LISTADO DE SECUENCIAS <110> MacroGenics, Inc. La Motte-Mohs, Ross Shah, Kalpana Smith, Douglas H. Johnson, Leslie Moore, Paul Bonvini, Ezio Koenig, Scott <120> MOLÉCULAS DE UNIÓN A LAG-3 Y MÉTODOS DE USO DE LAS MISMAS <130> 1301.0121PCT <150> US 62/255,094 <151> 2015-11-13 <150> US 62/172,277 <151> 2015-06-08 <160> 140 <170> PatentIn versión 3.5 <210> 1 <211> 217 <212> PRT <213> Homo sapiens <220> <221> CARACTERÍSTICA_MISCELÁNEA <222> (1)..(217) <223> Región Fc de IgG1 <220> <221> CARACTERÍSTICA_MISCELÁNEA <222> (217)..(217) <223> Xaa217 es Lisina (K) o Ausente <400> 1 Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys 1 5 10 15 Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val 20 25 30 Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr 35 40 45 Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu 50 55 60 Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His 65 70 75 80 Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys 85 90 95 Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln 100 105 110 Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met 115 120 125 Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro 130 135 140 Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn 145 150 155 160 Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu 165 170 175 Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val 180 185 190 Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln 195 200 205 Lys Ser Leu Ser Leu Ser Pro Gly Xaa 210 215 <210> 2 <211> 216 <212> PRT <213> Homo sapiens <220> <221> CARACTERÍSTICA_MISCELÁNEA <222> (1)..(216) <223> Región Fc de IgG2 <220> <221> CARACTERÍSTICA_MISCELÁNEA <222> (216)..(216) <223> Xaa216 es Lisina (K) o Ausente <400> 2 Ala Pro Pro Val Ala Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro 1 5 10 15 Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val 20 25 30 Val Asp Val Ser His Glu Asp Pro Glu Val Gln Phe Asn Trp Tyr Val 35 40 45 Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln 50 55 60 Phe Asn Ser Thr Phe Arg Val Val Ser Val Leu Thr Val Val His Gln 65 70 75 80 Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Gly 85 90 95 Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Thr Lys Gly Gln Pro 100 105 110 Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr 115 120 125 Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser 130 135 140 Asp Ile Ser Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr 145 150 155 160 Lys Thr Thr Pro Pro Met Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr 165 170 175 Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe 180 185 190 Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys 195 200 205 Ser Leu Ser Leu Ser Pro Gly Xaa 210 215 <210> 3 <211> 217 <212> PRT <213> Homo sapiens <220> <221> CARACTERÍSTICA_MISCELÁNEA <222> (1)..(217) <223> IgG3 Fc <220> <221> CARACTERÍSTICA_MISCELÁNEA <222> (217)..(217) <223> Xaa217 es Lisina (K) o Ausente <400> 3 Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys 1 5 10 15 Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val 20 25 30 Val Val Asp Val Ser His Glu Asp Pro Glu Val Gln Phe Lys Trp Tyr 35 40 45 Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu 50 55 60 Gln Tyr Asn Ser Thr Phe Arg Val Val Ser Val Leu Thr Val Leu His 65 70 75 80 Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys 85 90 95 Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Thr Lys Gly Gln 100 105 110 Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met 115 120 125 Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro 130 135 140 Ser Asp Ile Ala Val Glu Trp Glu Ser Ser Gly Gln Pro Glu Asn Asn 145 150 155 160 Tyr Asn Thr Thr Pro Pro Met Leu Asp Ser Asp Gly Ser Phe Phe Leu 165 170 175 Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Ile 180 185 190 Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn Arg Phe Thr Gln 195 200 205 Lys Ser Leu Ser Leu Ser Pro Gly Xaa 210 215 <210> 4 <211> 217 <212> PRT <213> Homo sapiens <220> <221> CARACTERÍSTICA_MISCELÁNEA <222> (1)..(217) <223> Región Fc de IgG4 <220> <221> CARACTERÍSTICA_MISCELÁNEA <222> (217)..(217) <223> Xaa217 es Lisina (K) o Ausente <400> 4 Ala Pro Glu Phe Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys 1 5 10 15 Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val 20 25 30 Val Val Asp Val Ser Gln Glu Asp Pro Glu Val Gln Phe Asn Trp Tyr 35 40 45 Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu 50 55 60 Gln Phe Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His 65 70 75 80 Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys 85 90 95 Gly Leu Pro Ser Ser Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln 100 105 110 Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Gln Glu Glu Met 115 120 125 Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro 130 135 140 Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn 145 150 155 160 Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu 165 170 175 Tyr Ser Arg Leu Thr Val Asp Lys Ser Arg Trp Gln Glu Gly Asn Val 180 185 190 Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln 195 200 205 Lys Ser Leu Ser Leu Ser Leu Gly Xaa 210 215 <210> 5 <211> 525 <212> PRT <213> Homo sapiens <220> <221> CARACTERÍSTICA_MISCELÁNEA <222> (1)..(525) <223> LAG-3 <400> 5 Met Trp Glu Ala Gln Phe Leu Gly Leu Leu Phe Leu Gln Pro Leu Trp 1 5 10 15 Val Ala Pro Val Lys Pro Leu Gln Pro Gly Ala Glu Val Pro Val Val 20 25 30 Trp Ala Gln Glu Gly Ala Pro Ala Gln Leu Pro Cys Ser Pro Thr Ile 35 40 45 Pro Leu Gln Asp Leu Ser Leu Leu Arg Arg Ala Gly Val Thr Trp Gln 50 55 60 His Gln Pro Asp Ser Gly Pro Pro Ala Ala Ala Pro Gly His Pro Leu 65 70 75 80 Ala Pro Gly Pro His Pro Ala Ala Pro Ser Ser Trp Gly Pro Arg Pro 85 90 95 Arg Arg Tyr Thr Val Leu Ser Val Gly Pro Gly Gly Leu Arg Ser Gly 100 105 110 Arg Leu Pro Leu Gln Pro Arg Val Gln Leu Asp Glu Arg Gly Arg Gln 115 120 125 Arg Gly Asp Phe Ser Leu Trp Leu Arg Pro Ala Arg Arg Ala Asp Ala 130 135 140 Gly Glu Tyr Arg Ala Ala Val His Leu Arg Asp Arg Ala Leu Ser Cys 145 150 155 160 Arg Leu Arg Leu Arg Leu Gly Gln Ala Ser Met Thr Ala Ser Pro Pro 165 170 175 Gly Ser Leu Arg Ala Ser Asp Trp Val Ile Leu Asn Cys Ser Phe Ser 180 185 190 Arg Pro Asp Arg Pro Ala Ser Val His Trp Phe Arg Asn Arg Gly Gln 195 200 205 Gly Arg Val Pro Val Arg Glu Ser Pro His His His Leu Ala Glu Ser 210 215 220 Phe Leu Phe Leu Pro Gln Val Ser Pro Met Asp Ser Gly Pro Trp Gly 225 230 235 240 Cys Ile Leu Thr Tyr Arg Asp Gly Phe Asn Val Ser Ile Met Tyr Asn 245 250 255 Leu Thr Val Leu Gly Leu Glu Pro Pro Thr Pro Leu Thr Val Tyr Ala 260 265 270 Gly Ala Gly Ser Arg Val Gly Leu Pro Cys Arg Leu Pro Ala Gly Val 275 280 285 Gly Thr Arg Ser Phe Leu Thr Ala Lys Trp Thr Pro Pro Gly Gly Gly 290 295 300 Pro Asp Leu Leu Val Thr Gly Asp Asn Gly Asp Phe Thr Leu Arg Leu 305 310 315 320 Glu Asp Val Ser Gln Ala Gln Ala Gly Thr Tyr Thr Cys His Ile His 325 330 335 Leu Gln Glu Gln Gln Leu Asn Ala Thr Val Thr Leu Ala Ile Ile Thr 340 345 350 Val Thr Pro Lys Ser Phe Gly Ser Pro Gly Ser Leu Gly Lys Leu Leu 355 360 365 Cys Glu Val Thr Pro Val Ser Gly Gln Glu Arg Phe Val Trp Ser Ser 370 375 380 Leu Asp Thr Pro Ser Gln Arg Ser Phe Ser Gly Pro Trp Leu Glu Ala 385 390 395 400 Gln Glu Ala Gln Leu Leu Ser Gln Pro Trp Gln Cys Gln Leu Tyr Gln 405 410 415 Gly Glu Arg Leu Leu Gly Ala Ala Val Tyr Phe Thr Glu Leu Ser Ser 420 425 430 Pro Gly Ala Gln Arg Ser Gly Arg Ala Pro Gly Ala Leu Pro Ala Gly 435 440 445 His Leu Leu Leu Phe Leu Ile Leu Gly Val Leu Ser Leu Leu Leu Leu 450 455 460 Val Thr Gly Ala Phe Gly Phe His Leu Trp Arg Arg Gln Trp Arg Pro 465 470 475 480 Arg Arg Phe Ser Ala Leu Glu Gln Gly Ile His Pro Pro Gln Ala Gln 485 490 495 Ser Lys Ile Glu Glu Leu Glu Gln Glu Pro Glu Pro Glu Pro Glu Pro 500 505 510 Glu Pro Glu Pro Glu Pro Glu Pro Glu Pro Glu Gln Leu 515 520 525 <210> 6 <211> 120 <212> PRT <213> Mus musculus <220> <221> CARACTERÍSTICA_MISCELÁNEA <222> (1)..(120) <223> LAG-3 mAb 1 VH <400> 6 Gln Ile Gln Leu Val Gln Ser Gly Pro Glu Leu Lys Lys Pro Gly Glu 1 5 10 15 Thr Val Lys Ile Ser Cys Lys Ala Ser Gly Tyr Thr Phe Arg Asn Tyr 20 25 30 Gly Met Asn Trp Val Lys Gln Ala Pro Gly Lys Val Leu Lys Trp Met 35 40 45 Gly Trp Ile Asn Thr Tyr Thr Gly Glu Ser Thr Tyr Ala Asp Asp Phe 50 55 60 Glu Gly Arg Phe Ala Phe Ser Leu Gly Thr Ser Ala Ser Thr Ala Tyr 65 70 75 80 Leu Gln Ile Asn Ile Leu Lys Asn Glu Asp Thr Ala Thr Tyr Phe Cys 85 90 95 Ala Arg Glu Ser Leu Tyr Asp Tyr Tyr Ser Met Asp Tyr Trp Gly Gln 100 105 110 Gly Thr Ser Val Thr Val Ser Ser 115 120 <210> 7 <211> 360 <212> ADN <213> Mus musculus <220> <221> CARACTERÍSTICA_MISCELÁNEA <223> Polinucleótido que codifica LAG-3 mAb 1 VH <400> 7 cagatccagt tggtgcagtc tggacctgag ctgaagaagc ctggagagac agtcaagatc 60 tcctgcaagg cttctgggta taccttcaga aactatggaa tgaactgggt gaagcaggct 120 ccaggaaagg ttttaaagtg gatgggctgg ataaacacct acactggaga gtcaacatat 180 gctgatgact tcgagggacg gtttgccttc tctttgggaa cctctgccag cactgcctat 240 ttgcagatca acatcctcaa aaatgaggac acggctacat atttctgtgc aagagaatcc 300 ctctatgatt actattctat ggactactgg ggtcaaggaa cctcagtcac cgtctcctca 360 <210> 8 <211> 5 <212> PRT <213> Mus musculus <220> <221> CARACTERÍSTICA_MISCELÁNEA <222> (1)..(5) <223> LAG-3 mAb 1 VH CDR 1 <400> 8 Asn Tyr Gly Met Asn 1 5 <210> 9 <211> 17 <212> PRT <213> Mus musculus <220> <221> CARACTERÍSTICA_MISCELÁNEA <222> (1)..(17) <223> LAG-3 mAb 1 VH CDR2 <400> 9 Trp Ile Asn Thr Tyr Thr Gly Glu Ser Thr Tyr Ala Asp Asp Phe Glu 1 5 10 15 Gly <210> 10 <211> 11 <212> PRT <213> Mus musculus <220> <221> CARACTERÍSTICA_MISCELÁNEA <222> (1)..(11) <223> LAG-3 mAb 1 VH CDR3 <400> 10 Glu Ser Leu Tyr Asp Tyr Tyr Ser Met Asp Tyr 1 5 10 <210> 11 <211> 112 <212> PRT <213> Mus musculus <220> <221> CARACTERÍSTICA_MISCELÁNEA <222> (1)..(112) <223> LAG-3 mAb 1 VL <400> 11 Asp Val Val Val Thr Gln Thr Pro Leu Thr Leu Ser Val Thr Ile Gly 1 5 10 15 Gln Pro Ala Ser Ile Ser Cys Lys Ser Ser Gln Ser Leu Leu His Ser 20 25 30 Asp Gly Lys Thr Tyr Leu Asn Trp Leu Leu Gln Arg Pro Gly Gln Ser 35 40 45 Pro Glu Arg Leu Ile Tyr Leu Val Ser Glu Leu Asp Ser Gly Val Pro 50 55 60 Asp Arg Phe Thr 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 Tyr Cys Trp Gln Gly 85 90 95 Thr His Phe Pro Tyr Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys 100 105 110 <210> 12 <211> 336 <212> ADN <213> Mus musculus <220> <221> CARACTERÍSTICA_MISCELÁNEA <223> Polinucleótido que codifica LAG-3 mAb 1 VL <400> 12 gatgttgtgg tgacccagac tccactcact ttgtcggtta ccattggaca accagcctcc 60 atctcttgca agtcaagtca gagcctctta catagtgatg gaaagacata tttgaattgg 120 ttgttacaga ggccaggcca gtctccagag cgcctaatct atctggtgtc tgaactggac 180 tctggagtcc ctgacaggtt cactggcagt ggatcaggga cagatttcac actgaaaatc 240 agcagagtgg aggctgagga tttgggagtt tattattgct ggcaaggtac acattttccg 300 tacacgttcg gaggggggac caagctggaa ataaaa 336 <210> 13 <211> 16 <212> PRT <213> Mus musculus <220> <221> CARACTERÍSTICA_MISCELÁNEA <222> (1)..(16) <223> LAG-3 mAb 1 VL CDR1 <400> 13 Lys Ser Ser Gln Ser Leu Leu His Ser Asp Gly Lys Thr Tyr Leu Asn 1 5 10 15 <210> 14 <211> 7 <212> PRT <213> Mus musculus <220> <221> CARACTERÍSTICA_MISCELÁNEA <222> (1)..(7) <223> LAG-3 mAb 1 VL CDR2 <400> 14 Leu Val Ser Glu Leu Asp Ser 1 5 <210> 15 <211> 9 <212> PRT <213> Mus musculus <220> <221> CARACTERÍSTICA_MISCELÁNEA <222> (1)..(9) <223> LAG-3 mAb 1 VL CDR3 <400> 15 Trp Gln Gly Thr His Phe Pro Tyr Thr 1 5 <210> 16 <211> 120 <212> PRT <213> Secuencia Artificial <220> <223> hLAG-3 mAb 1 VH1 <400> 16 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 Asn Tyr 20 25 30 Gly Met Asn Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met 35 40 45 Gly Trp Ile Asn Thr Tyr Thr Gly Glu Ser Thr Tyr Ala Asp Asp Phe 50 55 60 Glu Gly Arg Phe Val Phe Ser Met Asp Thr Ser Ala Ser Thr Ala Tyr 65 70 75 80 Leu Gln Ile Ser Ser Leu Lys Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Ala Arg Glu Ser Leu Tyr Asp Tyr Tyr Ser Met Asp Tyr Trp Gly Gln 100 105 110 Gly Thr Thr Val Thr Val Ser Ser 115 120 <210> 17 <211> 360 <212> ADN <213> Secuencia Artificial <220> <223> Polinucleótido que codifica hLAG-3 mAb 1 VH1 <400> 17 caggtgcaac tggttcaatc cggcgccgag gtgaaaaagc ctggcgcctc cgtgaaagtg 60 tcctgtaagg catctgggta tacgttcaca aattatggta tgaactgggt gcgacaggca 120 ccagggcagg gactggaatg gatggggtgg atcaatactt atacaggcga gagtacttat 180 gctgacgatt tcgagggcag atttgtcttc tccatggaca ccagcgctag taccgcttat 240 ctccagatta gttctctcaa ggcggaggac acagctgttt attattgtgc ccgcgagagt 300 ttgtatgact actatagcat ggattactgg ggacaaggta caaccgtgac agtgagttcc 360 <210> 18 <211> 120 <212> PRT <213> Secuencia Artificial <220> <223> hLAG-3 mAb 1 VH2 <400> 18 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 Asn Tyr 20 25 30 Gly Met Asn Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met 35 40 45 Gly Trp Ile Asn Thr Tyr Thr Gly Glu Ser Thr Tyr Ala Asp Asp Phe 50 55 60 Glu Gly Arg Phe Val Phe Ser Met Asp Thr Ser Ala Ser Thr Ala Tyr 65 70 75 80 Leu Gln Ile Ser Ser Leu Lys Ala Glu Asp Thr Ala Val Tyr Phe Cys 85 90 95 Ala Arg Glu Ser Leu Tyr Asp Tyr Tyr Ser Met Asp Tyr Trp Gly Gln 100 105 110 Gly Thr Thr Val Thr Val Ser Ser 115 120 <210> 19 <211> 360 <212> ADN <213> Secuencia Artificial <220> <223> Polinucleótido que codifica hLAG-3 mAb 1 VH2 <400> 19 caggtgcaac tggttcaatc cggcgccgag gtgaaaaagc ctggcgcctc cgtgaaagtg 60 tcctgtaagg catctgggta tacgttcaca aattatggta tgaactgggt gcgacaggca 120 ccagggcagg gactggaatg gatggggtgg atcaatactt atacaggcga gagtacttat 180 gctgacgatt tcgagggcag atttgtcttc tccatggaca ccagcgctag taccgcttat 240 ctccagatta gttctctcaa ggcggaggac acagctgttt atttctgtgc ccgcgagagt 300 ttgtatgact actatagcat ggattactgg ggacaaggta caaccgtgac agtgagttcc 360 <210> 20 <211> 112 <212> PRT <213> Secuencia Artificial <220> <223> hLAG-3 mAb 1 VL1 <400> 20 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 Lys Ser Ser Gln Ser Leu Leu His Ser 20 25 30 Asp Gly Lys Thr Tyr Leu Asn Trp Leu Leu Gln Lys Pro Gly Gln Ser 35 40 45 Pro Glu Arg Leu Ile Tyr Leu Val Ser Glu Leu Asp 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 Trp Gln Gly 85 90 95 Thr His Phe Pro Tyr Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys 100 105 110 <210> 21 <211> 336 <212> ADN <213> Secuencia Artificial <220> <223> Polinucleótido que codifica hLAG-3 mAb 1 VL1 <400> 21 gatatcgtta tgactcagac accactgtca ctgagtgtga ccccaggtca gcccgctagt 60 atttcctgta aatcatccca gtccctcctg catagcgatg gaaagaccta tttgaactgg 120 cttctgcaga aaccaggcca aagtccagag agattgatct acctcgtttc agaactcgac 180 agtggagtgc ccgatcgctt ctcagggtcc ggctctggga ctgattttac tctcaagatc 240 tcaagagtgg aggccgagga cgtcggggtt tactactgtt ggcagggtac ccacttccct 300 tatacatttg gcggaggcac aaaagtggag attaaa 336 <210> 22 <211> 112 <212> PRT <213> Secuencia Artificial <220> <223> hLAG-3 mAb 1 VL2 <400> 22 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 Lys Ser Ser Gln Ser Leu Leu His Ser 20 25 30 Asp Gly Lys Thr Tyr Leu Asn Trp Leu Leu Gln Arg Pro Gly Gln Ser 35 40 45 Pro Glu Arg Leu Ile Tyr Leu Val Ser Glu Leu Asp 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 Trp Gln Gly 85 90 95 Thr His Phe Pro Tyr Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys 100 105 110 <210> 23 <211> 336 <212> ADN <213> Secuencia Artificial <220> <223> Polinucleótido que codifica hLAG-3 mAb 1 VL2 <400> 23 gatatcgtta tgactcagac accactgtca ctgagtgtga ccccaggtca gcccgctagt 60 atttcctgta aatcatccca gtccctcctg catagcgatg gaaagaccta tttgaactgg 120 cttctgcaga gaccaggcca aagtccagag agattgatct acctcgtttc agaactcgac 180 agtggagtgc ccgatcgctt ctcagggtcc ggctctggga ctgattttac tctcaagatc 240 tcaagagtgg aggccgagga cgtcggggtt tactactgtt ggcagggtac ccacttccct 300 tatacatttg gcggaggcac aaaagtggag attaaa 336 <210> 24 <211> 112 <212> PRT <213> Secuencia Artificial <220> <223> hLAG-3 mAb 1 VL3 <400> 24 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 Lys Ser Ser Gln Ser Leu Leu His Ser 20 25 30 Asp Gly Lys Thr Tyr Leu Asn Trp Leu Leu Gln Lys Pro Gly Gln Pro 35 40 45 Pro Glu Arg Leu Ile Tyr Leu Val Ser Glu Leu Asp 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 Trp Gln Gly 85 90 95 Thr His Phe Pro Tyr Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys 100 105 110 <210> 25 <211> 336 <212> ADN <213> Secuencia Artificial <220> <223> Polinucleótido que codifica hLAG-3 mAb 1 VL3 <400> 25 gatatcgtta tgactcagac accactgtca ctgagtgtga ccccaggtca gcccgctagt 60 atttcctgta aatcatccca gtccctcctg catagcgatg gaaagaccta tttgaactgg 120 cttctgcaga aaccaggcca accgccagag agattgatct acctcgtttc agaactcgac 180 agtggagtgc ccgatcgctt ctcagggtcc ggctctggga ctgattttac tctcaagatc 240 tcaagagtgg aggccgagga cgtcggggtt tactactgtt ggcagggtac ccacttccct 300 tatacatttg gcggaggcac aaaagtggag attaaa 336 <210> 26 <211> 112 <212> PRT <213> Secuencia Artificial <220> <223> hLAG-3 mAb 1 VL4 <400> 26 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 Lys Ser Ser Gln Ser Leu Leu His Ser 20 25 30 Asp Ala Lys Thr Tyr Leu Asn Trp Leu Leu Gln Lys Pro Gly Gln Pro 35 40 45 Pro Glu Arg Leu Ile Tyr Leu Val Ser Glu Leu Asp 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 Trp Gln Gly 85 90 95 Thr His Phe Pro Tyr Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys 100 105 110 <210> 27 <211> 336 <212> ADN <213> Secuencia Artificial <220> <223> Polinucleótido que codifica hLAG-3 mAb 1 VL4 <400> 27 gatatcgtta tgactcagac accactgtca ctgagtgtga ccccaggtca gcccgctagt 60 atttcctgta aatcatccca gtccctcctg catagcgatg caaagaccta tttgaactgg 120 cttctgcaga aaccaggcca accgccagag agattgatct acctcgtttc agaactcgac 180 agtggagtgc ccgatcgctt ctcagggtcc ggctctggga ctgattttac tctcaagatc 240 tcaagagtgg aggccgagga cgtcggggtt tactactgtt ggcagggtac ccacttccct 300 tatacatttg gcggaggcac aaaagtggag attaaa 336 <210> 28 <211> 16 <212> PRT <213> Secuencia Artificial <220> <223> hLAG-3 mAb 1 VL4 CDR1 <400> 28 Lys Ser Ser Gln Ser Leu Leu His Ser Asp Ala Lys Thr Tyr Leu Asn 1 5 10 15 <210> 29 <211> 121 <212> PRT <213> Mus musculus <220> <221> CARACTERÍSTICA_MISCELÁNEA <222> (1)..(121) <223> LAG-3 mAb 2 VH <400> 29 Glu Val Gln Leu Gln Gln Ser Gly Pro Glu Leu Val Lys Pro Gly Ala 1 5 10 15 Ser Val Lys Ile Ser Cys Lys Thr Ser Gly Tyr Thr Phe Thr Asp Tyr 20 25 30 Asn Ile His Trp Leu Arg Gln Ser His Gly Glu Ser Leu Glu Trp Ile 35 40 45 Gly Tyr Ile Tyr Pro Tyr Ser Gly Asp Ile Gly Tyr Asn Gln Lys Phe 50 55 60 Lys Asn Arg Ala Thr Leu Thr Val Asp Asn Ser Ser Ser Thr Ala Tyr 65 70 75 80 Met Asp Leu Arg Ser Leu Thr Ser Glu Asp Ser Ala Val Phe Tyr Cys 85 90 95 Ala Arg Trp His Arg Asn Tyr Phe Gly Pro Trp Phe Ala Tyr Trp Gly 100 105 110 Gln Gly Thr Pro Val Thr Val Ser Ala 115 120 <210> 30 <211> 363 <212> ADN <213> Mus musculus <220> <221> CARACTERÍSTICA_MISCELÁNEA <223> Polinucleótido que codifica LAG-3 mAb 2 VH <400> 30 gaggtccagc ttcagcagtc aggacctgag ctggtgaaac ctggggcctc agtgaagatt 60 tcctgcaaga cttctggata cacatttact gactacaaca tacactggtt gaggcagagc 120 catggagaga gccttgagtg gattggatat atttatcctt acagtggtga tattggatac 180 aaccagaagt tcaagaacag ggccacattg actgtagaca attcctccag cacagcctac 240 atggatctcc gcagcctgac atctgaagac tctgcagtct tttactgtgc aagatggcac 300 aggaactact ttggcccctg gtttgcttac tggggccaag ggactccggt cactgtctct 360 gca 363 <210> 31 <211> 5 <212> PRT <213> Mus musculus <220> <221> CARACTERÍSTICA_MISCELÁNEA <222> (1)..(5) <223> LAG-3 mAb 2 VH CDR 1 <400> 31 Asp Tyr Asn Ile His 1 5 <210> 32 <211> 17 <212> PRT <213> Mus musculus <220> <221> CARACTERÍSTICA_MISCELÁNEA <222> (1)..(17) <223> LAG-3 mAb 2 VH CDR2 <400> 32 Tyr Ile Tyr Pro Tyr Ser Gly Asp Ile Gly Tyr Asn Gln Lys Phe Lys 1 5 10 15 Asn <210> 33 <211> 12 <212> PRT <213> Mus musculus <220> <221> CARACTERÍSTICA_MISCELÁNEA <222> (1)..(12) <223> LAG-3 mAb 2 VH CDR3 <400> 33 Trp His Arg Asn Tyr Phe Gly Pro Trp Phe Ala Tyr 1 5 10 <210> 34 <211> 111 <212> PRT <213> Mus musculus <220> <221> CARACTERÍSTICA_MISCELÁNEA <222> (1)..(111) <223> LAG-3 mAb 2 VL <400> 34 Asp Ile Val Leu Thr Gln Ser Pro Ala Ser Leu Ala Val Ser Leu Gly 1 5 10 15 Gln Arg Ala Thr Ile Ser Cys Lys Ala Ser Gln Ser Val Asp Tyr Asp 20 25 30 Gly Glu Ser Tyr Met Asn Trp Tyr Gln Gln Lys Pro Gly Gln Pro Pro 35 40 45 Lys Leu Leu Ile Tyr Val Val Ser Asn Leu Glu Ser Gly Ile Pro Ala 50 55 60 Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Asn Ile His 65 70 75 80 Pro Val Glu Glu Glu Asp Ala Ala Thr Tyr Tyr Cys Gln Gln Ser Ser 85 90 95 Glu Asp Pro Leu Thr Phe Gly Ala Gly Thr Lys Leu Glu Leu Lys 100 105 110 <210> 35 <211> 333 <212> ADN <213> Mus musculus <220> <221> CARACTERÍSTICA_MISCELÁNEA <223> Polinucleótido que codifica LAG-3 mAb 2 VL <400> 35 gacattgtgc tgacccaatc tccagcttct ttggctgtgt ctctagggca gagggccacc 60 atctcctgca aggccagcca aagtgttgat tatgatggtg aaagttatat gaactggtac 120 caacagaaac caggacagcc acccaaactc ctcatttatg ttgtatccaa tctagaatct 180 gggatcccag ccaggtttag tggcagtggg tctgggacag acttcaccct caacatccat 240 cctgtggagg aggaggatgc tgcaacctat tactgtcagc aaagtagtga ggatccgctc 300 acgttcggtg ctgggaccaa gctggagctg aaa 333 <210> 36 <211> 15 <212> PRT <213> Mus musculus <220> <221> CARACTERÍSTICA_MISCELÁNEA <222> (1)..(15) <223> LAG-3 mAb 2 VL CDR1 <400> 36 Lys Ala Ser Gln Ser Val Asp Tyr Asp Gly Glu Ser Tyr Met Asn 1 5 10 15 <210> 37 <211> 7 <212> PRT <213> Mus musculus <220> <221> CARACTERÍSTICA_MISCELÁNEA <222> (1)..(7) <223> LAG-3 mAb 2 VL CDR2 <400> 37 Val Val Ser Asn Leu Glu Ser 1 5 <210> 38 <211> 9 <212> PRT <213> Mus musculus <220> <221> CARACTERÍSTICA_MISCELÁNEA <222> (1)..(9) <223> LAG-3 mAb 2 VL CDR3 <400> 38 Gln Gln Ser Ser Glu Asp Pro Leu Thr 1 5 <210> 39 <211> 121 <212> PRT <213> Mus musculus <220> <221> CARACTERÍSTICA_MISCELÁNEA <222> (1)..(121) <223> LAG-3 mAb 3 VH <400> 39 Glu Val Arg Leu Gln Gln Ser Gly Pro Glu Leu Val Lys Pro Gly Ala 1 5 10 15 Ser Val Lys Ile Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asp Tyr 20 25 30 Asn Ile His Trp Val Arg Gln Ser His Gly Gln Ser Leu Glu Trp Ile 35 40 45 Gly Tyr Ile Tyr Pro Tyr Asn Gly Asp Thr Gly Tyr Asn Gln Lys Phe 50 55 60 Lys Thr Lys Ala Thr Leu Thr Val Asp Asn Ser Ser Asn Thr Ala Tyr 65 70 75 80 Met Glu Leu Arg Ser Leu Ala Ser Glu Asp Ser Ala Val Tyr Tyr Cys 85 90 95 Thr Arg Trp Ser Arg Asn Tyr Phe Gly Pro Trp Phe Ala Tyr Trp Gly 100 105 110 Gln Gly Thr Leu Val Thr Val Ser Ala 115 120 <210> 40 <211> 363 <212> ADN <213> Mus musculus <220> <221> CARACTERÍSTICA_MISCELÁNEA <223> Polinucleótido que codifica LAG-3 mAb 3 VH <400> 40 gaggtccggc ttcagcagtc aggacctgag ctggtgaaac ctggggcctc agtgaagata 60 tcctgcaagg cttctggata cacattcact gactacaaca ttcactgggt gaggcagagc 120 catggacaga gccttgagtg gattggatat atttatcctt ataatggtga tactggctac 180 aaccagaagt tcaagaccaa ggccacattg actgtagaca attcctccaa cacagcctac 240 atggaactcc gcagcctggc atctgaagac tctgcagtct attactgtac aagatggagc 300 aggaactact ttggcccctg gtttgcttac tggggccaag ggactctggt cactgtctct 360 gca 363 <210> 41 <211> 5 <212> PRT <213> Mus musculus <220> <221> CARACTERÍSTICA_MISCELÁNEA <222> (1)..(5) <223> LAG-3 mAb 3 VH CDR 1 <400> 41 Asp Tyr Asn Ile His 1 5 <210> 42 <211> 17 <212> PRT <213> Mus musculus <220> <221> CARACTERÍSTICA_MISCELÁNEA <222> (1)..(17) <223> LAG-3 mAb 3 VH CDR2 <400> 42 Tyr Ile Tyr Pro Tyr Asn Gly Asp Thr Gly Tyr Asn Gln Lys Phe Lys 1 5 10 15 Thr <210> 43 <211> 12 <212> PRT <213> Mus musculus <220> <221> CARACTERÍSTICA_MISCELÁNEA <222> (1)..(12) <223> LAG-3 mAb 3 VH CDR3 <400> 43 Trp Ser Arg Asn Tyr Phe Gly Pro Trp Phe Ala Tyr 1 5 10 <210> 44 <211> 111 <212> PRT <213> Mus musculus <220> <221> CARACTERÍSTICA_MISCELÁNEA <222> (1)..(111) <223> LAG-3 mAb 3 VL <400> 44 Asp Ile Val Leu Thr Gln Ser Pro Thr Ser Leu Ala Val Ser Leu Gly 1 5 10 15 Gln Arg Ala Thr Ile Ser Cys Lys Ala Ser Gln Ser Val Asp Tyr Asp 20 25 30 Gly Asp Ser Tyr Met Asn Trp Tyr Gln Gln Lys Pro Gly Gln Pro Pro 35 40 45 Lys Leu Leu Ile Tyr Ala Ala Ser Asn Leu Glu Ser Gly Ile Pro Ala 50 55 60 Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Asn Ile His 65 70 75 80 Pro Val Glu Glu Glu Asp Ala Ala Thr Tyr Tyr Cys Gln Gln Ser Ser 85 90 95 Glu Asp Pro Leu Thr Phe Gly Ala Gly Thr Lys Leu Glu Leu Lys 100 105 110 <210> 45 <211> 333 <212> ADN <213> Mus musculus <220> <221> CARACTERÍSTICA_MISCELÁNEA <223> Polinucleótido que codifica LAG-3 mAb 3 VL <400> 45 gacattgtgc tgacccaatc tccaacttct ttggctgtgt ctctagggca gagggccacc 60 atctcctgca aggccagcca aagtgttgat tatgatggtg atagttatat gaactggtat 120 caacagaaac caggacagcc acccaaactc ctcatctatg ctgcatccaa tctagaatct 180 gggatcccag ccaggtttag tggcagtggg tctgggacag acttcaccct caacatccat 240 cctgtggagg aggaggatgc tgcaacctat tactgtcagc aaagtagtga ggatccgctc 300 acgttcggtg ctgggaccaa gctggagctg aaa 333 <210> 46 <211> 15 <212> PRT <213> Mus musculus <220> <221> CARACTERÍSTICA_MISCELÁNEA <222> (1)..(15) <223> LAG-3 mAb 3 VL CDR1 <400> 46 Lys Ala Ser Gln Ser Val Asp Tyr Asp Gly Asp Ser Tyr Met Asn 1 5 10 15 <210> 47 <211> 7 <212> PRT <213> Mus musculus <220> <221> CARACTERÍSTICA_MISCELÁNEA <222> (1)..(7) <223> LAG-3 mAb 3 VL CDR2 <400> 47 Ala Ala Ser Asn Leu Glu Ser 1 5 <210> 48 <211> 9 <212> PRT <213> Mus musculus <220> <221> CARACTERÍSTICA_MISCELÁNEA <222> (1)..(9) <223> LAG-3 mAb 3 VL CDR3 <400> 48 Gln Gln Ser Ser Glu Asp Pro Leu Thr 1 5 <210> 49 <211> 121 <212> PRT <213> Mus musculus <220> <221> CARACTERÍSTICA_MISCELÁNEA <222> (1)..(121) <223> LAG-3 mAb 4 VH <400> 49 Glu Val Gln Leu His Gln Ser Gly Pro Glu Leu Val Lys Pro Gly Ala 1 5 10 15 Ser Val Lys Ile Ser Cys Lys Thr Ser Gly Tyr Thr Phe Thr Asp Tyr 20 25 30 Asn Ile His Trp Val Lys Gln Ser His Gly Lys Ser Leu Glu Trp Ile 35 40 45 Gly Tyr Ile Tyr Pro Tyr Asn Gly Asp Ala Gly Tyr Asn Gln Asn Phe 50 55 60 Lys Thr Lys Ala Thr Leu Thr Val Asp Asn 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 Trp Asn Met Asn Tyr Phe Gly Pro Trp Phe Ala Tyr Trp Gly 100 105 110 Gln Gly Thr Leu Val Thr Val Ser Ala 115 120 <210> 50 <211> 363 <212> ADN <213> Mus musculus <220> <221> CARACTERÍSTICA_MISCELÁNEA <223> Polinucleótido que codifica LAG-3 mAb 4 VH <400> 50 gaggtccagc ttcaccagtc aggacctgag ctggtgaaac ctggggcctc agtgaagata 60 tcctgcaaga cttctggata cactttcact gactacaaca tacactgggt gaagcagagc 120 catggaaaga gccttgagtg gattggatat atttatcctt acaatggtga tgctggctac 180 aaccagaact tcaagaccaa ggccacattg actgtagaca attcctccag cacagcctac 240 atggagctcc gcagcctgac atctgaggac tctgcagtct attactgtgc aagatggaac 300 atgaactact ttggcccctg gtttgcttac tggggccaag ggactctggt cactgtctct 360 gcg 363 <210> 51 <211> 5 <212> PRT <213> Mus musculus <220> <221> CARACTERÍSTICA_MISCELÁNEA <222> (1)..(5) <223> LAG-3 mAb 4 VH CDR 1 <400> 51 Asp Tyr Asn Ile His 1 5 <210> 52 <211> 17 <212> PRT <213> Mus musculus <220> <221> CARACTERÍSTICA_MISCELÁNEA <222> (1)..(17) <223> LAG-3 mAb 4 VH CDR2 <400> 52 Tyr Ile Tyr Pro Tyr Asn Gly Asp Ala Gly Tyr Asn Gln Asn Phe Lys 1 5 10 15 Thr <210> 53 <211> 12 <212> PRT <213> Mus musculus <220> <221> CARACTERÍSTICA_MISCELÁNEA <222> (1)..(12) <223> LAG-3 mAb 4 VH CDR3 <400> 53 Trp Asn Met Asn Tyr Phe Gly Pro Trp Phe Ala Tyr 1 5 10 <210> 54 <211> 111 <212> PRT <213> Mus musculus <220> <221> CARACTERÍSTICA_MISCELÁNEA <222> (1)..(111) <223> LAG-3 mAb 4 VL <400> 54 Asp Ile Val Leu Thr Gln Ser Pro Ala Ser Leu Ala Val Ser Leu Gly 1 5 10 15 Gln Arg Ala Thr Ile Ser Cys Lys Ala Ser Gln Ser Val Asp Tyr Asp 20 25 30 Gly Val Thr Tyr Ile Asn Trp Tyr Gln Gln Lys Pro Gly Gln Pro Pro 35 40 45 Lys Leu Leu Ile Phe Ala Ala Ser Asn Leu Glu Ser Gly Ile Pro Ala 50 55 60 Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Asn Ile His 65 70 75 80 Pro Val Glu Glu Glu Asp Ala Ala Thr Tyr Tyr Cys Gln Gln Ser Asn 85 90 95 Glu Asp Pro Leu Thr Phe Gly Ala Gly Thr Lys Leu Glu Leu Lys 100 105 110 <210> 55 <211> 333 <212> ADN <213> Mus musculus <220> <221> CARACTERÍSTICA_MISCELÁNEA <223> Polinucleótido que codifica LAG-3 mAb 4 VL <400> 55 gacattgtgc tgacccaatc tccagcttct ttggctgtgt ctctagggca gagggccacc 60 atctcctgca aggccagcca aagtgttgat tatgatggtg ttacttatat caactggtac 120 caacagaaac caggacagcc acccaaactc ctcatctttg ctgcatccaa tctagaatct 180 gggatcccag ccaggtttag tggcagtggg tctgggacag acttcaccct caacatccat 240 cctgtggagg aggaggatgc tgcaacctat tactgtcagc aaagtaatga ggatccgctc 300 acgttcggtg ctgggaccaa gctggagctg aaa 333 <210> 56 <211> 15 <212> PRT <213> Mus musculus <220> <221> CARACTERÍSTICA_MISCELÁNEA <222> (1)..(15) <223> LAG-3 mAb 4 VL CDR1 <400> 56 Lys Ala Ser Gln Ser Val Asp Tyr Asp Gly Val Thr Tyr Ile Asn 1 5 10 15 <210> 57 <211> 7 <212> PRT <213> Mus musculus <220> <221> CARACTERÍSTICA_MISCELÁNEA <222> (1)..(7) <223> LAG-3 mAb 4 VL CDR2 <400> 57 Ala Ala Ser Asn Leu Glu Ser 1 5 <210> 58 <211> 9 <212> PRT <213> Mus musculus <220> <221> CARACTERÍSTICA_MISCELÁNEA <222> (1)..(9) <223> LAG-3 mAb 4 VL CDR3 <400> 58 Gln Gln Ser Asn Glu Asp Pro Leu Thr 1 5 <210> 59 <211> 121 <212> PRT <213> Mus musculus <220> <221> CARACTERÍSTICA_MISCELÁNEA <222> (1)..(121) <223> LAG-3 mAb 5 VH <400> 59 Glu Val Gln Leu Gln Gln Ser Gly Pro Glu Leu Val Lys Pro Gly Ala 1 5 10 15 Ser Val Lys Ile Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asp Tyr 20 25 30 Asn Ile His Trp Val Lys Gln Ser Pro Gly Lys Ser Leu Glu Trp Ile 35 40 45 Gly Tyr Ile Tyr Pro Tyr Ser Gly Asp Phe Gly Tyr Asn Gln Lys Phe 50 55 60 Lys Ser Lys Ala Thr Leu Thr Val Asp Asn Ser Ser Ser Thr Ala Tyr 65 70 75 80 Met Asp Leu Arg Ser Leu Thr Ser Glu Asp Ser Ala Val Phe Tyr Cys 85 90 95 Ala Arg Trp His Arg Asn Tyr Phe Gly Pro Trp Phe Ala Tyr Trp Gly 100 105 110 Gln Gly Thr Leu Val Thr Val Ser Ala 115 120 <210> 60 <211> 363 <212> ADN <213> Mus musculus <220> <221> CARACTERÍSTICA_MISCELÁNEA <223> Polinucleótido que codifica LAG-3 mAb 5 VH <400> 60 gaggtccagc ttcagcagtc aggacctgag ctggtgaaac ctggggcctc agtgaagatt 60 tcctgcaaag cttctggata cacatttact gactacaaca tacactgggt gaagcagagc 120 cctggaaaga gccttgaatg gattggatat atttatcctt acagtggtga ttttggatac 180 aaccagaagt tcaagagcaa ggccacattg actgtagaca attcctccag cacagcctac 240 atggatctcc gcagcctgac atctgaggac tctgcagtct tttactgtgc aagatggcac 300 aggaactact ttggcccctg gtttgcttac tggggccaag ggactctggt cactgtctct 360 gca 363 <210> 61 <211> 5 <212> PRT <213> Mus musculus <220> <221> CARACTERÍSTICA_MISCELÁNEA <222> (1)..(5) <223> LAG-3 mAb 5 VH CDR 1 <400> 61 Asp Tyr Asn Ile His 1 5 <210> 62 <211> 17 <212> PRT <213> Mus musculus <220> <221> CARACTERÍSTICA_MISCELÁNEA <222> (1)..(17) <223> LAG-3 mAb 5 VH CDR2 <400> 62 Tyr Ile Tyr Pro Tyr Ser Gly Asp Phe Gly Tyr Asn Gln Lys Phe Lys 1 5 10 15 Ser <210> 63 <211> 12 <212> PRT <213> Mus musculus <220> <221> CARACTERÍSTICA_MISCELÁNEA <222> (1)..(12) <223> LAG-3 mAb 5 VH CDR3 <400> 63 Trp His Arg Asn Tyr Phe Gly Pro Trp Phe Ala Tyr 1 5 10 <210> 64 <211> 111 <212> PRT <213> Mus musculus <220> <221> CARACTERÍSTICA_MISCELÁNEA <222> (1)..(111) <223> LAG-3 mAb 5 VL <400> 64 Asp Ile Val Leu Thr Gln Ser Pro Ala Ser Leu Ala Val Ser Leu Gly 1 5 10 15 Gln Arg Ala Thr Ile Ser Cys Lys Ala Ser Gln Ser Val Asp Tyr Asp 20 25 30 Gly Glu Ser Tyr Met Asn Trp Tyr Gln Gln Lys Pro Gly Gln Pro Pro 35 40 45 Lys Leu Leu Ile Tyr Val Val Ser Asn Leu Glu Ser Gly Ile Pro Ala 50 55 60 Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Asn Ile His 65 70 75 80 Pro Val Glu Glu Glu Asp Ala Ala Thr Tyr Tyr Cys Gln Gln Ser Ser 85 90 95 Glu Asp Pro Leu Thr Phe Gly Ala Gly Thr Lys Leu Glu Leu Lys 100 105 110 <210> 65 <211> 333 <212> ADN <213> Mus musculus <220> <221> CARACTERÍSTICA_MISCELÁNEA <223> Polinucleótido que codifica LAG-3 mAb 5 VL <400> 65 gacattgtgc tgacccaatc tccagcttct ttggctgtgt ctctagggca gagggccacc 60 atctcctgca aggccagcca aagtgttgat tatgatggtg aaagttatat gaactggtac 120 caacagaaac caggacagcc acccaaactc ctcatttatg ttgtttccaa tctagaatct 180 gggatcccag ccaggtttag tggcagtggg tctgggacag acttcaccct caacatccat 240 cctgtggagg aggaggatgc tgcaacctat tactgtcagc aaagtagtga ggatccgctc 300 acgttcggtg ctgggaccaa gctggagctg aaa 333 <210> 66 <211> 15 <212> PRT <213> Mus musculus <220> <221> CARACTERÍSTICA_MISCELÁNEA <222> (1)..(15) <223> LAG-3 mAb 5 VL CDR1 <400> 66 Lys Ala Ser Gln Ser Val Asp Tyr Asp Gly Glu Ser Tyr Met Asn 1 5 10 15 <210> 67 <211> 7 <212> PRT <213> Mus musculus <220> <221> CARACTERÍSTICA_MISCELÁNEA <222> (1)..(7) <223> LAG-3 mAb 5 VL CDR2 <400> 67 Val Val Ser Asn Leu Glu Ser 1 5 <210> 68 <211> 9 <212> PRT <213> Mus musculus <220> <221> CARACTERÍSTICA_MISCELÁNEA <222> (1)..(9) <223> LAG-3 mAb 5 VL CDR3 <400> 68 Gln Gln Ser Ser Glu Asp Pro Leu Thr 1 5 <210> 69 <211> 118 <212> PRT <213> Mus musculus <220> <221> CARACTERÍSTICA_MISCELÁNEA <222> (1)..(118) <223> LAG-3 mAb 6 VH <400> 69 Glu Val Leu Leu Gln Gln Ser Gly Pro Glu Leu Val Lys Pro Gly Ala 1 5 10 15 Ser Val Lys Ile Pro Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asp Tyr 20 25 30 Asn Met Asp Trp Val Lys Gln Ser His Gly Glu Ser Leu Glu Trp Ile 35 40 45 Gly Asp Ile Asn Pro Asp Asn Gly Val Thr Ile Tyr Asn Gln Lys Phe 50 55 60 Glu Gly Lys Ala Thr 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 Thr Ala Val Tyr Tyr Cys 85 90 95 Ala Arg Glu Ala Asp Tyr Phe Tyr Phe Asp Tyr Trp Gly Gln Gly Thr 100 105 110 Thr Leu Thr Val Ser Ser 115 <210> 70 <211> 354 <212> ADN <213> Mus musculus <220> <221> CARACTERÍSTICA_MISCELÁNEA <223> Polinucleótido que codifica LAG-3 mAb 6 VH <400> 70 gaggtcctgc tgcaacagtc tggacctgag ctggtgaagc ctggggcttc agtgaagata 60 ccctgcaagg cttctggata cacattcact gactacaaca tggactgggt gaagcagagc 120 catggagaga gccttgagtg gattggagat attaatcctg acaatggtgt tactatctac 180 aaccagaagt ttgagggcaa ggccacactg actgtagaca agtcctccag tacagcctac 240 atggagctcc gcagcctgac atctgaggac actgcagtct attactgtgc aagagaggcg 300 gattacttct actttgacta ctggggccaa ggcaccactc tcacagtctc ctca 354 <210> 71 <211> 5 <212> PRT <213> Mus musculus <220> <221> CARACTERÍSTICA_MISCELÁNEA <222> (1)..(5) <223> LAG-3 mAb 6 VH CDR 1 <400> 71 Asp Tyr Asn Met Asp 1 5 <210> 72 <211> 17 <212> PRT <213> Mus musculus <220> <221> CARACTERÍSTICA_MISCELÁNEA <222> (1)..(17) <223> LAG-3 mAb 6 VH CDR2 <400> 72 Asp Ile Asn Pro Asp Asn Gly Val Thr Ile Tyr Asn Gln Lys Phe Glu 1 5 10 15 Gly <210> 73 <211> 9 <212> PRT <213> Mus musculus <220> <221> CARACTERÍSTICA_MISCELÁNEA <222> (1)..(9) <223> LAG-3 mAb 6 VH CDR3 <400> 73 Glu Ala Asp Tyr Phe Tyr Phe Asp Tyr 1 5 <210> 74 <211> 107 <212> PRT <213> Mus musculus <220> <221> CARACTERÍSTICA_MISCELÁNEA <222> (1)..(107) <223> LAG-3 mAb 6 VL <400> 74 Asp Ile Val Met Thr Gln Ser His Arg Phe Met Ser Thr Ser Val Gly 1 5 10 15 Asp Arg Val Ser Ile Thr Cys Lys Ala Ser Gln Asp Val Ser Ser Val 20 25 30 Val Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ser Pro Lys Leu Leu Ile 35 40 45 Phe Ser Ala Ser Tyr Arg Tyr Thr Gly Val Pro Asp Arg Phe Thr Gly 50 55 60 Ser Gly Ser Gly Thr Asp Phe Thr Phe Thr Ile Ser Ser Val Gln Ala 65 70 75 80 Ala Asp Leu Ala Val Tyr Tyr Cys Gln Gln His Tyr Ser Thr Pro Trp 85 90 95 Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys 100 105 <210> 75 <211> 321 <212> ADN <213> Mus musculus <220> <221> CARACTERÍSTICA_MISCELÁNEA <223> Polinucleótido que codifica LAG-3 mAb 6 VL <400> 75 gacattgtga tgacccagtc tcacagattc atgtccacat cagttggaga cagggtcagc 60 atcacctgca aggccagtca ggatgtgagt tctgttgtag cctggtatca acagaaacca 120 ggacaatctc ctaaattact gattttttcg gcatcctacc ggtacactgg agtccctgat 180 cgcttcactg gcagtggatc tgggacggat ttcactttca ccatcagcag tgtgcaggct 240 gcagacctgg cagtttatta ctgtcagcaa cattatagta ctccgtggac gttcggtgga 300 ggcaccaagc tggaaatcaa a 321 <210> 76 <211> 11 <212> PRT <213> Mus musculus <220> <221> CARACTERÍSTICA_MISCELÁNEA <222> (1)..(11) <223> LAG-3 mAb 6 VL CDR1 <400> 76 Lys Ala Ser Gln Asp Val Ser Ser Val Val Ala 1 5 10 <210> 77 <211> 7 <212> PRT <213> Mus musculus <220> <221> CARACTERÍSTICA_MISCELÁNEA <222> (1)..(7) <223> LAG-3 mAb 6 VL CDR2 <400> 77 Ser Ala Ser Tyr Arg Tyr Thr 1 5 <210> 78 <211> 9 <212> PRT <213> Mus musculus <220> <221> CARACTERÍSTICA_MISCELÁNEA <222> (1)..(9) <223> LAG-3 mAb 6 VL CDR3 <400> 78 Gln Gln His Tyr Ser Thr Pro Trp Thr 1 5 <210> 79 <211> 118 <212> PRT <213> Secuencia Artificial <220> <223> hLAG-3 mAb 6 VH-1 <400> 79 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 Asp Tyr 20 25 30 Asn Met Asp Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met 35 40 45 Gly Asp Ile Asn Pro Asp Asn Gly Val Thr Ile Tyr Asn Gln Lys Phe 50 55 60 Glu Gly Arg Val Thr Met Thr Thr Asp Thr Ser Thr Ser Thr Ala Tyr 65 70 75 80 Met Glu Leu Arg Ser Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Ala Arg Glu Ala Asp Tyr Phe Tyr Phe Asp Tyr Trp Gly Gln Gly Thr 100 105 110 Thr Leu Thr Val Ser Ser 115 <210> 80 <211> 354 <212> ADN <213> Secuencia Artificial <220> <223> Polinucleótido que codifica hLAG-3 mAb 6 VH-1 <400> 80 caggtccagc tggtgcagtc tggcgccgaa gtgaagaaac ctggcgcaag cgtgaaggtg 60 tcctgcaagg ccagcggcta caccttcacc gactacaaca tggactgggt ccgacaggcc 120 ccaggacagg gcctggaatg gatgggcgac atcaaccccg acaacggcgt gaccatctac 180 aaccagaaat tcgagggcag agtgaccatg accaccgaca ccagcaccag caccgcctac 240 atggaactgc ggtccctgcg gagcgacgac accgccgtgt actactgcgc cagagaggcc 300 gactacttct acttcgacta ctggggccag ggcaccaccc tgaccgtgtc ctcc 354 <210> 81 <211> 118 <212> PRT <213> Secuencia Artificial <220> <223> hLAG-3 mAb 6 VH-2 <400> 81 Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Lys Pro Gly Gly 1 5 10 15 Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Asp Tyr 20 25 30 Asn Met Asp Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45 Ser Asp Ile Asn Pro Asp Asn Gly Val Thr Ile Tyr Asn Gln Lys Phe 50 55 60 Glu Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Ser 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 Arg Glu Ala Asp Tyr Phe Tyr Phe Asp Tyr Trp Gly Gln Gly Thr 100 105 110 Thr Leu Thr Val Ser Ser 115 <210> 82 <211> 354 <212> ADN <213> Secuencia Artificial <220> <223> Polinucleótido que codifica hLAG-3 mAb 6 VH-2 <400> 82 gaggtccagc tggtggaatc tggcggcgga ctggtcaagc ctggcggcag cctgagactg 60 agctgcgctg ccagcggctt caccttcagc gactacaaca tggactgggt ccgacaggcc 120 cctggcaagg gcctggaatg ggtgtccgac atcaaccccg acaacggcgt gaccatctac 180 aaccagaagt tcgagggccg gttcaccatc agccgggaca acgccaagaa cagcctgtac 240 ctgcagatga acagcctgcg ggccgaggac accgccgtgt actactgcgc cagagaggcc 300 gactacttct acttcgacta ctggggccag ggcaccaccc tgaccgtgtc ctcc 354 <210> 83 <211> 107 <212> PRT <213> Secuencia Artificial <220> <223> hLAG-3 mAb 6 VL-1 <400> 83 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 Asp Val Ser Ser Val 20 25 30 Val Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile 35 40 45 Tyr Ser Ala Ser Tyr Arg Tyr Thr 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 His Tyr Ser Thr Pro Trp 85 90 95 Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys 100 105 <210> 84 <211> 321 <212> ADN <213> Secuencia Artificial <220> <223> Polinucleótido que codifica hLAG-3 mAb 6 VL-1 <400> 84 gacatccaga tgacccagag ccccagcagc ctgagcgcca gcgtgggcga cagagtgacc 60 atcacctgtc gggccagcca ggatgtgtcc agcgtggtgg cctggtatca gcagaagccc 120 ggcaaggccc ccaagctgct gatctacagc gccagctacc ggtacacagg cgtgcccagc 180 agattcagcg gcagcggctc cggcaccgac ttcaccctga ccatcagcag cctgcagccc 240 gaggacttcg ccacctacta ctgccagcag cactacagca ccccctggac cttcggcgga 300 ggcaccaagc tggaaatcaa g 321 <210> 85 <211> 107 <212> PRT <213> Secuencia Artificial <220> <223> hLAG-3 mAb 6 VL-2 <400> 85 Asp Ile Val 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 Asp Val Ser Ser Val 20 25 30 Val Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile 35 40 45 Tyr Ser Ala Ser Tyr Arg Tyr Thr Gly Val Pro Asp Arg Phe Ser Gly 50 55 60 Ser Gly Ser Gly Thr Asp Phe Thr Phe Thr Ile Ser Ser Leu Gln Pro 65 70 75 80 Glu Asp Ile Ala Val Tyr Tyr Cys Gln Gln His Tyr Ser Thr Pro Trp 85 90 95 Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys 100 105 <210> 86 <211> 321 <212> ADN <213> Secuencia Artificial <220> <223> Polinucleótido que codifica hLAG-3 mAb 6 VL-2 <400> 86 gacatcgtga tgacccagag ccccagcagc ctgagcgcca gcgtgggcga cagagtgacc 60 atcacctgtc gggccagcca ggatgtgtcc agcgtggtgg cctggtatca gcagaagccc 120 ggcaaggccc ccaagctgct gatctacagc gccagctacc ggtacacagg cgtgcccgat 180 agattcagcg gcagcggctc cggcaccgac ttcaccttca ccatcagcag cctgcagccc 240 gaggacatcg ccgtttacta ctgccagcag cactacagca ccccctggac cttcggcgga 300 ggcaccaagc tggaaatcaa g 321 <210> 87 <211> 11 <212> PRT <213> Secuencia Artificial <220> <223> hLAG-3 mAb 6 VL-1/VL-2 CDRL1 <400> 87 Arg Ala Ser Gln Asp Val Ser Ser Val Val Ala 1 5 10 <210> 88 <211> 8 <212> PRT <213> Secuencia Artificial <220> <223> Enlazador 1 <400> 88 Gly Gly Gly Ser Gly Gly Gly Gly 1 5 <210> 89 <211> 6 <212> PRT <213> Secuencia Artificial <220> <223> Cys Enlazador 2 <400> 89 Gly Gly Cys Gly Gly Gly 1 5 <210> 90 <211> 4 <212> PRT <213> Secuencia Artificial <220> <223> ABD Enlazador <400> 90 Gly Gly Gly Ser 1 <210> 91 <211> 6 <212> PRT <213> Secuencia Artificial <220> <223> Enlazador <400> 91 Leu Gly Gly Gly Ser Gly 1 5 <210> 92 <211> 11 <212> PRT <213> Secuencia Artificial <220> <223> Enlazador <400> 92 Gly Gly Gly Ser Gly Gly Gly Ser Gly Gly Gly 1 5 10 <210> 93 <211> 5 <212> PRT <213> Secuencia Artificial <220> <223> Enlazador <400> 93 Ala Ser Thr Lys Gly 1 5 <210> 94 <211> 6 <212> PRT <213> Secuencia Artificial <220> <223> Enlazador <400> 94 Leu Glu Pro Lys Ser Ser 1 5 <210> 95 <211> 5 <212> PRT <213> Secuencia Artificial <220> <223> Enlazador <400> 95 Ala Pro Ser Ser Ser 1 5 <210> 96 <211> 7 <212> PRT <213> Secuencia Artificial <220> <223> Dominio que Promueve Heterodímero <400> 96 Gly Val Glu Pro Lys Ser Cys 1 5 <210> 97 <211> 6 <212> PRT <213> Secuencia Artificial <220> <223> Dominio que Promueve Heterodímero <400> 97 Val Glu Pro Lys Ser Cys 1 5 <210> 98 <211> 6 <212> PRT <213> Secuencia Artificial <220> <223> Dominio que Promueve Heterodímero <400> 98 Ala Glu Pro Lys Ser Cys 1 5 <210> 99 <211> 7 <212> PRT <213> Secuencia Artificial <220> <223> Dominio que Promueve Heterodímero <400> 99 Gly Phe Asn Arg Gly Glu Cys 1 5 <210> 100 <211> 6 <212> PRT <213> Secuencia Artificial <220> <223> Dominio que Promueve Heterodímero <400> 100 Phe Asn Arg Gly Glu Cys 1 5 <210> 101 <211> 28 <212> PRT <213> Secuencia Artificial <220> <223> E-Espiral <400> 101 Glu Val Ala Ala Leu Glu Lys Glu Val Ala Ala Leu Glu Lys Glu Val 1 5 10 15 Ala Ala Leu Glu Lys Glu Val Ala Ala Leu Glu Lys 20 25 <210> 102 <211> 28 <212> PRT <213> Secuencia Artificial <220> <223> K-Espiral <400> 102 Lys Val Ala Ala Leu Lys Glu Lys Val Ala Ala Leu Lys Glu Lys Val 1 5 10 15 Ala Ala Leu Lys Glu Lys Val Ala Ala Leu Lys Glu 20 25 <210> 103 <211> 28 <212> PRT <213> Secuencia Artificial <220> <223> E-Espiral Modificada <400> 103 Glu Val Ala Ala Cys Glu Lys Glu Val Ala Ala Leu Glu Lys Glu Val 1 5 10 15 Ala Ala Leu Glu Lys Glu Val Ala Ala Leu Glu Lys 20 25 <210> 104 <211> 28 <212> PRT <213> Secuencia Artificial <220> <223> K-Espiral Modificada <400> 104 Lys Val Ala Ala Cys Lys Glu Lys Val Ala Ala Leu Lys Glu Lys Val 1 5 10 15 Ala Ala Leu Lys Glu Lys Val Ala Ala Leu Lys Glu 20 25 <210> 105 <211> 46 <212> PRT <213> Secuencia Artificial <220> <223> ABD <400> 105 Leu Ala Glu Ala Lys Val Leu Ala Asn Arg Glu Leu Asp Lys Tyr Gly 1 5 10 15 Val Ser Asp Tyr Tyr Lys Asn Leu Ile Asp Asn Ala Lys Ser Ala Glu 20 25 30 Gly Val Lys Ala Leu Ile Asp Glu Ile Leu Ala Ala Leu Pro 35 40 45 <210> 106 <211> 46 <212> PRT <213> Secuencia Artificial <220> <223> deimm ABD <400> 106 Leu Ala Glu Ala Lys Val Leu Ala Asn Arg Glu Leu Asp Lys Tyr Gly 1 5 10 15 Val Ser Asp Tyr Tyr Lys Asn Leu Ile Asp Asn Ala Lys Ser Ala Glu 20 25 30 Gly Val Lys Ala Leu Ile Asp Glu Ile Leu Ala Ala Leu Pro 35 40 45 <210> 107 <211> 46 <212> PRT <213> Secuencia Artificial <220> <223> deimm ABD <400> 107 Leu Ala Glu Ala Lys Val Leu Ala Asn Arg Glu Leu Asp Lys Tyr Gly 1 5 10 15 Val Ser Asp Tyr Tyr Lys Asn Ala Ala Asn Asn Ala Lys Thr Val Glu 20 25 30 Gly Val Lys Ala Leu Ile Ala Glu Ile Leu Ala Ala Leu Pro 35 40 45 <210> 108 <211> 46 <212> PRT <213> Secuencia Artificial <220> <223> deimm ABD <400> 108 Leu Ala Glu Ala Lys Val Leu Ala Asn Arg Glu Leu Asp Lys Tyr Gly 1 5 10 15 Val Ser Asp Tyr Tyr Lys Asn Leu Ile Ser Asn Ala Lys Ser Val Glu 20 25 30 Gly Val Lys Ala Leu Ile Ala Glu Ile Leu Ala Ala Leu Pro 35 40 45 <210> 109 <211> 10 <212> PRT <213> Secuencia Artificial <220> <223> Enlazador de Bisagra <400> 109 Asp Lys Thr His Thr Cys Pro Pro Cys Pro 1 5 10 <210> 110 <211> 8 <212> PRT <213> Secuencia Artificial <220> <223> Enlazador <400> 110 Ala Pro Ser Ser Ser Pro Met Glu 1 5 <210> 111 <211> 15 <212> PRT <213> Secuencia Artificial <220> <223> Cys Enlazador <400> 111 Leu Glu Pro Lys Ser Ala Asp Lys Thr His Thr Cys Pro Pro Cys 1 5 10 15 <210> 112 <211> 13 <212> PRT <213> Secuencia Artificial <220> <223> Enlazador <400> 112 Gly Gly Gly Asp Lys Thr His Thr Cys Pro Pro Cys Pro 1 5 10 <210> 113 <211> 16 <212> PRT <213> Secuencia Artificial <220> <223> Enlazador <400> 113 Leu Glu Pro Lys Ser Ser Asp Lys Thr His Thr Cys Pro Pro Cys Pro 1 5 10 15 <210> 114 <211> 15 <212> PRT <213> Homo sapiens <220> <221> CARACTERÍSTICA_MISCELÁNEA <222> (1)..(15) <223> IgG1 Bisagra <400> 114 Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro Pro Cys Pro 1 5 10 15 <210> 115 <211> 12 <212> PRT <213> Homo sapiens <220> <221> CARACTERÍSTICA_MISCELÁNEA <222> (1)..(12) <223> IgG2 Bisagra <400> 115 Glu Arg Lys Cys Cys Val Glu Cys Pro Pro Cys Pro 1 5 10 <210> 116 <211> 12 <212> PRT <213> Homo sapiens <220> <221> CARACTERÍSTICA_MISCELÁNEA <222> (1)..(12) <223> IgG4 Bisagra <400> 116 Glu Ser Lys Tyr Gly Pro Pro Cys Pro Ser Cys Pro 1 5 10 <210> 117 <211> 12 <212> PRT <213> Homo sapiens <220> <221> CARACTERÍSTICA_MISCELÁNEA <222> (1)..(12) <223> IgG4 Bisagra (S228P) <400> 117 Glu Ser Lys Tyr Gly Pro Pro Cys Pro Pro Cys Pro 1 5 10 <210> 118 <211> 107 <212> PRT <213> Homo sapiens <220> <221> CARACTERÍSTICA_MISCELÁNEA <222> (1)..(107) <223> LC kappa <400> 118 Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu 1 5 10 15 Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe 20 25 30 Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln 35 40 45 Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser 50 55 60 Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu 65 70 75 80 Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser 85 90 95 Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys 100 105 <210> 119 <211> 104 <212> PRT <213> Homo sapiens <220> <221> CARACTERÍSTICA_MISCELÁNEA <222> (1)..(104) <223> LC lambda <400> 119 Gln Pro Lys Ala Ala Pro Ser Val Thr Leu Phe Pro Pro Ser Ser Glu 1 5 10 15 Glu Leu Gln Ala Asn Lys Ala Thr Leu Val Cys Leu Ile Ser Asp Phe 20 25 30 Tyr Pro Gly Ala Val Thr Val Ala Trp Lys Ala Asp Ser Ser Pro Val 35 40 45 Lys Ala Gly Val Glu Thr Thr Pro Ser Lys Gln Ser Asn Asn Lys Tyr 50 55 60 Ala Ala Ser Ser Tyr Leu Ser Leu Thr Pro Glu Gln Trp Lys Ser His 65 70 75 80 Arg Ser Tyr Ser Cys Gln Val Thr His Glu Gly Ser Thr Val Glu Lys 85 90 95 Thr Val Ala Pro Thr Glu Cys Ser 100 <210> 120 <211> 98 <212> PRT <213> Homo sapiens <220> <221> CARACTERÍSTICA_MISCELÁNEA <222> (1)..(98) <223> IgG1 CH1 <400> 120 Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys 1 5 10 15 Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr 20 25 30 Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser 35 40 45 Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser 50 55 60 Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr 65 70 75 80 Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys 85 90 95 Lys Val <210> 121 <211> 98 <212> PRT <213> Homo sapiens <220> <221> CARACTERÍSTICA_MISCELÁNEA <222> (1)..(98) <223> IgG2 CH1 <400> 121 Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Cys Ser Arg 1 5 10 15 Ser Thr Ser Glu Ser Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr 20 25 30 Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser 35 40 45 Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser 50 55 60 Leu Ser Ser Val Val Thr Val Pro Ser Ser Asn Phe Gly Thr Gln Thr 65 70 75 80 Tyr Thr Cys Asn Val Asp His Lys Pro Ser Asn Thr Lys Val Asp Lys 85 90 95 Thr Val <210> 122 <211> 98 <212> PRT <213> Homo sapiens <220> <221> CARACTERÍSTICA_MISCELÁNEA <222> (1)..(98) <223> IgG4 CH1 <400> 122 Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Cys Ser Arg 1 5 10 15 Ser Thr Ser Glu Ser Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr 20 25 30 Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser 35 40 45 Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser 50 55 60 Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Lys Thr 65 70 75 80 Tyr Thr Cys Asn Val Asp His Lys Pro Ser Asn Thr Lys Val Asp Lys 85 90 95 Arg Val <210> 123 <211> 217 <212> PRT <213> Homo sapiens <220> <221> CARACTERÍSTICA_MISCELÁNEA <222> (1)..(217) <223> IgG1 (AA) <220> <221> CARACTERÍSTICA_MISCELÁNEA <222> (217)..(217) <223> Xaa217 es una Lisina (K) o está Ausente <400> 123 Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys 1 5 10 15 Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val 20 25 30 Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr 35 40 45 Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu 50 55 60 Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His 65 70 75 80 Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys 85 90 95 Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln 100 105 110 Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met 115 120 125 Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro 130 135 140 Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn 145 150 155 160 Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu 165 170 175 Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val 180 185 190 Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln 195 200 205 Lys Ser Leu Ser Leu Ser Pro Gly Xaa 210 215 <210> 124 <211> 217 <212> PRT <213> Homo sapiens <220> <221> CARACTERÍSTICA_MISCELÁNEA <222> (1)..(217) <223> IgG1 Fc (AA/YTE) <220> <221> CARACTERÍSTICA_MISCELÁNEA <222> (217)..(217) <223> Xaa217 es una Lisina (K) o está Ausente <400> 124 Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys 1 5 10 15 Pro Lys Asp Thr Leu Tyr Ile Thr Arg Glu Pro Glu Val Thr Cys Val 20 25 30 Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr 35 40 45 Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu 50 55 60 Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His 65 70 75 80 Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys 85 90 95 Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln 100 105 110 Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met 115 120 125 Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro 130 135 140 Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn 145 150 155 160 Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu 165 170 175 Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val 180 185 190 Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln 195 200 205 Lys Ser Leu Ser Leu Ser Pro Gly Xaa 210 215 <210> 125 <211> 217 <212> PRT <213> Homo sapiens <220> <221> CARACTERÍSTICA_MISCELÁNEA <222> (1)..(217) <223> IgG4 Fc (YTE) <220> <221> CARACTERÍSTICA_MISCELÁNEA <222> (217)..(217) <223> Xaa217 es una Lisina (K) o está Ausente <400> 125 Ala Pro Glu Phe Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys 1 5 10 15 Pro Lys Asp Thr Leu Tyr Ile Thr Arg Glu Pro Glu Val Thr Cys Val 20 25 30 Val Val Asp Val Ser Gln Glu Asp Pro Glu Val Gln Phe Asn Trp Tyr 35 40 45 Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu 50 55 60 Gln Phe Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His 65 70 75 80 Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys 85 90 95 Gly Leu Pro Ser Ser Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln 100 105 110 Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Gln Glu Glu Met 115 120 125 Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro 130 135 140 Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn 145 150 155 160 Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu 165 170 175 Tyr Ser Arg Leu Thr Val Asp Lys Ser Arg Trp Gln Glu Gly Asn Val 180 185 190 Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln 195 200 205 Lys Ser Leu Ser Leu Ser Leu Gly Xaa 210 215 <210> 126 <211> 217 <212> PRT <213> Homo sapiens <220> <221> CARACTERÍSTICA_MISCELÁNEA <222> (1)..(217) <223> Dominio Fc de Nudo <220> <221> CARACTERÍSTICA_MISCELÁNEA <222> (217)..(217) <223> Xaa217 es una Lisina (K) o está Ausente <400> 126 Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys 1 5 10 15 Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val 20 25 30 Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr 35 40 45 Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu 50 55 60 Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His 65 70 75 80 Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys 85 90 95 Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln 100 105 110 Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met 115 120 125 Thr Lys Asn Gln Val Ser Leu Trp Cys Leu Val Lys Gly Phe Tyr Pro 130 135 140 Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn 145 150 155 160 Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu 165 170 175 Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val 180 185 190 Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln 195 200 205 Lys Ser Leu Ser Leu Ser Pro Gly Xaa 210 215 <210> 127 <211> 217 <212> PRT <213> Homo sapiens <220> <221> CARACTERÍSTICA_MISCELÁNEA <222> (1)..(217) <223> Fc de Cavidad <220> <221> CARACTERÍSTICA_MISCELÁNEA <222> (217)..(217) <223> Xaa217 es una Lisina (K) o está Ausente <400> 127 Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys 1 5 10 15 Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val 20 25 30 Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr 35 40 45 Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu 50 55 60 Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His 65 70 75 80 Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys 85 90 95 Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln 100 105 110 Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met 115 120 125 Thr Lys Asn Gln Val Ser Leu Ser Cys Ala Val Lys Gly Phe Tyr Pro 130 135 140 Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn 145 150 155 160 Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu 165 170 175 Val Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val 180 185 190 Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn Arg Tyr Thr Gln 195 200 205 Lys Ser Leu Ser Leu Ser Pro Gly Xaa 210 215 <210> 128 <211> 217 <212> PRT <213> Homo sapiens <220> <221> CARACTERÍSTICA_MISCELÁNEA <222> (1)..(217) <223> IgG1 Fc universal <220> <221> CARACTERÍSTICA_MISCELÁNEA <222> (4)..(5) <223> Xaa4(X1) y Xaa5(X2) son ambos L (tipo silvestre), o son ambos A (unión FcR disminuida) <220> <221> CARACTERÍSTICA_MISCELÁNEA <222> (22)..(26) <223> Xaa22(X3), Xaa24(X4), y Xaa26(X5) son respectivamente M, S y T (tipo silvestre), o Y, T y E (vida media extendida) <220> <221> CARACTERÍSTICA_MISCELÁNEA <222> (136)..(138) <223> Xaa136(X6), y Xaa138(X7) son respectivamente T y L (tipo silvestre) o W y L (nudo), o son S y A (cavidad) <220> <221> CARACTERÍSTICA_MISCELÁNEA <222> (177)..(177) <223> Xaa177(X8) es Y (tipo silvestre) cuando Xaa136(X6) es T y Xaa138(X7) es L; Xaa177(X8) es Y (nudo) cuando Xaa136(X6) es W y Xaa138(X7) es L; Xaa177 (X8) es V (cavidad) cuando Xaa136(X6) es S y Xaa138(X7) is A <220> <221> CARACTERÍSTICA_MISCELÁNEA <222> (204)..(205) <223> Xaa204(X9) y Xaa205(X10) son respectivamente N y H (tipo silvestre), o son N y R (no unión de proteína A), o son A y K (no unión de proteína A) <220> <221> CARACTERÍSTICA_MISCELÁNEA <222> (217)..(217) <223> Xaa217(X11) es K o está Ausente <400> 128 Ala Pro Glu Xaa Xaa Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys 1 5 10 15 Pro Lys Asp Thr Leu Xaa Ile Xaa Arg Xaa Pro Glu Val Thr Cys Val 20 25 30 Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr 35 40 45 Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu 50 55 60 Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His 65 70 75 80 Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys 85 90 95 Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln 100 105 110 Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met 115 120 125 Thr Lys Asn Gln Val Ser Leu Xaa Cys Xaa Val Lys Gly Phe Tyr Pro 130 135 140 Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn 145 150 155 160 Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu 165 170 175 Xaa Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val 180 185 190 Phe Ser Cys Ser Val Met His Glu Ala Leu His Xaa Xaa Tyr Thr Gln 195 200 205 Lys Ser Leu Ser Leu Ser Pro Gly Xaa 210 215 <210> 129 <211> 120 <212> PRT <213> Mus musculus <220> <221> CARACTERÍSTICA_MISCELÁNEA <222> (1)..(120) <223> LAG-3 mAb A VH <400> 129 Gln Val Gln Leu Gln Gln Trp Gly Ala Gly Leu Leu Lys Pro Ser Glu 1 5 10 15 Thr Leu Ser Leu Thr Cys Ala Val Tyr Gly Gly Ser Phe Ser Asp Tyr 20 25 30 Tyr Trp Asn Trp Ile Arg Gln Pro Pro Gly Lys Gly Leu Glu Trp Ile 35 40 45 Gly Glu Ile Asn His Asn Gly Asn Thr Asn Ser Asn Pro Ser Leu Lys 50 55 60 Ser Arg Val Thr Leu Ser Leu Asp Thr Ser Lys Asn Gln Phe Ser Leu 65 70 75 80 Lys Leu Arg Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr Cys Ala 85 90 95 Phe Gly Tyr Ser Asp Tyr Glu Tyr Asn Trp Phe Asp Pro Trp Gly Gln 100 105 110 Gly Thr Leu Val Thr Val Ser Ser 115 120 <210> 130 <211> 107 <212> PRT <213> Mus musculus <220> <221> CARACTERÍSTICA_MISCELÁNEA <222> (1)..(107) <223> LAG-3 mAb A VL <400> 130 Glu Ile Val Leu Thr Gln Ser Pro Ala Thr Leu Ser Leu Ser Pro Gly 1 5 10 15 Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Ile Ser Ser Tyr 20 25 30 Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile 35 40 45 Tyr Asp Ala Ser Asn Arg Ala Thr Gly Ile Pro Ala Arg Phe Ser Gly 50 55 60 Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Glu Pro 65 70 75 80 Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Arg Ser Asn Trp Pro Leu 85 90 95 Thr Phe Gly Gln Gly Thr Asn Leu Glu Ile Lys 100 105 <210> 131 <211> 113 <212> PRT <213> Mus musculus <220> <221> CARACTERÍSTICA_MISCELÁNEA <222> (1)..(113) <223> PD-1 mAb 1 VH <400> 131 Gln Val Gln Leu Val Glu Ser Gly Gly Gly Val Val Gln Pro Gly Arg 1 5 10 15 Ser Leu Arg Leu Asp Cys Lys Ala Ser Gly Ile Thr Phe Ser Asn Ser 20 25 30 Gly Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45 Ala Val Ile Trp Tyr Asp Gly Ser Lys Arg Tyr Tyr Ala Asp Ser Val 50 55 60 Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Phe 65 70 75 80 Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Ala Thr Asn Asp Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser 100 105 110 Ser <210> 132 <211> 107 <212> PRT <213> Mus musculus <220> <221> CARACTERÍSTICA_MISCELÁNEA <222> (1)..(107) <223> PD-1 mAb 1 VL <400> 132 Glu Ile Val Leu Thr Gln Ser Pro Ala 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 Tyr 20 25 30 Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile 35 40 45 Tyr Asp Ala Ser Asn Arg Ala Thr Gly Ile Pro Ala Arg Phe Ser Gly 50 55 60 Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Glu Pro 65 70 75 80 Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Ser Ser Asn Trp Pro Arg 85 90 95 Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys 100 105 <210> 133 <211> 120 <212> PRT <213> Mus musculus <400> 133 Gln Val Gln Leu Val Gln Ser Gly Val 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 Asn Tyr 20 25 30 Tyr Met Tyr Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met 35 40 45 Gly Gly Ile Asn Pro Ser Asn Gly Gly Thr Asn Phe Asn Glu Lys Phe 50 55 60 Lys Asn Arg Val Thr Leu Thr Thr Asp Ser Ser Thr Thr Thr Ala Tyr 65 70 75 80 Met Glu Leu Lys Ser Leu Gln Phe Asp Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Ala Arg Arg Asp Tyr Arg Phe Asp Met Gly Phe Asp Tyr Trp Gly Gln 100 105 110 Gly Thr Thr Val Thr Val Ser Ser 115 120 <210> 134 <211> 111 <212> PRT <213> Mus musculus <220> <221> CARACTERÍSTICA_MISCELÁNEA <222> (1)..(111) <223> PD-1 mAb 2 VL <400> 134 Glu Ile Val Leu Thr Gln Ser Pro Ala Thr Leu Ser Leu Ser Pro Gly 1 5 10 15 Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Lys Gly Val Ser Thr Ser 20 25 30 Gly Tyr Ser Tyr Leu His Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro 35 40 45 Arg Leu Leu Ile Tyr Leu Ala Ser Tyr Leu Glu Ser Gly Val Pro Ala 50 55 60 Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser 65 70 75 80 Ser Leu Glu Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln His Ser Arg 85 90 95 Asp Leu Pro Leu Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys 100 105 110 <210> 135 <211> 121 <212> PRT <213> Mus musculus <220> <221> CARACTERÍSTICA_MISCELÁNEA <222> (1)..(121) <223> PD-1 mAb 3 VH <400> 135 Gln Val Gln Leu Gln Gln Ser Gly Ala Glu Leu Ala Lys Pro Gly Ala 1 5 10 15 Ser Val Gln Met Ser Cys Lys Ala Ser Gly Tyr Ser Phe Thr Ser Ser 20 25 30 Trp Ile His Trp Val Lys Gln Arg Pro Gly Gln Gly Leu Glu Trp Ile 35 40 45 Gly Tyr Ile Tyr Pro Ser Thr Gly Phe Thr Glu Tyr Asn Gln Lys Phe 50 55 60 Lys Asp Lys Ala Thr Leu Thr Ala Asp Lys Ser Ser Ser Thr Ala Tyr 65 70 75 80 Met Gln Leu Ser Ser Leu Thr Ser Glu Asp Ser Ala Val Tyr Tyr Cys 85 90 95 Ala Arg Trp Arg Asp Ser Ser Gly Tyr His Ala Met Asp Tyr Trp Gly 100 105 110 Gln Gly Thr Ser Val Thr Val Ser Ser 115 120 <210> 136 <211> 111 <212> PRT <213> Mus musculus <220> <221> CARACTERÍSTICA_MISCELÁNEA <222> (1)..(111) <223> PD-1 mAb 3 VL <400> 136 Asp Ile Val Leu Thr Gln Ser Pro Ala Ser Leu Thr Val Ser Leu Gly 1 5 10 15 Gln Arg Ala Thr Ile Ser Cys Arg Ala Ser Gln Ser Val Ser Thr Ser 20 25 30 Gly Tyr Ser Tyr Met His Trp Tyr Gln Gln Lys Pro Gly Gln Pro Pro 35 40 45 Lys Leu Leu Ile Lys Phe Gly Ser Asn Leu Glu Ser Gly Ile Pro Ala 50 55 60 Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Asn Ile His 65 70 75 80 Pro Val Glu Glu Glu Asp Thr Ala Thr Tyr Tyr Cys Gln His Ser Trp 85 90 95 Glu Ile Pro Tyr Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys 100 105 110 <210> 137 <211> 117 <212> PRT <213> Mus musculus <220> <221> CARACTERÍSTICA_MISCELÁNEA <222> (1)..(117) <223> PD-1 mAb 4 VH <400> 137 Gln Val Gln Leu Val Gln Ser Gly Ser Glu Leu Lys Lys Pro Gly Ala 1 5 10 15 Ser Val Lys Ile Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asn Tyr 20 25 30 Gly Met Asn Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Gln Trp Met 35 40 45 Gly Trp Ile Asn Thr Asp Ser Gly Glu Ser Thr Tyr Ala Glu Glu Phe 50 55 60 Lys Gly Arg Phe Val Phe Ser Leu Asp Thr Ser Val Asn Thr Ala Tyr 65 70 75 80 Leu Gln Ile Thr Ser Leu Thr Ala Glu Asp Thr Gly Met Tyr Phe Cys 85 90 95 Val Arg Val Gly Tyr Asp Ala Leu Asp Tyr Trp Gly Gln Gly Thr Leu 100 105 110 Val Thr Val Ser Ser 115 <210> 138 <211> 106 <212> PRT <213> Mus musculus <220> <221> CARACTERÍSTICA_MISCELÁNEA <222> (1)..(106) <223> PD-1 mAb 4 VL <400> 138 Glu Ile Val Leu Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 1 5 10 15 Asp Arg Val Thr Ile Thr Cys Ser Ala Arg Ser Ser Val Ser Tyr Met 20 25 30 His Trp Phe Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Trp Ile Tyr 35 40 45 Arg Thr Ser Asn Leu Ala Ser Gly Val Pro Ser Arg Phe Ser Gly Ser 50 55 60 Gly Ser Gly Thr Ser Tyr Cys Leu Thr Ile Asn Ser Leu Gln Pro Glu 65 70 75 80 Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Arg Ser Ser Phe Pro Leu Thr 85 90 95 Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys 100 105 <210> 139 <211> 330 <212> PRT <213> Homo sapiens <220> <221> CARACTERÍSTICA_MISCELÁNEA <222> (1)..(330) <223> región constante completa de IgG1 (AA) <220> <221> CARACTERÍSTICA_MISCELÁNEA <222> (330)..(330) <223> Xaa330 es una Lisina (K) o está Ausente <400> 139 Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys 1 5 10 15 Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr 20 25 30 Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser 35 40 45 Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser 50 55 60 Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr 65 70 75 80 Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys 85 90 95 Arg Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro Pro Cys 100 105 110 Pro Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro 115 120 125 Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys 130 135 140 Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp 145 150 155 160 Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu 165 170 175 Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu 180 185 190 His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn 195 200 205 Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly 210 215 220 Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu 225 230 235 240 Met Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr 245 250 255 Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn 260 265 270 Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe 275 280 285 Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn 290 295 300 Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr 305 310 315 320 Gln Lys Ser Leu Ser Leu Ser Pro Gly Xaa 325 330 <210> 140 <211> 327 <212> PRT <213> Homo sapiens <220> <221> CARACTERÍSTICA_MISCELÁNEA <222> (1)..(327) <223> región constante completa de IgG4 (P) <220> <221> CARACTERÍSTICA_MISCELÁNEA <222> (327)..(327) <223> Xaa327 es una Lisina (K) o está Ausente <400> 140 Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Cys Ser Arg 1 5 10 15 Ser Thr Ser Glu Ser Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr 20 25 30 Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser 35 40 45 Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser 50 55 60 Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Lys Thr 65 70 75 80 Tyr Thr Cys Asn Val Asp His Lys Pro Ser Asn Thr Lys Val Asp Lys 85 90 95 Arg Val Glu Ser Lys Tyr Gly Pro Pro Cys Pro Pro Cys Pro Ala Pro 100 105 110 Glu Phe Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys 115 120 125 Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val 130 135 140 Asp Val Ser Gln Glu Asp Pro Glu Val Gln Phe Asn Trp Tyr Val Asp 145 150 155 160 Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Phe 165 170 175 Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp 180 185 190 Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Gly Leu 195 200 205 Pro Ser Ser Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg 210 215 220 Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Gln Glu Glu Met Thr Lys 225 230 235 240 Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp 245 250 255 Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys 260 265 270 Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser 275 280 285 Arg Leu Thr Val Asp Lys Ser Arg Trp Gln Glu Gly Asn Val Phe Ser 290 295 300 Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser 305 310 315 320 Leu Ser Leu Ser Leu Gly Xaa 325