thr Thr Val Thr Val 100 105 110 Ser Ser +ADw-210+AD4- 175 +ADw-211+AD4- 112 +ADw-212+AD4- PRT +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- VL1a (CD40) +ADw-400+AD4- 175 Asp Ile Val Met Thr Gln Thr Pro Leu Ser Leu Ser Val Thr Pro Gly 1 5 10 15 Gln Pro Ala Ser Ile Ser Cys Arg Ser Ser Gln Ser Leu Val His Ser 20 25 30 Asn Gly Asn Thr Phe Leu His Trp Tyr Leu Gln Lys Pro Gly Gln Ser 35 40 45 Pro Gln Leu Leu Ile Tyr Thr Val Ser Asn Arg Phe Ser Gly Val Pro 50 55 60 Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile 65 70 75 80 Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Phe Cys Ser Gln Thr 85 90 95 Thr His Val Pro Trp Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys 100 105 110 +ADw-210+AD4- 176 +ADw-211+AD4- 112 +ADw-212+AD4- PRT +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- VL1b (CD40) +ADw-400+AD4- 176 Asp Ile Val Val Thr Gln Thr Pro Leu Ser Leu Ser Val Thr Pro Gly 1 5 10 15 Gln Pro Ala Ser Ile Ser Cys Arg Ser Ser Gln Ser Leu Val His Ser 20 25 30 Asn Gly Asn Thr Phe Leu His Trp Tyr Leu Gln Lys Pro Gly Gln Ser 35 40 45 Pro Gln Leu Leu Ile Tyr Thr Val Ser Asn Arg Phe Ser Gly Val Pro 50 55 60 Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile 65 70 75 80 Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Phe Cys Ser Gln Thr 85 90 95 Thr His Val Pro Trp Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys 100 105 110 +ADw-210+AD4- 177 +ADw-211+AD4- 112 +ADw-212+AD4- PRT +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- VL1c (CD40) +ADw-400+AD4- 177 Asp Val Val Val Thr Gln Thr Pro Leu Ser Leu Ser Val Thr Pro Gly 1 5 10 15 Gln Pro Ala Ser Ile Ser Cys Arg Ser Ser Gln Ser Leu Val His Ser 20 25 30 Asn Gly Asn Thr Phe Leu His Trp Tyr Leu Gln Lys Pro Gly Gln Ser 35 40 45 Pro Gln Leu Leu Ile Tyr Thr Val Ser Asn Arg Phe Ser Gly Val Pro 50 55 60 Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile 65 70 75 80 Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Phe Cys Ser Gln Thr 85 90 95 Thr His Val Pro Trp Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys 100 105 110 +ADw-210+AD4- 178 +ADw-211+AD4- 112 +ADw-212+AD4- PRT +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- VL1d (CD40) +ADw-400+AD4- 178 Asp Val Val Val Thr Gln Thr Pro Leu Ser Leu Ser Val Thr Pro Gly 1 5 10 15 Gln Pro Ala Ser Ile Ser Cys Arg Ser Ser Gln Ser Leu Val His Ser 20 25 30 Asn Gly Asn Thr Phe Leu His Trp Tyr Leu Gln Lys Pro Gly Gln Ser 35 40 45 Pro Gln Leu Leu Ile Tyr Thr Val Ser Asn Arg Phe Ser Gly Val Pro 50 55 60 Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile 65 70 75 80 Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Phe Cys Ser Gln Thr 85 90 95 Thr His Val Pro Trp Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys 100 105 110 +ADw-210+AD4- 179 +ADw-211+AD4- 114 +ADw-212+AD4- PRT +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- VH2a (CD40) +ADw-400+AD4- 179 Glu Val Gln Leu Leu Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 1 5 10 15 Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Tyr Ser Phe Thr Gly Tyr 20 25 30 Tyr Ile His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45 Gly Arg Val Ile Pro Asn Ala Gly Gly Thr Ser Tyr Asn Gln Lys Phe 50 55 60 Lys Gly Arg Phe Thr Ile Ser Val Asp Asn Ser Lys Asn Thr Ala Tyr 65 70 75 80 Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Ala Arg Glu Gly Ile Tyr Trp Trp Gly Gln Gly Thr Thr Val Thr Val 100 105 110 Ser Ser +ADw-210+AD4- 180 +ADw-211+AD4- 114 +ADw-212+AD4- PRT +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- VH2b (CD40) +ADw-400+AD4- 180 Glu Val Gln Leu Leu Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 1 5 10 15 Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Tyr Ser Phe Thr Gly Tyr 20 25 30 Tyr Ile His Trp Val Arg Gln Ala Pro Gly Lys Ser Leu Glu Trp Val 35 40 45 Gly Arg Val Ile Pro Asn Ala Gly Gly Thr Ser Tyr Asn Gln Lys Phe 50 55 60 Lys Gly Arg Phe Thr Ile Ser Val Asp Asn Ser Lys Asn Thr Ala Tyr 65 70 75 80 Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Ala Arg Glu Gly Ile Tyr Trp Trp Gly Gln Gly Thr Thr Val Thr Val 100 105 110 Ser Ser +ADw-210+AD4- 181 +ADw-211+AD4- 114 +ADw-212+AD4- PRT +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- VH2c (CD40) +ADw-400+AD4- 181 Glu Val Gln Leu Leu Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 1 5 10 15 Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Tyr Ser Phe Thr Gly Tyr 20 25 30 Tyr Ile His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45 Gly Arg Val Ile Pro Asn Ala Gly Gly Thr Ser Tyr Asn Gln Lys Phe 50 55 60 Lys Gly Arg Phe Thr Ile Ser Val Asp Asn Ser Lys Asn Thr Ala Tyr 65 70 75 80 Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Ala Arg Glu Gly Ile Tyr Trp Trp Gly His Gly Thr Thr Val Thr Val 100 105 110 Ser Ser +ADw-210+AD4- 182 +ADw-211+AD4- 114 +ADw-212+AD4- PRT +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- VH2d (CD40) +ADw-400+AD4- 182 Glu Val Gln Leu Leu Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 1 5 10 15 Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Tyr Ser Phe Thr Gly Tyr 20 25 30 Tyr Ile His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45 Gly Arg Val Ile Pro Asn Ala Gly Gly Thr Ser Tyr Gly Asp Ser Val 50 55 60 Lys Gly Arg Phe Thr Ile Ser Val Asp Asn Ser Lys Asn Thr Ala Tyr 65 70 75 80 Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Ala Arg Glu Gly Ile Tyr Trp Trp Gly Gln Gly Thr Thr Val Thr Val 100 105 110 Ser Ser +ADw-210+AD4- 183 +ADw-211+AD4- 114 +ADw-212+AD4- PRT +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- VH2ab (CD40) +ADw-400+AD4- 183 Glu Val Gln Leu Leu Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 1 5 10 15 Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Tyr Ser Phe Thr Gly Tyr 20 25 30 Tyr Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45 Gly Arg Val Ile Pro Asn Ala Gly Gly Thr Ser Tyr Asn Gln Lys Phe 50 55 60 Lys Gly Arg Phe Thr Ile Ser Val Asp Asn Ser Lys Asn Thr Ala Tyr 65 70 75 80 Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Ala Arg Glu Gly Ile Tyr Trp Trp Gly Gln Gly Thr Thr Val Thr Val 100 105 110 Ser Ser +ADw-210+AD4- 184 +ADw-211+AD4- 114 +ADw-212+AD4- PRT +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- VH2ac (CD40) +ADw-400+AD4- 184 Glu Val Gln Leu Leu Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 1 5 10 15 Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Tyr Ser Phe Thr Gly Tyr 20 25 30 Tyr Ile His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45 Gly Arg Val Ile Pro Asn Ala Gly Gly Thr Ser Tyr Asn Gln Lys Val 50 55 60 Lys Gly Arg Phe Thr Ile Ser Val Asp Asn Ser Lys Asn Thr Ala Tyr 65 70 75 80 Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Ala Arg Glu Gly Ile Tyr Trp Trp Gly Gln Gly Thr Thr Val Thr Val 100 105 110 Ser Ser +ADw-210+AD4- 185 +ADw-211+AD4- 112 +ADw-212+AD4- PRT +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- VL2a (CD40) +ADw-400+AD4- 185 Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 1 5 10 15 Asp Arg Val Thr Ile Thr Cys Arg Ser Ser Gln Ser Leu Val His Ser 20 25 30 Asn Gly Asn Thr Phe Leu His Trp Tyr Gln Gln Lys Pro Gly Lys Ala 35 40 45 Pro Lys Leu Leu Ile Tyr Thr Val Ser Asn Arg Phe Ser Gly Val Pro 50 55 60 Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile 65 70 75 80 Ser Ser Leu Gln Pro Glu Asp Phe Ala Thr Tyr Phe Cys Ser Gln Thr 85 90 95 Thr His Val Pro Trp Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys 100 105 110 +ADw-210+AD4- 186 +ADw-211+AD4- 112 +ADw-212+AD4- PRT +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- VL2b (CD40) +ADw-400+AD4- 186 Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 1 5 10 15 Asp Arg Val Thr Ile Thr Cys Arg Ser Ser Gln Ser Leu Val His Ser 20 25 30 Asn Gly Asn Thr Phe Leu His Trp Tyr Gln Gln Lys Pro Gly Gln Ser 35 40 45 Pro Lys Leu Leu Ile Tyr Thr Val Ser Asn Arg Phe Ser Gly Val Pro 50 55 60 Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile 65 70 75 80 Ser Ser Leu Gln Pro Glu Asp Phe Ala Thr Tyr Phe Cys Ser Gln Thr 85 90 95 Thr His Val Pro Trp Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys 100 105 110 +ADw-210+AD4- 187 +ADw-211+AD4- 112 +ADw-212+AD4- PRT +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- VL2ab (CD40) +ADw-400+AD4- 187 Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 1 5 10 15 Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Ser Leu Val His Ser 20 25 30 Asn Gly Asn Thr Phe Leu His Trp Tyr Gln Gln Lys Pro Gly Lys Ala 35 40 45 Pro Lys Leu Leu Ile Tyr Thr Val Ser Asn Arg Phe Ser Gly Val Pro 50 55 60 Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile 65 70 75 80 Ser Ser Leu Gln Pro Glu Asp Phe Ala Thr Tyr Phe Cys Ser Gln Thr 85 90 95 Thr His Val Pro Trp Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys 100 105 110 +ADw-210+AD4- 188 +ADw-211+AD4- 112 +ADw-212+AD4- PRT +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- VL2ac (CD40) +ADw-400+AD4- 188 Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 1 5 10 15 Asp Arg Val Thr Ile Thr Cys Arg Ser Ser Gln Ser Ile Val His Ser 20 25 30 Asn Gly Asn Thr Phe Leu His Trp Tyr Gln Gln Lys Pro Gly Lys Ala 35 40 45 Pro Lys Leu Leu Ile Tyr Thr Val Ser Asn Arg Phe Ser Gly Val Pro 50 55 60 Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile 65 70 75 80 Ser Ser Leu Gln Pro Glu Asp Phe Ala Thr Tyr Phe Cys Ser Gln Thr 85 90 95 Thr His Val Pro Trp Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys 100 105 110 +ADw-210+AD4- 189 +ADw-211+AD4- 443 +ADw-212+AD4- PRT +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- P1AE0400 cadena pesada +ADw-400+AD4- 189 Glu Val Gln Leu Leu Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 1 5 10 15 Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Tyr Ser Phe Thr Gly Tyr 20 25 30 Tyr Ile His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45 Gly Arg Val Ile Pro Asn Ala Gly Gly Thr Ser Tyr Asn Gln Lys Phe 50 55 60 Lys Gly Arg Phe Thr Ile Ser Val Asp Asn Ser Lys Asn Thr Ala Tyr 65 70 75 80 Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Ala Arg Glu Gly Ile Tyr Trp Trp Gly Gln Gly Thr Thr Val Thr Val 100 105 110 Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser 115 120 125 Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Lys 130 135 140 Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu 145 150 155 160 Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu 165 170 175 Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr 180 185 190 Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys Val 195 200 205 Asp Lys Lys Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro 210 215 220 Pro Cys Pro Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe 225 230 235 240 Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val 245 250 255 Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe 260 265 270 Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro 275 280 285 Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr 290 295 300 Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val 305 310 315 320 Ser Asn Lys Ala Leu Gly Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala 325 330 335 Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg 340 345 350 Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly 355 360 365 Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro 370 375 380 Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser 385 390 395 400 Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln 405 410 415 Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His 420 425 430 Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly 435 440 +ADw-210+AD4- 190 +ADw-211+AD4- 219 +ADw-212+AD4- PRT +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- P1AE0400 cadena ligera +ADw-400+AD4- 190 Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 1 5 10 15 Asp Arg Val Thr Ile Thr Cys Arg Ser Ser Gln Ser Leu Val His Ser 20 25 30 Asn Gly Asn Thr Phe Leu His Trp Tyr Gln Gln Lys Pro Gly Lys Ala 35 40 45 Pro Lys Leu Leu Ile Tyr Thr Val Ser Asn Arg Phe Ser Gly Val Pro 50 55 60 Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile 65 70 75 80 Ser Ser Leu Gln Pro Glu Asp Phe Ala Thr Tyr Phe Cys Ser Gln Thr 85 90 95 Thr His Val Pro Trp Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys 100 105 110 Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu 115 120 125 Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe 130 135 140 Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln 145 150 155 160 Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser 165 170 175 Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu 180 185 190 Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser 195 200 205 Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys 210 215 +ADw-210+AD4- 191 +ADw-211+AD4- 443 +ADw-212+AD4- PRT +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- P1AE0401 cadena pesada +ADw-400+AD4- 191 Glu Val Gln Leu Leu Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 1 5 10 15 Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Tyr Ser Phe Thr Gly Tyr 20 25 30 Tyr Ile His Trp Val Arg Gln Ala Pro Gly Lys Ser Leu Glu Trp Val 35 40 45 Gly Arg Val Ile Pro Asn Ala Gly Gly Thr Ser Tyr Asn Gln Lys Phe 50 55 60 Lys Gly Arg Phe Thr Ile Ser Val Asp Asn Ser Lys Asn Thr Ala Tyr 65 70 75 80 Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Ala Arg Glu Gly Ile Tyr Trp Trp Gly Gln Gly Thr Thr Val Thr Val 100 105 110 Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser 115 120 125 Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Lys 130 135 140 Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu 145 150 155 160 Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu 165 170 175 Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr 180 185 190 Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys Val 195 200 205 Asp Lys Lys Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro 210 215 220 Pro Cys Pro Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe 225 230 235 240 Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val 245 250 255 Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe 260 265 270 Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro 275 280 285 Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr 290 295 300 Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val 305 310 315 320 Ser Asn Lys Ala Leu Gly Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala 325 330 335 Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg 340 345 350 Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly 355 360 365 Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro 370 375 380 Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser 385 390 395 400 Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln 405 410 415 Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His 420 425 430 Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly 435 440 +ADw-210+AD4- 192 +ADw-211+AD4- 219 +ADw-212+AD4- PRT +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- P1AE0401 cadena ligera +ADw-400+AD4- 192 Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 1 5 10 15 Asp Arg Val Thr Ile Thr Cys Arg Ser Ser Gln Ser Leu Val His Ser 20 25 30 Asn Gly Asn Thr Phe Leu His Trp Tyr Gln Gln Lys Pro Gly Lys Ala 35 40 45 Pro Lys Leu Leu Ile Tyr Thr Val Ser Asn Arg Phe Ser Gly Val Pro 50 55 60 Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile 65 70 75 80 Ser Ser Leu Gln Pro Glu Asp Phe Ala Thr Tyr Phe Cys Ser Gln Thr 85 90 95 Thr His Val Pro Trp Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys 100 105 110 Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu 115 120 125 Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe 130 135 140 Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln 145 150 155 160 Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser 165 170 175 Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu 180 185 190 Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser 195 200 205 Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys 210 215 +ADw-210+AD4- 193 +ADw-211+AD4- 443 +ADw-212+AD4- PRT +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- P1AE0402 cadena pesada +ADw-400+AD4- 193 Glu Val Gln Leu Leu Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 1 5 10 15 Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Tyr Ser Phe Thr Gly Tyr 20 25 30 Tyr Ile His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45 Gly Arg Val Ile Pro Asn Ala Gly Gly Thr Ser Tyr Asn Gln Lys Phe 50 55 60 Lys Gly Arg Phe Thr Ile Ser Val Asp Asn Ser Lys Asn Thr Ala Tyr 65 70 75 80 Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Ala Arg Glu Gly Ile Tyr Trp Trp Gly His Gly Thr Thr Val Thr Val 100 105 110 Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser 115 120 125 Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Lys 130 135 140 Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu 145 150 155 160 Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu 165 170 175 Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr 180 185 190 Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys Val 195 200 205 Asp Lys Lys Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro 210 215 220 Pro Cys Pro Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe 225 230 235 240 Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val 245 250 255 Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe 260 265 270 Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro 275 280 285 Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr 290 295 300 Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val 305 310 315 320 Ser Asn Lys Ala Leu Gly Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala 325 330 335 Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg 340 345 350 Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly 355 360 365 Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro 370 375 380 Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser 385 390 395 400 Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln 405 410 415 Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His 420 425 430 Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly 435 440 +ADw-210+AD4- 194 +ADw-211+AD4- 219 +ADw-212+AD4- PRT +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- P1AE0402 cadena ligera +ADw-400+AD4- 194 Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 1 5 10 15 Asp Arg Val Thr Ile Thr Cys Arg Ser Ser Gln Ser Leu Val His Ser 20 25 30 Asn Gly Asn Thr Phe Leu His Trp Tyr Gln Gln Lys Pro Gly Lys Ala 35 40 45 Pro Lys Leu Leu Ile Tyr Thr Val Ser Asn Arg Phe Ser Gly Val Pro 50 55 60 Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile 65 70 75 80 Ser Ser Leu Gln Pro Glu Asp Phe Ala Thr Tyr Phe Cys Ser Gln Thr 85 90 95 Thr His Val Pro Trp Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys 100 105 110 Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu 115 120 125 Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe 130 135 140 Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln 145 150 155 160 Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser 165 170 175 Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu 180 185 190 Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser 195 200 205 Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys 210 215 +ADw-210+AD4- 195 +ADw-211+AD4- 443 +ADw-212+AD4- PRT +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- P1AE0403 cadena pesada +ADw-400+AD4- 195 Glu Val Gln Leu Leu Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 1 5 10 15 Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Tyr Ser Phe Thr Gly Tyr 20 25 30 Tyr Ile His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45 Gly Arg Val Ile Pro Asn Ala Gly Gly Thr Ser Tyr Gly Asp Ser Val 50 55 60 Lys Gly Arg Phe Thr Ile Ser Val Asp Asn Ser Lys Asn Thr Ala Tyr 65 70 75 80 Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Ala Arg Glu Gly Ile Tyr Trp Trp Gly Gln Gly Thr Thr Val Thr Val 100 105 110 Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser 115 120 125 Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Lys 130 135 140 Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu 145 150 155 160 Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu 165 170 175 Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr 180 185 190 Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys Val 195 200 205 Asp Lys Lys Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro 210 215 220 Pro Cys Pro Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe 225 230 235 240 Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val 245 250 255 Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe 260 265 270 Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro 275 280 285 Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr 290 295 300 Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val 305 310 315 320 Ser Asn Lys Ala Leu Gly Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala 325 330 335 Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg 340 345 350 Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly 355 360 365 Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro 370 375 380 Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser 385 390 395 400 Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln 405 410 415 Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His 420 425 430 Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly 435 440 +ADw-210+AD4- 196 +ADw-211+AD4- 219 +ADw-212+AD4- PRT +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- P1AE0403 cadena ligera +ADw-400+AD4- 196 Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 1 5 10 15 Asp Arg Val Thr Ile Thr Cys Arg Ser Ser Gln Ser Leu Val His Ser 20 25 30 Asn Gly Asn Thr Phe Leu His Trp Tyr Gln Gln Lys Pro Gly Lys Ala 35 40 45 Pro Lys Leu Leu Ile Tyr Thr Val Ser Asn Arg Phe Ser Gly Val Pro 50 55 60 Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile 65 70 75 80 Ser Ser Leu Gln Pro Glu Asp Phe Ala Thr Tyr Phe Cys Ser Gln Thr 85 90 95 Thr His Val Pro Trp Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys 100 105 110 Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu 115 120 125 Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe 130 135 140 Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln 145 150 155 160 Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser 165 170 175 Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu 180 185 190 Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser 195 200 205 Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys 210 215 +ADw-210+AD4- 197 +ADw-211+AD4- 443 +ADw-212+AD4- PRT +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- P1AE0404 cadena pesada +ADw-400+AD4- 197 Glu Val Gln Leu Leu Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 1 5 10 15 Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Tyr Ser Phe Thr Gly Tyr 20 25 30 Tyr Ile His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45 Gly Arg Val Ile Pro Asn Ala Gly Gly Thr Ser Tyr Asn Gln Lys Phe 50 55 60 Lys Gly Arg Phe Thr Ile Ser Val Asp Asn Ser Lys Asn Thr Ala Tyr 65 70 75 80 Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Ala Arg Glu Gly Ile Tyr Trp Trp Gly Gln Gly Thr Thr Val Thr Val 100 105 110 Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser 115 120 125 Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Lys 130 135 140 Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu 145 150 155 160 Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu 165 170 175 Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr 180 185 190 Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys Val 195 200 205 Asp Lys Lys Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro 210 215 220 Pro Cys Pro Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe 225 230 235 240 Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val 245 250 255 Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe 260 265 270 Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro 275 280 285 Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr 290 295 300 Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val 305 310 315 320 Ser Asn Lys Ala Leu Gly Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala 325 330 335 Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg 340 345 350 Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly 355 360 365 Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro 370 375 380 Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser 385 390 395 400 Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln 405 410 415 Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His 420 425 430 Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly 435 440 +ADw-210+AD4- 198 +ADw-211+AD4- 219 +ADw-212+AD4- PRT +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- P1AE0404 cadena ligera +ADw-400+AD4- 198 Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 1 5 10 15 Asp Arg Val Thr Ile Thr Cys Arg Ser Ser Gln Ser Leu Val His Ser 20 25 30 Asn Gly Asn Thr Phe Leu His Trp Tyr Gln Gln Lys Pro Gly Gln Ser 35 40 45 Pro Lys Leu Leu Ile Tyr Thr Val Ser Asn Arg Phe Ser Gly Val Pro 50 55 60 Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile 65 70 75 80 Ser Ser Leu Gln Pro Glu Asp Phe Ala Thr Tyr Phe Cys Ser Gln Thr 85 90 95 Thr His Val Pro Trp Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys 100 105 110 Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu 115 120 125 Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe 130 135 140 Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln 145 150 155 160 Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser 165 170 175 Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu 180 185 190 Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser 195 200 205 Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys 210 215 +ADw-210+AD4- 199 +ADw-211+AD4- 443 +ADw-212+AD4- PRT +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- P1AE0405 cadena pesada +ADw-400+AD4- 199 Glu Val Gln Leu Leu Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 1 5 10 15 Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Tyr Ser Phe Thr Gly Tyr 20 25 30 Tyr Ile His Trp Val Arg Gln Ala Pro Gly Lys Ser Leu Glu Trp Val 35 40 45 Gly Arg Val Ile Pro Asn Ala Gly Gly Thr Ser Tyr Asn Gln Lys Phe 50 55 60 Lys Gly Arg Phe Thr Ile Ser Val Asp Asn Ser Lys Asn Thr Ala Tyr 65 70 75 80 Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Ala Arg Glu Gly Ile Tyr Trp Trp Gly Gln Gly Thr Thr Val Thr Val 100 105 110 Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser 115 120 125 Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Lys 130 135 140 Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu 145 150 155 160 Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu 165 170 175 Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr 180 185 190 Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys Val 195 200 205 Asp Lys Lys Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro 210 215 220 Pro Cys Pro Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe 225 230 235 240 Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val 245 250 255 Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe 260 265 270 Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro 275 280 285 Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr 290 295 300 Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val 305 310 315 320 Ser Asn Lys Ala Leu Gly Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala 325 330 335 Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg 340 345 350 Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly 355 360 365 Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro 370 375 380 Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser 385 390 395 400 Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln 405 410 415 Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His 420 425 430 Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly 435 440 +ADw-210+AD4- 200 +ADw-211+AD4- 219 +ADw-212+AD4- PRT +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- P1AE0405 cadena ligera +ADw-400+AD4- 200 Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 1 5 10 15 Asp Arg Val Thr Ile Thr Cys Arg Ser Ser Gln Ser Leu Val His Ser 20 25 30 Asn Gly Asn Thr Phe Leu His Trp Tyr Gln Gln Lys Pro Gly Gln Ser 35 40 45 Pro Lys Leu Leu Ile Tyr Thr Val Ser Asn Arg Phe Ser Gly Val Pro 50 55 60 Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile 65 70 75 80 Ser Ser Leu Gln Pro Glu Asp Phe Ala Thr Tyr Phe Cys Ser Gln Thr 85 90 95 Thr His Val Pro Trp Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys 100 105 110 Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu 115 120 125 Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe 130 135 140 Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln 145 150 155 160 Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser 165 170 175 Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu 180 185 190 Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser 195 200 205 Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys 210 215 +ADw-210+AD4- 201 +ADw-211+AD4- 443 +ADw-212+AD4- PRT +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- P1AE0406 cadena pesada +ADw-400+AD4- 201 Glu Val Gln Leu Leu Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 1 5 10 15 Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Tyr Ser Phe Thr Gly Tyr 20 25 30 Tyr Ile His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45 Gly Arg Val Ile Pro Asn Ala Gly Gly Thr Ser Tyr Asn Gln Lys Phe 50 55 60 Lys Gly Arg Phe Thr Ile Ser Val Asp Asn Ser Lys Asn Thr Ala Tyr 65 70 75 80 Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Ala Arg Glu Gly Ile Tyr Trp Trp Gly His Gly Thr Thr Val Thr Val 100 105 110 Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser 115 120 125 Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Lys 130 135 140 Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu 145 150 155 160 Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu 165 170 175 Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr 180 185 190 Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys Val 195 200 205 Asp Lys Lys Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro 210 215 220 Pro Cys Pro Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe 225 230 235 240 Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val 245 250 255 Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe 260 265 270 Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro 275 280 285 Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr 290 295 300 Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val 305 310 315 320 Ser Asn Lys Ala Leu Gly Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala 325 330 335 Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg 340 345 350 Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly 355 360 365 Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro 370 375 380 Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser 385 390 395 400 Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln 405 410 415 Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His 420 425 430 Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly 435 440 +ADw-210+AD4- 202 +ADw-211+AD4- 219 +ADw-212+AD4- PRT +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- P1AE0406 cadena ligera +ADw-400+AD4- 202 Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 1 5 10 15 Asp Arg Val Thr Ile Thr Cys Arg Ser Ser Gln Ser Leu Val His Ser 20 25 30 Asn Gly Asn Thr Phe Leu His Trp Tyr Gln Gln Lys Pro Gly Gln Ser 35 40 45 Pro Lys Leu Leu Ile Tyr Thr Val Ser Asn Arg Phe Ser Gly Val Pro 50 55 60 Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile 65 70 75 80 Ser Ser Leu Gln Pro Glu Asp Phe Ala Thr Tyr Phe Cys Ser Gln Thr 85 90 95 Thr His Val Pro Trp Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys 100 105 110 Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu 115 120 125 Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe 130 135 140 Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln 145 150 155 160 Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser 165 170 175 Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu 180 185 190 Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser 195 200 205 Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys 210 215 +ADw-210+AD4- 203 +ADw-211+AD4- 443 +ADw-212+AD4- PRT +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- P1AE0407 cadena pesada +ADw-400+AD4- 203 Glu Val Gln Leu Leu Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 1 5 10 15 Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Tyr Ser Phe Thr Gly Tyr 20 25 30 Tyr Ile His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45 Gly Arg Val Ile Pro Asn Ala Gly Gly Thr Ser Tyr Gly Asp Ser Val 50 55 60 Lys Gly Arg Phe Thr Ile Ser Val Asp Asn Ser Lys Asn Thr Ala Tyr 65 70 75 80 Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Ala Arg Glu Gly Ile Tyr Trp Trp Gly Gln Gly Thr Thr Val Thr Val 100 105 110 Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser 115 120 125 Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Lys 130 135 140 Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu 145 150 155 160 Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu 165 170 175 Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr 180 185 190 Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys Val 195 200 205 Asp Lys Lys Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro 210 215 220 Pro Cys Pro Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe 225 230 235 240 Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val 245 250 255 Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe 260 265 270 Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro 275 280 285 Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr 290 295 300 Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val 305 310 315 320 Ser Asn Lys Ala Leu Gly Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala 325 330 335 Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg 340 345 350 Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly 355 360 365 Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro 370 375 380 Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser 385 390 395 400 Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln 405 410 415 Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His 420 425 430 Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly 435 440 +ADw-210+AD4- 204 +ADw-211+AD4- 219 +ADw-212+AD4- PRT +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- P1AE0407 cadena ligera +ADw-400+AD4- 204 Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 1 5 10 15 Asp Arg Val Thr Ile Thr Cys Arg Ser Ser Gln Ser Leu Val His Ser 20 25 30 Asn Gly Asn Thr Phe Leu His Trp Tyr Gln Gln Lys Pro Gly Gln Ser 35 40 45 Pro Lys Leu Leu Ile Tyr Thr Val Ser Asn Arg Phe Ser Gly Val Pro 50 55 60 Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile 65 70 75 80 Ser Ser Leu Gln Pro Glu Asp Phe Ala Thr Tyr Phe Cys Ser Gln Thr 85 90 95 Thr His Val Pro Trp Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys 100 105 110 Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu 115 120 125 Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe 130 135 140 Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln 145 150 155 160 Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser 165 170 175 Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu 180 185 190 Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser 195 200 205 Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys 210 215 +ADw-210+AD4- 205 +ADw-211+AD4- 443 +ADw-212+AD4- PRT +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- P1AE0817 cadena pesada +ADw-400+AD4- 205 Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala 1 5 10 15 Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Ser Phe Thr Gly Tyr 20 25 30 Tyr Ile His Trp Val Arg Gln Ala Pro Gly Gln Ser Leu Glu Trp Met 35 40 45 Gly Arg Val Ile Pro Asn Ala Gly Gly Thr Ser Tyr Asn Gln Lys Phe 50 55 60 Lys Gly Arg Val Thr Leu Thr Val Asp Lys Ser Ile Ser Thr Ala Tyr 65 70 75 80 Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Ala Arg Glu Gly Ile Tyr Trp Trp Gly Gln Gly Thr Thr Val Thr Val 100 105 110 Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser 115 120 125 Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Lys 130 135 140 Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu 145 150 155 160 Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu 165 170 175 Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr 180 185 190 Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys Val 195 200 205 Asp Lys Lys Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro 210 215 220 Pro Cys Pro Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe 225 230 235 240 Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val 245 250 255 Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe 260 265 270 Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro 275 280 285 Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr 290 295 300 Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val 305 310 315 320 Ser Asn Lys Ala Leu Gly Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala 325 330 335 Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg 340 345 350 Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly 355 360 365 Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro 370 375 380 Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser 385 390 395 400 Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln 405 410 415 Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His 420 425 430 Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly 435 440 +ADw-210+AD4- 206 +ADw-211+AD4- 219 +ADw-212+AD4- PRT +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- P1AE0817 cadena ligera +ADw-400+AD4- 206 Asp Ile Val Met Thr Gln Thr Pro Leu Ser Leu Ser Val Thr Pro Gly 1 5 10 15 Gln Pro Ala Ser Ile Ser Cys Arg Ser Ser Gln Ser Leu Val His Ser 20 25 30 Asn Gly Asn Thr Phe Leu His Trp Tyr Leu Gln Lys Pro Gly Gln Ser 35 40 45 Pro Gln Leu Leu Ile Tyr Thr Val Ser Asn Arg Phe Ser Gly Val Pro 50 55 60 Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile 65 70 75 80 Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Phe Cys Ser Gln Thr 85 90 95 Thr His Val Pro Trp Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys 100 105 110 Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu 115 120 125 Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe 130 135 140 Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln 145 150 155 160 Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser 165 170 175 Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu 180 185 190 Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser 195 200 205 Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys 210 215 +ADw-210+AD4- 207 +ADw-211+AD4- 443 +ADw-212+AD4- PRT +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- P1AE0818 cadena pesada +ADw-400+AD4- 207 Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala 1 5 10 15 Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Ser Phe Thr Gly Tyr 20 25 30 Tyr Ile His Trp Val Arg Gln Ala Pro Gly Gln Ser Leu Glu Trp Met 35 40 45 Gly Arg Val Ile Pro Asn Ala Gly Gly Thr Ser Tyr Asn Gln Lys Phe 50 55 60 Lys Gly Arg Val Thr Leu Thr Val Asp Lys Ser Ile Ser Thr Ala Tyr 65 70 75 80 Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Ala Arg Glu Gly Ile Tyr Trp Trp Gly His Gly Thr Thr Val Thr Val 100 105 110 Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser 115 120 125 Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Lys 130 135 140 Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu 145 150 155 160 Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu 165 170 175 Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr 180 185 190 Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys Val 195 200 205 Asp Lys Lys Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro 210 215 220 Pro Cys Pro Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe 225 230 235 240 Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val 245 250 255 Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe 260 265 270 Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro 275 280 285 Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr 290 295 300 Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val 305 310 315 320 Ser Asn Lys Ala Leu Gly Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala 325 330 335 Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg 340 345 350 Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly 355 360 365 Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro 370 375 380 Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser 385 390 395 400 Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln 405 410 415 Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His 420 425 430 Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly 435 440 +ADw-210+AD4- 208 +ADw-211+AD4- 219 +ADw-212+AD4- PRT +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- P1AE0818 cadena ligera +ADw-400+AD4- 208 Asp Val Val Val Thr Gln Thr Pro Leu Ser Leu Ser Val Thr Pro Gly 1 5 10 15 Gln Pro Ala Ser Ile Ser Cys Arg Ser Ser Gln Ser Leu Val His Ser 20 25 30 Asn Gly Asn Thr Phe Leu His Trp Tyr Leu Gln Lys Pro Gly Gln Ser 35 40 45 Pro Gln Leu Leu Ile Tyr Thr Val Ser Asn Arg Phe Ser Gly Val Pro 50 55 60 Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile 65 70 75 80 Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Phe Cys Ser Gln Thr 85 90 95 Thr His Val Pro Trp Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys 100 105 110 Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu 115 120 125 Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe 130 135 140 Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln 145 150 155 160 Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser 165 170 175 Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu 180 185 190 Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser 195 200 205 Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys 210 215 +ADw-210+AD4- 209 +ADw-211+AD4- 443 +ADw-212+AD4- PRT +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- P1AE0819 cadena pesada +ADw-400+AD4- 209 Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala 1 5 10 15 Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Ser Phe Thr Gly Tyr 20 25 30 Tyr Ile His Trp Val Arg Gln Ala Pro Gly Gln Ser Leu Glu Trp Met 35 40 45 Gly Arg Val Ile Pro Asn Ala Gly Gly Thr Ser Tyr Asn Gln Lys Phe 50 55 60 Lys Gly Arg Val Thr Leu Ser Val Asp Lys Ser Ile Ser Thr Ala Tyr 65 70 75 80 Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Ala Arg Glu Gly Ile Tyr Trp Trp Gly Gln Gly Thr Thr Val Thr Val 100 105 110 Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser 115 120 125 Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Lys 130 135 140 Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu 145 150 155 160 Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu 165 170 175 Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr 180 185 190 Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys Val 195 200 205 Asp Lys Lys Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro 210 215 220 Pro Cys Pro Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe 225 230 235 240 Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val 245 250 255 Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe 260 265 270 Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro 275 280 285 Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr 290 295 300 Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val 305 310 315 320 Ser Asn Lys Ala Leu Gly Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala 325 330 335 Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg 340 345 350 Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly 355 360 365 Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro 370 375 380 Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser 385 390 395 400 Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln 405 410 415 Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His 420 425 430 Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly 435 440 +ADw-210+AD4- 210 +ADw-211+AD4- 219 +ADw-212+AD4- PRT +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- P1AE0819 cadena ligera +ADw-400+AD4- 210 Asp Val Val Val Thr Gln Thr Pro Leu Ser Leu Ser Val Thr Pro Gly 1 5 10 15 Gln Pro Ala Ser Ile Ser Cys Arg Ser Ser Gln Ser Leu Val His Ser 20 25 30 Asn Gly Asn Thr Phe Leu His Trp Tyr Leu Gln Lys Pro Gly Gln Ser 35 40 45 Pro Gln Leu Leu Ile Tyr Thr Val Ser Asn Arg Phe Ser Gly Val Pro 50 55 60 Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile 65 70 75 80 Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Phe Cys Ser Gln Thr 85 90 95 Thr His Val Pro Trp Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys 100 105 110 Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu 115 120 125 Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe 130 135 140 Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln 145 150 155 160 Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser 165 170 175 Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu 180 185 190 Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser 195 200 205 Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys 210 215 +ADw-210+AD4- 211 +ADw-211+AD4- 443 +ADw-212+AD4- PRT +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- P1AE0993 cadena pesada +ADw-400+AD4- 211 Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala 1 5 10 15 Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Ser Phe Thr Gly Tyr 20 25 30 Tyr Ile His Trp Val Arg Gln Ala Pro Gly Gln Ser Leu Glu Trp Met 35 40 45 Gly Arg Val Ile Pro Asn Ala Gly Gly Thr Ser Tyr Asn Gln Lys Phe 50 55 60 Lys Gly Arg Val Thr Leu Thr Val Asp Lys Ser Ile Ser Thr Ala Tyr 65 70 75 80 Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Ala Arg Glu Gly Ile Tyr Trp Trp Gly Gln Gly Thr Thr Val Thr Val 100 105 110 Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser 115 120 125 Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Lys 130 135 140 Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu 145 150 155 160 Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu 165 170 175 Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr 180 185 190 Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys Val 195 200 205 Asp Lys Lys Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro 210 215 220 Pro Cys Pro Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe 225 230 235 240 Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val 245 250 255 Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe 260 265 270 Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro 275 280 285 Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr 290 295 300 Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val 305 310 315 320 Ser Asn Lys Ala Leu Gly Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala 325 330 335 Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg 340 345 350 Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly 355 360 365 Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro 370 375 380 Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser 385 390 395 400 Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln 405 410 415 Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His 420 425 430 Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly 435 440 +ADw-210+AD4- 212 +ADw-211+AD4- 219 +ADw-212+AD4- PRT +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- P1AE0993 cadena ligera +ADw-400+AD4- 212 Asp Val Val Val Thr Gln Thr Pro Leu Ser Leu Ser Val Thr Pro Gly 1 5 10 15 Gln Pro Ala Ser Ile Ser Cys Arg Ser Ser Gln Ser Leu Val His Ser 20 25 30 Asn Gly Asn Thr Phe Leu His Trp Tyr Leu Gln Lys Pro Gly Gln Ser 35 40 45 Pro Gln Leu Leu Ile Tyr Thr Val Ser Asn Arg Phe Ser Gly Val Pro 50 55 60 Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile 65 70 75 80 Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Phe Cys Ser Gln Thr 85 90 95 Thr His Val Pro Trp Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys 100 105 110 Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu 115 120 125 Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe 130 135 140 Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln 145 150 155 160 Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser 165 170 175 Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu 180 185 190 Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser 195 200 205 Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys 210 215 +ADw-210+AD4- 213 +ADw-211+AD4- 443 +ADw-212+AD4- PRT +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- P1AE0996 cadena pesada +ADw-400+AD4- 213 Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala 1 5 10 15 Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Ser Phe Thr Gly Tyr 20 25 30 Tyr Ile His Trp Val Arg Gln Ala Pro Gly Gln Ser Leu Glu Trp Met 35 40 45 Gly Arg Val Ile Pro Asn Ala Gly Gly Thr Ser Tyr Asn Gln Lys Phe 50 55 60 Lys Gly Arg Val Thr Leu Thr Val Asp Lys Ser Ile Ser Thr Ala Tyr 65 70 75 80 Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Ala Arg Glu Gly Ile Tyr Trp Trp Gly Gln Gly Thr Thr Val Thr Val 100 105 110 Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser 115 120 125 Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Lys 130 135 140 Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu 145 150 155 160 Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu 165 170 175 Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr 180 185 190 Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys Val 195 200 205 Asp Lys Lys Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro 210 215 220 Pro Cys Pro Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe 225 230 235 240 Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val 245 250 255 Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe 260 265 270 Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro 275 280 285 Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr 290 295 300 Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val 305 310 315 320 Ser Asn Lys Ala Leu Gly Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala 325 330 335 Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg 340 345 350 Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly 355 360 365 Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro 370 375 380 Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser 385 390 395 400 Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln 405 410 415 Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His 420 425 430 Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly 435 440 +ADw-210+AD4- 214 +ADw-211+AD4- 219 +ADw-212+AD4- PRT +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- P1AE0996 cadena ligera +ADw-400+AD4- 214 Asp Val Val Val Thr Gln Thr Pro Leu Ser Leu Ser Val Thr Pro Gly 1 5 10 15 Gln Pro Ala Ser Ile Ser Cys Arg Ser Ser Gln Ser Leu Val His Ser 20 25 30 Asn Gly Asn Thr Phe Leu His Trp Tyr Leu Gln Lys Pro Gly Gln Ser 35 40 45 Pro Gln Leu Leu Ile Tyr Thr Val Ser Asn Arg Phe Ser Gly Val Pro 50 55 60 Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile 65 70 75 80 Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Phe Cys Ser Gln Thr 85 90 95 Thr His Val Pro Trp Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys 100 105 110 Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu 115 120 125 Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe 130 135 140 Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln 145 150 155 160 Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser 165 170 175 Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu 180 185 190 Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser 195 200 205 Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys 210 215 +ADw-210+AD4- 215 +ADw-211+AD4- 443 +ADw-212+AD4- PRT +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- P1AE0997 cadena pesada +ADw-400+AD4- 215 Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala 1 5 10 15 Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Ser Phe Thr Gly Tyr 20 25 30 Tyr Ile His Trp Val Arg Gln Ala Pro Gly Gln Ser Leu Glu Trp Met 35 40 45 Gly Arg Val Ile Pro Asn Ala Gly Gly Thr Ser Tyr Asn Gln Lys Phe 50 55 60 Lys Gly Arg Val Thr Leu Thr Val Asp Lys Ser Ile Ser Thr Ala Tyr 65 70 75 80 Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Ala Arg Glu Gly Ile Tyr Trp Trp Gly His Gly Thr Thr Val Thr Val 100 105 110 Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser 115 120 125 Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Lys 130 135 140 Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu 145 150 155 160 Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu 165 170 175 Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr 180 185 190 Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys Val 195 200 205 Asp Lys Lys Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro 210 215 220 Pro Cys Pro Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe 225 230 235 240 Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val 245 250 255 Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe 260 265 270 Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro 275 280 285 Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr 290 295 300 Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val 305 310 315 320 Ser Asn Lys Ala Leu Gly Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala 325 330 335 Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg 340 345 350 Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly 355 360 365 Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro 370 375 380 Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser 385 390 395 400 Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln 405 410 415 Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His 420 425 430 Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly 435 440 +ADw-210+AD4- 216 +ADw-211+AD4- 219 +ADw-212+AD4- PRT +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- P1AE0997 cadena ligera +ADw-400+AD4- 216 Asp Ile Val Met Thr Gln Thr Pro Leu Ser Leu Ser Val Thr Pro Gly 1 5 10 15 Gln Pro Ala Ser Ile Ser Cys Arg Ser Ser Gln Ser Leu Val His Ser 20 25 30 Asn Gly Asn Thr Phe Leu His Trp Tyr Leu Gln Lys Pro Gly Gln Ser 35 40 45 Pro Gln Leu Leu Ile Tyr Thr Val Ser Asn Arg Phe Ser Gly Val Pro 50 55 60 Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile 65 70 75 80 Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Phe Cys Ser Gln Thr 85 90 95 Thr His Val Pro Trp Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys 100 105 110 Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu 115 120 125 Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe 130 135 140 Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln 145 150 155 160 Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser 165 170 175 Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu 180 185 190 Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser 195 200 205 Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys 210 215 +ADw-210+AD4- 217 +ADw-211+AD4- 443 +ADw-212+AD4- PRT +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- P1AE0998 cadena pesada +ADw-400+AD4- 217 Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala 1 5 10 15 Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Ser Phe Thr Gly Tyr 20 25 30 Tyr Ile His Trp Val Arg Gln Ala Pro Gly Gln Ser Leu Glu Trp Met 35 40 45 Gly Arg Val Ile Pro Asn Ala Gly Gly Thr Ser Tyr Asn Gln Lys Phe 50 55 60 Lys Gly Arg Val Thr Leu Thr Val Asp Lys Ser Ile Ser Thr Ala Tyr 65 70 75 80 Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Ala Arg Glu Gly Ile Tyr Trp Trp Gly His Gly Thr Thr Val Thr Val 100 105 110 Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser 115 120 125 Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Lys 130 135 140 Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu 145 150 155 160 Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu 165 170 175 Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr 180 185 190 Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys Val 195 200 205 Asp Lys Lys Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro 210 215 220 Pro Cys Pro Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe 225 230 235 240 Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val 245 250 255 Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe 260 265 270 Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro 275 280 285 Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr 290 295 300 Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val 305 310 315 320 Ser Asn Lys Ala Leu Gly Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala 325 330 335 Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg 340 345 350 Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly 355 360 365 Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro 370 375 380 Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser 385 390 395 400 Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln 405 410 415 Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His 420 425 430 Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly 435 440 +ADw-210+AD4- 218 +ADw-211+AD4- 219 +ADw-212+AD4- PRT +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- P1AE0998 cadena ligera +ADw-400+AD4- 218 Asp Val Val Val Thr Gln Thr Pro Leu Ser Leu Ser Val Thr Pro Gly 1 5 10 15 Gln Pro Ala Ser Ile Ser Cys Arg Ser Ser Gln Ser Leu Val His Ser 20 25 30 Asn Gly Asn Thr Phe Leu His Trp Tyr Leu Gln Lys Pro Gly Gln Ser 35 40 45 Pro Gln Leu Leu Ile Tyr Thr Val Ser Asn Arg Phe Ser Gly Val Pro 50 55 60 Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile 65 70 75 80 Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Phe Cys Ser Gln Thr 85 90 95 Thr His Val Pro Trp Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys 100 105 110 Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu 115 120 125 Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe 130 135 140 Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln 145 150 155 160 Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser 165 170 175 Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu 180 185 190 Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser 195 200 205 Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys 210 215 +ADw-210+AD4- 219 +ADw-211+AD4- 443 +ADw-212+AD4- PRT +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- P1AE0999 cadena pesada +ADw-400+AD4- 219 Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala 1 5 10 15 Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Ser Phe Thr Gly Tyr 20 25 30 Tyr Ile His Trp Val Arg Gln Ala Pro Gly Gln Ser Leu Glu Trp Met 35 40 45 Gly Arg Val Ile Pro Asn Ala Gly Gly Thr Ser Tyr Asn Gln Lys Phe 50 55 60 Lys Gly Arg Val Thr Leu Ser Val Asp Lys Ser Ile Ser Thr Ala Tyr 65 70 75 80 Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Ala Arg Glu Gly Ile Tyr Trp Trp Gly Gln Gly Thr Thr Val Thr Val 100 105 110 Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser 115 120 125 Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Lys 130 135 140 Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu 145 150 155 160 Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu 165 170 175 Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr 180 185 190 Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys Val 195 200 205 Asp Lys Lys Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro 210 215 220 Pro Cys Pro Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe 225 230 235 240 Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val 245 250 255 Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe 260 265 270 Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro 275 280 285 Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr 290 295 300 Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val 305 310 315 320 Ser Asn Lys Ala Leu Gly Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala 325 330 335 Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg 340 345 350 Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly 355 360 365 Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro 370 375 380 Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser 385 390 395 400 Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln 405 410 415 Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His 420 425 430 Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly 435 440 +ADw-210+AD4- 220 +ADw-211+AD4- 219 +ADw-212+AD4- PRT +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- P1AE0999 cadena ligera +ADw-400+AD4- 220 Asp Ile Val Met Thr Gln Thr Pro Leu Ser Leu Ser Val Thr Pro Gly 1 5 10 15 Gln Pro Ala Ser Ile Ser Cys Arg Ser Ser Gln Ser Leu Val His Ser 20 25 30 Asn Gly Asn Thr Phe Leu His Trp Tyr Leu Gln Lys Pro Gly Gln Ser 35 40 45 Pro Gln Leu Leu Ile Tyr Thr Val Ser Asn Arg Phe Ser Gly Val Pro 50 55 60 Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile 65 70 75 80 Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Phe Cys Ser Gln Thr 85 90 95 Thr His Val Pro Trp Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys 100 105 110 Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu 115 120 125 Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe 130 135 140 Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln 145 150 155 160 Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser 165 170 175 Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu 180 185 190 Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser 195 200 205 Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys 210 215 +ADw-210+AD4- 221 +ADw-211+AD4- 443 +ADw-212+AD4- PRT +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- P1AE1000 cadena pesada +ADw-400+AD4- 221 Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala 1 5 10 15 Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Ser Phe Thr Gly Tyr 20 25 30 Tyr Ile His Trp Val Arg Gln Ala Pro Gly Gln Ser Leu Glu Trp Met 35 40 45 Gly Arg Val Ile Pro Asn Ala Gly Gly Thr Ser Tyr Asn Gln Lys Phe 50 55 60 Lys Gly Arg Val Thr Leu Ser Val Asp Lys Ser Ile Ser Thr Ala Tyr 65 70 75 80 Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Ala Arg Glu Gly Ile Tyr Trp Trp Gly Gln Gly Thr Thr Val Thr Val 100 105 110 Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser 115 120 125 Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Lys 130 135 140 Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu 145 150 155 160 Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu 165 170 175 Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr 180 185 190 Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys Val 195 200 205 Asp Lys Lys Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro 210 215 220 Pro Cys Pro Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe 225 230 235 240 Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val 245 250 255 Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe 260 265 270 Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro 275 280 285 Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr 290 295 300 Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val 305 310 315 320 Ser Asn Lys Ala Leu Gly Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala 325 330 335 Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg 340 345 350 Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly 355 360 365 Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro 370 375 380 Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser 385 390 395 400 Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln 405 410 415 Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His 420 425 430 Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly 435 440 +ADw-210+AD4- 222 +ADw-211+AD4- 219 +ADw-212+AD4- PRT +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- P1AE1000 cadena ligera +ADw-400+AD4- 222 Asp Val Val Val Thr Gln Thr Pro Leu Ser Leu Ser Val Thr Pro Gly 1 5 10 15 Gln Pro Ala Ser Ile Ser Cys Arg Ser Ser Gln Ser Leu Val His Ser 20 25 30 Asn Gly Asn Thr Phe Leu His Trp Tyr Leu Gln Lys Pro Gly Gln Ser 35 40 45 Pro Gln Leu Leu Ile Tyr Thr Val Ser Asn Arg Phe Ser Gly Val Pro 50 55 60 Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile 65 70 75 80 Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Phe Cys Ser Gln Thr 85 90 95 Thr His Val Pro Trp Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys 100 105 110 Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu 115 120 125 Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe 130 135 140 Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln 145 150 155 160 Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser 165 170 175 Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu 180 185 190 Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser 195 200 205 Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys 210 215 +ADw-210+AD4- 223 +ADw-211+AD4- 443 +ADw-212+AD4- PRT +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- P1AE1001 cadena pesada +ADw-400+AD4- 223 Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala 1 5 10 15 Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Ser Phe Thr Gly Tyr 20 25 30 Tyr Ile His Trp Val Arg Gln Ala Pro Gly Gln Ser Leu Glu Trp Met 35 40 45 Gly Arg Val Ile Pro Asn Ala Gly Gly Thr Ser Tyr Asn Gln Lys Phe 50 55 60 Lys Gly Arg Val Thr Leu Thr Val Asp Lys Ser Ile Ser Thr Ala Tyr 65 70 75 80 Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Ala Arg Glu Gly Ile Tyr Trp Trp Gly Gln Gly Thr Thr Val Thr Val 100 105 110 Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser 115 120 125 Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Lys 130 135 140 Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu 145 150 155 160 Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu 165 170 175 Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr 180 185 190 Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys Val 195 200 205 Asp Lys Lys Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro 210 215 220 Pro Cys Pro Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe 225 230 235 240 Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val 245 250 255 Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe 260 265 270 Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro 275 280 285 Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr 290 295 300 Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val 305 310 315 320 Ser Asn Lys Ala Leu Gly Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala 325 330 335 Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg 340 345 350 Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly 355 360 365 Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro 370 375 380 Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser 385 390 395 400 Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln 405 410 415 Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His 420 425 430 Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly 435 440 +ADw-210+AD4- 224 +ADw-211+AD4- 219 +ADw-212+AD4- PRT +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- P1AE1001 cadena ligera +ADw-400+AD4- 224 Asp Ile Val Val Thr Gln Thr Pro Leu Ser Leu Ser Val Thr Pro Gly 1 5 10 15 Gln Pro Ala Ser Ile Ser Cys Arg Ser Ser Gln Ser Leu Val His Ser 20 25 30 Asn Gly Asn Thr Phe Leu His Trp Tyr Leu Gln Lys Pro Gly Gln Ser 35 40 45 Pro Gln Leu Leu Ile Tyr Thr Val Ser Asn Arg Phe Ser Gly Val Pro 50 55 60 Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile 65 70 75 80 Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Phe Cys Ser Gln Thr 85 90 95 Thr His Val Pro Trp Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys 100 105 110 Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu 115 120 125 Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe 130 135 140 Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln 145 150 155 160 Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser 165 170 175 Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu 180 185 190 Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser 195 200 205 Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys 210 215 +ADw-210+AD4- 225 +ADw-211+AD4- 443 +ADw-212+AD4- PRT +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- P1AE1002 cadena pesada +ADw-400+AD4- 225 Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala 1 5 10 15 Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Ser Phe Thr Gly Tyr 20 25 30 Tyr Ile His Trp Val Arg Gln Ala Pro Gly Lys Ser Leu Glu Trp Met 35 40 45 Gly Arg Val Ile Pro Asn Ala Gly Gly Thr Ser Tyr Asn Gln Lys Phe 50 55 60 Lys Gly Arg Val Thr Leu Thr Val Asp Lys Ser Ile Ser Thr Ala Tyr 65 70 75 80 Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Ala Arg Glu Gly Ile Tyr Trp Trp Gly Gln Gly Thr Thr Val Thr Val 100 105 110 Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser 115 120 125 Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Lys 130 135 140 Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu 145 150 155 160 Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu 165 170 175 Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr 180 185 190 Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys Val 195 200 205 Asp Lys Lys Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro 210 215 220 Pro Cys Pro Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe 225 230 235 240 Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val 245 250 255 Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe 260 265 270 Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro 275 280 285 Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr 290 295 300 Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val 305 310 315 320 Ser Asn Lys Ala Leu Gly Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala 325 330 335 Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg 340 345 350 Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly 355 360 365 Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro 370 375 380 Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser 385 390 395 400 Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln 405 410 415 Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His 420 425 430 Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly 435 440 +ADw-210+AD4- 226 +ADw-211+AD4- 219 +ADw-212+AD4- PRT +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- P1AE1002 cadena ligera +ADw-400+AD4- 226 Asp Ile Val Met Thr Gln Thr Pro Leu Ser Leu Ser Val Thr Pro Gly 1 5 10 15 Gln Pro Ala Ser Ile Ser Cys Arg Ser Ser Gln Ser Leu Val His Ser 20 25 30 Asn Gly Asn Thr Phe Leu His Trp Tyr Leu Gln Lys Pro Gly Gln Ser 35 40 45 Pro Gln Leu Leu Ile Tyr Thr Val Ser Asn Arg Phe Ser Gly Val Pro 50 55 60 Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile 65 70 75 80 Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Phe Cys Ser Gln Thr 85 90 95 Thr His Val Pro Trp Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys 100 105 110 Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu 115 120 125 Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe 130 135 140 Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln 145 150 155 160 Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser 165 170 175 Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu 180 185 190 Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser 195 200 205 Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys 210 215 +ADw-210+AD4- 227 +ADw-211+AD4- 443 +ADw-212+AD4- PRT +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- P1AE1003 cadena pesada +ADw-400+AD4- 227 Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala 1 5 10 15 Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Ser Phe Thr Gly Tyr 20 25 30 Tyr Ile His Trp Val Arg Gln Ala Pro Gly Lys Ser Leu Glu Trp Met 35 40 45 Gly Arg Val Ile Pro Asn Ala Gly Gly Thr Ser Tyr Asn Gln Lys Phe 50 55 60 Lys Gly Arg Val Thr Leu Thr Val Asp Lys Ser Ile Ser Thr Ala Tyr 65 70 75 80 Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Ala Arg Glu Gly Ile Tyr Trp Trp Gly Gln Gly Thr Thr Val Thr Val 100 105 110 Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser 115 120 125 Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Lys 130 135 140 Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu 145 150 155 160 Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu 165 170 175 Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr 180 185 190 Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys Val 195 200 205 Asp Lys Lys Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro 210 215 220 Pro Cys Pro Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe 225 230 235 240 Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val 245 250 255 Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe 260 265 270 Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro 275 280 285 Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr 290 295 300 Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val 305 310 315 320 Ser Asn Lys Ala Leu Gly Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala 325 330 335 Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg 340 345 350 Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly 355 360 365 Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro 370 375 380 Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser 385 390 395 400 Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln 405 410 415 Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His 420 425 430 Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly 435 440 +ADw-210+AD4- 228 +ADw-211+AD4- 219 +ADw-212+AD4- PRT +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- P1AE1003 cadena ligera +ADw-400+AD4- 228 Asp Ile Val Val Thr Gln Thr Pro Leu Ser Leu Ser Val Thr Pro Gly 1 5 10 15 Gln Pro Ala Ser Ile Ser Cys Arg Ser Ser Gln Ser Leu Val His Ser 20 25 30 Asn Gly Asn Thr Phe Leu His Trp Tyr Leu Gln Lys Pro Gly Gln Ser 35 40 45 Pro Gln Leu Leu Ile Tyr Thr Val Ser Asn Arg Phe Ser Gly Val Pro 50 55 60 Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile 65 70 75 80 Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Phe Cys Ser Gln Thr 85 90 95 Thr His Val Pro Trp Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys 100 105 110 Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu 115 120 125 Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe 130 135 140 Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln 145 150 155 160 Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser 165 170 175 Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu 180 185 190 Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser 195 200 205 Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys 210 215 +ADw-210+AD4- 229 +ADw-211+AD4- 443 +ADw-212+AD4- PRT +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- P1AE1004 cadena pesada +ADw-400+AD4- 229 Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala 1 5 10 15 Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Ser Phe Thr Gly Tyr 20 25 30 Tyr Ile His Trp Val Arg Gln Ala Pro Gly Lys Ser Leu Glu Trp Met 35 40 45 Gly Arg Val Ile Pro Asn Ala Gly Gly Thr Ser Tyr Asn Gln Lys Phe 50 55 60 Lys Gly Arg Val Thr Leu Thr Val Asp Lys Ser Ile Ser Thr Ala Tyr 65 70 75 80 Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Ala Arg Glu Gly Ile Tyr Trp Trp Gly Gln Gly Thr Thr Val Thr Val 100 105 110 Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser 115 120 125 Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Lys 130 135 140 Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu 145 150 155 160 Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu 165 170 175 Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr 180 185 190 Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys Val 195 200 205 Asp Lys Lys Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro 210 215 220 Pro Cys Pro Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe 225 230 235 240 Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val 245 250 255 Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe 260 265 270 Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro 275 280 285 Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr 290 295 300 Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val 305 310 315 320 Ser Asn Lys Ala Leu Gly Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala 325 330 335 Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg 340 345 350 Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly 355 360 365 Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro 370 375 380 Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser 385 390 395 400 Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln 405 410 415 Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His 420 425 430 Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly 435 440 +ADw-210+AD4- 230 +ADw-211+AD4- 219 +ADw-212+AD4- PRT +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- P1AE1004 cadena ligera +ADw-400+AD4- 230 Asp Val Val Val Thr Gln Thr Pro Leu Ser Leu Ser Val Thr Pro Gly 1 5 10 15 Gln Pro Ala Ser Ile Ser Cys Arg Ser Ser Gln Ser Leu Val His Ser 20 25 30 Asn Gly Asn Thr Phe Leu His Trp Tyr Leu Gln Lys Pro Gly Gln Ser 35 40 45 Pro Gln Leu Leu Ile Tyr Thr Val Ser Asn Arg Phe Ser Gly Val Pro 50 55 60 Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile 65 70 75 80 Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Phe Cys Ser Gln Thr 85 90 95 Thr His Val Pro Trp Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys 100 105 110 Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu 115 120 125 Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe 130 135 140 Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln 145 150 155 160 Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser 165 170 175 Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu 180 185 190 Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser 195 200 205 Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys 210 215 +ADw-210+AD4- 231 +ADw-211+AD4- 443 +ADw-212+AD4- PRT +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- P1AE1005 cadena pesada +ADw-400+AD4- 231 Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala 1 5 10 15 Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Ser Phe Thr Gly Tyr 20 25 30 Tyr Ile His Trp Val Arg Gln Ala Pro Gly Lys Ser Leu Glu Trp Met 35 40 45 Gly Arg Val Ile Pro Asn Ala Gly Gly Thr Ser Tyr Asn Gln Lys Phe 50 55 60 Lys Gly Arg Val Thr Leu Thr Val Asp Lys Ser Ile Ser Thr Ala Tyr 65 70 75 80 Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Ala Arg Glu Gly Ile Tyr Trp Trp Gly Gln Gly Thr Thr Val Thr Val 100 105 110 Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser 115 120 125 Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Lys 130 135 140 Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu 145 150 155 160 Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu 165 170 175 Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr 180 185 190 Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys Val 195 200 205 Asp Lys Lys Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro 210 215 220 Pro Cys Pro Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe 225 230 235 240 Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val 245 250 255 Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe 260 265 270 Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro 275 280 285 Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr 290 295 300 Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val 305 310 315 320 Ser Asn Lys Ala Leu Gly Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala 325 330 335 Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg 340 345 350 Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly 355 360 365 Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro 370 375 380 Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser 385 390 395 400 Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln 405 410 415 Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His 420 425 430 Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly 435 440 +ADw-210+AD4- 232 +ADw-211+AD4- 219 +ADw-212+AD4- PRT +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- P1AE1005 cadena ligera +ADw-400+AD4- 232 Asp Val Val Val Thr Gln Thr Pro Leu Ser Leu Ser Val Thr Pro Gly 1 5 10 15 Gln Pro Ala Ser Ile Ser Cys Arg Ser Ser Gln Ser Leu Val His Ser 20 25 30 Asn Gly Asn Thr Phe Leu His Trp Tyr Leu Gln Lys Pro Gly Gln Ser 35 40 45 Pro Gln Leu Leu Ile Tyr Thr Val Ser Asn Arg Phe Ser Gly Val Pro 50 55 60 Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile 65 70 75 80 Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Phe Cys Ser Gln Thr 85 90 95 Thr His Val Pro Trp Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys 100 105 110 Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu 115 120 125 Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe 130 135 140 Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln 145 150 155 160 Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser 165 170 175 Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu 180 185 190 Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser 195 200 205 Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys 210 215 +ADw-210+AD4- 233 +ADw-211+AD4- 443 +ADw-212+AD4- PRT +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- P1AE1006 cadena pesada +ADw-400+AD4- 233 Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala 1 5 10 15 Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Ser Phe Thr Gly Tyr 20 25 30 Tyr Ile His Trp Val Arg Gln Ala Pro Gly Gln Ser Leu Glu Trp Met 35 40 45 Gly Arg Val Ile Pro Asn Ala Gly Gly Thr Ser Tyr Asn Gln Lys Phe 50 55 60 Lys Gly Arg Val Thr Leu Thr Val Asp Lys Ser Ile Ser Thr Ala Tyr 65 70 75 80 Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Ala Arg Glu Gly Ile Tyr Trp Trp Gly His Gly Thr Thr Val Thr Val 100 105 110 Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser 115 120 125 Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Lys 130 135 140 Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu 145 150 155 160 Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu 165 170 175 Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr 180 185 190 Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys Val 195 200 205 Asp Lys Lys Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro 210 215 220 Pro Cys Pro Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe 225 230 235 240 Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val 245 250 255 Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe 260 265 270 Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro 275 280 285 Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr 290 295 300 Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val 305 310 315 320 Ser Asn Lys Ala Leu Gly Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala 325 330 335 Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg 340 345 350 Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly 355 360 365 Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro 370 375 380 Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser 385 390 395 400 Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln 405 410 415 Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His 420 425 430 Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly 435 440 +ADw-210+AD4- 234 +ADw-211+AD4- 219 +ADw-212+AD4- PRT +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- P1AE1006 cadena ligera +ADw-400+AD4- 234 Asp Ile Val Val Thr Gln Thr Pro Leu Ser Leu Ser Val Thr Pro Gly 1 5 10 15 Gln Pro Ala Ser Ile Ser Cys Arg Ser Ser Gln Ser Leu Val His Ser 20 25 30 Asn Gly Asn Thr Phe Leu His Trp Tyr Leu Gln Lys Pro Gly Gln Ser 35 40 45 Pro Gln Leu Leu Ile Tyr Thr Val Ser Asn Arg Phe Ser Gly Val Pro 50 55 60 Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile 65 70 75 80 Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Phe Cys Ser Gln Thr 85 90 95 Thr His Val Pro Trp Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys 100 105 110 Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu 115 120 125 Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe 130 135 140 Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln 145 150 155 160 Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser 165 170 175 Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu 180 185 190 Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser 195 200 205 Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys 210 215 +ADw-210+AD4- 235 +ADw-211+AD4- 443 +ADw-212+AD4- PRT +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- P1AE1007 cadena pesada +ADw-400+AD4- 235 Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala 1 5 10 15 Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Ser Phe Thr Gly Tyr 20 25 30 Tyr Ile His Trp Val Arg Gln Ala Pro Gly Gln Ser Leu Glu Trp Met 35 40 45 Gly Arg Val Ile Pro Asn Ala Gly Gly Thr Ser Tyr Asn Gln Lys Phe 50 55 60 Lys Gly Arg Val Thr Leu Ser Val Asp Lys Ser Ile Ser Thr Ala Tyr 65 70 75 80 Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Ala Arg Glu Gly Ile Tyr Trp Trp Gly Gln Gly Thr Thr Val Thr Val 100 105 110 Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser 115 120 125 Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Lys 130 135 140 Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu 145 150 155 160 Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu 165 170 175 Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr 180 185 190 Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys Val 195 200 205 Asp Lys Lys Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro 210 215 220 Pro Cys Pro Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe 225 230 235 240 Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val 245 250 255 Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe 260 265 270 Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro 275 280 285 Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr 290 295 300 Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val 305 310 315 320 Ser Asn Lys Ala Leu Gly Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala 325 330 335 Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg 340 345 350 Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly 355 360 365 Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro 370 375 380 Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser 385 390 395 400 Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln 405 410 415 Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His 420 425 430 Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly 435 440 +ADw-210+AD4- 236 +ADw-211+AD4- 219 +ADw-212+AD4- PRT +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- P1AE1007 cadena ligera +ADw-400+AD4- 236 Asp Ile Val Val Thr Gln Thr Pro Leu Ser Leu Ser Val Thr Pro Gly 1 5 10 15 Gln Pro Ala Ser Ile Ser Cys Arg Ser Ser Gln Ser Leu Val His Ser 20 25 30 Asn Gly Asn Thr Phe Leu His Trp Tyr Leu Gln Lys Pro Gly Gln Ser 35 40 45 Pro Gln Leu Leu Ile Tyr Thr Val Ser Asn Arg Phe Ser Gly Val Pro 50 55 60 Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile 65 70 75 80 Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Phe Cys Ser Gln Thr 85 90 95 Thr His Val Pro Trp Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys 100 105 110 Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu 115 120 125 Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe 130 135 140 Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln 145 150 155 160 Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser 165 170 175 Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu 180 185 190 Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser 195 200 205 Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys 210 215 +ADw-210+AD4- 237 +ADw-211+AD4- 443 +ADw-212+AD4- PRT +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- P1AE1125 cadena pesada +ADw-400+AD4- 237 Glu Val Gln Leu Leu Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 1 5 10 15 Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Tyr Ser Phe Thr Gly Tyr 20 25 30 Tyr Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45 Gly Arg Val Ile Pro Asn Ala Gly Gly Thr Ser Tyr Asn Gln Lys Phe 50 55 60 Lys Gly Arg Phe Thr Ile Ser Val Asp Asn Ser Lys Asn Thr Ala Tyr 65 70 75 80 Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Ala Arg Glu Gly Ile Tyr Trp Trp Gly Gln Gly Thr Thr Val Thr Val 100 105 110 Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser 115 120 125 Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Lys 130 135 140 Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu 145 150 155 160 Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu 165 170 175 Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr 180 185 190 Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys Val 195 200 205 Asp Lys Lys Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro 210 215 220 Pro Cys Pro Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe 225 230 235 240 Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val 245 250 255 Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe 260 265 270 Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro 275 280 285 Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr 290 295 300 Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val 305 310 315 320 Ser Asn Lys Ala Leu Gly Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala 325 330 335 Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg 340 345 350 Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly 355 360 365 Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro 370 375 380 Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser 385 390 395 400 Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln 405 410 415 Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His 420 425 430 Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly 435 440 +ADw-210+AD4- 238 +ADw-211+AD4- 219 +ADw-212+AD4- PRT +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- P1AE1125 cadena ligera +ADw-400+AD4- 238 Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 1 5 10 15 Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Ser Leu Val His Ser 20 25 30 Asn Gly Asn Thr Phe Leu His Trp Tyr Gln Gln Lys Pro Gly Lys Ala 35 40 45 Pro Lys Leu Leu Ile Tyr Thr Val Ser Asn Arg Phe Ser Gly Val Pro 50 55 60 Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile 65 70 75 80 Ser Ser Leu Gln Pro Glu Asp Phe Ala Thr Tyr Phe Cys Ser Gln Thr 85 90 95 Thr His Val Pro Trp Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys 100 105 110 Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu 115 120 125 Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe 130 135 140 Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln 145 150 155 160 Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser 165 170 175 Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu 180 185 190 Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser 195 200 205 Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys 210 215 +ADw-210+AD4- 239 +ADw-211+AD4- 443 +ADw-212+AD4- PRT +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- P1AE1126 cadena pesada +ADw-400+AD4- 239 Glu Val Gln Leu Leu Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 1 5 10 15 Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Tyr Ser Phe Thr Gly Tyr 20 25 30 Tyr Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45 Gly Arg Val Ile Pro Asn Ala Gly Gly Thr Ser Tyr Asn Gln Lys Phe 50 55 60 Lys Gly Arg Phe Thr Ile Ser Val Asp Asn Ser Lys Asn Thr Ala Tyr 65 70 75 80 Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Ala Arg Glu Gly Ile Tyr Trp Trp Gly Gln Gly Thr Thr Val Thr Val 100 105 110 Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser 115 120 125 Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Lys 130 135 140 Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu 145 150 155 160 Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu 165 170 175 Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr 180 185 190 Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys Val 195 200 205 Asp Lys Lys Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro 210 215 220 Pro Cys Pro Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe 225 230 235 240 Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val 245 250 255 Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe 260 265 270 Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro 275 280 285 Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr 290 295 300 Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val 305 310 315 320 Ser Asn Lys Ala Leu Gly Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala 325 330 335 Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg 340 345 350 Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly 355 360 365 Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro 370 375 380 Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser 385 390 395 400 Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln 405 410 415 Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His 420 425 430 Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly 435 440 +ADw-210+AD4- 240 +ADw-211+AD4- 219 +ADw-212+AD4- PRT +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- P1AE1126 cadena ligera +ADw-400+AD4- 240 Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 1 5 10 15 Asp Arg Val Thr Ile Thr Cys Arg Ser Ser Gln Ser Ile Val His Ser 20 25 30 Asn Gly Asn Thr Phe Leu His Trp Tyr Gln Gln Lys Pro Gly Lys Ala 35 40 45 Pro Lys Leu Leu Ile Tyr Thr Val Ser Asn Arg Phe Ser Gly Val Pro 50 55 60 Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile 65 70 75 80 Ser Ser Leu Gln Pro Glu Asp Phe Ala Thr Tyr Phe Cys Ser Gln Thr 85 90 95 Thr His Val Pro Trp Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys 100 105 110 Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu 115 120 125 Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe 130 135 140 Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln 145 150 155 160 Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser 165 170 175 Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu 180 185 190 Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser 195 200 205 Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys 210 215 +ADw-210+AD4- 241 +ADw-211+AD4- 443 +ADw-212+AD4- PRT +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- P1AE1135 cadena pesada +ADw-400+AD4- 241 Glu Val Gln Leu Leu Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 1 5 10 15 Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Tyr Ser Phe Thr Gly Tyr 20 25 30 Tyr Ile His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45 Gly Arg Val Ile Pro Asn Ala Gly Gly Thr Ser Tyr Asn Gln Lys Val 50 55 60 Lys Gly Arg Phe Thr Ile Ser Val Asp Asn Ser Lys Asn Thr Ala Tyr 65 70 75 80 Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Ala Arg Glu Gly Ile Tyr Trp Trp Gly Gln Gly Thr Thr Val Thr Val 100 105 110 Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser 115 120 125 Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Lys 130 135 140 Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu 145 150 155 160 Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu 165 170 175 Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr 180 185 190 Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys Val 195 200 205 Asp Lys Lys Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro 210 215 220 Pro Cys Pro Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe 225 230 235 240 Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val 245 250 255 Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe 260 265 270 Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro 275 280 285 Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr 290 295 300 Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val 305 310 315 320 Ser Asn Lys Ala Leu Gly Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala 325 330 335 Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg 340 345 350 Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly 355 360 365 Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro 370 375 380 Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser 385 390 395 400 Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln 405 410 415 Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His 420 425 430 Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly 435 440 +ADw-210+AD4- 242 +ADw-211+AD4- 219 +ADw-212+AD4- PRT +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- P1AE1135 cadena ligera +ADw-400+AD4- 242 Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 1 5 10 15 Asp Arg Val Thr Ile Thr Cys Arg Ser Ser Gln Ser Ile Val His Ser 20 25 30 Asn Gly Asn Thr Phe Leu His Trp Tyr Gln Gln Lys Pro Gly Lys Ala 35 40 45 Pro Lys Leu Leu Ile Tyr Thr Val Ser Asn Arg Phe Ser Gly Val Pro 50 55 60 Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile 65 70 75 80 Ser Ser Leu Gln Pro Glu Asp Phe Ala Thr Tyr Phe Cys Ser Gln Thr 85 90 95 Thr His Val Pro Trp Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys 100 105 110 Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu 115 120 125 Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe 130 135 140 Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln 145 150 155 160 Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser 165 170 175 Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu 180 185 190 Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser 195 200 205 Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys 210 215 +ADw-210+AD4- 243 +ADw-211+AD4- 219 +ADw-212+AD4- PRT +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- VL2a (CD40) cadena ligera (cargado) +ADw-400+AD4- 243 Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 1 5 10 15 Asp Arg Val Thr Ile Thr Cys Arg Ser Ser Gln Ser Leu Val His Ser 20 25 30 Asn Gly Asn Thr Phe Leu His Trp Tyr Gln Gln Lys Pro Gly Lys Ala 35 40 45 Pro Lys Leu Leu Ile Tyr Thr Val Ser Asn Arg Phe Ser Gly Val Pro 50 55 60 Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile 65 70 75 80 Ser Ser Leu Gln Pro Glu Asp Phe Ala Thr Tyr Phe Cys Ser Gln Thr 85 90 95 Thr His Val Pro Trp Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys 100 105 110 Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Arg 115 120 125 Lys Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe 130 135 140 Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln 145 150 155 160 Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser 165 170 175 Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu 180 185 190 Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser 195 200 205 Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys 210 215 +ADw-210+AD4- 244 +ADw-211+AD4- 904 +ADw-212+AD4- PRT +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- VH2a (CD40) (VHCH1 cargado+AF8-VH2a (CD40) (VHCH1 cargado)-Fc pomo+AF8-PGLALA+AF8-28H1 (VLCH1) +ADw-400+AD4- 244 Glu Val Gln Leu Leu Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 1 5 10 15 Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Tyr Ser Phe Thr Gly Tyr 20 25 30 Tyr Ile His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45 Gly Arg Val Ile Pro Asn Ala Gly Gly Thr Ser Tyr Asn Gln Lys Phe 50 55 60 Lys Gly Arg Phe Thr Ile Ser Val Asp Asn Ser Lys Asn Thr Ala Tyr 65 70 75 80 Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Ala Arg Glu Gly Ile Tyr Trp Trp Gly Gln Gly Thr Thr Val Thr Val 100 105 110 Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser 115 120 125 Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Glu 130 135 140 Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu 145 150 155 160 Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu 165 170 175 Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr 180 185 190 Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys Val 195 200 205 Asp Glu Lys Val Glu Pro Lys Ser Cys Asp Gly Gly Gly Gly Ser Gly 210 215 220 Gly Gly Gly Ser Glu Val Gln Leu Leu Glu Ser Gly Gly Gly Leu Val 225 230 235 240 Gln Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Tyr Ser 245 250 255 Phe Thr Gly Tyr Tyr Ile His Trp Val Arg Gln Ala Pro Gly Lys Gly 260 265 270 Leu Glu Trp Val Gly Arg Val Ile Pro Asn Ala Gly Gly Thr Ser Tyr 275 280 285 Asn Gln Lys Phe Lys Gly Arg Phe Thr Ile Ser Val Asp Asn Ser Lys 290 295 300 Asn Thr Ala Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala 305 310 315 320 Val Tyr Tyr Cys Ala Arg Glu Gly Ile Tyr Trp Trp Gly Gln Gly Thr 325 330 335 Thr Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro 340 345 350 Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly 355 360 365 Cys Leu Val Glu Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn 370 375 380 Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln 385 390 395 400 Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser 405 410 415 Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser 420 425 430 Asn Thr Lys Val Asp Glu Lys Val Glu Pro Lys Ser Cys Asp Lys Thr 435 440 445 His Thr Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly Gly Pro Ser 450 455 460 Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg 465 470 475 480 Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro 485 490 495 Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala 500 505 510 Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val 515 520 525 Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr 530 535 540 Lys Cys Lys Val Ser Asn Lys Ala Leu Gly Ala Pro Ile Glu Lys Thr 545 550 555 560 Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu 565 570 575 Pro Pro Cys Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Trp Cys 580 585 590 Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser 595 600 605 Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp 610 615 620 Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser 625 630 635 640 Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala 645 650 655 Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Gly 660 665 670 Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly 675 680 685 Gly Gly Ser Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu 690 695 700 Ser Pro Gly Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val 705 710 715 720 Ser Arg Ser Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro 725 730 735 Arg Leu Leu Ile Ile Gly Ala Ser Thr Arg Ala Thr Gly Ile Pro Asp 740 745 750 Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser 755 760 765 Arg Leu Glu Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Gly Gln 770 775 780 Val Ile Pro Pro Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Ser 785 790 795 800 Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser Ser 805 810 815 Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Lys Asp 820 825 830 Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr 835 840 845 Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr 850 855 860 Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Gln 865 870 875 880 Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys Val Asp 885 890 895 Lys Lys Val Glu Pro Lys Ser Cys 900 +ADw-210+AD4- 245 +ADw-211+AD4- 671 +ADw-212+AD4- PRT +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- VH2a (CD40) (VHCH1 cargado+AF8-VH2a (CD40) (VHCH1 cargado)-Fc agujero+AF8-PGLALA +ADw-400+AD4- 245 Glu Val Gln Leu Leu Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 1 5 10 15 Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Tyr Ser Phe Thr Gly Tyr 20 25 30 Tyr Ile His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45 Gly Arg Val Ile Pro Asn Ala Gly Gly Thr Ser Tyr Asn Gln Lys Phe 50 55 60 Lys Gly Arg Phe Thr Ile Ser Val Asp Asn Ser Lys Asn Thr Ala Tyr 65 70 75 80 Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Ala Arg Glu Gly Ile Tyr Trp Trp Gly Gln Gly Thr Thr Val Thr Val 100 105 110 Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser 115 120 125 Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Glu 130 135 140 Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu 145 150 155 160 Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu 165 170 175 Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr 180 185 190 Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys Val 195 200 205 Asp Glu Lys Val Glu Pro Lys Ser Cys Asp Gly Gly Gly Gly Ser Gly 210 215 220 Gly Gly Gly Ser Glu Val Gln Leu Leu Glu Ser Gly Gly Gly Leu Val 225 230 235 240 Gln Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Tyr Ser 245 250 255 Phe Thr Gly Tyr Tyr Ile His Trp Val Arg Gln Ala Pro Gly Lys Gly 260 265 270 Leu Glu Trp Val Gly Arg Val Ile Pro Asn Ala Gly Gly Thr Ser Tyr 275 280 285 Asn Gln Lys Phe Lys Gly Arg Phe Thr Ile Ser Val Asp Asn Ser Lys 290 295 300 Asn Thr Ala Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala 305 310 315 320 Val Tyr Tyr Cys Ala Arg Glu Gly Ile Tyr Trp Trp Gly Gln Gly Thr 325 330 335 Thr Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro 340 345 350 Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly 355 360 365 Cys Leu Val Glu Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn 370 375 380 Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln 385 390 395 400 Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser 405 410 415 Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser 420 425 430 Asn Thr Lys Val Asp Glu Lys Val Glu Pro Lys Ser Cys Asp Lys Thr 435 440 445 His Thr Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly Gly Pro Ser 450 455 460 Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg 465 470 475 480 Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro 485 490 495 Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala 500 505 510 Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val 515 520 525 Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr 530 535 540 Lys Cys Lys Val Ser Asn Lys Ala Leu Gly Ala Pro Ile Glu Lys Thr 545 550 555 560 Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Cys Thr Leu 565 570 575 Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Ser Cys 580 585 590 Ala Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser 595 600 605 Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp 610 615 620 Ser Asp Gly Ser Phe Phe Leu Val Ser Lys Leu Thr Val Asp Lys Ser 625 630 635 640 Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala 645 650 655 Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly 660 665 670 +ADw-210+AD4- 246 +ADw-211+AD4- 904 +ADw-212+AD4- PRT +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- VH2d (CD40) (VHCH1 cargado+AF8-VH2d (CD40) (VHCH1 cargado)-Fc pomo+AF8-PGLALA+AF8-28H1 (VLCH1) +ADw-400+AD4- 246 Glu Val Gln Leu Leu Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 1 5 10 15 Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Tyr Ser Phe Thr Gly Tyr 20 25 30 Tyr Ile His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45 Gly Arg Val Ile Pro Asn Ala Gly Gly Thr Ser Tyr Gly Asp Ser Val 50 55 60 Lys Gly Arg Phe Thr Ile Ser Val Asp Asn Ser Lys Asn Thr Ala Tyr 65 70 75 80 Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Ala Arg Glu Gly Ile Tyr Trp Trp Gly Gln Gly Thr Thr Val Thr Val 100 105 110 Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser 115 120 125 Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Glu 130 135 140 Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu 145 150 155 160 Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu 165 170 175 Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr 180 185 190 Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys Val 195 200 205 Asp Glu Lys Val Glu Pro Lys Ser Cys Asp Gly Gly Gly Gly Ser Gly 210 215 220 Gly Gly Gly Ser Glu Val Gln Leu Leu Glu Ser Gly Gly Gly Leu Val 225 230 235 240 Gln Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Tyr Ser 245 250 255 Phe Thr Gly Tyr Tyr Ile His Trp Val Arg Gln Ala Pro Gly Lys Gly 260 265 270 Leu Glu Trp Val Gly Arg Val Ile Pro Asn Ala Gly Gly Thr Ser Tyr 275 280 285 Gly Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Val Asp Asn Ser Lys 290 295 300 Asn Thr Ala Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala 305 310 315 320 Val Tyr Tyr Cys Ala Arg Glu Gly Ile Tyr Trp Trp Gly Gln Gly Thr 325 330 335 Thr Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro 340 345 350 Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly 355 360 365 Cys Leu Val Glu Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn 370 375 380 Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln 385 390 395 400 Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser 405 410 415 Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser 420 425 430 Asn Thr Lys Val Asp Glu Lys Val Glu Pro Lys Ser Cys Asp Lys Thr 435 440 445 His Thr Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly Gly Pro Ser 450 455 460 Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg 465 470 475 480 Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro 485 490 495 Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala 500 505 510 Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val 515 520 525 Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr 530 535 540 Lys Cys Lys Val Ser Asn Lys Ala Leu Gly Ala Pro Ile Glu Lys Thr 545 550 555 560 Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu 565 570 575 Pro Pro Cys Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Trp Cys 580 585 590 Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser 595 600 605 Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp 610 615 620 Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser 625 630 635 640 Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala 645 650 655 Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Gly 660 665 670 Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly 675 680 685 Gly Gly Ser Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu 690 695 700 Ser Pro Gly Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val 705 710 715 720 Ser Arg Ser Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro 725 730 735 Arg Leu Leu Ile Ile Gly Ala Ser Thr Arg Ala Thr Gly Ile Pro Asp 740 745 750 Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser 755 760 765 Arg Leu Glu Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Gly Gln 770 775 780 Val Ile Pro Pro Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Ser 785 790 795 800 Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser Ser 805 810 815 Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Lys Asp 820 825 830 Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr 835 840 845 Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr 850 855 860 Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Gln 865 870 875 880 Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys Val Asp 885 890 895 Lys Lys Val Glu Pro Lys Ser Cys 900 +ADw-210+AD4- 247 +ADw-211+AD4- 671 +ADw-212+AD4- PRT +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- VH2d (CD40) (VHCH1 cargado+AF8-VH2d (CD40) (VHCH1 cargado)-Fc agujero+AF8-PGLALA +ADw-400+AD4- 247 Glu Val Gln Leu Leu Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 1 5 10 15 Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Tyr Ser Phe Thr Gly Tyr 20 25 30 Tyr Ile His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45 Gly Arg Val Ile Pro Asn Ala Gly Gly Thr Ser Tyr Gly Asp Ser Val 50 55 60 Lys Gly Arg Phe Thr Ile Ser Val Asp Asn Ser Lys Asn Thr Ala Tyr 65 70 75 80 Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Ala Arg Glu Gly Ile Tyr Trp Trp Gly Gln Gly Thr Thr Val Thr Val 100 105 110 Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser 115 120 125 Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Glu 130 135 140 Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu 145 150 155 160 Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu 165 170 175 Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr 180 185 190 Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys Val 195 200 205 Asp Glu Lys Val Glu Pro Lys Ser Cys Asp Gly Gly Gly Gly Ser Gly 210 215 220 Gly Gly Gly Ser Glu Val Gln Leu Leu Glu Ser Gly Gly Gly Leu Val 225 230 235 240 Gln Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Tyr Ser 245 250 255 Phe Thr Gly Tyr Tyr Ile His Trp Val Arg Gln Ala Pro Gly Lys Gly 260 265 270 Leu Glu Trp Val Gly Arg Val Ile Pro Asn Ala Gly Gly Thr Ser Tyr 275 280 285 Gly Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Val Asp Asn Ser Lys 290 295 300 Asn Thr Ala Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala 305 310 315 320 Val Tyr Tyr Cys Ala Arg Glu Gly Ile Tyr Trp Trp Gly Gln Gly Thr 325 330 335 Thr Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro 340 345 350 Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly 355 360 365 Cys Leu Val Glu Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn 370 375 380 Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln 385 390 395 400 Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser 405 410 415 Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser 420 425 430 Asn Thr Lys Val Asp Glu Lys Val Glu Pro Lys Ser Cys Asp Lys Thr 435 440 445 His Thr Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly Gly Pro Ser 450 455 460 Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg 465 470 475 480 Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro 485 490 495 Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala 500 505 510 Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val 515 520 525 Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr 530 535 540 Lys Cys Lys Val Ser Asn Lys Ala Leu Gly Ala Pro Ile Glu Lys Thr 545 550 555 560 Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Cys Thr Leu 565 570 575 Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Ser Cys 580 585 590 Ala Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser 595 600 605 Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp 610 615 620 Ser Asp Gly Ser Phe Phe Leu Val Ser Lys Leu Thr Val Asp Lys Ser 625 630 635 640 Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala 645 650 655 Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly 660 665 670 +ADw-210+AD4- 248 +ADw-211+AD4- 219 +ADw-212+AD4- PRT +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- VL1a (CD40) cadena ligera (cargado) +ADw-400+AD4- 248 Asp Ile Val Met Thr Gln Thr Pro Leu Ser Leu Ser Val Thr Pro Gly 1 5 10 15 Gln Pro Ala Ser Ile Ser Cys Arg Ser Ser Gln Ser Leu Val His Ser 20 25 30 Asn Gly Asn Thr Phe Leu His Trp Tyr Leu Gln Lys Pro Gly Gln Ser 35 40 45 Pro Gln Leu Leu Ile Tyr Thr Val Ser Asn Arg Phe Ser Gly Val Pro 50 55 60 Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile 65 70 75 80 Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Phe Cys Ser Gln Thr 85 90 95 Thr His Val Pro Trp Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys 100 105 110 Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Arg 115 120 125 Lys Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe 130 135 140 Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln 145 150 155 160 Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser 165 170 175 Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu 180 185 190 Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser 195 200 205 Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys 210 215 +ADw-210+AD4- 249 +ADw-211+AD4- 904 +ADw-212+AD4- PRT +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- VH1a (CD40) (VHCH1) +AF8-VH1a (CD40) (VHCH1) Fc pomo+AF8-PGLALA+AF8-28H1 (VLCH1) (cargado) +ADw-400+AD4- 249 Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala 1 5 10 15 Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Ser Phe Thr Gly Tyr 20 25 30 Tyr Ile His Trp Val Arg Gln Ala Pro Gly Gln Ser Leu Glu Trp Met 35 40 45 Gly Arg Val Ile Pro Asn Ala Gly Gly Thr Ser Tyr Asn Gln Lys Phe 50 55 60 Lys Gly Arg Val Thr Leu Thr Val Asp Lys Ser Ile Ser Thr Ala Tyr 65 70 75 80 Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Ala Arg Glu Gly Ile Tyr Trp Trp Gly Gln Gly Thr Thr Val Thr Val 100 105 110 Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser 115 120 125 Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Glu 130 135 140 Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu 145 150 155 160 Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu 165 170 175 Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr 180 185 190 Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys Val 195 200 205 Asp Glu Lys Val Glu Pro Lys Ser Cys Asp Gly Gly Gly Gly Ser Gly 210 215 220 Gly Gly Gly Ser Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys 225 230 235 240 Lys Pro Gly Ala Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Ser 245 250 255 Phe Thr Gly Tyr Tyr Ile His Trp Val Arg Gln Ala Pro Gly Gln Ser 260 265 270 Leu Glu Trp Met Gly Arg Val Ile Pro Asn Ala Gly Gly Thr Ser Tyr 275 280 285 Asn Gln Lys Phe Lys Gly Arg Val Thr Leu Thr Val Asp Lys Ser Ile 290 295 300 Ser Thr Ala Tyr Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala 305 310 315 320 Val Tyr Tyr Cys Ala Arg Glu Gly Ile Tyr Trp Trp Gly Gln Gly Thr 325 330 335 Thr Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro 340 345 350 Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly 355 360 365 Cys Leu Val Glu Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn 370 375 380 Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln 385 390 395 400 Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser 405 410 415 Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser 420 425 430 Asn Thr Lys Val Asp Glu Lys Val Glu Pro Lys Ser Cys Asp Lys Thr 435 440 445 His Thr Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly Gly Pro Ser 450 455 460 Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg 465 470 475 480 Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro 485 490 495 Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala 500 505 510 Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val 515 520 525 Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr 530 535 540 Lys Cys Lys Val Ser Asn Lys Ala Leu Gly Ala Pro Ile Glu Lys Thr 545 550 555 560 Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu 565 570 575 Pro Pro Cys Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Trp Cys 580 585 590 Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser 595 600 605 Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp 610 615 620 Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser 625 630 635 640 Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala 645 650 655 Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Gly 660 665 670 Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly 675 680 685 Gly Gly Ser Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu 690 695 700 Ser Pro Gly Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val 705 710 715 720 Ser Arg Ser Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro 725 730 735 Arg Leu Leu Ile Ile Gly Ala Ser Thr Arg Ala Thr Gly Ile Pro Asp 740 745 750 Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser 755 760 765 Arg Leu Glu Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Gly Gln 770 775 780 Val Ile Pro Pro Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Ser 785 790 795 800 Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser Ser 805 810 815 Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Lys Asp 820 825 830 Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr 835 840 845 Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr 850 855 860 Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Gln 865 870 875 880 Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys Val Asp 885 890 895 Lys Lys Val Glu Pro Lys Ser Cys 900 +ADw-210+AD4- 250 +ADw-211+AD4- 671 +ADw-212+AD4- PRT +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- VH1a (CD40) (VHCH1) +AF8-VH1a (CD40) (VHCH1)-Fc agujero+AF8-PGLALA (cargado) +ADw-400+AD4- 250 Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala 1 5 10 15 Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Ser Phe Thr Gly Tyr 20 25 30 Tyr Ile His Trp Val Arg Gln Ala Pro Gly Gln Ser Leu Glu Trp Met 35 40 45 Gly Arg Val Ile Pro Asn Ala Gly Gly Thr Ser Tyr Asn Gln Lys Phe 50 55 60 Lys Gly Arg Val Thr Leu Thr Val Asp Lys Ser Ile Ser Thr Ala Tyr 65 70 75 80 Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Ala Arg Glu Gly Ile Tyr Trp Trp Gly Gln Gly Thr Thr Val Thr Val 100 105 110 Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser 115 120 125 Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Glu 130 135 140 Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu 145 150 155 160 Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu 165 170 175 Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr 180 185 190 Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys Val 195 200 205 Asp Glu Lys Val Glu Pro Lys Ser Cys Asp Gly Gly Gly Gly Ser Gly 210 215 220 Gly Gly Gly Ser Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys 225 230 235 240 Lys Pro Gly Ala Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Ser 245 250 255 Phe Thr Gly Tyr Tyr Ile His Trp Val Arg Gln Ala Pro Gly Gln Ser 260 265 270 Leu Glu Trp Met Gly Arg Val Ile Pro Asn Ala Gly Gly Thr Ser Tyr 275 280 285 Asn Gln Lys Phe Lys Gly Arg Val Thr Leu Thr Val Asp Lys Ser Ile 290 295 300 Ser Thr Ala Tyr Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala 305 310 315 320 Val Tyr Tyr Cys Ala Arg Glu Gly Ile Tyr Trp Trp Gly Gln Gly Thr 325 330 335 Thr Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro 340 345 350 Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly 355 360 365 Cys Leu Val Glu Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn 370 375 380 Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln 385 390 395 400 Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser 405 410 415 Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser 420 425 430 Asn Thr Lys Val Asp Glu Lys Val Glu Pro Lys Ser Cys Asp Lys Thr 435 440 445 His Thr Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly Gly Pro Ser 450 455 460 Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg 465 470 475 480 Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro 485 490 495 Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala 500 505 510 Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val 515 520 525 Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr 530 535 540 Lys Cys Lys Val Ser Asn Lys Ala Leu Gly Ala Pro Ile Glu Lys Thr 545 550 555 560 Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Cys Thr Leu 565 570 575 Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Ser Cys 580 585 590 Ala Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser 595 600 605 Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp 610 615 620 Ser Asp Gly Ser Phe Phe Leu Val Ser Lys Leu Thr Val Asp Lys Ser 625 630 635 640 Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala 645 650 655 Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly 660 665 670 +ADw-210+AD4- 251 +ADw-211+AD4- 676 +ADw-212+AD4- PRT +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- VH1a (CD40) (VHCH1) Fc pomo+AF8-PGLALA+AF8-28H1 (VLCH1) (cargado) +ADw-400+AD4- 251 Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala 1 5 10 15 Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Ser Phe Thr Gly Tyr 20 25 30 Tyr Ile His Trp Val Arg Gln Ala Pro Gly Gln Ser Leu Glu Trp Met 35 40 45 Gly Arg Val Ile Pro Asn Ala Gly Gly Thr Ser Tyr Asn Gln Lys Phe 50 55 60 Lys Gly Arg Val Thr Leu Thr Val Asp Lys Ser Ile Ser Thr Ala Tyr 65 70 75 80 Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Ala Arg Glu Gly Ile Tyr Trp Trp Gly Gln Gly Thr Thr Val Thr Val 100 105 110 Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser 115 120 125 Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Glu 130 135 140 Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu 145 150 155 160 Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu 165 170 175 Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr 180 185 190 Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys Val 195 200 205 Asp Glu Lys Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro 210 215 220 Pro Cys Pro Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe 225 230 235 240 Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val 245 250 255 Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe 260 265 270 Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro 275 280 285 Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr 290 295 300 Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val 305 310 315 320 Ser Asn Lys Ala Leu Gly Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala 325 330 335 Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Cys Arg 340 345 350 Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Trp Cys Leu Val Lys Gly 355 360 365 Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro 370 375 380 Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser 385 390 395 400 Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln 405 410 415 Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His 420 425 430 Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Gly Gly Gly Gly Ser 435 440 445 Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Glu 450 455 460 Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly Glu 465 470 475 480 Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Arg Ser Tyr 485 490 495 Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile 500 505 510 Ile Gly Ala Ser Thr Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser Gly 515 520 525 Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu Pro 530 535 540 Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Gly Gln Val Ile Pro Pro 545 550 555 560 Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Ser Ser Ala Ser Thr 565 570 575 Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser 580 585 590 Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu 595 600 605 Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His 610 615 620 Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser 625 630 635 640 Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys 645 650 655 Asn Val Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Lys Val Glu 660 665 670 Pro Lys Ser Cys 675 +ADw-210+AD4- 252 +ADw-211+AD4- 443 +ADw-212+AD4- PRT +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- VH1a (CD40) (VHCH1) Fc agujero+AF8-PGLALA (cargado) +ADw-400+AD4- 252 Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala 1 5 10 15 Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Ser Phe Thr Gly Tyr 20 25 30 Tyr Ile His Trp Val Arg Gln Ala Pro Gly Gln Ser Leu Glu Trp Met 35 40 45 Gly Arg Val Ile Pro Asn Ala Gly Gly Thr Ser Tyr Asn Gln Lys Phe 50 55 60 Lys Gly Arg Val Thr Leu Thr Val Asp Lys Ser Ile Ser Thr Ala Tyr 65 70 75 80 Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Ala Arg Glu Gly Ile Tyr Trp Trp Gly Gln Gly Thr Thr Val Thr Val 100 105 110 Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser 115 120 125 Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Glu 130 135 140 Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu 145 150 155 160 Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu 165 170 175 Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr 180 185 190 Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys Val 195 200 205 Asp Glu Lys Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro 210 215 220 Pro Cys Pro Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe 225 230 235 240 Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val 245 250 255 Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe 260 265 270 Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro 275 280 285 Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr 290 295 300 Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val 305 310 315 320 Ser Asn Lys Ala Leu Gly Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala 325 330 335 Lys Gly Gln Pro Arg Glu Pro Gln Val Cys Thr Leu Pro Pro Ser Arg 340 345 350 Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Ser Cys Ala Val Lys Gly 355 360 365 Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro 370 375 380 Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser 385 390 395 400 Phe Phe Leu Val Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln 405 410 415 Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His 420 425 430 Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly 435 440 +ADw-210+AD4- 253 +ADw-211+AD4- 676 +ADw-212+AD4- PRT +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- VH1a (CD40) (VHCH1) Fc pomo+AF8-PGLALA+AF8-4B9 (VLCH1) (cargado) +ADw-400+AD4- 253 Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala 1 5 10 15 Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Ser Phe Thr Gly Tyr 20 25 30 Tyr Ile His Trp Val Arg Gln Ala Pro Gly Gln Ser Leu Glu Trp Met 35 40 45 Gly Arg Val Ile Pro Asn Ala Gly Gly Thr Ser Tyr Asn Gln Lys Phe 50 55 60 Lys Gly Arg Val Thr Leu Thr Val Asp Lys Ser Ile Ser Thr Ala Tyr 65 70 75 80 Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Ala Arg Glu Gly Ile Tyr Trp Trp Gly Gln Gly Thr Thr Val Thr Val 100 105 110 Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser 115 120 125 Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Glu 130 135 140 Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu 145 150 155 160 Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu 165 170 175 Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr 180 185 190 Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys Val 195 200 205 Asp Glu Lys Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro 210 215 220 Pro Cys Pro Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe 225 230 235 240 Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val 245 250 255 Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe 260 265 270 Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro 275 280 285 Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr 290 295 300 Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val 305 310 315 320 Ser Asn Lys Ala Leu Gly Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala 325 330 335 Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Cys Arg 340 345 350 Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Trp Cys Leu Val Lys Gly 355 360 365 Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro 370 375 380 Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser 385 390 395 400 Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln 405 410 415 Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His 420 425 430 Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Gly Gly Gly Gly Ser 435 440 445 Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Glu 450 455 460 Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly Glu 465 470 475 480 Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Thr Ser Ser Tyr 485 490 495 Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile 500 505 510 Asn Val Gly Ser Arg Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser Gly 515 520 525 Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu Pro 530 535 540 Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Gly Ile Met Leu Pro Pro 545 550 555 560 Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Ser Ser Ala Ser Thr 565 570 575 Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser 580 585 590 Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu 595 600 605 Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His 610 615 620 Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser 625 630 635 640 Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys 645 650 655 Asn Val Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Lys Val Glu 660 665 670 Pro Lys Ser Cys 675 +ADw-210+AD4- 254 +ADw-211+AD4- 213 +ADw-212+AD4- PRT +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- 4B9 cadena ligera cruzada VLCH1 +ADw-400+AD4- 254 Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly 1 5 10 15 Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Thr Ser Ser 20 25 30 Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu 35 40 45 Ile Asn Val Gly Ser Arg Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser 50 55 60 Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu 65 70 75 80 Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Gly Ile Met Leu Pro 85 90 95 Pro Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Ser Ser Ala Ser 100 105 110 Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr 115 120 125 Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro 130 135 140 Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val 145 150 155 160 His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser 165 170 175 Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile 180 185 190 Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Lys Val 195 200 205 Glu Pro Lys Ser Cys 210 +ADw-210+AD4- 255 +ADw-211+AD4- 687 +ADw-212+AD4- PRT +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- VH1a (CD40) (VHCH1) Fc pomo+AF8-PGLALA+AF8-4B9 (VHCL) (cargado) +ADw-400+AD4- 255 Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala 1 5 10 15 Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Ser Phe Thr Gly Tyr 20 25 30 Tyr Ile His Trp Val Arg Gln Ala Pro Gly Gln Ser Leu Glu Trp Met 35 40 45 Gly Arg Val Ile Pro Asn Ala Gly Gly Thr Ser Tyr Asn Gln Lys Phe 50 55 60 Lys Gly Arg Val Thr Leu Thr Val Asp Lys Ser Ile Ser Thr Ala Tyr 65 70 75 80 Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Ala Arg Glu Gly Ile Tyr Trp Trp Gly Gln Gly Thr Thr Val Thr Val 100 105 110 Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser 115 120 125 Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Glu 130 135 140 Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu 145 150 155 160 Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu 165 170 175 Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr 180 185 190 Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys Val 195 200 205 Asp Glu Lys Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro 210 215 220 Pro Cys Pro Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe 225 230 235 240 Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val 245 250 255 Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe 260 265 270 Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro 275 280 285 Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr 290 295 300 Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val 305 310 315 320 Ser Asn Lys Ala Leu Gly Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala 325 330 335 Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Cys Arg 340 345 350 Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Trp Cys Leu Val Lys Gly 355 360 365 Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro 370 375 380 Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser 385 390 395 400 Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln 405 410 415 Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His 420 425 430 Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Gly Gly Gly Gly Ser 435 440 445 Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Glu 450 455 460 Val Gln Leu Leu Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser 465 470 475 480 Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Ser Tyr Ala 485 490 495 Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ser 500 505 510 Ala Ile Ile Gly Ser Gly Ala Ser Thr Tyr Tyr Ala Asp Ser Val Lys 515 520 525 Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr Leu 530 535 540 Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala 545 550 555 560 Lys Gly Trp Phe Gly Gly Phe Asn Tyr Trp Gly Gln Gly Thr Leu Val 565 570 575 Thr Val Ser Ser Ala Ser Val Ala Ala Pro Ser Val Phe Ile Phe Pro 580 585 590 Pro Ser Asp Glu Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu 595 600 605 Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp 610 615 620 Asn Ala Leu Gln Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp 625 630 635 640 Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys 645 650 655 Ala Asp Tyr Glu Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln 660 665 670 Gly Leu Ser Ser Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys 675 680 685 +ADw-210+AD4- 256 +ADw-211+AD4- 219 +ADw-212+AD4- PRT +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- VL1a (CD40) cadena ligera +ADw-400+AD4- 256 Asp Ile Val Met Thr Gln Thr Pro Leu Ser Leu Ser Val Thr Pro Gly 1 5 10 15 Gln Pro Ala Ser Ile Ser Cys Arg Ser Ser Gln Ser Leu Val His Ser 20 25 30 Asn Gly Asn Thr Phe Leu His Trp Tyr Leu Gln Lys Pro Gly Gln Ser 35 40 45 Pro Gln Leu Leu Ile Tyr Thr Val Ser Asn Arg Phe Ser Gly Val Pro 50 55 60 Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile 65 70 75 80 Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Phe Cys Ser Gln Thr 85 90 95 Thr His Val Pro Trp Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys 100 105 110 Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu 115 120 125 Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe 130 135 140 Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln 145 150 155 160 Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser 165 170 175 Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu 180 185 190 Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser 195 200 205 Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys 210 215 +ADw-210+AD4- 257 +ADw-211+AD4- 687 +ADw-212+AD4- PRT +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- VH1a (CD40) (VHCH1) Fc pomo+AF8-PGLALA+AF8-4B9 (VHCL) +ADw-400+AD4- 257 Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala 1 5 10 15 Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Ser Phe Thr Gly Tyr 20 25 30 Tyr Ile His Trp Val Arg Gln Ala Pro Gly Gln Ser Leu Glu Trp Met 35 40 45 Gly Arg Val Ile Pro Asn Ala Gly Gly Thr Ser Tyr Asn Gln Lys Phe 50 55 60 Lys Gly Arg Val Thr Leu Thr Val Asp Lys Ser Ile Ser Thr Ala Tyr 65 70 75 80 Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Ala Arg Glu Gly Ile Tyr Trp Trp Gly Gln Gly Thr Thr Val Thr Val 100 105 110 Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser 115 120 125 Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Lys 130 135 140 Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu 145 150 155 160 Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu 165 170 175 Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr 180 185 190 Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys Val 195 200 205 Asp Lys Lys Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro 210 215 220 Pro Cys Pro Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe 225 230 235 240 Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val 245 250 255 Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe 260 265 270 Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro 275 280 285 Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr 290 295 300 Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val 305 310 315 320 Ser Asn Lys Ala Leu Gly Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala 325 330 335 Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Cys Arg 340 345 350 Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Trp Cys Leu Val Lys Gly 355 360 365 Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro 370 375 380 Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser 385 390 395 400 Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln 405 410 415 Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His 420 425 430 Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Gly Gly Gly Gly Ser 435 440 445 Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Glu 450 455 460 Val Gln Leu Leu Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser 465 470 475 480 Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Ser Tyr Ala 485 490 495 Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ser 500 505 510 Ala Ile Ile Gly Ser Gly Ala Ser Thr Tyr Tyr Ala Asp Ser Val Lys 515 520 525 Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr Leu 530 535 540 Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala 545 550 555 560 Lys Gly Trp Phe Gly Gly Phe Asn Tyr Trp Gly Gln Gly Thr Leu Val 565 570 575 Thr Val Ser Ser Ala Ser Val Ala Ala Pro Ser Val Phe Ile Phe Pro 580 585 590 Pro Ser Asp Glu Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu 595 600 605 Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp 610 615 620 Asn Ala Leu Gln Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp 625 630 635 640 Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys 645 650 655 Ala Asp Tyr Glu Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln 660 665 670 Gly Leu Ser Ser Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys 675 680 685 +ADw-210+AD4- 258 +ADw-211+AD4- 443 +ADw-212+AD4- PRT +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- VH1a (CD40) (VHCH1) Fc agujero+AF8-PGLALA +ADw-400+AD4- 258 Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala 1 5 10 15 Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Ser Phe Thr Gly Tyr 20 25 30 Tyr Ile His Trp Val Arg Gln Ala Pro Gly Gln Ser Leu Glu Trp Met 35 40 45 Gly Arg Val Ile Pro Asn Ala Gly Gly Thr Ser Tyr Asn Gln Lys Phe 50 55 60 Lys Gly Arg Val Thr Leu Thr Val Asp Lys Ser Ile Ser Thr Ala Tyr 65 70 75 80 Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Ala Arg Glu Gly Ile Tyr Trp Trp Gly Gln Gly Thr Thr Val Thr Val 100 105 110 Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser 115 120 125 Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Lys 130 135 140 Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu 145 150 155 160 Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu 165 170 175 Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr 180 185 190 Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys Val 195 200 205 Asp Lys Lys Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro 210 215 220 Pro Cys Pro Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe 225 230 235 240 Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val 245 250 255 Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe 260 265 270 Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro 275 280 285 Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr 290 295 300 Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val 305 310 315 320 Ser Asn Lys Ala Leu Gly Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala 325 330 335 Lys Gly Gln Pro Arg Glu Pro Gln Val Cys Thr Leu Pro Pro Ser Arg 340 345 350 Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Ser Cys Ala Val Lys Gly 355 360 365 Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro 370 375 380 Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser 385 390 395 400 Phe Phe Leu Val Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln 405 410 415 Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His 420 425 430 Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly 435 440 +ADw-210+AD4- 259 +ADw-211+AD4- 443 +ADw-212+AD4- PRT +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- P1AE0816 cadena pesada (control) +ADw-400+AD4- 259 Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala 1 5 10 15 Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Ser Phe Thr Gly Tyr 20 25 30 Tyr Ile His Trp Val Arg Gln Ala Pro Gly Gln Ser Leu Glu Trp Met 35 40 45 Gly Arg Val Ile Pro Asn Asn Gly Gly Thr Ser Tyr Asn Gln Lys Phe 50 55 60 Gln Gly Arg Val Thr Ile Ser Val Asp Lys Ser Ile Ser Thr Ala Tyr 65 70 75 80 Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Ala Arg Glu Gly Ile Tyr Trp Trp Gly His Gly Thr Thr Val Thr Val 100 105 110 Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser 115 120 125 Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Lys 130 135 140 Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu 145 150 155 160 Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu 165 170 175 Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr 180 185 190 Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys Val 195 200 205 Asp Lys Lys Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro 210 215 220 Pro Cys Pro Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe 225 230 235 240 Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val 245 250 255 Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe 260 265 270 Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro 275 280 285 Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr 290 295 300 Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val 305 310 315 320 Ser Asn Lys Ala Leu Gly Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala 325 330 335 Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg 340 345 350 Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly 355 360 365 Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro 370 375 380 Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser 385 390 395 400 Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln 405 410 415 Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His 420 425 430 Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly 435 440 +ADw-210+AD4- 260 +ADw-211+AD4- 219 +ADw-212+AD4- PRT +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- P1AE0816 cadena ligera (control) +ADw-400+AD4- 260 Asp Val Val Val Thr Gln Ser Pro Leu Ser Leu Pro Val Thr Pro Gly 1 5 10 15 Glu Pro Ala Ser Ile Ser Cys Arg Ser Ser Gln Ser Leu Val His Ser 20 25 30 Asn Gly Asn Thr Phe Leu His Trp Tyr Leu Gln Lys Pro Gly Gln Ser 35 40 45 Pro Gln Leu Leu Ile Tyr Thr Val Ser Asn Arg Phe Ser Gly Val Pro 50 55 60 Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile 65 70 75 80 Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Phe Cys Ser Gln Thr 85 90 95 Thr His Val Pro Trp Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys 100 105 110 Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu 115 120 125 Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe 130 135 140 Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln 145 150 155 160 Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser 165 170 175 Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu 180 185 190 Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser 195 200 205 Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys 210 215 +ADw-210+AD4- 261 +ADw-211+AD4- 5 +ADw-212+AD4- PRT +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- hu CD40 CDR-H1 (VH2ab) +ADw-400+AD4- 261 Gly Tyr Tyr Met His 1 5 +ADw-210+AD4- 262 +ADw-211+AD4- 17 +ADw-212+AD4- PRT +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- hu CD40 CDR-H2 (VH2ab) +ADw-400+AD4- 262 Arg Val Ile Pro Asn Ala Gly Gly Thr Ser Tyr Asn Gln Lys Phe Lys 1 5 10 15 Gly +ADw-210+AD4- 263 +ADw-211+AD4- 17 +ADw-212+AD4- PRT +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- hu CD40 CDR-H2 (VH2ac) +ADw-400+AD4- 263 Arg Val Ile Pro Asn Ala Gly Gly Thr Ser Tyr Asn Gln Lys Val Lys 1 5 10 15 Gly +ADw-210+AD4- 264 +ADw-211+AD4- 16 +ADw-212+AD4- PRT +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- hu CD40 CDR-L1 (VL2ab) +ADw-400+AD4- 264 Arg Ala Ser Gln Ser Leu Val His Ser Asn Gly Asn Thr Phe Leu His 1 5 10 15 +ADw-210+AD4- 265 +ADw-211+AD4- 16 +ADw-212+AD4- PRT +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- hu CD40 CDR-L1 (VL2ac) +ADw-400+AD4- 265 Arg Ser Ser Gln Ser Ile Val His Ser Asn Gly Asn Thr Phe Leu His 1 5 10 15 +ADw-210+AD4- 266 +ADw-211+AD4- 201 +ADw-212+AD4- PRT +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- Hu+AF8-CD40+AF8-ECD+AF8-His+AF8-Avi +ADw-400+AD4- 266 Glu Pro Pro Thr Ala Cys Arg Glu Lys Gln Tyr Leu Ile Asn Ser Gln 1 5 10 15 Cys Cys Ser Leu Cys Gln Pro Gly Gln Lys Leu Val Ser Asp Cys Thr 20 25 30 Glu Phe Thr Glu Thr Glu Cys Leu Pro Cys Gly Glu Ser Glu Phe Leu 35 40 45 Asp Thr Trp Asn Arg Glu Thr His Cys His Gln His Lys Tyr Cys Asp 50 55 60 Pro Asn Leu Gly Leu Arg Val Gln Gln Lys Gly Thr Ser Glu Thr Asp 65 70 75 80 Thr Ile Cys Thr Cys Glu Glu Gly Trp His Cys Thr Ser Glu Ala Cys 85 90 95 Glu Ser Cys Val Leu His Arg Ser Cys Ser Pro Gly Phe Gly Val Lys 100 105 110 Gln Ile Ala Thr Gly Val Ser Asp Thr Ile Cys Glu Pro Cys Pro Val 115 120 125 Gly Phe Phe Ser Asn Val Ser Ser Ala Phe Glu Lys Cys His Pro Trp 130 135 140 Thr Ser Cys Glu Thr Lys Asp Leu Val Val Gln Gln Ala Gly Thr Asn 145 150 155 160 Lys Thr Asp Val Val Cys Gly Pro Gln Asp Arg Leu Arg Gly Gly Gly 165 170 175 Gly Ser His His His His His His Gly Ser Gly Leu Asn Asp Ile Phe 180 185 190 Glu Ala Gln Lys Ile Glu Trp His Glu 195 200 +ADw-210+AD4- 267 +ADw-211+AD4- 201 +ADw-212+AD4- PRT +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- cyno+AF8-CD40+AF8-ECD+AF8-His+AF8-Avi +ADw-400+AD4- 267 Glu Pro Pro Thr Ala Cys Arg Glu Lys Gln Tyr Leu Ile Asn Ser Gln 1 5 10 15 Cys Cys Ser Leu Cys Gln Pro Gly Gln Lys Leu Val Ser Asp Cys Thr 20 25 30 Glu Phe Thr Glu Thr Glu Cys Leu Pro Cys Ser Glu Ser Glu Phe Leu 35 40 45 Asp Thr Trp Asn Arg Glu Thr Arg Cys His Gln His Lys Tyr Cys Asp 50 55 60 Pro Asn Leu Gly Leu Arg Val Gln Gln Lys Gly Thr Ser Glu Thr Asp 65 70 75 80 Thr Ile Cys Thr Cys Glu Glu Gly Leu His Cys Thr Ser Glu Ser Cys 85 90 95 Glu Ser Cys Val Pro His Arg Ser Cys Leu Pro Gly Phe Gly Val Lys 100 105 110 Gln Ile Ala Thr Gly Val Ser Asp Thr Ile Cys Glu Pro Cys Pro Val 115 120 125 Gly Phe Phe Ser Asn Val Ser Ser Ala Phe Glu Lys Cys Arg Pro Trp 130 135 140 Thr Ser Cys Glu Thr Lys Asp Leu Val Val Gln Gln Ala Gly Thr Asn 145 150 155 160 Lys Thr Asp Val Val Cys Gly Pro Gln Asp Arg Gln Arg Gly Gly Gly 165 170 175 Gly Ser His His His His His His Gly Ser Gly Leu Asn Asp Ile Phe 180 185 190 Glu Ala Gln Lys Ile Glu Trp His Glu 195 200 +ADw-210+AD4- 268 +ADw-211+AD4- 451 +ADw-212+AD4- PRT +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- Cadena pesada de IgG2 de Selicrelumab +ADw-400+AD4- 268 Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala 1 5 10 15 Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Gly Tyr 20 25 30 Tyr Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met 35 40 45 Gly Trp Ile Asn Pro Asp Ser Gly Gly Thr Asn Tyr Ala Gln Lys Phe 50 55 60 Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Ile Ser Thr Ala Tyr 65 70 75 80 Met Glu Leu Asn Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Ala Arg Asp Gln Pro Leu Gly Tyr Cys Thr Asn Gly Val Cys Ser Tyr 100 105 110 Phe Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Ala Ser 115 120 125 Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Cys Ser Arg Ser Thr 130 135 140 Ser Glu Ser Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro 145 150 155 160 Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val 165 170 175 His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser 180 185 190 Ser Val Val Thr Val Pro Ser Ser Asn Phe Gly Thr Gln Thr Tyr Thr 195 200 205 Cys Asn Val Asp His Lys Pro Ser Asn Thr Lys Val Asp Lys Thr Val 210 215 220 Glu Arg Lys Cys Cys Val Glu Cys Pro Pro Cys Pro Ala Pro Pro Val 225 230 235 240 Ala Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu 245 250 255 Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser 260 265 270 His Glu Asp Pro Glu Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu 275 280 285 Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr 290 295 300 Arg Phe Val Val Ser Val Leu Thr Val Val His Gln Asp Trp Leu Asn 305 310 315 320 Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ala Pro 325 330 335 Ile Glu Lys Thr Ile Ser Lys Thr Lys Gly Gln Pro Arg Glu Pro Gln 340 345 350 Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val 355 360 365 Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val 370 375 380 Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro 385 390 395 400 Pro Met Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr 405 410 415 Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val 420 425 430 Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu 435 440 445 Ser Pro Gly 450 +ADw-210+AD4- 269 +ADw-211+AD4- 214 +ADw-212+AD4- PRT +ADw-213+AD4- Secuencia artificial +ADw-220+AD4- +ADw-223+AD4- Cadena ligera de IgG2 de Selicrelumab +ADw-400+AD4- 269 Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Val Ser Ala Ser Val Gly 1 5 10 15 Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Gly Ile Tyr Ser Trp 20 25 30 Leu Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Asn Leu Leu Ile 35 40 45 Tyr Thr Ala Ser Thr Leu Gln Ser Gly Val Pro Ser Arg Phe Ser Gly 50 55 60 Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro 65 70 75 80 Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Ala Asn Ile Phe Pro Leu 85 90 95 Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys Arg Thr Val Ala Ala 100 105 110 Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly 115 120 125 Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala 130 135 140 Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln 145 150 155 160 Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser 165 170 175 Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr 180 185 190 Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser 195 200 205 Phe Asn Arg Gly Glu Cys 210