LISTADO DE SECUENCIAS <110> National Research Council of Canada Stanimirovic, Danica Kemmerich, Kristin Sulea, Traian Arbabi-Ghahroudi, Mehdi Haqqani, Arsalan Gilbert, Renald Massie, Bernard <120> Anticuerpos específicos del receptor del factor 1 de crecimiento similar a la insulina y usos de los mismos <130> 12600-98 <150> 61/948,831 <151> 2014-03-06 <160> 42 <170> PatentIn version 3.5 <210> 1 <211> 8 <212> PRT <213> Artificial <220> <223> IGF1R-5 CDR1 <400> 1 Gly Arg Thr Ile Asp Asn Tyr Ala 1 5 <210> 2 <211> 8 <212> PRT <213> Artificial <220> <223> IGF1R-5 CDR2 <220> <221> MISC_FEATURE <222> (8)..(8) <223> Xaa es Ala o Thr <400> 2 Ile Asp Trp Gly Asp Gly Gly Xaa 1 5 <210> 3 <211> 17 <212> PRT <213> Artificial <220> <223> IGF1R-5 CDR3 <400> 3 Ala Met Ala Arg Gln Ser Arg Val Asn Leu Asp Val Ala Arg Tyr Asp 1 5 10 15 Tyr <210> 4 <211> 124 <212> PRT <213> Artificial <220> <223> IGF1R-5 Consenso <220> <221> MISC_FEATURE <222> (1)..(1) <223> Xaa es Glu o Gln <220> <221> MISC_FEATURE <222> (3)..(3) <223> Xaa es Lys o Gln <220> <221> MISC_FEATURE <222> (5)..(5) <223> Xaa es Val o Glu <220> <221> MISC_FEATURE <222> (14)..(14) <223> Xaa es Ala o Pro <220> <221> MISC_FEATURE <222> (37)..(37) <223> Xaa es Val o Ser <220> <221> MISC_FEATURE <222> (44)..(44) <223> Xaa es Asp o Gly <220> <221> MISC_FEATURE <222> (45)..(45) <223> Xaa es Leu o Arg <220> <221> MISC_FEATURE <222> (47)..(47) <223> Xaa es Phe o Trp <220> <221> MISC_FEATURE <222> (49)..(49) <223> Xaa es Ala o Ser <220> <221> MISC_FEATURE <222> (58)..(58) <223> Xaa es Ala o Thr <220> <221> MISC_FEATURE <222> (75)..(75) <223> Xaa es Ala o Ser <220> <221> MISC_FEATURE <222> (77)..(77) <223> Xaa es Gly o Asn <220> <221> MISC_FEATURE <222> (79)..(79) <223> Xaa es Met o Leu <220> <221> MISC_FEATURE <222> (85)..(85) <223> Xaa es Asn o Arg <220> <221> MISC_FEATURE <222> (87)..(87) <223> Xaa es Glu o Arg <220> <221> MISC_FEATURE <222> (88)..(88) <223> Xaa es Pro o Ala <220> <221> MISC_FEATURE <222> (95)..(95) <223> Xaa es Ser o Tyr <220> <221> MISC_FEATURE <222> (119)..(119) <223> Xaa es Gln o Leu <400> 4 Xaa Val Xaa Leu Xaa Glu Ser Gly Gly Gly Leu Val Gln Xaa Gly Gly 1 5 10 15 Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Arg Thr Ile Asp Asn Tyr 20 25 30 Ala Met Ala Trp Xaa Arg Gln Ala Pro Gly Lys Xaa Xaa Glu Xaa Val 35 40 45 Xaa Thr Ile Asp Trp Gly Asp Gly Gly Xaa Arg Tyr Ala Asn Ser Val 50 55 60 Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Xaa Lys Xaa Thr Xaa Tyr 65 70 75 80 Leu Gln Met Asn Xaa Leu Xaa Xaa Glu Asp Thr Ala Val Tyr Xaa Cys 85 90 95 Ala Met Ala Arg Gln Ser Arg Val Asn Leu Asp Val Ala Arg Tyr Asp 100 105 110 Tyr Trp Gly Gln Gly Thr Xaa Val Thr Val Ser Ser 115 120 <210> 5 <211> 124 <212> PRT <213> Artificial <220> <223> IGF1R-5 VHH <400> 5 Gln Val Lys Leu Glu Glu Ser Gly Gly Gly Leu Val Gln Ala Gly Gly 1 5 10 15 Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Arg Thr Ile Asp Asn Tyr 20 25 30 Ala Met Ala Trp Ser Arg Gln Ala Pro Gly Lys Asp Arg Glu Phe Val 35 40 45 Ala Thr Ile Asp Trp Gly Asp Gly Gly Ala Arg Tyr Ala Asn Ser Val 50 55 60 Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Gly Thr Met Tyr 65 70 75 80 Leu Gln Met Asn Asn Leu Glu Pro Glu Asp Thr Ala Val Tyr Ser Cys 85 90 95 Ala Met Ala Arg Gln Ser Arg Val Asn Leu Asp Val Ala Arg Tyr Asp 100 105 110 Tyr Trp Gly Gln Gly Thr Gln Val Thr Val Ser Ser 115 120 <210> 6 <211> 124 <212> PRT <213> Artificial <220> <223> IGF1R-5_H1 <400> 6 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 Arg Thr Ile Asp Asn Tyr 20 25 30 Ala Met Ala Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45 Ser Thr Ile Asp Trp Gly Asp Gly Gly Thr Arg Tyr Ala Asn 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 Met Ala Arg Gln Ser Arg Val Asn Leu Asp Val Ala Arg Tyr Asp 100 105 110 Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser 115 120 <210> 7 <211> 124 <212> PRT <213> Artificial <220> <223> IGF1R-5_H2 <400> 7 Gln 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 Arg Thr Ile Asp Asn Tyr 20 25 30 Ala Met Ala Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45 Ala Thr Ile Asp Trp Gly Asp Gly Gly Thr Arg Tyr Ala Asn Ser Val 50 55 60 Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Met 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 Met Ala Arg Gln Ser Arg Val Asn Leu Asp Val Ala Arg Tyr Asp 100 105 110 Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser 115 120 <210> 8 <211> 124 <212> PRT <213> Artificial <220> <223> IGF1R-5_H3 <400> 8 Gln 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 Arg Thr Ile Asp Asn Tyr 20 25 30 Ala Met Ala Trp Ser Arg Gln Ala Pro Gly Lys Gly Leu Glu Phe Val 35 40 45 Ala Thr Ile Asp Trp Gly Asp Gly Gly Thr Arg Tyr Ala Asn Ser Val 50 55 60 Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Met 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 Met Ala Arg Gln Ser Arg Val Asn Leu Asp Val Ala Arg Tyr Asp 100 105 110 Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser 115 120 <210> 9 <211> 124 <212> PRT <213> Artificial <220> <223> IGF1R-5_H5 <400> 9 Gln 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 Arg Thr Ile Asp Asn Tyr 20 25 30 Ala Met Ala Trp Ser Arg Gln Ala Pro Gly Lys Asp Arg Glu Phe Val 35 40 45 Ala Thr Ile Asp Trp Gly Asp Gly Gly Thr Arg Tyr Ala Asn Ser Val 50 55 60 Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Gly Thr Met Tyr 65 70 75 80 Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Ser Cys 85 90 95 Ala Met Ala Arg Gln Ser Arg Val Asn Leu Asp Val Ala Arg Tyr Asp 100 105 110 Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser 115 120 <210> 10 <211> 124 <212> PRT <213> Artificial <220> <223> IGF1R-5_H6 <400> 10 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 Arg Thr Ile Asp Asn Tyr 20 25 30 Ala Met Ala Trp Ser Arg Gln Ala Pro Gly Lys Asp Arg Glu Phe Val 35 40 45 Ser Thr Ile Asp Trp Gly Asp Gly Gly Thr Arg Tyr Ala Asn 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 Met Ala Arg Gln Ser Arg Val Asn Leu Asp Val Ala Arg Tyr Asp 100 105 110 Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser 115 120 <210> 11 <211> 13 <212> PRT <213> Artificial <220> <223> Epítopo de IGF1R-5 <400> 11 Phe Glu Asn Phe Leu His Asn Ser Ile Phe Val Pro Arg 1 5 10 <210> 12 <211> 370 <212> PRT <213> Artificial <220> <223> Fusión IGF1R-5-mFc <400> 12 Gln Val Lys Leu Glu Glu Ser Gly Gly Gly Leu Val Gln Ala Gly Gly 1 5 10 15 Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Arg Thr Ile Asp Asn Tyr 20 25 30 Ala Met Ala Trp Ser Arg Gln Ala Pro Gly Lys Asp Arg Glu Phe Val 35 40 45 Ala Thr Ile Asp Trp Gly Asp Gly Gly Ala Arg Tyr Ala Asn Ser Val 50 55 60 Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Gly Thr Met Tyr 65 70 75 80 Leu Gln Met Asn Asn Leu Glu Pro Glu Asp Thr Ala Val Tyr Ser Cys 85 90 95 Ala Met Ala Arg Gln Ser Arg Val Asn Leu Asp Val Ala Arg Tyr Asp 100 105 110 Tyr Trp Gly Gln Gly Thr Gln Val Thr Val Ser Ser Met Thr Val Asp 115 120 125 Lys Lys Leu Glu Pro Ser Gly Pro Ile Ser Thr Ile Asn Pro Cys Pro 130 135 140 Pro Cys Lys Glu Cys His Lys Cys Pro Ala Pro Asn Leu Glu Gly Gly 145 150 155 160 Pro Ser Val Phe Ile Phe Pro Pro Asn Ile Lys Asp Val Leu Met Ile 165 170 175 Ser Leu Thr Pro Lys Val Thr Cys Val Val Val Asp Val Ser Glu Asp 180 185 190 Asp Pro Asp Val Gln Ile Ser Trp Phe Val Asn Asn Val Glu Val His 195 200 205 Thr Ala Gln Thr Gln Thr His Arg Glu Asp Tyr Asn Ser Thr Ile Arg 210 215 220 Val Val Ser Thr Leu Pro Ile Gln His Gln Asp Trp Met Ser Gly Lys 225 230 235 240 Glu Phe Lys Cys Lys Val Asn Asn Lys Asp Leu Pro Ser Pro Ile Glu 245 250 255 Arg Thr Ile Ser Lys Ile Lys Gly Leu Val Arg Ala Pro Gln Val Tyr 260 265 270 Ile Leu Pro Pro Pro Ala Glu Gln Leu Ser Arg Lys Asp Val Ser Leu 275 280 285 Thr Cys Leu Val Val Gly Phe Asn Pro Gly Asp Ile Ser Val Glu Trp 290 295 300 Thr Ser Asn Gly His Thr Glu Glu Asn Tyr Lys Asp Thr Ala Pro Val 305 310 315 320 Leu Asp Ser Asp Gly Ser Tyr Phe Ile Tyr Ser Lys Leu Asn Met Lys 325 330 335 Thr Ser Lys Trp Glu Lys Thr Asp Ser Phe Ser Cys Asn Val Arg His 340 345 350 Glu Gly Leu Lys Asn Tyr Tyr Leu Lys Lys Thr Ile Ser Arg Ser Pro 355 360 365 Gly Lys 370 <210> 13 <211> 371 <212> PRT <213> Artificial <220> <223> Fusión mFc-IGF1R-5 <400> 13 Glu Pro Ser Gly Pro Ile Ser Thr Ile Asn Pro Cys Pro Pro Cys Lys 1 5 10 15 Glu Cys His Lys Cys Pro Ala Pro Asn Leu Glu Gly Gly Pro Ser Val 20 25 30 Phe Ile Phe Pro Pro Asn Ile Lys Asp Val Leu Met Ile Ser Leu Thr 35 40 45 Pro Lys Val Thr Cys Val Val Val Asp Val Ser Glu Asp Asp Pro Asp 50 55 60 Val Gln Ile Ser Trp Phe Val Asn Asn Val Glu Val His Thr Ala Gln 65 70 75 80 Thr Gln Thr His Arg Glu Asp Tyr Asn Ser Thr Ile Arg Val Val Ser 85 90 95 Thr Leu Pro Ile Gln His Gln Asp Trp Met Ser Gly Lys Glu Phe Lys 100 105 110 Cys Lys Val Asn Asn Lys Asp Leu Pro Ser Pro Ile Glu Arg Thr Ile 115 120 125 Ser Lys Ile Lys Gly Leu Val Arg Ala Pro Gln Val Tyr Ile Leu Pro 130 135 140 Pro Pro Ala Glu Gln Leu Ser Arg Lys Asp Val Ser Leu Thr Cys Leu 145 150 155 160 Val Val Gly Phe Asn Pro Gly Asp Ile Ser Val Glu Trp Thr Ser Asn 165 170 175 Gly His Thr Glu Glu Asn Tyr Lys Asp Thr Ala Pro Val Leu Asp Ser 180 185 190 Asp Gly Ser Tyr Phe Ile Tyr Ser Lys Leu Asn Met Lys Thr Ser Lys 195 200 205 Trp Glu Lys Thr Asp Ser Phe Ser Cys Asn Val Arg His Glu Gly Leu 210 215 220 Lys Asn Tyr Tyr Leu Lys Lys Thr Ile Ser Arg Ser Pro Gly Gly Gly 225 230 235 240 Gly Ser Gly Gly Gly Gly Ser Gln Val Lys Leu Glu Glu Ser Gly Gly 245 250 255 Gly Leu Val Gln Ala Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser 260 265 270 Gly Arg Thr Ile Asp Asn Tyr Ala Met Ala Trp Ser Arg Gln Ala Pro 275 280 285 Gly Lys Asp Arg Glu Phe Val Ala Thr Ile Asp Trp Gly Asp Gly Gly 290 295 300 Ala Arg Tyr Ala Asn Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp 305 310 315 320 Asn Ala Lys Gly Thr Met Tyr Leu Gln Met Asn Asn Leu Glu Pro Glu 325 330 335 Asp Thr Ala Val Tyr Ser Cys Ala Met Ala Arg Gln Ser Arg Val Asn 340 345 350 Leu Asp Val Ala Arg Tyr Asp Tyr Trp Gly Gln Gly Thr Gln Val Thr 355 360 365 Val Ser Ser 370 <210> 14 <211> 1367 <212> PRT <213> Artificial <220> <223> IGF1R humana <400> 14 Met Lys Ser Gly Ser Gly Gly Gly Ser Pro Thr Ser Leu Trp Gly Leu 1 5 10 15 Leu Phe Leu Ser Ala Ala Leu Ser Leu Trp Pro Thr Ser Gly Glu Ile 20 25 30 Cys Gly Pro Gly Ile Asp Ile Arg Asn Asp Tyr Gln Gln Leu Lys Arg 35 40 45 Leu Glu Asn Cys Thr Val Ile Glu Gly Tyr Leu His Ile Leu Leu Ile 50 55 60 Ser Lys Ala Glu Asp Tyr Arg Ser Tyr Arg Phe Pro Lys Leu Thr Val 65 70 75 80 Ile Thr Glu Tyr Leu Leu Leu Phe Arg Val Ala Gly Leu Glu Ser Leu 85 90 95 Gly Asp Leu Phe Pro Asn Leu Thr Val Ile Arg Gly Trp Lys Leu Phe 100 105 110 Tyr Asn Tyr Ala Leu Val Ile Phe Glu Met Thr Asn Leu Lys Asp Ile 115 120 125 Gly Leu Tyr Asn Leu Arg Asn Ile Thr Arg Gly Ala Ile Arg Ile Glu 130 135 140 Lys Asn Ala Asp Leu Cys Tyr Leu Ser Thr Val Asp Trp Ser Leu Ile 145 150 155 160 Leu Asp Ala Val Ser Asn Asn Tyr Ile Val Gly Asn Lys Pro Pro Lys 165 170 175 Glu Cys Gly Asp Leu Cys Pro Gly Thr Met Glu Glu Lys Pro Met Cys 180 185 190 Glu Lys Thr Thr Ile Asn Asn Glu Tyr Asn Tyr Arg Cys Trp Thr Thr 195 200 205 Asn Arg Cys Gln Lys Met Cys Pro Ser Thr Cys Gly Lys Arg Ala Cys 210 215 220 Thr Glu Asn Asn Glu Cys Cys His Pro Glu Cys Leu Gly Ser Cys Ser 225 230 235 240 Ala Pro Asp Asn Asp Thr Ala Cys Val Ala Cys Arg His Tyr Tyr Tyr 245 250 255 Ala Gly Val Cys Val Pro Ala Cys Pro Pro Asn Thr Tyr Arg Phe Glu 260 265 270 Gly Trp Arg Cys Val Asp Arg Asp Phe Cys Ala Asn Ile Leu Ser Ala 275 280 285 Glu Ser Ser Asp Ser Glu Gly Phe Val Ile His Asp Gly Glu Cys Met 290 295 300 Gln Glu Cys Pro Ser Gly Phe Ile Arg Asn Gly Ser Gln Ser Met Tyr 305 310 315 320 Cys Ile Pro Cys Glu Gly Pro Cys Pro Lys Val Cys Glu Glu Glu Lys 325 330 335 Lys Thr Lys Thr Ile Asp Ser Val Thr Ser Ala Gln Met Leu Gln Gly 340 345 350 Cys Thr Ile Phe Lys Gly Asn Leu Leu Ile Asn Ile Arg Arg Gly Asn 355 360 365 Asn Ile Ala Ser Glu Leu Glu Asn Phe Met Gly Leu Ile Glu Val Val 370 375 380 Thr Gly Tyr Val Lys Ile Arg His Ser His Ala Leu Val Ser Leu Ser 385 390 395 400 Phe Leu Lys Asn Leu Arg Leu Ile Leu Gly Glu Glu Gln Leu Glu Gly 405 410 415 Asn Tyr Ser Phe Tyr Val Leu Asp Asn Gln Asn Leu Gln Gln Leu Trp 420 425 430 Asp Trp Asp His Arg Asn Leu Thr Ile Lys Ala Gly Lys Met Tyr Phe 435 440 445 Ala Phe Asn Pro Lys Leu Cys Val Ser Glu Ile Tyr Arg Met Glu Glu 450 455 460 Val Thr Gly Thr Lys Gly Arg Gln Ser Lys Gly Asp Ile Asn Thr Arg 465 470 475 480 Asn Asn Gly Glu Arg Ala Ser Cys Glu Ser Asp Val Leu His Phe Thr 485 490 495 Ser Thr Thr Thr Ser Lys Asn Arg Ile Ile Ile Thr Trp His Arg Tyr 500 505 510 Arg Pro Pro Asp Tyr Arg Asp Leu Ile Ser Phe Thr Val Tyr Tyr Lys 515 520 525 Glu Ala Pro Phe Lys Asn Val Thr Glu Tyr Asp Gly Gln Asp Ala Cys 530 535 540 Gly Ser Asn Ser Trp Asn Met Val Asp Val Asp Leu Pro Pro Asn Lys 545 550 555 560 Asp Val Glu Pro Gly Ile Leu Leu His Gly Leu Lys Pro Trp Thr Gln 565 570 575 Tyr Ala Val Tyr Val Lys Ala Val Thr Leu Thr Met Val Glu Asn Asp 580 585 590 His Ile Arg Gly Ala Lys Ser Glu Ile Leu Tyr Ile Arg Thr Asn Ala 595 600 605 Ser Val Pro Ser Ile Pro Leu Asp Val Leu Ser Ala Ser Asn Ser Ser 610 615 620 Ser Gln Leu Ile Val Lys Trp Asn Pro Pro Ser Leu Pro Asn Gly Asn 625 630 635 640 Leu Ser Tyr Tyr Ile Val Arg Trp Gln Arg Gln Pro Gln Asp Gly Tyr 645 650 655 Leu Tyr Arg His Asn Tyr Cys Ser Lys Asp Lys Ile Pro Ile Arg Lys 660 665 670 Tyr Ala Asp Gly Thr Ile Asp Ile Glu Glu Val Thr Glu Asn Pro Lys 675 680 685 Thr Glu Val Cys Gly Gly Glu Lys Gly Pro Cys Cys Ala Cys Pro Lys 690 695 700 Thr Glu Ala Glu Lys Gln Ala Glu Lys Glu Glu Ala Glu Tyr Arg Lys 705 710 715 720 Val Phe Glu Asn Phe Leu His Asn Ser Ile Phe Val Pro Arg Pro Glu 725 730 735 Arg Lys Arg Arg Asp Val Met Gln Val Ala Asn Thr Thr Met Ser Ser 740 745 750 Arg Ser Arg Asn Thr Thr Ala Ala Asp Thr Tyr Asn Ile Thr Asp Pro 755 760 765 Glu Glu Leu Glu Thr Glu Tyr Pro Phe Phe Glu Ser Arg Val Asp Asn 770 775 780 Lys Glu Arg Thr Val Ile Ser Asn Leu Arg Pro Phe Thr Leu Tyr Arg 785 790 795 800 Ile Asp Ile His Ser Cys Asn His Glu Ala Glu Lys Leu Gly Cys Ser 805 810 815 Ala Ser Asn Phe Val Phe Ala Arg Thr Met Pro Ala Glu Gly Ala Asp 820 825 830 Asp Ile Pro Gly Pro Val Thr Trp Glu Pro Arg Pro Glu Asn Ser Ile 835 840 845 Phe Leu Lys Trp Pro Glu Pro Glu Asn Pro Asn Gly Leu Ile Leu Met 850 855 860 Tyr Glu Ile Lys Tyr Gly Ser Gln Val Glu Asp Gln Arg Glu Cys Val 865 870 875 880 Ser Arg Gln Glu Tyr Arg Lys Tyr Gly Gly Ala Lys Leu Asn Arg Leu 885 890 895 Asn Pro Gly Asn Tyr Thr Ala Arg Ile Gln Ala Thr Ser Leu Ser Gly 900 905 910 Asn Gly Ser Trp Thr Asp Pro Val Phe Phe Tyr Val Gln Ala Lys Thr 915 920 925 Gly Tyr Glu Asn Phe Ile His Leu Ile Ile Ala Leu Pro Val Ala Val 930 935 940 Leu Leu Ile Val Gly Gly Leu Val Ile Met Leu Tyr Val Phe His Arg 945 950 955 960 Lys Arg Asn Asn Ser Arg Leu Gly Asn Gly Val Leu Tyr Ala Ser Val 965 970 975 Asn Pro Glu Tyr Phe Ser Ala Ala Asp Val Tyr Val Pro Asp Glu Trp 980 985 990 Glu Val Ala Arg Glu Lys Ile Thr Met Ser Arg Glu Leu Gly Gln Gly 995 1000 1005 Ser Phe Gly Met Val Tyr Glu Gly Val Ala Lys Gly Val Val Lys 1010 1015 1020 Asp Glu Pro Glu Thr Arg Val Ala Ile Lys Thr Val Asn Glu Ala 1025 1030 1035 Ala Ser Met Arg Glu Arg Ile Glu Phe Leu Asn Glu Ala Ser Val 1040 1045 1050 Met Lys Glu Phe Asn Cys His His Val Val Arg Leu Leu Gly Val 1055 1060 1065 Val Ser Gln Gly Gln Pro Thr Leu Val Ile Met Glu Leu Met Thr 1070 1075 1080 Arg Gly Asp Leu Lys Ser Tyr Leu Arg Ser Leu Arg Pro Glu Met 1085 1090 1095 Glu Asn Asn Pro Val Leu Ala Pro Pro Ser Leu Ser Lys Met Ile 1100 1105 1110 Gln Met Ala Gly Glu Ile Ala Asp Gly Met Ala Tyr Leu Asn Ala 1115 1120 1125 Asn Lys Phe Val His Arg Asp Leu Ala Ala Arg Asn Cys Met Val 1130 1135 1140 Ala Glu Asp Phe Thr Val Lys Ile Gly Asp Phe Gly Met Thr Arg 1145 1150 1155 Asp Ile Tyr Glu Thr Asp Tyr Tyr Arg Lys Gly Gly Lys Gly Leu 1160 1165 1170 Leu Pro Val Arg Trp Met Ser Pro Glu Ser Leu Lys Asp Gly Val 1175 1180 1185 Phe Thr Thr Tyr Ser Asp Val Trp Ser Phe Gly Val Val Leu Trp 1190 1195 1200 Glu Ile Ala Thr Leu Ala Glu Gln Pro Tyr Gln Gly Leu Ser Asn 1205 1210 1215 Glu Gln Val Leu Arg Phe Val Met Glu Gly Gly Leu Leu Asp Lys 1220 1225 1230 Pro Asp Asn Cys Pro Asp Met Leu Phe Glu Leu Met Arg Met Cys 1235 1240 1245 Trp Gln Tyr Asn Pro Lys Met Arg Pro Ser Phe Leu Glu Ile Ile 1250 1255 1260 Ser Ser Ile Lys Glu Glu Met Glu Pro Gly Phe Arg Glu Val Ser 1265 1270 1275 Phe Tyr Tyr Ser Glu Glu Asn Lys Leu Pro Glu Pro Glu Glu Leu 1280 1285 1290 Asp Leu Glu Pro Glu Asn Met Glu Ser Val Pro Leu Asp Pro Ser 1295 1300 1305 Ala Ser Ser Ser Ser Leu Pro Leu Pro Asp Arg His Ser Gly His 1310 1315 1320 Lys Ala Glu Asn Gly Pro Gly Pro Gly Val Leu Val Leu Arg Ala 1325 1330 1335 Ser Phe Asp Glu Arg Gln Pro Tyr Ala His Met Asn Gly Gly Arg 1340 1345 1350 Lys Asn Glu Arg Ala Leu Pro Leu Pro Gln Ser Ser Thr Cys 1355 1360 1365 <210> 15 <211> 4 <212> PRT <213> Artificial <220> <223> Sitio de escisión de la furina <400> 15 Arg Lys Arg Arg 1 <210> 16 <211> 33 <212> ADN <213> Artificial <220> <223> Cebador directo <400> 16 cgggatccgc caccatgaag tctggctccg gag 33 <210> 17 <211> 34 <212> ADN <213> Artificial <220> <223> Cebador inverso <400> 17 gctctagatc agaagttttc atatcctgtt ttgg 34 <210> 18 <211> 45 <212> ADN <213> Artificial <220> <223> Cebador MJ1 <400> 18 gcccagccgg ccatggccsm kgtgcagctg gtggaktctg gggga 45 <210> 19 <211> 45 <212> ADN <213> Artificial <220> <223> Cebador MJ2 <400> 19 gcccagccgg ccatggccca ggtaaagctg gaggagtctg gggga 45 <210> 20 <211> 45 <212> ADN <213> Artificial <220> <223> Cebador MJ3 <400> 20 gcccagccgg ccatggccca ggctcaggta cagctggtgg agtct 45 <210> 21 <211> 21 <212> ADN <213> Artificial <220> <223> Cebador CH2 <400> 21 cgccatcaag gtaccagttg a 21 <210> 22 <211> 29 <212> ADN <213> Artificial <220> <223> Cebador CH2b3 <400> 22 ggggtacctg tcatccacgg accagctga 29 <210> 23 <211> 34 <212> ADN <213> Artificial <220> <223> Cebador MJ7 <400> 23 catgtgtaga ctcgcggccc agccggccat ggcc 34 <210> 24 <211> 47 <212> ADN <213> Artificial <220> <223> Cebador MJ8 <400> 24 catgtgtaga ttcctggccg gcctggcctg aggagacggt gacctgg 47 <210> 25 <211> 38 <212> ADN <213> Artificial <220> <223> Cebador directo <400> 25 tatgaagaca ccaggcccag gtaaagctgg aggagtct 38 <210> 26 <211> 30 <212> ADN <213> Artificial <220> <223> Cebador inverso <400> 26 ttgttcggat cctgaggaga cggtgacctg 30 <210> 27 <211> 14 <212> PRT <213> Artificial <220> <223> Péptido IGF1R-5 <400> 27 Glu Phe Val Ala Thr Ile Asp Trp Gly Asp Gly Gly Ala Arg 1 5 10 <210> 28 <211> 11 <212> PRT <213> Artificial <220> <223> Péptido IGF1R-5 <400> 28 Thr Ile Asp Asn Tyr Ala Met Ala Trp Ser Arg 1 5 10 <210> 29 <211> 16 <212> PRT <213> Artificial <220> <223> Péptido IGF1R-5 <400> 29 Leu Glu Glu Ser Gly Gly Gly Leu Val Gln Ala Gly Gly Ser Leu Arg 1 5 10 15 <210> 30 <211> 15 <212> PRT <213> Artificial <220> <223> Péptido FC5 y FC5_ILIS <400> 30 Ile Thr Trp Gly Gly Asp Asn Thr Phe Tyr Ser Asn Ser Val Lys 1 5 10 15 <210> 31 <211> 9 <212> PRT <213> Artificial <220> <223> Péptido A20.1 <400> 31 Thr Thr Tyr Tyr Ala Asp Ser Val Lys 1 5 <210> 32 <211> 11 <212> PRT <213> Artificial <220> <223> Péptido A20.1 <400> 32 Glu Phe Val Ala Ala Gly Ser Ser Thr Gly Arg 1 5 10 <210> 33 <211> 11 <212> PRT <213> Artificial <220> <223> Péptido A20.1 <400> 33 Thr Phe Ser Met Asp Pro Met Ala Trp Phe Arg 1 5 10 <210> 34 <211> 26 <212> PRT <213> Artificial <220> <223> Péptido A20.1 <400> 34 Asp Glu Tyr Ala Tyr Trp Gly Gln Gly Thr Gln Val Thr Val Ser Ser 1 5 10 15 Gly Gln Ala Gly Gln Gly Ser Glu Gln Lys 20 25 <210> 35 <211> 11 <212> PRT <213> Artificial <220> <223> Péptido EG2 <400> 35 Asp Phe Ser Asp Tyr Val Met Gly Trp Phe Arg 1 5 10 <210> 36 <211> 16 <212> PRT <213> Artificial <220> <223> Péptido EG2 <400> 36 Leu Glu Glu Ser Gly Gly Gly Leu Val Gln Ala Gly Asp Ser Leu Arg 1 5 10 15 <210> 37 <211> 32 <212> PRT <213> Artificial <220> <223> Péptido EG2 <400> 37 Asn Met Val Tyr Leu Gln Met Asn Ser Leu Lys Pro Glu Asp Thr Ala 1 5 10 15 Val Tyr Tyr Cys Ala Val Asn Ser Ala Gly Thr Tyr Val Ser Pro Arg 20 25 30 <210> 38 <211> 14 <212> PRT <213> Artificial <220> <223> Péptido de albúmina <400> 38 Ala Pro Gln Val Ser Thr Pro Thr Leu Val Glu Ala Ala Arg 1 5 10 <210> 39 <211> 29 <212> PRT <213> Artificial <220> <223> Galanin-cisteamida <400> 39 Gly Trp Thr Leu Asn Ser Ala Gly Tyr Leu Leu Gly Pro His Ala Ile 1 5 10 15 Asp Asn His Arg Ser Phe Ser Asp Lys His Gly Leu Thr 20 25 <210> 40 <211> 19 <212> PRT <213> Artificial <220> <223> Señal <400> 40 Met Glu Phe Gly Leu Ser Trp Val Phe Leu Val Ala Ile Leu Lys Gly 1 5 10 15 Val Gln Cys <210> 41 <211> 370 <212> PRT <213> Artificial <220> <223> Fusión consenso IGF1R-5-mFc <220> <221> MISC_FEATURE <222> (1)..(1) <223> Xaa es Glu o Gln <220> <221> MISC_FEATURE <222> (3)..(3) <223> Xaa es Lys o Gln <220> <221> MISC_FEATURE <222> (5)..(5) <223> Xaa es Val o Glu <220> <221> MISC_FEATURE <222> (14)..(14) <223> Xaa es Ala o Pro <220> <221> MISC_FEATURE <222> (37)..(37) <223> Xaa es Val o Ser <220> <221> MISC_FEATURE <222> (44)..(44) <223> Xaa es Asp o Gly <220> <221> MISC_FEATURE <222> (45)..(45) <223> Xaa es Leu o Arg <220> <221> MISC_FEATURE <222> (47)..(47) <223> Xaa es Phe o Trp <220> <221> MISC_FEATURE <222> (49)..(49) <223> Xaa es Ala o Ser <220> <221> MISC_FEATURE <222> (58)..(58) <223> Xaa es Ala o Thr <220> <221> MISC_FEATURE <222> (75)..(75) <223> Xaa es Ala o Ser <220> <221> MISC_FEATURE <222> (77)..(77) <223> Xaa es Gly o Asn <220> <221> MISC_FEATURE <222> (79)..(79) <223> Xaa es Met o Leu <220> <221> MISC_FEATURE <222> (85)..(85) <223> Xaa es Asn o Arg <220> <221> MISC_FEATURE <222> (87)..(87) <223> Xaa es Glu o Arg <220> <221> MISC_FEATURE <222> (88)..(88) <223> Xaa es Pro o Ala <220> <221> MISC_FEATURE <222> (95)..(95) <223> Xaa es Ser o Tyr <220> <221> MISC_FEATURE <222> (119)..(119) <223> Xaa es Gln o Leu <400> 41 Xaa Val Xaa Leu Xaa Glu Ser Gly Gly Gly Leu Val Gln Xaa Gly Gly 1 5 10 15 Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Arg Thr Ile Asp Asn Tyr 20 25 30 Ala Met Ala Trp Xaa Arg Gln Ala Pro Gly Lys Xaa Xaa Glu Xaa Val 35 40 45 Xaa Thr Ile Asp Trp Gly Asp Gly Gly Xaa Arg Tyr Ala Asn Ser Val 50 55 60 Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Xaa Lys Xaa Thr Xaa Tyr 65 70 75 80 Leu Gln Met Asn Xaa Leu Xaa Xaa Glu Asp Thr Ala Val Tyr Xaa Cys 85 90 95 Ala Met Ala Arg Gln Ser Arg Val Asn Leu Asp Val Ala Arg Tyr Asp 100 105 110 Tyr Trp Gly Gln Gly Thr Xaa Val Thr Val Ser Ser Met Thr Val Asp 115 120 125 Lys Lys Leu Glu Pro Ser Gly Pro Ile Ser Thr Ile Asn Pro Cys Pro 130 135 140 Pro Cys Lys Glu Cys His Lys Cys Pro Ala Pro Asn Leu Glu Gly Gly 145 150 155 160 Pro Ser Val Phe Ile Phe Pro Pro Asn Ile Lys Asp Val Leu Met Ile 165 170 175 Ser Leu Thr Pro Lys Val Thr Cys Val Val Val Asp Val Ser Glu Asp 180 185 190 Asp Pro Asp Val Gln Ile Ser Trp Phe Val Asn Asn Val Glu Val His 195 200 205 Thr Ala Gln Thr Gln Thr His Arg Glu Asp Tyr Asn Ser Thr Ile Arg 210 215 220 Val Val Ser Thr Leu Pro Ile Gln His Gln Asp Trp Met Ser Gly Lys 225 230 235 240 Glu Phe Lys Cys Lys Val Asn Asn Lys Asp Leu Pro Ser Pro Ile Glu 245 250 255 Arg Thr Ile Ser Lys Ile Lys Gly Leu Val Arg Ala Pro Gln Val Tyr 260 265 270 Ile Leu Pro Pro Pro Ala Glu Gln Leu Ser Arg Lys Asp Val Ser Leu 275 280 285 Thr Cys Leu Val Val Gly Phe Asn Pro Gly Asp Ile Ser Val Glu Trp 290 295 300 Thr Ser Asn Gly His Thr Glu Glu Asn Tyr Lys Asp Thr Ala Pro Val 305 310 315 320 Leu Asp Ser Asp Gly Ser Tyr Phe Ile Tyr Ser Lys Leu Asn Met Lys 325 330 335 Thr Ser Lys Trp Glu Lys Thr Asp Ser Phe Ser Cys Asn Val Arg His 340 345 350 Glu Gly Leu Lys Asn Tyr Tyr Leu Lys Lys Thr Ile Ser Arg Ser Pro 355 360 365 Gly Lys 370 <210> 42 <211> 371 <212> PRT <213> Artificial <220> <223> mFc-IGF1R-5 consensus fusion <220> <221> MISC_FEATURE <222> (248)..(248) <223> Xaa es Glu o Gln <220> <221> MISC_FEATURE <222> (250)..(250) <223> Xaa es Lys o Gln <220> <221> MISC_FEATURE <222> (252)..(252) <223> Xaa es Val o Glu <220> <221> MISC_FEATURE <222> (261)..(261) <223> Xaa es Ala o Pro <220> <221> MISC_FEATURE <222> (284)..(284) <223> Xaa es Val o Ser <220> <221> MISC_FEATURE <222> (291)..(291) <223> Xaa es Asp o Gly <220> <221> MISC_FEATURE <222> (292)..(292) <223> Xaa es Leu o Arg <220> <221> MISC_FEATURE <222> (294)..(294) <223> Xaa es Phe o Trp <220> <221> MISC_FEATURE <222> (296)..(296) <223> Xaa es Ala o Ser <220> <221> MISC_FEATURE <222> (305)..(305) <223> Xaa es Ala o Thr <220> <221> MISC_FEATURE <222> (322)..(322) <223> Xaa es Ala o Ser <220> <221> MISC_FEATURE <222> (324)..(324) <223> Xaa es Ala o Ser <220> <221> MISC_FEATURE <222> (326)..(326) <223> Xaa es Gly o Asn <220> <221> MISC_FEATURE <222> (332)..(332) <223> Xaa es Met o Leu <220> <221> MISC_FEATURE <222> (332)..(332) <223> Xaa es Asn o Arg <220> <221> MISC_FEATURE <222> (334)..(334) <223> Xaa es Glu o Arg <220> <221> MISC_FEATURE <222> (335)..(335) <223> Xaa es Pro o Ala <220> <221> MISC_FEATURE <222> (342)..(342) <223> Xaa es Ser o Tyr <220> <221> MISC_FEATURE <222> (366)..(366) <223> Xaa es Gln o Leu <400> 42 Glu Pro Ser Gly Pro Ile Ser Thr Ile Asn Pro Cys Pro Pro Cys Lys 1 5 10 15 Glu Cys His Lys Cys Pro Ala Pro Asn Leu Glu Gly Gly Pro Ser Val 20 25 30 Phe Ile Phe Pro Pro Asn Ile Lys Asp Val Leu Met Ile Ser Leu Thr 35 40 45 Pro Lys Val Thr Cys Val Val Val Asp Val Ser Glu Asp Asp Pro Asp 50 55 60 Val Gln Ile Ser Trp Phe Val Asn Asn Val Glu Val His Thr Ala Gln 65 70 75 80 Thr Gln Thr His Arg Glu Asp Tyr Asn Ser Thr Ile Arg Val Val Ser 85 90 95 Thr Leu Pro Ile Gln His Gln Asp Trp Met Ser Gly Lys Glu Phe Lys 100 105 110 Cys Lys Val Asn Asn Lys Asp Leu Pro Ser Pro Ile Glu Arg Thr Ile 115 120 125 Ser Lys Ile Lys Gly Leu Val Arg Ala Pro Gln Val Tyr Ile Leu Pro 130 135 140 Pro Pro Ala Glu Gln Leu Ser Arg Lys Asp Val Ser Leu Thr Cys Leu 145 150 155 160 Val Val Gly Phe Asn Pro Gly Asp Ile Ser Val Glu Trp Thr Ser Asn 165 170 175 Gly His Thr Glu Glu Asn Tyr Lys Asp Thr Ala Pro Val Leu Asp Ser 180 185 190 Asp Gly Ser Tyr Phe Ile Tyr Ser Lys Leu Asn Met Lys Thr Ser Lys 195 200 205 Trp Glu Lys Thr Asp Ser Phe Ser Cys Asn Val Arg His Glu Gly Leu 210 215 220 Lys Asn Tyr Tyr Leu Lys Lys Thr Ile Ser Arg Ser Pro Gly Gly Gly 225 230 235 240 Gly Ser Gly Gly Gly Gly Ser Xaa Val Xaa Leu Xaa Glu Ser Gly Gly 245 250 255 Gly Leu Val Gln Xaa Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser 260 265 270 Gly Arg Thr Ile Asp Asn Tyr Ala Met Ala Trp Xaa Arg Gln Ala Pro 275 280 285 Gly Lys Xaa Xaa Glu Xaa Val Xaa Thr Ile Asp Trp Gly Asp Gly Gly 290 295 300 Xaa Arg Tyr Ala Asn Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp 305 310 315 320 Asn Xaa Lys Xaa Thr Xaa Tyr Leu Gln Met Asn Xaa Leu Xaa Xaa Glu 325 330 335 Asp Thr Ala Val Tyr Xaa Cys Ala Met Ala Arg Gln Ser Arg Val Asn 340 345 350 Leu Asp Val Ala Arg Tyr Asp Tyr Trp Gly Gln Gly Thr Xaa Val Thr 355 360 365 Val Ser Ser 370