LISTADO DE SECUENCIAS <110> F. Hoffmann-La Roche AG <120> Moléculas de unión a antígeno que comprenden trímero de ligando de la familia de TNF y resto de unión a PD1 <130> P33618-EP <150> EP16169487.2 <151> 13-05-2016 <160> 171 <170> PatentIn versión 3.5 <210> 1 <211> 184 <212> PRT <213> Homo sapiens <400> 1 Arg Glu Gly Pro Glu Leu Ser Pro Asp Asp Pro Ala Gly Leu Leu Asp 1 5 10 15 Leu Arg Gln Gly Met Phe Ala Gln Leu Val Ala Gln Asn Val Leu Leu 20 25 30 Ile Asp Gly Pro Leu Ser Trp Tyr Ser Asp Pro Gly Leu Ala Gly Val 35 40 45 Ser Leu Thr Gly Gly Leu Ser Tyr Lys Glu Asp Thr Lys Glu Leu Val 50 55 60 Val Ala Lys Ala Gly Val Tyr Tyr Val Phe Phe Gln Leu Glu Leu Arg 65 70 75 80 Arg Val Val Ala Gly Glu Gly Ser Gly Ser Val Ser Leu Ala Leu His 85 90 95 Leu Gln Pro Leu Arg Ser Ala Ala Gly Ala Ala Ala Leu Ala Leu Thr 100 105 110 Val Asp Leu Pro Pro Ala Ser Ser Glu Ala Arg Asn Ser Ala Phe Gly 115 120 125 Phe Gln Gly Arg Leu Leu His Leu Ser Ala Gly Gln Arg Leu Gly Val 130 135 140 His Leu His Thr Glu Ala Arg Ala Arg His Ala Trp Gln Leu Thr Gln 145 150 155 160 Gly Ala Thr Val Leu Gly Leu Phe Arg Val Thr Pro Glu Ile Pro Ala 165 170 175 Gly Leu Pro Ser Pro Arg Ser Glu 180 <210> 2 <211> 170 <212> PRT <213> Homo sapiens <400> 2 Leu Asp Leu Arg Gln Gly Met Phe Ala Gln Leu Val Ala Gln Asn Val 1 5 10 15 Leu Leu Ile Asp Gly Pro Leu Ser Trp Tyr Ser Asp Pro Gly Leu Ala 20 25 30 Gly Val Ser Leu Thr Gly Gly Leu Ser Tyr Lys Glu Asp Thr Lys Glu 35 40 45 Leu Val Val Ala Lys Ala Gly Val Tyr Tyr Val Phe Phe Gln Leu Glu 50 55 60 Leu Arg Arg Val Val Ala Gly Glu Gly Ser Gly Ser Val Ser Leu Ala 65 70 75 80 Leu His Leu Gln Pro Leu Arg Ser Ala Ala Gly Ala Ala Ala Leu Ala 85 90 95 Leu Thr Val Asp Leu Pro Pro Ala Ser Ser Glu Ala Arg Asn Ser Ala 100 105 110 Phe Gly Phe Gln Gly Arg Leu Leu His Leu Ser Ala Gly Gln Arg Leu 115 120 125 Gly Val His Leu His Thr Glu Ala Arg Ala Arg His Ala Trp Gln Leu 130 135 140 Thr Gln Gly Ala Thr Val Leu Gly Leu Phe Arg Val Thr Pro Glu Ile 145 150 155 160 Pro Ala Gly Leu Pro Ser Pro Arg Ser Glu 165 170 <210> 3 <211> 175 <212> PRT <213> Homo sapiens <400> 3 Asp Pro Ala Gly Leu Leu Asp Leu Arg Gln Gly Met Phe Ala Gln Leu 1 5 10 15 Val Ala Gln Asn Val Leu Leu Ile Asp Gly Pro Leu Ser Trp Tyr Ser 20 25 30 Asp Pro Gly Leu Ala Gly Val Ser Leu Thr Gly Gly Leu Ser Tyr Lys 35 40 45 Glu Asp Thr Lys Glu Leu Val Val Ala Lys Ala Gly Val Tyr Tyr Val 50 55 60 Phe Phe Gln Leu Glu Leu Arg Arg Val Val Ala Gly Glu Gly Ser Gly 65 70 75 80 Ser Val Ser Leu Ala Leu His Leu Gln Pro Leu Arg Ser Ala Ala Gly 85 90 95 Ala Ala Ala Leu Ala Leu Thr Val Asp Leu Pro Pro Ala Ser Ser Glu 100 105 110 Ala Arg Asn Ser Ala Phe Gly Phe Gln Gly Arg Leu Leu His Leu Ser 115 120 125 Ala Gly Gln Arg Leu Gly Val His Leu His Thr Glu Ala Arg Ala Arg 130 135 140 His Ala Trp Gln Leu Thr Gln Gly Ala Thr Val Leu Gly Leu Phe Arg 145 150 155 160 Val Thr Pro Glu Ile Pro Ala Gly Leu Pro Ser Pro Arg Ser Glu 165 170 175 <210> 4 <211> 203 <212> PRT <213> Homo sapiens <400> 4 Pro Trp Ala Val Ser Gly Ala Arg Ala Ser Pro Gly Ser Ala Ala Ser 1 5 10 15 Pro Arg Leu Arg Glu Gly Pro Glu Leu Ser Pro Asp Asp Pro Ala Gly 20 25 30 Leu Leu Asp Leu Arg Gln Gly Met Phe Ala Gln Leu Val Ala Gln Asn 35 40 45 Val Leu Leu Ile Asp Gly Pro Leu Ser Trp Tyr Ser Asp Pro Gly Leu 50 55 60 Ala Gly Val Ser Leu Thr Gly Gly Leu Ser Tyr Lys Glu Asp Thr Lys 65 70 75 80 Glu Leu Val Val Ala Lys Ala Gly Val Tyr Tyr Val Phe Phe Gln Leu 85 90 95 Glu Leu Arg Arg Val Val Ala Gly Glu Gly Ser Gly Ser Val Ser Leu 100 105 110 Ala Leu His Leu Gln Pro Leu Arg Ser Ala Ala Gly Ala Ala Ala Leu 115 120 125 Ala Leu Thr Val Asp Leu Pro Pro Ala Ser Ser Glu Ala Arg Asn Ser 130 135 140 Ala Phe Gly Phe Gln Gly Arg Leu Leu His Leu Ser Ala Gly Gln Arg 145 150 155 160 Leu Gly Val His Leu His Thr Glu Ala Arg Ala Arg His Ala Trp Gln 165 170 175 Leu Thr Gln Gly Ala Thr Val Leu Gly Leu Phe Arg Val Thr Pro Glu 180 185 190 Ile Pro Ala Gly Leu Pro Ser Pro Arg Ser Glu 195 200 <210> 5 <211> 178 <212> PRT <213> Homo sapiens <400> 5 Arg Glu Gly Pro Glu Leu Ser Pro Asp Asp Pro Ala Gly Leu Leu Asp 1 5 10 15 Leu Arg Gln Gly Met Phe Ala Gln Leu Val Ala Gln Asn Val Leu Leu 20 25 30 Ile Asp Gly Pro Leu Ser Trp Tyr Ser Asp Pro Gly Leu Ala Gly Val 35 40 45 Ser Leu Thr Gly Gly Leu Ser Tyr Lys Glu Asp Thr Lys Glu Leu Val 50 55 60 Val Ala Lys Ala Gly Val Tyr Tyr Val Phe Phe Gln Leu Glu Leu Arg 65 70 75 80 Arg Val Val Ala Gly Glu Gly Ser Gly Ser Val Ser Leu Ala Leu His 85 90 95 Leu Gln Pro Leu Arg Ser Ala Ala Gly Ala Ala Ala Leu Ala Leu Thr 100 105 110 Val Asp Leu Pro Pro Ala Ser Ser Glu Ala Arg Asn Ser Ala Phe Gly 115 120 125 Phe Gln Gly Arg Leu Leu His Leu Ser Ala Gly Gln Arg Leu Gly Val 130 135 140 His Leu His Thr Glu Ala Arg Ala Arg His Ala Trp Gln Leu Thr Gln 145 150 155 160 Gly Ala Thr Val Leu Gly Leu Phe Arg Val Thr Pro Glu Ile Pro Ala 165 170 175 Gly Leu <210> 6 <211> 164 <212> PRT <213> Homo sapiens <400> 6 Leu Asp Leu Arg Gln Gly Met Phe Ala Gln Leu Val Ala Gln Asn Val 1 5 10 15 Leu Leu Ile Asp Gly Pro Leu Ser Trp Tyr Ser Asp Pro Gly Leu Ala 20 25 30 Gly Val Ser Leu Thr Gly Gly Leu Ser Tyr Lys Glu Asp Thr Lys Glu 35 40 45 Leu Val Val Ala Lys Ala Gly Val Tyr Tyr Val Phe Phe Gln Leu Glu 50 55 60 Leu Arg Arg Val Val Ala Gly Glu Gly Ser Gly Ser Val Ser Leu Ala 65 70 75 80 Leu His Leu Gln Pro Leu Arg Ser Ala Ala Gly Ala Ala Ala Leu Ala 85 90 95 Leu Thr Val Asp Leu Pro Pro Ala Ser Ser Glu Ala Arg Asn Ser Ala 100 105 110 Phe Gly Phe Gln Gly Arg Leu Leu His Leu Ser Ala Gly Gln Arg Leu 115 120 125 Gly Val His Leu His Thr Glu Ala Arg Ala Arg His Ala Trp Gln Leu 130 135 140 Thr Gln Gly Ala Thr Val Leu Gly Leu Phe Arg Val Thr Pro Glu Ile 145 150 155 160 Pro Ala Gly Leu <210> 7 <211> 169 <212> PRT <213> Homo sapiens <400> 7 Asp Pro Ala Gly Leu Leu Asp Leu Arg Gln Gly Met Phe Ala Gln Leu 1 5 10 15 Val Ala Gln Asn Val Leu Leu Ile Asp Gly Pro Leu Ser Trp Tyr Ser 20 25 30 Asp Pro Gly Leu Ala Gly Val Ser Leu Thr Gly Gly Leu Ser Tyr Lys 35 40 45 Glu Asp Thr Lys Glu Leu Val Val Ala Lys Ala Gly Val Tyr Tyr Val 50 55 60 Phe Phe Gln Leu Glu Leu Arg Arg Val Val Ala Gly Glu Gly Ser Gly 65 70 75 80 Ser Val Ser Leu Ala Leu His Leu Gln Pro Leu Arg Ser Ala Ala Gly 85 90 95 Ala Ala Ala Leu Ala Leu Thr Val Asp Leu Pro Pro Ala Ser Ser Glu 100 105 110 Ala Arg Asn Ser Ala Phe Gly Phe Gln Gly Arg Leu Leu His Leu Ser 115 120 125 Ala Gly Gln Arg Leu Gly Val His Leu His Thr Glu Ala Arg Ala Arg 130 135 140 His Ala Trp Gln Leu Thr Gln Gly Ala Thr Val Leu Gly Leu Phe Arg 145 150 155 160 Val Thr Pro Glu Ile Pro Ala Gly Leu 165 <210> 8 <211> 197 <212> PRT <213> Homo sapiens <400> 8 Pro Trp Ala Val Ser Gly Ala Arg Ala Ser Pro Gly Ser Ala Ala Ser 1 5 10 15 Pro Arg Leu Arg Glu Gly Pro Glu Leu Ser Pro Asp Asp Pro Ala Gly 20 25 30 Leu Leu Asp Leu Arg Gln Gly Met Phe Ala Gln Leu Val Ala Gln Asn 35 40 45 Val Leu Leu Ile Asp Gly Pro Leu Ser Trp Tyr Ser Asp Pro Gly Leu 50 55 60 Ala Gly Val Ser Leu Thr Gly Gly Leu Ser Tyr Lys Glu Asp Thr Lys 65 70 75 80 Glu Leu Val Val Ala Lys Ala Gly Val Tyr Tyr Val Phe Phe Gln Leu 85 90 95 Glu Leu Arg Arg Val Val Ala Gly Glu Gly Ser Gly Ser Val Ser Leu 100 105 110 Ala Leu His Leu Gln Pro Leu Arg Ser Ala Ala Gly Ala Ala Ala Leu 115 120 125 Ala Leu Thr Val Asp Leu Pro Pro Ala Ser Ser Glu Ala Arg Asn Ser 130 135 140 Ala Phe Gly Phe Gln Gly Arg Leu Leu His Leu Ser Ala Gly Gln Arg 145 150 155 160 Leu Gly Val His Leu His Thr Glu Ala Arg Ala Arg His Ala Trp Gln 165 170 175 Leu Thr Gln Gly Ala Thr Val Leu Gly Leu Phe Arg Val Thr Pro Glu 180 185 190 Ile Pro Ala Gly Leu 195 <210> 9 <211> 378 <212> PRT <213> Secuencia artificial <220> <223> 4-1BBL hu dimérico (71-254) conectado mediante enlazador (G4S)2 <400> 9 Arg Glu Gly Pro Glu Leu Ser Pro Asp Asp Pro Ala Gly Leu Leu Asp 1 5 10 15 Leu Arg Gln Gly Met Phe Ala Gln Leu Val Ala Gln Asn Val Leu Leu 20 25 30 Ile Asp Gly Pro Leu Ser Trp Tyr Ser Asp Pro Gly Leu Ala Gly Val 35 40 45 Ser Leu Thr Gly Gly Leu Ser Tyr Lys Glu Asp Thr Lys Glu Leu Val 50 55 60 Val Ala Lys Ala Gly Val Tyr Tyr Val Phe Phe Gln Leu Glu Leu Arg 65 70 75 80 Arg Val Val Ala Gly Glu Gly Ser Gly Ser Val Ser Leu Ala Leu His 85 90 95 Leu Gln Pro Leu Arg Ser Ala Ala Gly Ala Ala Ala Leu Ala Leu Thr 100 105 110 Val Asp Leu Pro Pro Ala Ser Ser Glu Ala Arg Asn Ser Ala Phe Gly 115 120 125 Phe Gln Gly Arg Leu Leu His Leu Ser Ala Gly Gln Arg Leu Gly Val 130 135 140 His Leu His Thr Glu Ala Arg Ala Arg His Ala Trp Gln Leu Thr Gln 145 150 155 160 Gly Ala Thr Val Leu Gly Leu Phe Arg Val Thr Pro Glu Ile Pro Ala 165 170 175 Gly Leu Pro Ser Pro Arg Ser Glu Gly Gly Gly Gly Ser Gly Gly Gly 180 185 190 Gly Ser Arg Glu Gly Pro Glu Leu Ser Pro Asp Asp Pro Ala Gly Leu 195 200 205 Leu Asp Leu Arg Gln Gly Met Phe Ala Gln Leu Val Ala Gln Asn Val 210 215 220 Leu Leu Ile Asp Gly Pro Leu Ser Trp Tyr Ser Asp Pro Gly Leu Ala 225 230 235 240 Gly Val Ser Leu Thr Gly Gly Leu Ser Tyr Lys Glu Asp Thr Lys Glu 245 250 255 Leu Val Val Ala Lys Ala Gly Val Tyr Tyr Val Phe Phe Gln Leu Glu 260 265 270 Leu Arg Arg Val Val Ala Gly Glu Gly Ser Gly Ser Val Ser Leu Ala 275 280 285 Leu His Leu Gln Pro Leu Arg Ser Ala Ala Gly Ala Ala Ala Leu Ala 290 295 300 Leu Thr Val Asp Leu Pro Pro Ala Ser Ser Glu Ala Arg Asn Ser Ala 305 310 315 320 Phe Gly Phe Gln Gly Arg Leu Leu His Leu Ser Ala Gly Gln Arg Leu 325 330 335 Gly Val His Leu His Thr Glu Ala Arg Ala Arg His Ala Trp Gln Leu 340 345 350 Thr Gln Gly Ala Thr Val Leu Gly Leu Phe Arg Val Thr Pro Glu Ile 355 360 365 Pro Ala Gly Leu Pro Ser Pro Arg Ser Glu 370 375 <210> 10 <211> 366 <212> PRT <213> Secuencia artificial <220> <223> 4-1BBL hu dimérico (71-248) conectado mediante enlazador (G4S)2 <400> 10 Arg Glu Gly Pro Glu Leu Ser Pro Asp Asp Pro Ala Gly Leu Leu Asp 1 5 10 15 Leu Arg Gln Gly Met Phe Ala Gln Leu Val Ala Gln Asn Val Leu Leu 20 25 30 Ile Asp Gly Pro Leu Ser Trp Tyr Ser Asp Pro Gly Leu Ala Gly Val 35 40 45 Ser Leu Thr Gly Gly Leu Ser Tyr Lys Glu Asp Thr Lys Glu Leu Val 50 55 60 Val Ala Lys Ala Gly Val Tyr Tyr Val Phe Phe Gln Leu Glu Leu Arg 65 70 75 80 Arg Val Val Ala Gly Glu Gly Ser Gly Ser Val Ser Leu Ala Leu His 85 90 95 Leu Gln Pro Leu Arg Ser Ala Ala Gly Ala Ala Ala Leu Ala Leu Thr 100 105 110 Val Asp Leu Pro Pro Ala Ser Ser Glu Ala Arg Asn Ser Ala Phe Gly 115 120 125 Phe Gln Gly Arg Leu Leu His Leu Ser Ala Gly Gln Arg Leu Gly Val 130 135 140 His Leu His Thr Glu Ala Arg Ala Arg His Ala Trp Gln Leu Thr Gln 145 150 155 160 Gly Ala Thr Val Leu Gly Leu Phe Arg Val Thr Pro Glu Ile Pro Ala 165 170 175 Gly Leu Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Arg Glu Gly Pro 180 185 190 Glu Leu Ser Pro Asp Asp Pro Ala Gly Leu Leu Asp Leu Arg Gln Gly 195 200 205 Met Phe Ala Gln Leu Val Ala Gln Asn Val Leu Leu Ile Asp Gly Pro 210 215 220 Leu Ser Trp Tyr Ser Asp Pro Gly Leu Ala Gly Val Ser Leu Thr Gly 225 230 235 240 Gly Leu Ser Tyr Lys Glu Asp Thr Lys Glu Leu Val Val Ala Lys Ala 245 250 255 Gly Val Tyr Tyr Val Phe Phe Gln Leu Glu Leu Arg Arg Val Val Ala 260 265 270 Gly Glu Gly Ser Gly Ser Val Ser Leu Ala Leu His Leu Gln Pro Leu 275 280 285 Arg Ser Ala Ala Gly Ala Ala Ala Leu Ala Leu Thr Val Asp Leu Pro 290 295 300 Pro Ala Ser Ser Glu Ala Arg Asn Ser Ala Phe Gly Phe Gln Gly Arg 305 310 315 320 Leu Leu His Leu Ser Ala Gly Gln Arg Leu Gly Val His Leu His Thr 325 330 335 Glu Ala Arg Ala Arg His Ala Trp Gln Leu Thr Gln Gly Ala Thr Val 340 345 350 Leu Gly Leu Phe Arg Val Thr Pro Glu Ile Pro Ala Gly Leu 355 360 365 <210> 11 <211> 360 <212> PRT <213> Secuencia artificial <220> <223> 4-1BBL hu dimérico (80-254) conectado mediante enlazador (G4S)2 <400> 11 Asp Pro Ala Gly Leu Leu Asp Leu Arg Gln Gly Met Phe Ala Gln Leu 1 5 10 15 Val Ala Gln Asn Val Leu Leu Ile Asp Gly Pro Leu Ser Trp Tyr Ser 20 25 30 Asp Pro Gly Leu Ala Gly Val Ser Leu Thr Gly Gly Leu Ser Tyr Lys 35 40 45 Glu Asp Thr Lys Glu Leu Val Val Ala Lys Ala Gly Val Tyr Tyr Val 50 55 60 Phe Phe Gln Leu Glu Leu Arg Arg Val Val Ala Gly Glu Gly Ser Gly 65 70 75 80 Ser Val Ser Leu Ala Leu His Leu Gln Pro Leu Arg Ser Ala Ala Gly 85 90 95 Ala Ala Ala Leu Ala Leu Thr Val Asp Leu Pro Pro Ala Ser Ser Glu 100 105 110 Ala Arg Asn Ser Ala Phe Gly Phe Gln Gly Arg Leu Leu His Leu Ser 115 120 125 Ala Gly Gln Arg Leu Gly Val His Leu His Thr Glu Ala Arg Ala Arg 130 135 140 His Ala Trp Gln Leu Thr Gln Gly Ala Thr Val Leu Gly Leu Phe Arg 145 150 155 160 Val Thr Pro Glu Ile Pro Ala Gly Leu Pro Ser Pro Arg Ser Glu Gly 165 170 175 Gly Gly Gly Ser Gly Gly Gly Gly Ser Asp Pro Ala Gly Leu Leu Asp 180 185 190 Leu Arg Gln Gly Met Phe Ala Gln Leu Val Ala Gln Asn Val Leu Leu 195 200 205 Ile Asp Gly Pro Leu Ser Trp Tyr Ser Asp Pro Gly Leu Ala Gly Val 210 215 220 Ser Leu Thr Gly Gly Leu Ser Tyr Lys Glu Asp Thr Lys Glu Leu Val 225 230 235 240 Val Ala Lys Ala Gly Val Tyr Tyr Val Phe Phe Gln Leu Glu Leu Arg 245 250 255 Arg Val Val Ala Gly Glu Gly Ser Gly Ser Val Ser Leu Ala Leu His 260 265 270 Leu Gln Pro Leu Arg Ser Ala Ala Gly Ala Ala Ala Leu Ala Leu Thr 275 280 285 Val Asp Leu Pro Pro Ala Ser Ser Glu Ala Arg Asn Ser Ala Phe Gly 290 295 300 Phe Gln Gly Arg Leu Leu His Leu Ser Ala Gly Gln Arg Leu Gly Val 305 310 315 320 His Leu His Thr Glu Ala Arg Ala Arg His Ala Trp Gln Leu Thr Gln 325 330 335 Gly Ala Thr Val Leu Gly Leu Phe Arg Val Thr Pro Glu Ile Pro Ala 340 345 350 Gly Leu Pro Ser Pro Arg Ser Glu 355 360 <210> 12 <211> 416 <212> PRT <213> Secuencia artificial <220> <223> 4-1BBL hu dimérico (52-254) conectado mediante enlazador (G4S)2 <400> 12 Pro Trp Ala Val Ser Gly Ala Arg Ala Ser Pro Gly Ser Ala Ala Ser 1 5 10 15 Pro Arg Leu Arg Glu Gly Pro Glu Leu Ser Pro Asp Asp Pro Ala Gly 20 25 30 Leu Leu Asp Leu Arg Gln Gly Met Phe Ala Gln Leu Val Ala Gln Asn 35 40 45 Val Leu Leu Ile Asp Gly Pro Leu Ser Trp Tyr Ser Asp Pro Gly Leu 50 55 60 Ala Gly Val Ser Leu Thr Gly Gly Leu Ser Tyr Lys Glu Asp Thr Lys 65 70 75 80 Glu Leu Val Val Ala Lys Ala Gly Val Tyr Tyr Val Phe Phe Gln Leu 85 90 95 Glu Leu Arg Arg Val Val Ala Gly Glu Gly Ser Gly Ser Val Ser Leu 100 105 110 Ala Leu His Leu Gln Pro Leu Arg Ser Ala Ala Gly Ala Ala Ala Leu 115 120 125 Ala Leu Thr Val Asp Leu Pro Pro Ala Ser Ser Glu Ala Arg Asn Ser 130 135 140 Ala Phe Gly Phe Gln Gly Arg Leu Leu His Leu Ser Ala Gly Gln Arg 145 150 155 160 Leu Gly Val His Leu His Thr Glu Ala Arg Ala Arg His Ala Trp Gln 165 170 175 Leu Thr Gln Gly Ala Thr Val Leu Gly Leu Phe Arg Val Thr Pro Glu 180 185 190 Ile Pro Ala Gly Leu Pro Ser Pro Arg Ser Glu Gly Gly Gly Gly Ser 195 200 205 Gly Gly Gly Gly Ser Pro Trp Ala Val Ser Gly Ala Arg Ala Ser Pro 210 215 220 Gly Ser Ala Ala Ser Pro Arg Leu Arg Glu Gly Pro Glu Leu Ser Pro 225 230 235 240 Asp Asp Pro Ala Gly Leu Leu Asp Leu Arg Gln Gly Met Phe Ala Gln 245 250 255 Leu Val Ala Gln Asn Val Leu Leu Ile Asp Gly Pro Leu Ser Trp Tyr 260 265 270 Ser Asp Pro Gly Leu Ala Gly Val Ser Leu Thr Gly Gly Leu Ser Tyr 275 280 285 Lys Glu Asp Thr Lys Glu Leu Val Val Ala Lys Ala Gly Val Tyr Tyr 290 295 300 Val Phe Phe Gln Leu Glu Leu Arg Arg Val Val Ala Gly Glu Gly Ser 305 310 315 320 Gly Ser Val Ser Leu Ala Leu His Leu Gln Pro Leu Arg Ser Ala Ala 325 330 335 Gly Ala Ala Ala Leu Ala Leu Thr Val Asp Leu Pro Pro Ala Ser Ser 340 345 350 Glu Ala Arg Asn Ser Ala Phe Gly Phe Gln Gly Arg Leu Leu His Leu 355 360 365 Ser Ala Gly Gln Arg Leu Gly Val His Leu His Thr Glu Ala Arg Ala 370 375 380 Arg His Ala Trp Gln Leu Thr Gln Gly Ala Thr Val Leu Gly Leu Phe 385 390 395 400 Arg Val Thr Pro Glu Ile Pro Ala Gly Leu Pro Ser Pro Arg Ser Glu 405 410 415 <210> 13 <211> 7 <212> PRT <213> Mus musculus <400> 13 Gly Phe Ser Phe Ser Ser Tyr 1 5 <210> 14 <211> 3 <212> PRT <213> Mus musculus <400> 14 Gly Gly Arg 1 <210> 15 <211> 9 <212> PRT <213> Mus musculus <400> 15 Thr Gly Arg Val Tyr Phe Ala Leu Asp 1 5 <210> 16 <211> 11 <212> PRT <213> Mus musculus <400> 16 Ser Glu Ser Val Asp Thr Ser Asp Asn Ser Phe 1 5 10 <210> 17 <211> 3 <212> PRT <213> Mus musculus <400> 17 Arg Ser Ser 1 <210> 18 <211> 6 <212> PRT <213> Mus musculus <400> 18 Asn Tyr Asp Val Pro Trp 1 5 <210> 19 <211> 120 <212> PRT <213> Mus musculus <400> 19 Glu Val Ile Leu Val Glu Ser Gly Gly Gly Leu Val Lys Pro Gly Gly 1 5 10 15 Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Ser Phe Ser Ser Tyr 20 25 30 Thr Met Ser Trp Val Arg Gln Thr Pro Glu Lys Arg Leu Asp Trp Val 35 40 45 Ala Thr Ile Ser Gly Gly Gly Arg Asp Ile Tyr Tyr Pro Asp Ser Val 50 55 60 Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Leu Tyr 65 70 75 80 Leu Glu Met Ser Ser Leu Met Ser Glu Asp Thr Ala Leu Tyr Tyr Cys 85 90 95 Val Leu Leu Thr Gly Arg Val Tyr Phe Ala Leu Asp Ser Trp Gly Gln 100 105 110 Gly Thr Ser Val Thr Val Ser Ser 115 120 <210> 20 <211> 111 <212> PRT <213> Mus musculus <400> 20 Lys Ile Val Leu Thr Gln Ser Pro Ala Ser Leu Pro Val Ser Leu Gly 1 5 10 15 Gln Arg Ala Thr Ile Ser Cys Arg Ala Ser Glu Ser Val Asp Thr Ser 20 25 30 Asp Asn Ser Phe Ile His Trp Tyr Gln Gln Arg Pro Gly Gln Ser Pro 35 40 45 Lys Leu Leu Ile Tyr Arg Ser Ser Thr Leu Glu Ser Gly Val Pro Ala 50 55 60 Arg Phe Ser Gly Ser Gly Ser Arg Thr Asp Phe Thr Leu Thr Ile Asp 65 70 75 80 Pro Val Glu Ala Asp Asp Val Ala Thr Tyr Tyr Cys Gln Gln Asn Tyr 85 90 95 Asp Val Pro Trp Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys 100 105 110 <210> 21 <211> 120 <212> PRT <213> Secuencia artificial <220> <223> variante humanizada - dominio variable de cadena pesada VH de PD1-0103-0312, -0313, -0314 y -0315 <400> 21 Glu Val Gln Leu Leu Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 1 5 10 15 Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Ser Phe Ser Ser Tyr 20 25 30 Thr Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45 Ala Thr Ile Ser Gly Gly Gly Arg Asp Ile Tyr Tyr Pro Asp Ser Val 50 55 60 Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 65 70 75 80 Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Val Leu Leu Thr Gly Arg Val Tyr Phe Ala Leu Asp Ser Trp Gly Gln 100 105 110 Gly Thr Leu Val Thr Val Ser Ser 115 120 <210> 22 <211> 111 <212> PRT <213> Secuencia artificial <220> <223> variante humanizada - dominio variable de cadena ligera VL de PD1-0103-0312 <400> 22 Asp Ile Val Met Thr Gln Ser Pro Asp Ser Leu Ala Val Ser Leu Gly 1 5 10 15 Glu Arg Ala Thr Ile Asn Cys Lys Ala Ser Glu Ser Val Asp Thr Ser 20 25 30 Asp Asn Ser Phe Ile His Trp Tyr Gln Gln Lys Pro Gly Gln Ser Pro 35 40 45 Lys Leu Leu Ile Tyr Arg Ser Ser Thr Leu Glu Ser Gly Val Pro Asp 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 Gln Ala Glu Asp Val Ala Val Tyr Tyr Cys Gln Gln Asn Tyr 85 90 95 Asp Val Pro Trp Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys 100 105 110 <210> 23 <211> 111 <212> PRT <213> Secuencia artificial <220> <223> variante humanizada - dominio variable de cadena ligera VL de PD1-0103-0313 <400> 23 Asp Val Val Met Thr Gln Ser Pro Leu Ser Leu Pro Val Thr Leu Gly 1 5 10 15 Gln Pro Ala Ser Ile Ser Cys Arg Ala Ser Glu Ser Val Asp Thr Ser 20 25 30 Asp Asn Ser Phe Ile His Trp Tyr Gln Gln Arg Pro Gly Gln Ser Pro 35 40 45 Arg Leu Leu Ile Tyr Arg Ser Ser Thr Leu Glu Ser Gly Val Pro Asp 50 55 60 Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile Ser 65 70 75 80 Arg Val Glu Ala Glu Asp Val Gly Val Tyr Tyr Cys Gln Gln Asn Tyr 85 90 95 Asp Val Pro Trp Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys 100 105 110 <210> 24 <211> 111 <212> PRT <213> Secuencia artificial <220> <223> variante humanizada - dominio variable de cadena ligera VL de PD1-0103-0314 <400> 24 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 Glu Ser Val Asp Thr Ser 20 25 30 Asp Asn Ser Phe Ile His Trp Tyr Gln Gln Lys Pro Gly Gln Ser Pro 35 40 45 Arg Leu Leu Ile Tyr Arg Ser Ser Thr Leu Glu Ser Gly Ile 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 Gln Asn Tyr 85 90 95 Asp Val Pro Trp Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys 100 105 110 <210> 25 <211> 111 <212> PRT <213> Secuencia artificial <220> <223> variante humanizada - dominio variable de cadena ligera VL de PD1-0103-0315 <400> 25 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 Glu Ser Val Asp Thr Ser 20 25 30 Asp Asn Ser Phe Ile His Trp Tyr Gln Gln Lys Pro Gly Gln Ser Pro 35 40 45 Arg Leu Leu Ile Tyr Arg Ser Ser Thr Leu Glu Ser Gly Ile 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 Gln Asn Tyr 85 90 95 Asp Val Pro Trp Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys 100 105 110 <210> 26 <211> 8 <212> PRT <213> Secuencia artificial <220> <223> HVR-H1 de cadena pesada, PD1-0098 <400> 26 Gly Tyr Ser Ile Thr Ser Asp Tyr 1 5 <210> 27 <211> 3 <212> PRT <213> Secuencia artificial <220> <223> HVR-H2 de cadena pesada, PD1-0098 <400> 27 Tyr Ser Gly 1 <210> 28 <211> 9 <212> PRT <213> Secuencia artificial <220> <223> HVR-H3 de cadena pesada, PD1-0098 <400> 28 His Gly Ser Ala Pro Trp Tyr Phe Asp 1 5 <210> 29 <211> 12 <212> PRT <213> Secuencia artificial <220> <223> HVR-L1 de cadena ligera, PD1-0098 <400> 29 Ser Gln Asn Ile Val His Ser Asp Gly Asn Thr Tyr 1 5 10 <210> 30 <211> 3 <212> PRT <213> Secuencia artificial <220> <223> HVR-L2 de cadena ligera, PD1-0098 <400> 30 Lys Val Ser 1 <210> 31 <211> 6 <212> PRT <213> Secuencia artificial <220> <223> HVR-L3 de cadena ligera, PD1-0098 <400> 31 Gly Ser His Phe Pro Leu 1 5 <210> 32 <211> 120 <212> PRT <213> Secuencia artificial <220> <223> dominio variable de cadena pesada VH, PD1-0098 <400> 32 Asp Val Gln Leu Gln Glu Ser Gly Pro Gly Leu Val Lys Pro Ser Gln 1 5 10 15 Ser Leu Ser Leu Thr Cys Thr Val Thr Gly Tyr Ser Ile Thr Ser Asp 20 25 30 Tyr Ala Trp Asn Trp Ile Arg Gln Phe Pro Gly Asp Lys Leu Glu Trp 35 40 45 Leu Gly Tyr Ile Thr Tyr Ser Gly Phe Thr Asn Tyr Asn Pro Ser Leu 50 55 60 Lys Ser Arg Ile Ser Ile Ser Arg Asp Thr Ser Lys Asn Gln Phe Phe 65 70 75 80 Leu Gln Leu Asn Ser Val Ala Thr Glu Asp Thr Ala Thr Tyr Tyr Cys 85 90 95 Ala Arg Trp His Gly Ser Ala Pro Trp Tyr Phe Asp Tyr Trp Gly Arg 100 105 110 Gly Thr Thr Leu Thr Val Ser Ser 115 120 <210> 33 <211> 112 <212> PRT <213> Secuencia artificial <220> <223> dominio variable de cadena ligera VL, PD1-0098 <400> 33 Asp Val Leu Met Thr Gln Thr Pro Leu Ser Leu Pro Val Ser Leu Gly 1 5 10 15 Asp Gln Ala Ser Ile Ser Cys Arg Ser Ser Gln Asn Ile Val His Ser 20 25 30 Asp Gly Asn Thr Tyr Leu Glu Trp Tyr Leu Gln Lys Pro Gly Gln Ser 35 40 45 Pro Asn Leu Leu Ile Tyr Lys Val Ser Arg Arg Phe Ser Gly Val Pro 50 55 60 Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile 65 70 75 80 Ser Arg Val Glu Ala Glu Asp Leu Gly Val Tyr Tyr Cys Phe Gln Gly 85 90 95 Ser His Phe Pro Leu Thr Phe Gly Ala Gly Thr Lys Leu Glu Leu Lys 100 105 110 <210> 34 <211> 8 <212> PRT <213> Secuencia artificial <220> <223> HVR-H1 de cadena pesada, PD1-0050 <400> 34 Gly Tyr Ser Ile Thr Ser Asp Tyr 1 5 <210> 35 <211> 3 <212> PRT <213> Secuencia artificial <220> <223> HVR-H2 de cadena pesada, PD1-0050 <400> 35 Tyr Thr Gly 1 <210> 36 <211> 9 <212> PRT <213> Secuencia artificial <220> <223> HVR-H3 de cadena pesada, PD1-0050 <400> 36 Met Asp Tyr Tyr Gly Ser Thr Leu Asp 1 5 <210> 37 <211> 11 <212> PRT <213> Secuencia artificial <220> <223> HVR-L1 de cadena ligera, PD1-0050 <400> 37 Ser Glu Ser Val Asp Arg Tyr Gly Asn Ser Phe 1 5 10 <210> 38 <211> 3 <212> PRT <213> Secuencia artificial <220> <223> HVR-L2 de cadena ligera, PD1-0050 <400> 38 Arg Ala Ser 1 <210> 39 <211> 6 <212> PRT <213> Secuencia artificial <220> <223> HVR-L3 de cadena ligera, PD1-0050 <400> 39 Asn Asn Glu Asp Pro Tyr 1 5 <210> 40 <211> 120 <212> PRT <213> Secuencia artificial <220> <223> dominio variable de cadena pesada VH, PD1-0050 <400> 40 Asp Val Gln Leu Gln Glu Ser Gly Pro Gly Leu Val Lys Pro Ser Gln 1 5 10 15 Ser Leu Ser Leu Thr Cys Thr Val Thr Gly Tyr Ser Ile Thr Ser Asp 20 25 30 Tyr Ala Trp Asn Trp Ile Arg Gln Phe Pro Gly Asn Lys Leu Glu Trp 35 40 45 Met Gly Tyr Ile Thr Tyr Thr Gly Arg Thr Ser Tyr Asn Pro Ser Leu 50 55 60 Lys Ser Arg Ile Ser Ile Thr Arg Asp Thr Ser Lys Asn Gln Phe Phe 65 70 75 80 Leu Gln Leu Asn Ser Val Thr Thr Glu Asp Thr Ala Thr Tyr Tyr Cys 85 90 95 Ala Arg Glu Met Asp Tyr Tyr Gly Ser Thr Leu Asp Tyr Trp Gly Gln 100 105 110 Gly Thr Thr Leu Thr Val Ser Ser 115 120 <210> 41 <211> 111 <212> PRT <213> Secuencia artificial <220> <223> dominio variable de cadena ligera VL, PD1-0050 <400> 41 Lys Ile Val Leu Thr Gln Ser Pro Ala Ser Leu Ala Val Ser Leu Arg 1 5 10 15 Gln Arg Ala Thr Ile Ser Cys Arg Ala Ser Glu Ser Val Asp Arg Tyr 20 25 30 Gly Asn Ser Phe Ile His Trp Tyr Gln Gln Lys Pro Gly Gln Pro Pro 35 40 45 Lys Val Leu Ile Tyr Arg Ala Ser Asn Leu Glu Ser Gly Phe Pro Ala 50 55 60 Arg Phe Ser Gly Ser Gly Ser Arg Thr Asp Phe Thr Leu Thr Ile Asp 65 70 75 80 Pro Val Glu Ala Asp Asp Ala Ala Thr Tyr Tyr Cys Gln Gln Asn Asn 85 90 95 Glu Asp Pro Tyr Thr Phe Gly Ser Gly Thr Lys Leu Glu Ile Lys 100 105 110 <210> 42 <211> 7 <212> PRT <213> Secuencia artificial <220> <223> HVR-H1 de cadena pesada, PD1-0069 <400> 42 Gly Tyr Thr Phe Thr Asp Tyr 1 5 <210> 43 <211> 3 <212> PRT <213> Secuencia artificial <220> <223> HVR-H2 de cadena pesada, PD1-0069 <400> 43 Tyr Ser Gly 1 <210> 44 <211> 7 <212> PRT <213> Secuencia artificial <220> <223> HVR-H3 de cadena pesada, PD1-0069 <400> 44 Gly Ile Thr Thr Gly Phe Ala 1 5 <210> 45 <211> 11 <212> PRT <213> Secuencia artificial <220> <223> HVR-L1 de cadena ligera, PD1-0069 <400> 45 Ser Lys Gly Val Ser Thr Ser Ser Tyr Ser Phe 1 5 10 <210> 46 <211> 3 <212> PRT <213> Secuencia artificial <220> <223> HVR-L2 de cadena ligera, PD1-0069 <400> 46 Tyr Ala Ser 1 <210> 47 <211> 6 <212> PRT <213> Secuencia artificial <220> <223> HVR-L3 de cadena ligera, PD1-0069 <400> 47 Ser Arg Glu Phe Pro Trp 1 5 <210> 48 <211> 118 <212> PRT <213> Secuencia artificial <220> <223> dominio variable de cadena pesada VH, PD1-0069 <400> 48 Gln Val Gln Leu Gln Gln Ser Gly Pro Glu Leu Val Arg Pro Gly Val 1 5 10 15 Ser Val Lys Ile Ser Cys Lys Gly Ser Gly Tyr Thr Phe Thr Asp Tyr 20 25 30 Ala Met His Trp Val Lys Gln Ser His Ala Arg Thr Leu Glu Trp Ile 35 40 45 Gly Val Ile Ser Thr Tyr Ser Gly Asp Thr Asn Tyr Asn Gln Lys Phe 50 55 60 Lys Asp Lys Ala Thr Met Thr Val Asp Lys Ser Ser Ser Thr Ala Tyr 65 70 75 80 Leu Glu Leu Ala Arg Met Thr Ser Glu Asp Ser Ala Ile Tyr Tyr Cys 85 90 95 Ala Arg Leu Gly Ile Thr Thr Gly Phe Ala Tyr Trp Gly Gln Gly Thr 100 105 110 Leu Val Thr Val Ser Ala 115 <210> 49 <211> 111 <212> PRT <213> Secuencia artificial <220> <223> dominio variable de cadena ligera VL, PD1-0069 <400> 49 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 Arg Ala Ser Lys Gly Val Ser Thr Ser 20 25 30 Ser Tyr Ser Phe Met His Trp Tyr Gln Gln Lys Pro Arg Gln Pro Pro 35 40 45 Lys Leu Leu Ile Lys Tyr 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 Asn Ile His 65 70 75 80 Pro Val Glu Glu Glu Asp Ala Ala Thr Tyr Tyr Cys His His Ser Arg 85 90 95 Glu Phe Pro Trp Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys 100 105 110 <210> 50 <211> 7 <212> PRT <213> Secuencia artificial <220> <223> HVR-H1 de cadena pesada, PD1-0073 <400> 50 Gly Phe Thr Phe Ser Asn Tyr 1 5 <210> 51 <211> 3 <212> PRT <213> Secuencia artificial <220> <223> HVR-H2 de cadena pesada, PD1-0073 <400> 51 Gly Gly Arg 1 <210> 52 <211> 5 <212> PRT <213> Secuencia artificial <220> <223> HVR-H3 de cadena pesada, PD1-0073 <400> 52 Tyr Tyr Gly Ile Asp 1 5 <210> 53 <211> 7 <212> PRT <213> Secuencia artificial <220> <223> HVR-L1 de cadena ligera, PD1-0073 <400> 53 Ser Gln Asp Val Thr Thr Ala 1 5 <210> 54 <211> 3 <212> PRT <213> Secuencia artificial <220> <223> HVR-L2 de cadena ligera, PD1-0073 <400> 54 Trp Ala Ser 1 <210> 55 <211> 6 <212> PRT <213> Secuencia artificial <220> <223> HVR-L3 de cadena ligera, PD1-0073 <400> 55 His Tyr Ser Ile Pro Trp 1 5 <210> 56 <211> 116 <212> PRT <213> Secuencia artificial <220> <223> dominio variable de cadena pesada VH, PD1-0073 <400> 56 Glu Val Lys Leu Val Glu Ser Gly Gly Gly Leu Val Lys Pro Gly Gly 1 5 10 15 Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Asn Tyr 20 25 30 Gly Met Ser Trp Ile Arg Gln Thr Pro Glu Lys Gly Leu Glu Trp Val 35 40 45 Ala Thr Ile Ser Gly Gly Gly Arg Asp Thr Tyr Tyr Pro Asp Ser Val 50 55 60 Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Val Lys Asn Asn Leu Tyr 65 70 75 80 Leu Gln Met Ser Ser Leu Arg Ser Glu Asp Thr Ala Phe Tyr Tyr Cys 85 90 95 Ala Ser Tyr Tyr Tyr Gly Ile Asp Tyr Trp Gly Gln Gly Thr Ser Val 100 105 110 Thr Val Ser Ser 115 <210> 57 <211> 107 <212> PRT <213> Secuencia artificial <220> <223> dominio variable de cadena ligera VL, PD1-0073 <400> 57 Asp Ile Val Met Thr Gln Pro His Lys Phe Met Ser Thr Ser Val Gly 1 5 10 15 Asp Arg Val Arg Ile Thr Cys Lys Ala Ser Gln Asp Val Thr Thr Ala 20 25 30 Val Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ser Pro Lys Leu Leu Ile 35 40 45 Tyr Trp Ala Ser Thr Arg His Thr Gly Val Pro Asp Arg Phe Thr Gly 50 55 60 Ser Gly Ser Gly Thr Glu Phe Thr Leu Thr Ile Ser Ser Val Gln Ala 65 70 75 80 Glu Asp Leu Ala Leu Tyr Tyr Cys Gln Gln His Tyr Ser Ile Pro Trp 85 90 95 Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys 100 105 <210> 58 <211> 7 <212> PRT <213> Secuencia artificial <220> <223> HVR-H1 de cadena pesada, PD1-0078 <400> 58 Gly Tyr Thr Phe Thr Ser Thr 1 5 <210> 59 <211> 3 <212> PRT <213> Secuencia artificial <220> <223> HVR-H2 de cadena pesada, PD1-0078 <400> 59 Ser Asp Ser 1 <210> 60 <211> 3 <212> PRT <213> Secuencia artificial <220> <223> HVR-H3 de cadena pesada, PD1-0078 <400> 60 Pro Phe Asp 1 <210> 61 <211> 7 <212> PRT <213> Secuencia artificial <220> <223> HVR-L1 de cadena ligera, PD1-0078 <400> 61 Ser Gln Asp Val Ser Thr Ala 1 5 <210> 62 <211> 3 <212> PRT <213> Secuencia artificial <220> <223> HVR-L2 de cadena ligera, PD1-0078 <400> 62 Ser Ala Ser 1 <210> 63 <211> 6 <212> PRT <213> Secuencia artificial <220> <223> HVR-L3 de cadena ligera, PD1-0078 <400> 63 His Tyr Ser His Pro Phe 1 5 <210> 64 <211> 114 <212> PRT <213> Secuencia artificial <220> <223> dominio variable de cadena pesada VH, PD1-0078 <400> 64 Gln Val Gln Leu Gln Gln Pro Gly Ala Glu Leu Val Lys Pro Gly Ala 1 5 10 15 Ser Val Lys Met Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser Thr 20 25 30 Trp Met His Trp Val Lys Gln Arg Pro Gly Gln Gly Leu Glu Trp Ile 35 40 45 Gly Ala Ile Asp Pro Ser Asp Ser Tyr Thr Thr Tyr Asn Gln Lys Phe 50 55 60 Lys Gly Lys Ala Thr Leu Thr Val Asp Thr Ser Ser Thr 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 Thr Arg Ser Pro Phe Asp Tyr Trp Gly Gln Gly Thr Thr Leu Thr Val 100 105 110 Ser Ser <210> 65 <211> 107 <212> PRT <213> Secuencia artificial <220> <223> dominio variable de cadena ligera VL, PD1-0078 <400> 65 Asp Ile Val Met Thr Gln Ser His Lys 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 Thr Ala 20 25 30 Val Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ser Pro Lys Leu Leu Ile 35 40 45 Tyr 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 Ala Ile Ser Ser Val Gln Ala 65 70 75 80 Glu Asp Leu Ala Val Tyr Tyr Cys Gln Gln His Tyr Ser His Pro Phe 85 90 95 Thr Phe Gly Ser Gly Thr Lys Leu Glu Ile Lys 100 105 <210> 66 <211> 8 <212> PRT <213> Secuencia artificial <220> <223> HVR-H1 de cadena pesada, PD1-0102 <400> 66 Gly Tyr Ser Ile Thr Ser Gly Tyr 1 5 <210> 67 <211> 3 <212> PRT <213> Secuencia artificial <220> <223> HVR-H2 de cadena pesada, PD1-0102 <400> 67 Ser Ser Gly 1 <210> 68 <211> 6 <212> PRT <213> Secuencia artificial <220> <223> HVR-H3 de cadena pesada, PD1-0102 <400> 68 Arg Asn Trp Tyr Phe Asp 1 5 <210> 69 <211> 13 <212> PRT <213> Secuencia artificial <220> <223> HVR-L1 de cadena ligera, PD1-0102 <400> 69 Ser Gln Ser Leu Leu Asn Ser Gly Thr Gln Lys Asn Tyr 1 5 10 <210> 70 <211> 3 <212> PRT <213> Secuencia artificial <220> <223> HVR-L2 de cadena ligera, PD1-0102 <400> 70 Trp Ala Ser 1 <210> 71 <211> 6 <212> PRT <213> Secuencia artificial <220> <223> HVR-L3 de cadena ligera, PD1-0102 <400> 71 Asp Tyr Thr Phe Pro Leu 1 5 <210> 72 <211> 117 <212> PRT <213> Secuencia artificial <220> <223> dominio variable de cadena pesada VH, PD1-0102 <400> 72 Asp Val Gln Leu Gln Glu Ser Gly Pro Asp Leu Val Lys Pro Ser Gln 1 5 10 15 Ser Leu Ser Leu Thr Cys Thr Val Thr Gly Tyr Ser Ile Thr Ser Gly 20 25 30 Tyr Ser Trp His Trp Ile Arg Gln Phe Pro Gly Asn Lys Leu Glu Trp 35 40 45 Met Gly Phe Ile His Ser Ser Gly Asp Thr Asn Tyr Asn Pro Ser Leu 50 55 60 Lys Ser Arg Ile Ser Phe Thr Arg Asp Thr Ser Lys Asn Gln Phe Phe 65 70 75 80 Leu Gln Leu Ser Ser Leu Thr Asp Glu Asp Thr Ala Thr Tyr Tyr Cys 85 90 95 Ala Thr Tyr Arg Asn Trp Tyr Phe Asp Val Trp Gly Ala Gly Thr Thr 100 105 110 Val Thr Val Ser Ser 115 <210> 73 <211> 113 <212> PRT <213> Secuencia artificial <220> <223> dominio variable de cadena ligera VL, PD1-0102 <400> 73 Asp Ile Val Met Thr Gln Ser Pro Ser Ser Leu Thr Val Thr Ala Gly 1 5 10 15 Glu Lys Val Thr Met Arg Cys Lys Ser Ser Gln Ser Leu Leu Asn Ser 20 25 30 Gly Thr Gln Lys Asn Tyr Leu Thr Trp Tyr Gln Gln Lys Pro Gly Gln 35 40 45 Pro Pro Lys Leu Leu Ile Tyr Trp Ala Ser Thr Arg Glu Ser Gly Val 50 55 60 Pro Asn Arg Phe Thr Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr 65 70 75 80 Ile Ser Ser Val Gln Ala Glu Asp Leu Ser Val Tyr Tyr Cys Gln Ser 85 90 95 Asp Tyr Thr Phe Pro Leu Thr Phe Gly Gly Gly Thr Lys Leu Glu Leu 100 105 110 Lys <210> 74 <211> 722 <212> PRT <213> Secuencia artificial <220> <223> 4-1BBL hu dimérico (71-254) - CL* cadena pomo Fc <400> 74 Arg Glu Gly Pro Glu Leu Ser Pro Asp Asp Pro Ala Gly Leu Leu Asp 1 5 10 15 Leu Arg Gln Gly Met Phe Ala Gln Leu Val Ala Gln Asn Val Leu Leu 20 25 30 Ile Asp Gly Pro Leu Ser Trp Tyr Ser Asp Pro Gly Leu Ala Gly Val 35 40 45 Ser Leu Thr Gly Gly Leu Ser Tyr Lys Glu Asp Thr Lys Glu Leu Val 50 55 60 Val Ala Lys Ala Gly Val Tyr Tyr Val Phe Phe Gln Leu Glu Leu Arg 65 70 75 80 Arg Val Val Ala Gly Glu Gly Ser Gly Ser Val Ser Leu Ala Leu His 85 90 95 Leu Gln Pro Leu Arg Ser Ala Ala Gly Ala Ala Ala Leu Ala Leu Thr 100 105 110 Val Asp Leu Pro Pro Ala Ser Ser Glu Ala Arg Asn Ser Ala Phe Gly 115 120 125 Phe Gln Gly Arg Leu Leu His Leu Ser Ala Gly Gln Arg Leu Gly Val 130 135 140 His Leu His Thr Glu Ala Arg Ala Arg His Ala Trp Gln Leu Thr Gln 145 150 155 160 Gly Ala Thr Val Leu Gly Leu Phe Arg Val Thr Pro Glu Ile Pro Ala 165 170 175 Gly Leu Pro Ser Pro Arg Ser Glu Gly Gly Gly Gly Ser Gly Gly Gly 180 185 190 Gly Ser Arg Glu Gly Pro Glu Leu Ser Pro Asp Asp Pro Ala Gly Leu 195 200 205 Leu Asp Leu Arg Gln Gly Met Phe Ala Gln Leu Val Ala Gln Asn Val 210 215 220 Leu Leu Ile Asp Gly Pro Leu Ser Trp Tyr Ser Asp Pro Gly Leu Ala 225 230 235 240 Gly Val Ser Leu Thr Gly Gly Leu Ser Tyr Lys Glu Asp Thr Lys Glu 245 250 255 Leu Val Val Ala Lys Ala Gly Val Tyr Tyr Val Phe Phe Gln Leu Glu 260 265 270 Leu Arg Arg Val Val Ala Gly Glu Gly Ser Gly Ser Val Ser Leu Ala 275 280 285 Leu His Leu Gln Pro Leu Arg Ser Ala Ala Gly Ala Ala Ala Leu Ala 290 295 300 Leu Thr Val Asp Leu Pro Pro Ala Ser Ser Glu Ala Arg Asn Ser Ala 305 310 315 320 Phe Gly Phe Gln Gly Arg Leu Leu His Leu Ser Ala Gly Gln Arg Leu 325 330 335 Gly Val His Leu His Thr Glu Ala Arg Ala Arg His Ala Trp Gln Leu 340 345 350 Thr Gln Gly Ala Thr Val Leu Gly Leu Phe Arg Val Thr Pro Glu Ile 355 360 365 Pro Ala Gly Leu Pro Ser Pro Arg Ser Glu Gly Gly Gly Gly Ser Gly 370 375 380 Gly Gly Gly Ser Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro 385 390 395 400 Pro Ser Asp Arg Lys Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu 405 410 415 Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp 420 425 430 Asn Ala Leu Gln Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp 435 440 445 Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys 450 455 460 Ala Asp Tyr Glu Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln 465 470 475 480 Gly Leu Ser Ser Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys Asp 485 490 495 Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly Gly 500 505 510 Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile 515 520 525 Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu 530 535 540 Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His 545 550 555 560 Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg 565 570 575 Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys 580 585 590 Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Gly Ala Pro Ile Glu 595 600 605 Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr 610 615 620 Thr Leu Pro Pro Cys Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu 625 630 635 640 Trp Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp 645 650 655 Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val 660 665 670 Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp 675 680 685 Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His 690 695 700 Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro 705 710 715 720 Gly Lys <210> 75 <211> 297 <212> PRT <213> Secuencia artificial <220> <223> 4-1BBL hu monomérico (71-254) - CH1* <400> 75 Arg Glu Gly Pro Glu Leu Ser Pro Asp Asp Pro Ala Gly Leu Leu Asp 1 5 10 15 Leu Arg Gln Gly Met Phe Ala Gln Leu Val Ala Gln Asn Val Leu Leu 20 25 30 Ile Asp Gly Pro Leu Ser Trp Tyr Ser Asp Pro Gly Leu Ala Gly Val 35 40 45 Ser Leu Thr Gly Gly Leu Ser Tyr Lys Glu Asp Thr Lys Glu Leu Val 50 55 60 Val Ala Lys Ala Gly Val Tyr Tyr Val Phe Phe Gln Leu Glu Leu Arg 65 70 75 80 Arg Val Val Ala Gly Glu Gly Ser Gly Ser Val Ser Leu Ala Leu His 85 90 95 Leu Gln Pro Leu Arg Ser Ala Ala Gly Ala Ala Ala Leu Ala Leu Thr 100 105 110 Val Asp Leu Pro Pro Ala Ser Ser Glu Ala Arg Asn Ser Ala Phe Gly 115 120 125 Phe Gln Gly Arg Leu Leu His Leu Ser Ala Gly Gln Arg Leu Gly Val 130 135 140 His Leu His Thr Glu Ala Arg Ala Arg His Ala Trp Gln Leu Thr Gln 145 150 155 160 Gly Ala Thr Val Leu Gly Leu Phe Arg Val Thr Pro Glu Ile Pro Ala 165 170 175 Gly Leu Pro Ser Pro Arg Ser Glu Gly Gly Gly Gly Ser Gly Gly Gly 180 185 190 Gly Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser 195 200 205 Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Glu 210 215 220 Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu 225 230 235 240 Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu 245 250 255 Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr 260 265 270 Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys Val 275 280 285 Asp Glu Lys Val Glu Pro Lys Ser Cys 290 295 <210> 76 <211> 722 <212> PRT <213> Secuencia artificial <220> <223> 4-1BBL hu dimérico (71-254) - CL cadena pomo Fc <400> 76 Arg Glu Gly Pro Glu Leu Ser Pro Asp Asp Pro Ala Gly Leu Leu Asp 1 5 10 15 Leu Arg Gln Gly Met Phe Ala Gln Leu Val Ala Gln Asn Val Leu Leu 20 25 30 Ile Asp Gly Pro Leu Ser Trp Tyr Ser Asp Pro Gly Leu Ala Gly Val 35 40 45 Ser Leu Thr Gly Gly Leu Ser Tyr Lys Glu Asp Thr Lys Glu Leu Val 50 55 60 Val Ala Lys Ala Gly Val Tyr Tyr Val Phe Phe Gln Leu Glu Leu Arg 65 70 75 80 Arg Val Val Ala Gly Glu Gly Ser Gly Ser Val Ser Leu Ala Leu His 85 90 95 Leu Gln Pro Leu Arg Ser Ala Ala Gly Ala Ala Ala Leu Ala Leu Thr 100 105 110 Val Asp Leu Pro Pro Ala Ser Ser Glu Ala Arg Asn Ser Ala Phe Gly 115 120 125 Phe Gln Gly Arg Leu Leu His Leu Ser Ala Gly Gln Arg Leu Gly Val 130 135 140 His Leu His Thr Glu Ala Arg Ala Arg His Ala Trp Gln Leu Thr Gln 145 150 155 160 Gly Ala Thr Val Leu Gly Leu Phe Arg Val Thr Pro Glu Ile Pro Ala 165 170 175 Gly Leu Pro Ser Pro Arg Ser Glu Gly Gly Gly Gly Ser Gly Gly Gly 180 185 190 Gly Ser Arg Glu Gly Pro Glu Leu Ser Pro Asp Asp Pro Ala Gly Leu 195 200 205 Leu Asp Leu Arg Gln Gly Met Phe Ala Gln Leu Val Ala Gln Asn Val 210 215 220 Leu Leu Ile Asp Gly Pro Leu Ser Trp Tyr Ser Asp Pro Gly Leu Ala 225 230 235 240 Gly Val Ser Leu Thr Gly Gly Leu Ser Tyr Lys Glu Asp Thr Lys Glu 245 250 255 Leu Val Val Ala Lys Ala Gly Val Tyr Tyr Val Phe Phe Gln Leu Glu 260 265 270 Leu Arg Arg Val Val Ala Gly Glu Gly Ser Gly Ser Val Ser Leu Ala 275 280 285 Leu His Leu Gln Pro Leu Arg Ser Ala Ala Gly Ala Ala Ala Leu Ala 290 295 300 Leu Thr Val Asp Leu Pro Pro Ala Ser Ser Glu Ala Arg Asn Ser Ala 305 310 315 320 Phe Gly Phe Gln Gly Arg Leu Leu His Leu Ser Ala Gly Gln Arg Leu 325 330 335 Gly Val His Leu His Thr Glu Ala Arg Ala Arg His Ala Trp Gln Leu 340 345 350 Thr Gln Gly Ala Thr Val Leu Gly Leu Phe Arg Val Thr Pro Glu Ile 355 360 365 Pro Ala Gly Leu Pro Ser Pro Arg Ser Glu Gly Gly Gly Gly Ser Gly 370 375 380 Gly Gly Gly Ser Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro 385 390 395 400 Pro Ser Asp Glu Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu 405 410 415 Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp 420 425 430 Asn Ala Leu Gln Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp 435 440 445 Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys 450 455 460 Ala Asp Tyr Glu Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln 465 470 475 480 Gly Leu Ser Ser Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys Asp 485 490 495 Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly Gly 500 505 510 Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile 515 520 525 Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu 530 535 540 Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His 545 550 555 560 Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg 565 570 575 Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys 580 585 590 Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Gly Ala Pro Ile Glu 595 600 605 Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr 610 615 620 Thr Leu Pro Pro Cys Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu 625 630 635 640 Trp Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp 645 650 655 Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val 660 665 670 Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp 675 680 685 Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His 690 695 700 Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro 705 710 715 720 Gly Lys <210> 77 <211> 297 <212> PRT <213> Secuencia artificial <220> <223> 4-1BBL hu monomérico (71-254) - CH1 <400> 77 Arg Glu Gly Pro Glu Leu Ser Pro Asp Asp Pro Ala Gly Leu Leu Asp 1 5 10 15 Leu Arg Gln Gly Met Phe Ala Gln Leu Val Ala Gln Asn Val Leu Leu 20 25 30 Ile Asp Gly Pro Leu Ser Trp Tyr Ser Asp Pro Gly Leu Ala Gly Val 35 40 45 Ser Leu Thr Gly Gly Leu Ser Tyr Lys Glu Asp Thr Lys Glu Leu Val 50 55 60 Val Ala Lys Ala Gly Val Tyr Tyr Val Phe Phe Gln Leu Glu Leu Arg 65 70 75 80 Arg Val Val Ala Gly Glu Gly Ser Gly Ser Val Ser Leu Ala Leu His 85 90 95 Leu Gln Pro Leu Arg Ser Ala Ala Gly Ala Ala Ala Leu Ala Leu Thr 100 105 110 Val Asp Leu Pro Pro Ala Ser Ser Glu Ala Arg Asn Ser Ala Phe Gly 115 120 125 Phe Gln Gly Arg Leu Leu His Leu Ser Ala Gly Gln Arg Leu Gly Val 130 135 140 His Leu His Thr Glu Ala Arg Ala Arg His Ala Trp Gln Leu Thr Gln 145 150 155 160 Gly Ala Thr Val Leu Gly Leu Phe Arg Val Thr Pro Glu Ile Pro Ala 165 170 175 Gly Leu Pro Ser Pro Arg Ser Glu Gly Gly Gly Gly Ser Gly Gly Gly 180 185 190 Gly Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser 195 200 205 Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Lys 210 215 220 Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu 225 230 235 240 Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu 245 250 255 Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr 260 265 270 Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys Val 275 280 285 Asp Lys Lys Val Glu Pro Lys Ser Cys 290 295 <210> 78 <211> 710 <212> PRT <213> Secuencia artificial <220> <223> 4-1BBL hu dimérico (71-248) - CL* cadena pomo Fc <400> 78 Arg Glu Gly Pro Glu Leu Ser Pro Asp Asp Pro Ala Gly Leu Leu Asp 1 5 10 15 Leu Arg Gln Gly Met Phe Ala Gln Leu Val Ala Gln Asn Val Leu Leu 20 25 30 Ile Asp Gly Pro Leu Ser Trp Tyr Ser Asp Pro Gly Leu Ala Gly Val 35 40 45 Ser Leu Thr Gly Gly Leu Ser Tyr Lys Glu Asp Thr Lys Glu Leu Val 50 55 60 Val Ala Lys Ala Gly Val Tyr Tyr Val Phe Phe Gln Leu Glu Leu Arg 65 70 75 80 Arg Val Val Ala Gly Glu Gly Ser Gly Ser Val Ser Leu Ala Leu His 85 90 95 Leu Gln Pro Leu Arg Ser Ala Ala Gly Ala Ala Ala Leu Ala Leu Thr 100 105 110 Val Asp Leu Pro Pro Ala Ser Ser Glu Ala Arg Asn Ser Ala Phe Gly 115 120 125 Phe Gln Gly Arg Leu Leu His Leu Ser Ala Gly Gln Arg Leu Gly Val 130 135 140 His Leu His Thr Glu Ala Arg Ala Arg His Ala Trp Gln Leu Thr Gln 145 150 155 160 Gly Ala Thr Val Leu Gly Leu Phe Arg Val Thr Pro Glu Ile Pro Ala 165 170 175 Gly Leu Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Arg Glu Gly Pro 180 185 190 Glu Leu Ser Pro Asp Asp Pro Ala Gly Leu Leu Asp Leu Arg Gln Gly 195 200 205 Met Phe Ala Gln Leu Val Ala Gln Asn Val Leu Leu Ile Asp Gly Pro 210 215 220 Leu Ser Trp Tyr Ser Asp Pro Gly Leu Ala Gly Val Ser Leu Thr Gly 225 230 235 240 Gly Leu Ser Tyr Lys Glu Asp Thr Lys Glu Leu Val Val Ala Lys Ala 245 250 255 Gly Val Tyr Tyr Val Phe Phe Gln Leu Glu Leu Arg Arg Val Val Ala 260 265 270 Gly Glu Gly Ser Gly Ser Val Ser Leu Ala Leu His Leu Gln Pro Leu 275 280 285 Arg Ser Ala Ala Gly Ala Ala Ala Leu Ala Leu Thr Val Asp Leu Pro 290 295 300 Pro Ala Ser Ser Glu Ala Arg Asn Ser Ala Phe Gly Phe Gln Gly Arg 305 310 315 320 Leu Leu His Leu Ser Ala Gly Gln Arg Leu Gly Val His Leu His Thr 325 330 335 Glu Ala Arg Ala Arg His Ala Trp Gln Leu Thr Gln Gly Ala Thr Val 340 345 350 Leu Gly Leu Phe Arg Val Thr Pro Glu Ile Pro Ala Gly Leu Gly Gly 355 360 365 Gly Gly Ser Gly Gly Gly Gly Ser Arg Thr Val Ala Ala Pro Ser Val 370 375 380 Phe Ile Phe Pro Pro Ser Asp Arg Lys Leu Lys Ser Gly Thr Ala Ser 385 390 395 400 Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys Val Gln 405 410 415 Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln Glu Ser Val 420 425 430 Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser Thr Leu 435 440 445 Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr Ala Cys Glu 450 455 460 Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser Phe Asn Arg 465 470 475 480 Gly Glu Cys Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu 485 490 495 Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp 500 505 510 Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp 515 520 525 Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly 530 535 540 Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn 545 550 555 560 Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp 565 570 575 Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Gly 580 585 590 Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu 595 600 605 Pro Gln Val Tyr Thr Leu Pro Pro Cys Arg Asp Glu Leu Thr Lys Asn 610 615 620 Gln Val Ser Leu Trp Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile 625 630 635 640 Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr 645 650 655 Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys 660 665 670 Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys 675 680 685 Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu 690 695 700 Ser Leu Ser Pro Gly Lys 705 710 <210> 79 <211> 291 <212> PRT <213> Secuencia artificial <220> <223> 4-1BBL hu monomérico (71-248) - CH1* <400> 79 Arg Glu Gly Pro Glu Leu Ser Pro Asp Asp Pro Ala Gly Leu Leu Asp 1 5 10 15 Leu Arg Gln Gly Met Phe Ala Gln Leu Val Ala Gln Asn Val Leu Leu 20 25 30 Ile Asp Gly Pro Leu Ser Trp Tyr Ser Asp Pro Gly Leu Ala Gly Val 35 40 45 Ser Leu Thr Gly Gly Leu Ser Tyr Lys Glu Asp Thr Lys Glu Leu Val 50 55 60 Val Ala Lys Ala Gly Val Tyr Tyr Val Phe Phe Gln Leu Glu Leu Arg 65 70 75 80 Arg Val Val Ala Gly Glu Gly Ser Gly Ser Val Ser Leu Ala Leu His 85 90 95 Leu Gln Pro Leu Arg Ser Ala Ala Gly Ala Ala Ala Leu Ala Leu Thr 100 105 110 Val Asp Leu Pro Pro Ala Ser Ser Glu Ala Arg Asn Ser Ala Phe Gly 115 120 125 Phe Gln Gly Arg Leu Leu His Leu Ser Ala Gly Gln Arg Leu Gly Val 130 135 140 His Leu His Thr Glu Ala Arg Ala Arg His Ala Trp Gln Leu Thr Gln 145 150 155 160 Gly Ala Thr Val Leu Gly Leu Phe Arg Val Thr Pro Glu Ile Pro Ala 165 170 175 Gly Leu Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Ala Ser Thr Lys 180 185 190 Gly Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly 195 200 205 Gly Thr Ala Ala Leu Gly Cys Leu Val Glu Asp Tyr Phe Pro Glu Pro 210 215 220 Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr 225 230 235 240 Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val 245 250 255 Val Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn 260 265 270 Val Asn His Lys Pro Ser Asn Thr Lys Val Asp Glu Lys Val Glu Pro 275 280 285 Lys Ser Cys 290 <210> 80 <211> 710 <212> PRT <213> Secuencia artificial <220> <223> 4-1BBL hu dimérico (71-248) - CL cadena pomo Fc <400> 80 Arg Glu Gly Pro Glu Leu Ser Pro Asp Asp Pro Ala Gly Leu Leu Asp 1 5 10 15 Leu Arg Gln Gly Met Phe Ala Gln Leu Val Ala Gln Asn Val Leu Leu 20 25 30 Ile Asp Gly Pro Leu Ser Trp Tyr Ser Asp Pro Gly Leu Ala Gly Val 35 40 45 Ser Leu Thr Gly Gly Leu Ser Tyr Lys Glu Asp Thr Lys Glu Leu Val 50 55 60 Val Ala Lys Ala Gly Val Tyr Tyr Val Phe Phe Gln Leu Glu Leu Arg 65 70 75 80 Arg Val Val Ala Gly Glu Gly Ser Gly Ser Val Ser Leu Ala Leu His 85 90 95 Leu Gln Pro Leu Arg Ser Ala Ala Gly Ala Ala Ala Leu Ala Leu Thr 100 105 110 Val Asp Leu Pro Pro Ala Ser Ser Glu Ala Arg Asn Ser Ala Phe Gly 115 120 125 Phe Gln Gly Arg Leu Leu His Leu Ser Ala Gly Gln Arg Leu Gly Val 130 135 140 His Leu His Thr Glu Ala Arg Ala Arg His Ala Trp Gln Leu Thr Gln 145 150 155 160 Gly Ala Thr Val Leu Gly Leu Phe Arg Val Thr Pro Glu Ile Pro Ala 165 170 175 Gly Leu Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Arg Glu Gly Pro 180 185 190 Glu Leu Ser Pro Asp Asp Pro Ala Gly Leu Leu Asp Leu Arg Gln Gly 195 200 205 Met Phe Ala Gln Leu Val Ala Gln Asn Val Leu Leu Ile Asp Gly Pro 210 215 220 Leu Ser Trp Tyr Ser Asp Pro Gly Leu Ala Gly Val Ser Leu Thr Gly 225 230 235 240 Gly Leu Ser Tyr Lys Glu Asp Thr Lys Glu Leu Val Val Ala Lys Ala 245 250 255 Gly Val Tyr Tyr Val Phe Phe Gln Leu Glu Leu Arg Arg Val Val Ala 260 265 270 Gly Glu Gly Ser Gly Ser Val Ser Leu Ala Leu His Leu Gln Pro Leu 275 280 285 Arg Ser Ala Ala Gly Ala Ala Ala Leu Ala Leu Thr Val Asp Leu Pro 290 295 300 Pro Ala Ser Ser Glu Ala Arg Asn Ser Ala Phe Gly Phe Gln Gly Arg 305 310 315 320 Leu Leu His Leu Ser Ala Gly Gln Arg Leu Gly Val His Leu His Thr 325 330 335 Glu Ala Arg Ala Arg His Ala Trp Gln Leu Thr Gln Gly Ala Thr Val 340 345 350 Leu Gly Leu Phe Arg Val Thr Pro Glu Ile Pro Ala Gly Leu Gly Gly 355 360 365 Gly Gly Ser Gly Gly Gly Gly Ser Arg Thr Val Ala Ala Pro Ser Val 370 375 380 Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly Thr Ala Ser 385 390 395 400 Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys Val Gln 405 410 415 Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln Glu Ser Val 420 425 430 Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser Thr Leu 435 440 445 Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr Ala Cys Glu 450 455 460 Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser Phe Asn Arg 465 470 475 480 Gly Glu Cys Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu 485 490 495 Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp 500 505 510 Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp 515 520 525 Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly 530 535 540 Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn 545 550 555 560 Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp 565 570 575 Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Gly 580 585 590 Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu 595 600 605 Pro Gln Val Tyr Thr Leu Pro Pro Cys Arg Asp Glu Leu Thr Lys Asn 610 615 620 Gln Val Ser Leu Trp Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile 625 630 635 640 Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr 645 650 655 Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys 660 665 670 Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys 675 680 685 Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu 690 695 700 Ser Leu Ser Pro Gly Lys 705 710 <210> 81 <211> 291 <212> PRT <213> Secuencia artificial <220> <223> 4-1BBL hu monomérico (71-248) - CH1 <400> 81 Arg Glu Gly Pro Glu Leu Ser Pro Asp Asp Pro Ala Gly Leu Leu Asp 1 5 10 15 Leu Arg Gln Gly Met Phe Ala Gln Leu Val Ala Gln Asn Val Leu Leu 20 25 30 Ile Asp Gly Pro Leu Ser Trp Tyr Ser Asp Pro Gly Leu Ala Gly Val 35 40 45 Ser Leu Thr Gly Gly Leu Ser Tyr Lys Glu Asp Thr Lys Glu Leu Val 50 55 60 Val Ala Lys Ala Gly Val Tyr Tyr Val Phe Phe Gln Leu Glu Leu Arg 65 70 75 80 Arg Val Val Ala Gly Glu Gly Ser Gly Ser Val Ser Leu Ala Leu His 85 90 95 Leu Gln Pro Leu Arg Ser Ala Ala Gly Ala Ala Ala Leu Ala Leu Thr 100 105 110 Val Asp Leu Pro Pro Ala Ser Ser Glu Ala Arg Asn Ser Ala Phe Gly 115 120 125 Phe Gln Gly Arg Leu Leu His Leu Ser Ala Gly Gln Arg Leu Gly Val 130 135 140 His Leu His Thr Glu Ala Arg Ala Arg His Ala Trp Gln Leu Thr Gln 145 150 155 160 Gly Ala Thr Val Leu Gly Leu Phe Arg Val Thr Pro Glu Ile Pro Ala 165 170 175 Gly Leu Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Ala Ser Thr Lys 180 185 190 Gly Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly 195 200 205 Gly Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro 210 215 220 Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr 225 230 235 240 Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val 245 250 255 Val Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn 260 265 270 Val Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro 275 280 285 Lys Ser Cys 290 <210> 82 <211> 450 <212> PRT <213> Secuencia artificial <220> <223> cadena pomo Fc de anti-PD1 (0314) <400> 82 Glu Val Gln Leu Leu Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 1 5 10 15 Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Ser Phe Ser Ser Tyr 20 25 30 Thr Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45 Ala Thr Ile Ser Gly Gly Gly Arg Asp Ile Tyr Tyr Pro Asp Ser Val 50 55 60 Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 65 70 75 80 Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Val Leu Leu Thr Gly Arg Val Tyr Phe Ala Leu Asp Ser Trp Gly Gln 100 105 110 Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val 115 120 125 Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala 130 135 140 Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser 145 150 155 160 Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val 165 170 175 Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro 180 185 190 Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys 195 200 205 Pro Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp 210 215 220 Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly Gly 225 230 235 240 Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile 245 250 255 Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu 260 265 270 Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His 275 280 285 Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg 290 295 300 Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys 305 310 315 320 Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Gly Ala Pro Ile Glu 325 330 335 Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Cys 340 345 350 Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu 355 360 365 Ser Cys Ala Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp 370 375 380 Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val 385 390 395 400 Leu Asp Ser Asp Gly Ser Phe Phe Leu Val Ser Lys Leu Thr Val Asp 405 410 415 Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His 420 425 430 Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro 435 440 445 Gly Lys 450 <210> 83 <211> 218 <212> PRT <213> Secuencia artificial <220> <223> cadena ligera de anti-PD1 (0314) <400> 83 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 Glu Ser Val Asp Thr Ser 20 25 30 Asp Asn Ser Phe Ile His Trp Tyr Gln Gln Lys Pro Gly Gln Ser Pro 35 40 45 Arg Leu Leu Ile Tyr Arg Ser Ser Thr Leu Glu Ser Gly Ile 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 Gln Asn Tyr 85 90 95 Asp Val Pro Trp Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Arg 100 105 110 Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln 115 120 125 Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr 130 135 140 Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser 145 150 155 160 Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr 165 170 175 Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys 180 185 190 His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro 195 200 205 Val Thr Lys Ser Phe Asn Arg Gly Glu Cys 210 215 <210> 84 <211> 837 <212> PRT <213> Secuencia artificial <220> <223> cadena agujero Fc de anti-PD1(0314) fusionada a 4-1BBL hu dimérico (71-254) <400> 84 Glu Val Gln Leu Leu Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 1 5 10 15 Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Ser Phe Ser Ser Tyr 20 25 30 Thr Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45 Ala Thr Ile Ser Gly Gly Gly Arg Asp Ile Tyr Tyr Pro Asp Ser Val 50 55 60 Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 65 70 75 80 Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Val Leu Leu Thr Gly Arg Val Tyr Phe Ala Leu Asp Ser Trp Gly Gln 100 105 110 Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val 115 120 125 Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala 130 135 140 Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser 145 150 155 160 Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val 165 170 175 Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro 180 185 190 Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys 195 200 205 Pro Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp 210 215 220 Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly Gly 225 230 235 240 Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile 245 250 255 Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu 260 265 270 Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His 275 280 285 Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg 290 295 300 Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys 305 310 315 320 Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Gly Ala Pro Ile Glu 325 330 335 Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Cys 340 345 350 Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu 355 360 365 Ser Cys Ala Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp 370 375 380 Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val 385 390 395 400 Leu Asp Ser Asp Gly Ser Phe Phe Leu Val Ser Lys Leu Thr Val Asp 405 410 415 Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His 420 425 430 Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro 435 440 445 Gly Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Arg Glu Gly Pro Glu 450 455 460 Leu Ser Pro Asp Asp Pro Ala Gly Leu Leu Asp Leu Arg Gln Gly Met 465 470 475 480 Phe Ala Gln Leu Val Ala Gln Asn Val Leu Leu Ile Asp Gly Pro Leu 485 490 495 Ser Trp Tyr Ser Asp Pro Gly Leu Ala Gly Val Ser Leu Thr Gly Gly 500 505 510 Leu Ser Tyr Lys Glu Asp Thr Lys Glu Leu Val Val Ala Lys Ala Gly 515 520 525 Val Tyr Tyr Val Phe Phe Gln Leu Glu Leu Arg Arg Val Val Ala Gly 530 535 540 Glu Gly Ser Gly Ser Val Ser Leu Ala Leu His Leu Gln Pro Leu Arg 545 550 555 560 Ser Ala Ala Gly Ala Ala Ala Leu Ala Leu Thr Val Asp Leu Pro Pro 565 570 575 Ala Ser Ser Glu Ala Arg Asn Ser Ala Phe Gly Phe Gln Gly Arg Leu 580 585 590 Leu His Leu Ser Ala Gly Gln Arg Leu Gly Val His Leu His Thr Glu 595 600 605 Ala Arg Ala Arg His Ala Trp Gln Leu Thr Gln Gly Ala Thr Val Leu 610 615 620 Gly Leu Phe Arg Val Thr Pro Glu Ile Pro Ala Gly Leu Pro Ser Pro 625 630 635 640 Arg Ser Glu Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Arg Glu Gly 645 650 655 Pro Glu Leu Ser Pro Asp Asp Pro Ala Gly Leu Leu Asp Leu Arg Gln 660 665 670 Gly Met Phe Ala Gln Leu Val Ala Gln Asn Val Leu Leu Ile Asp Gly 675 680 685 Pro Leu Ser Trp Tyr Ser Asp Pro Gly Leu Ala Gly Val Ser Leu Thr 690 695 700 Gly Gly Leu Ser Tyr Lys Glu Asp Thr Lys Glu Leu Val Val Ala Lys 705 710 715 720 Ala Gly Val Tyr Tyr Val Phe Phe Gln Leu Glu Leu Arg Arg Val Val 725 730 735 Ala Gly Glu Gly Ser Gly Ser Val Ser Leu Ala Leu His Leu Gln Pro 740 745 750 Leu Arg Ser Ala Ala Gly Ala Ala Ala Leu Ala Leu Thr Val Asp Leu 755 760 765 Pro Pro Ala Ser Ser Glu Ala Arg Asn Ser Ala Phe Gly Phe Gln Gly 770 775 780 Arg Leu Leu His Leu Ser Ala Gly Gln Arg Leu Gly Val His Leu His 785 790 795 800 Thr Glu Ala Arg Ala Arg His Ala Trp Gln Leu Thr Gln Gly Ala Thr 805 810 815 Val Leu Gly Leu Phe Arg Val Thr Pro Glu Ile Pro Ala Gly Leu Pro 820 825 830 Ser Pro Arg Ser Glu 835 <210> 85 <211> 643 <212> PRT <213> Secuencia artificial <220> <223> cadena pomo Fc de anti-PD1 (0314) fusionada a 4-1BBL hu monomérico (71-254) <400> 85 Glu Val Gln Leu Leu Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 1 5 10 15 Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Ser Phe Ser Ser Tyr 20 25 30 Thr Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45 Ala Thr Ile Ser Gly Gly Gly Arg Asp Ile Tyr Tyr Pro Asp Ser Val 50 55 60 Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 65 70 75 80 Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Val Leu Leu Thr Gly Arg Val Tyr Phe Ala Leu Asp Ser Trp Gly Gln 100 105 110 Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val 115 120 125 Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala 130 135 140 Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser 145 150 155 160 Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val 165 170 175 Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro 180 185 190 Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys 195 200 205 Pro Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp 210 215 220 Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly Gly 225 230 235 240 Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile 245 250 255 Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu 260 265 270 Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His 275 280 285 Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg 290 295 300 Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys 305 310 315 320 Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Gly Ala Pro Ile Glu 325 330 335 Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr 340 345 350 Thr Leu Pro Pro Cys Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu 355 360 365 Trp Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp 370 375 380 Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val 385 390 395 400 Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp 405 410 415 Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His 420 425 430 Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro 435 440 445 Gly Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Arg Glu Gly Pro Glu 450 455 460 Leu Ser Pro Asp Asp Pro Ala Gly Leu Leu Asp Leu Arg Gln Gly Met 465 470 475 480 Phe Ala Gln Leu Val Ala Gln Asn Val Leu Leu Ile Asp Gly Pro Leu 485 490 495 Ser Trp Tyr Ser Asp Pro Gly Leu Ala Gly Val Ser Leu Thr Gly Gly 500 505 510 Leu Ser Tyr Lys Glu Asp Thr Lys Glu Leu Val Val Ala Lys Ala Gly 515 520 525 Val Tyr Tyr Val Phe Phe Gln Leu Glu Leu Arg Arg Val Val Ala Gly 530 535 540 Glu Gly Ser Gly Ser Val Ser Leu Ala Leu His Leu Gln Pro Leu Arg 545 550 555 560 Ser Ala Ala Gly Ala Ala Ala Leu Ala Leu Thr Val Asp Leu Pro Pro 565 570 575 Ala Ser Ser Glu Ala Arg Asn Ser Ala Phe Gly Phe Gln Gly Arg Leu 580 585 590 Leu His Leu Ser Ala Gly Gln Arg Leu Gly Val His Leu His Thr Glu 595 600 605 Ala Arg Ala Arg His Ala Trp Gln Leu Thr Gln Gly Ala Thr Val Leu 610 615 620 Gly Leu Phe Arg Val Thr Pro Glu Ile Pro Ala Gly Leu Pro Ser Pro 625 630 635 640 Arg Ser Glu <210> 86 <211> 825 <212> PRT <213> Secuencia artificial <220> <223> cadena agujero Fc de anti-PD1(0314) fusionada a 4-1BBL hu dimérico (71-248) <400> 86 Glu Val Gln Leu Leu Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 1 5 10 15 Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Ser Phe Ser Ser Tyr 20 25 30 Thr Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45 Ala Thr Ile Ser Gly Gly Gly Arg Asp Ile Tyr Tyr Pro Asp Ser Val 50 55 60 Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 65 70 75 80 Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Val Leu Leu Thr Gly Arg Val Tyr Phe Ala Leu Asp Ser Trp Gly Gln 100 105 110 Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val 115 120 125 Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala 130 135 140 Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser 145 150 155 160 Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val 165 170 175 Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro 180 185 190 Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys 195 200 205 Pro Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp 210 215 220 Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly Gly 225 230 235 240 Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile 245 250 255 Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu 260 265 270 Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His 275 280 285 Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg 290 295 300 Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys 305 310 315 320 Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Gly Ala Pro Ile Glu 325 330 335 Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Cys 340 345 350 Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu 355 360 365 Ser Cys Ala Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp 370 375 380 Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val 385 390 395 400 Leu Asp Ser Asp Gly Ser Phe Phe Leu Val Ser Lys Leu Thr Val Asp 405 410 415 Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His 420 425 430 Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro 435 440 445 Gly Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Arg Glu Gly Pro Glu 450 455 460 Leu Ser Pro Asp Asp Pro Ala Gly Leu Leu Asp Leu Arg Gln Gly Met 465 470 475 480 Phe Ala Gln Leu Val Ala Gln Asn Val Leu Leu Ile Asp Gly Pro Leu 485 490 495 Ser Trp Tyr Ser Asp Pro Gly Leu Ala Gly Val Ser Leu Thr Gly Gly 500 505 510 Leu Ser Tyr Lys Glu Asp Thr Lys Glu Leu Val Val Ala Lys Ala Gly 515 520 525 Val Tyr Tyr Val Phe Phe Gln Leu Glu Leu Arg Arg Val Val Ala Gly 530 535 540 Glu Gly Ser Gly Ser Val Ser Leu Ala Leu His Leu Gln Pro Leu Arg 545 550 555 560 Ser Ala Ala Gly Ala Ala Ala Leu Ala Leu Thr Val Asp Leu Pro Pro 565 570 575 Ala Ser Ser Glu Ala Arg Asn Ser Ala Phe Gly Phe Gln Gly Arg Leu 580 585 590 Leu His Leu Ser Ala Gly Gln Arg Leu Gly Val His Leu His Thr Glu 595 600 605 Ala Arg Ala Arg His Ala Trp Gln Leu Thr Gln Gly Ala Thr Val Leu 610 615 620 Gly Leu Phe Arg Val Thr Pro Glu Ile Pro Ala Gly Leu Gly Gly Gly 625 630 635 640 Gly Ser Gly Gly Gly Gly Ser Arg Glu Gly Pro Glu Leu Ser Pro Asp 645 650 655 Asp Pro Ala Gly Leu Leu Asp Leu Arg Gln Gly Met Phe Ala Gln Leu 660 665 670 Val Ala Gln Asn Val Leu Leu Ile Asp Gly Pro Leu Ser Trp Tyr Ser 675 680 685 Asp Pro Gly Leu Ala Gly Val Ser Leu Thr Gly Gly Leu Ser Tyr Lys 690 695 700 Glu Asp Thr Lys Glu Leu Val Val Ala Lys Ala Gly Val Tyr Tyr Val 705 710 715 720 Phe Phe Gln Leu Glu Leu Arg Arg Val Val Ala Gly Glu Gly Ser Gly 725 730 735 Ser Val Ser Leu Ala Leu His Leu Gln Pro Leu Arg Ser Ala Ala Gly 740 745 750 Ala Ala Ala Leu Ala Leu Thr Val Asp Leu Pro Pro Ala Ser Ser Glu 755 760 765 Ala Arg Asn Ser Ala Phe Gly Phe Gln Gly Arg Leu Leu His Leu Ser 770 775 780 Ala Gly Gln Arg Leu Gly Val His Leu His Thr Glu Ala Arg Ala Arg 785 790 795 800 His Ala Trp Gln Leu Thr Gln Gly Ala Thr Val Leu Gly Leu Phe Arg 805 810 815 Val Thr Pro Glu Ile Pro Ala Gly Leu 820 825 <210> 87 <211> 637 <212> PRT <213> Secuencia artificial <220> <223> cadena pomo Fc de anti-PD1 (0314) fusionada a 4-1BBL hu monomérico (71-248) <400> 87 Glu Val Gln Leu Leu Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 1 5 10 15 Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Ser Phe Ser Ser Tyr 20 25 30 Thr Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45 Ala Thr Ile Ser Gly Gly Gly Arg Asp Ile Tyr Tyr Pro Asp Ser Val 50 55 60 Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 65 70 75 80 Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Val Leu Leu Thr Gly Arg Val Tyr Phe Ala Leu Asp Ser Trp Gly Gln 100 105 110 Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val 115 120 125 Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala 130 135 140 Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser 145 150 155 160 Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val 165 170 175 Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro 180 185 190 Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys 195 200 205 Pro Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp 210 215 220 Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly Gly 225 230 235 240 Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile 245 250 255 Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu 260 265 270 Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His 275 280 285 Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg 290 295 300 Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys 305 310 315 320 Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Gly Ala Pro Ile Glu 325 330 335 Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr 340 345 350 Thr Leu Pro Pro Cys Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu 355 360 365 Trp Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp 370 375 380 Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val 385 390 395 400 Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp 405 410 415 Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His 420 425 430 Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro 435 440 445 Gly Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Arg Glu Gly Pro Glu 450 455 460 Leu Ser Pro Asp Asp Pro Ala Gly Leu Leu Asp Leu Arg Gln Gly Met 465 470 475 480 Phe Ala Gln Leu Val Ala Gln Asn Val Leu Leu Ile Asp Gly Pro Leu 485 490 495 Ser Trp Tyr Ser Asp Pro Gly Leu Ala Gly Val Ser Leu Thr Gly Gly 500 505 510 Leu Ser Tyr Lys Glu Asp Thr Lys Glu Leu Val Val Ala Lys Ala Gly 515 520 525 Val Tyr Tyr Val Phe Phe Gln Leu Glu Leu Arg Arg Val Val Ala Gly 530 535 540 Glu Gly Ser Gly Ser Val Ser Leu Ala Leu His Leu Gln Pro Leu Arg 545 550 555 560 Ser Ala Ala Gly Ala Ala Ala Leu Ala Leu Thr Val Asp Leu Pro Pro 565 570 575 Ala Ser Ser Glu Ala Arg Asn Ser Ala Phe Gly Phe Gln Gly Arg Leu 580 585 590 Leu His Leu Ser Ala Gly Gln Arg Leu Gly Val His Leu His Thr Glu 595 600 605 Ala Arg Ala Arg His Ala Trp Gln Leu Thr Gln Gly Ala Thr Val Leu 610 615 620 Gly Leu Phe Arg Val Thr Pro Glu Ile Pro Ala Gly Leu 625 630 635 <210> 88 <211> 602 <212> PRT <213> Secuencia artificial <220> <223> cadena de ligando dimérico (71-248) de Fc agujero <400> 88 Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly 1 5 10 15 Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met 20 25 30 Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His 35 40 45 Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val 50 55 60 His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr 65 70 75 80 Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly 85 90 95 Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Gly Ala Pro Ile 100 105 110 Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val 115 120 125 Cys Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser 130 135 140 Leu Ser Cys Ala Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu 145 150 155 160 Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro 165 170 175 Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Val Ser Lys Leu Thr Val 180 185 190 Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met 195 200 205 His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser 210 215 220 Pro Gly Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Arg Glu Gly Pro 225 230 235 240 Glu Leu Ser Pro Asp Asp Pro Ala Gly Leu Leu Asp Leu Arg Gln Gly 245 250 255 Met Phe Ala Gln Leu Val Ala Gln Asn Val Leu Leu Ile Asp Gly Pro 260 265 270 Leu Ser Trp Tyr Ser Asp Pro Gly Leu Ala Gly Val Ser Leu Thr Gly 275 280 285 Gly Leu Ser Tyr Lys Glu Asp Thr Lys Glu Leu Val Val Ala Lys Ala 290 295 300 Gly Val Tyr Tyr Val Phe Phe Gln Leu Glu Leu Arg Arg Val Val Ala 305 310 315 320 Gly Glu Gly Ser Gly Ser Val Ser Leu Ala Leu His Leu Gln Pro Leu 325 330 335 Arg Ser Ala Ala Gly Ala Ala Ala Leu Ala Leu Thr Val Asp Leu Pro 340 345 350 Pro Ala Ser Ser Glu Ala Arg Asn Ser Ala Phe Gly Phe Gln Gly Arg 355 360 365 Leu Leu His Leu Ser Ala Gly Gln Arg Leu Gly Val His Leu His Thr 370 375 380 Glu Ala Arg Ala Arg His Ala Trp Gln Leu Thr Gln Gly Ala Thr Val 385 390 395 400 Leu Gly Leu Phe Arg Val Thr Pro Glu Ile Pro Ala Gly Leu Gly Gly 405 410 415 Gly Gly Ser Gly Gly Gly Gly Ser Arg Glu Gly Pro Glu Leu Ser Pro 420 425 430 Asp Asp Pro Ala Gly Leu Leu Asp Leu Arg Gln Gly Met Phe Ala Gln 435 440 445 Leu Val Ala Gln Asn Val Leu Leu Ile Asp Gly Pro Leu Ser Trp Tyr 450 455 460 Ser Asp Pro Gly Leu Ala Gly Val Ser Leu Thr Gly Gly Leu Ser Tyr 465 470 475 480 Lys Glu Asp Thr Lys Glu Leu Val Val Ala Lys Ala Gly Val Tyr Tyr 485 490 495 Val Phe Phe Gln Leu Glu Leu Arg Arg Val Val Ala Gly Glu Gly Ser 500 505 510 Gly Ser Val Ser Leu Ala Leu His Leu Gln Pro Leu Arg Ser Ala Ala 515 520 525 Gly Ala Ala Ala Leu Ala Leu Thr Val Asp Leu Pro Pro Ala Ser Ser 530 535 540 Glu Ala Arg Asn Ser Ala Phe Gly Phe Gln Gly Arg Leu Leu His Leu 545 550 555 560 Ser Ala Gly Gln Arg Leu Gly Val His Leu His Thr Glu Ala Arg Ala 565 570 575 Arg His Ala Trp Gln Leu Thr Gln Gly Ala Thr Val Leu Gly Leu Phe 580 585 590 Arg Val Thr Pro Glu Ile Pro Ala Gly Leu 595 600 <210> 89 <211> 404 <212> PRT <213> Secuencia artificial <220> <223> cadena de ligando monomérico (71-248) de Fc agujero <400> 89 Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly 1 5 10 15 Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met 20 25 30 Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His 35 40 45 Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val 50 55 60 His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr 65 70 75 80 Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly 85 90 95 Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Gly Ala Pro Ile 100 105 110 Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val 115 120 125 Cys Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser 130 135 140 Leu Ser Cys Ala Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu 145 150 155 160 Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro 165 170 175 Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Val Ser Lys Leu Thr Val 180 185 190 Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met 195 200 205 His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser 210 215 220 Pro Gly Arg Glu Gly Pro Glu Leu Ser Pro Asp Asp Pro Ala Gly Leu 225 230 235 240 Leu Asp Leu Arg Gln Gly Met Phe Ala Gln Leu Val Ala Gln Asn Val 245 250 255 Leu Leu Ile Asp Gly Pro Leu Ser Trp Tyr Ser Asp Pro Gly Leu Ala 260 265 270 Gly Val Ser Leu Thr Gly Gly Leu Ser Tyr Lys Glu Asp Thr Lys Glu 275 280 285 Leu Val Val Ala Lys Ala Gly Val Tyr Tyr Val Phe Phe Gln Leu Glu 290 295 300 Leu Arg Arg Val Val Ala Gly Glu Gly Ser Gly Ser Val Ser Leu Ala 305 310 315 320 Leu His Leu Gln Pro Leu Arg Ser Ala Ala Gly Ala Ala Ala Leu Ala 325 330 335 Leu Thr Val Asp Leu Pro Pro Ala Ser Ser Glu Ala Arg Asn Ser Ala 340 345 350 Phe Gly Phe Gln Gly Arg Leu Leu His Leu Ser Ala Gly Gln Arg Leu 355 360 365 Gly Val His Leu His Thr Glu Ala Arg Ala Arg His Ala Trp Gln Leu 370 375 380 Thr Gln Gly Ala Thr Val Leu Gly Leu Phe Arg Val Thr Pro Glu Ile 385 390 395 400 Pro Ala Gly Leu <210> 90 <211> 815 <212> PRT <213> Secuencia artificial <220> <223> cadena pomo Fc de anti-PD1 (0314) fusionada a 4-1BBL hu dimérico (71-248) <400> 90 Glu Val Gln Leu Leu Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 1 5 10 15 Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Ser Phe Ser Ser Tyr 20 25 30 Thr Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45 Ala Thr Ile Ser Gly Gly Gly Arg Asp Ile Tyr Tyr Pro Asp Ser Val 50 55 60 Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 65 70 75 80 Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Val Leu Leu Thr Gly Arg Val Tyr Phe Ala Leu Asp Ser Trp Gly Gln 100 105 110 Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val 115 120 125 Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala 130 135 140 Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser 145 150 155 160 Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val 165 170 175 Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro 180 185 190 Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys 195 200 205 Pro Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp 210 215 220 Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly Gly 225 230 235 240 Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile 245 250 255 Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu 260 265 270 Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His 275 280 285 Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg 290 295 300 Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys 305 310 315 320 Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Gly Ala Pro Ile Glu 325 330 335 Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr 340 345 350 Thr Leu Pro Pro Cys Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu 355 360 365 Trp Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp 370 375 380 Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val 385 390 395 400 Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp 405 410 415 Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His 420 425 430 Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro 435 440 445 Gly Arg Glu Gly Pro Glu Leu Ser Pro Asp Asp Pro Ala Gly Leu Leu 450 455 460 Asp Leu Arg Gln Gly Met Phe Ala Gln Leu Val Ala Gln Asn Val Leu 465 470 475 480 Leu Ile Asp Gly Pro Leu Ser Trp Tyr Ser Asp Pro Gly Leu Ala Gly 485 490 495 Val Ser Leu Thr Gly Gly Leu Ser Tyr Lys Glu Asp Thr Lys Glu Leu 500 505 510 Val Val Ala Lys Ala Gly Val Tyr Tyr Val Phe Phe Gln Leu Glu Leu 515 520 525 Arg Arg Val Val Ala Gly Glu Gly Ser Gly Ser Val Ser Leu Ala Leu 530 535 540 His Leu Gln Pro Leu Arg Ser Ala Ala Gly Ala Ala Ala Leu Ala Leu 545 550 555 560 Thr Val Asp Leu Pro Pro Ala Ser Ser Glu Ala Arg Asn Ser Ala Phe 565 570 575 Gly Phe Gln Gly Arg Leu Leu His Leu Ser Ala Gly Gln Arg Leu Gly 580 585 590 Val His Leu His Thr Glu Ala Arg Ala Arg His Ala Trp Gln Leu Thr 595 600 605 Gln Gly Ala Thr Val Leu Gly Leu Phe Arg Val Thr Pro Glu Ile Pro 610 615 620 Ala Gly Leu Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Arg Glu Gly 625 630 635 640 Pro Glu Leu Ser Pro Asp Asp Pro Ala Gly Leu Leu Asp Leu Arg Gln 645 650 655 Gly Met Phe Ala Gln Leu Val Ala Gln Asn Val Leu Leu Ile Asp Gly 660 665 670 Pro Leu Ser Trp Tyr Ser Asp Pro Gly Leu Ala Gly Val Ser Leu Thr 675 680 685 Gly Gly Leu Ser Tyr Lys Glu Asp Thr Lys Glu Leu Val Val Ala Lys 690 695 700 Ala Gly Val Tyr Tyr Val Phe Phe Gln Leu Glu Leu Arg Arg Val Val 705 710 715 720 Ala Gly Glu Gly Ser Gly Ser Val Ser Leu Ala Leu His Leu Gln Pro 725 730 735 Leu Arg Ser Ala Ala Gly Ala Ala Ala Leu Ala Leu Thr Val Asp Leu 740 745 750 Pro Pro Ala Ser Ser Glu Ala Arg Asn Ser Ala Phe Gly Phe Gln Gly 755 760 765 Arg Leu Leu His Leu Ser Ala Gly Gln Arg Leu Gly Val His Leu His 770 775 780 Thr Glu Ala Arg Ala Arg His Ala Trp Gln Leu Thr Gln Gly Ala Thr 785 790 795 800 Val Leu Gly Leu Phe Arg Val Thr Pro Glu Ile Pro Ala Gly Leu 805 810 815 <210> 91 <211> 414 <212> PRT <213> Secuencia artificial <220> <223> cadena pomo Fc fusionada a 4-1BBL hu monomérico (71-248) <400> 91 Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly 1 5 10 15 Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met 20 25 30 Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His 35 40 45 Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val 50 55 60 His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr 65 70 75 80 Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly 85 90 95 Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Gly Ala Pro Ile 100 105 110 Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val 115 120 125 Tyr Thr Leu Pro Pro Cys Arg Asp Glu Leu Thr Lys Asn Gln Val Ser 130 135 140 Leu Trp Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu 145 150 155 160 Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro 165 170 175 Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val 180 185 190 Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met 195 200 205 His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser 210 215 220 Pro Gly Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Arg Glu Gly Pro 225 230 235 240 Glu Leu Ser Pro Asp Asp Pro Ala Gly Leu Leu Asp Leu Arg Gln Gly 245 250 255 Met Phe Ala Gln Leu Val Ala Gln Asn Val Leu Leu Ile Asp Gly Pro 260 265 270 Leu Ser Trp Tyr Ser Asp Pro Gly Leu Ala Gly Val Ser Leu Thr Gly 275 280 285 Gly Leu Ser Tyr Lys Glu Asp Thr Lys Glu Leu Val Val Ala Lys Ala 290 295 300 Gly Val Tyr Tyr Val Phe Phe Gln Leu Glu Leu Arg Arg Val Val Ala 305 310 315 320 Gly Glu Gly Ser Gly Ser Val Ser Leu Ala Leu His Leu Gln Pro Leu 325 330 335 Arg Ser Ala Ala Gly Ala Ala Ala Leu Ala Leu Thr Val Asp Leu Pro 340 345 350 Pro Ala Ser Ser Glu Ala Arg Asn Ser Ala Phe Gly Phe Gln Gly Arg 355 360 365 Leu Leu His Leu Ser Ala Gly Gln Arg Leu Gly Val His Leu His Thr 370 375 380 Glu Ala Arg Ala Arg His Ala Trp Gln Leu Thr Gln Gly Ala Thr Val 385 390 395 400 Leu Gly Leu Phe Arg Val Thr Pro Glu Ile Pro Ala Gly Leu 405 410 <210> 92 <211> 637 <212> PRT <213> Secuencia artificial <220> <223> cadena de ligando monomérico (71-248) Fc agujero de anti-PD1(0314) <400> 92 Glu Val Gln Leu Leu Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 1 5 10 15 Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Ser Phe Ser Ser Tyr 20 25 30 Thr Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45 Ala Thr Ile Ser Gly Gly Gly Arg Asp Ile Tyr Tyr Pro Asp Ser Val 50 55 60 Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 65 70 75 80 Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Val Leu Leu Thr Gly Arg Val Tyr Phe Ala Leu Asp Ser Trp Gly Gln 100 105 110 Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val 115 120 125 Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala 130 135 140 Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser 145 150 155 160 Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val 165 170 175 Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro 180 185 190 Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys 195 200 205 Pro Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp 210 215 220 Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly Gly 225 230 235 240 Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile 245 250 255 Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu 260 265 270 Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His 275 280 285 Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg 290 295 300 Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys 305 310 315 320 Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Gly Ala Pro Ile Glu 325 330 335 Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Cys 340 345 350 Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu 355 360 365 Ser Cys Ala Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp 370 375 380 Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val 385 390 395 400 Leu Asp Ser Asp Gly Ser Phe Phe Leu Val Ser Lys Leu Thr Val Asp 405 410 415 Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His 420 425 430 Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro 435 440 445 Gly Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Arg Glu Gly Pro Glu 450 455 460 Leu Ser Pro Asp Asp Pro Ala Gly Leu Leu Asp Leu Arg Gln Gly Met 465 470 475 480 Phe Ala Gln Leu Val Ala Gln Asn Val Leu Leu Ile Asp Gly Pro Leu 485 490 495 Ser Trp Tyr Ser Asp Pro Gly Leu Ala Gly Val Ser Leu Thr Gly Gly 500 505 510 Leu Ser Tyr Lys Glu Asp Thr Lys Glu Leu Val Val Ala Lys Ala Gly 515 520 525 Val Tyr Tyr Val Phe Phe Gln Leu Glu Leu Arg Arg Val Val Ala Gly 530 535 540 Glu Gly Ser Gly Ser Val Ser Leu Ala Leu His Leu Gln Pro Leu Arg 545 550 555 560 Ser Ala Ala Gly Ala Ala Ala Leu Ala Leu Thr Val Asp Leu Pro Pro 565 570 575 Ala Ser Ser Glu Ala Arg Asn Ser Ala Phe Gly Phe Gln Gly Arg Leu 580 585 590 Leu His Leu Ser Ala Gly Gln Arg Leu Gly Val His Leu His Thr Glu 595 600 605 Ala Arg Ala Arg His Ala Trp Gln Leu Thr Gln Gly Ala Thr Val Leu 610 615 620 Gly Leu Phe Arg Val Thr Pro Glu Ile Pro Ala Gly Leu 625 630 635 <210> 93 <211> 602 <212> PRT <213> Secuencia artificial <220> <223> cadena pomo Fc fusionada a 4-1BBL hu dimérico (71-248) <400> 93 Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly 1 5 10 15 Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met 20 25 30 Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His 35 40 45 Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val 50 55 60 His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr 65 70 75 80 Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly 85 90 95 Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Gly Ala Pro Ile 100 105 110 Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val 115 120 125 Tyr Thr Leu Pro Pro Cys Arg Asp Glu Leu Thr Lys Asn Gln Val Ser 130 135 140 Leu Trp Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu 145 150 155 160 Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro 165 170 175 Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val 180 185 190 Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met 195 200 205 His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser 210 215 220 Pro Gly Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Arg Glu Gly Pro 225 230 235 240 Glu Leu Ser Pro Asp Asp Pro Ala Gly Leu Leu Asp Leu Arg Gln Gly 245 250 255 Met Phe Ala Gln Leu Val Ala Gln Asn Val Leu Leu Ile Asp Gly Pro 260 265 270 Leu Ser Trp Tyr Ser Asp Pro Gly Leu Ala Gly Val Ser Leu Thr Gly 275 280 285 Gly Leu Ser Tyr Lys Glu Asp Thr Lys Glu Leu Val Val Ala Lys Ala 290 295 300 Gly Val Tyr Tyr Val Phe Phe Gln Leu Glu Leu Arg Arg Val Val Ala 305 310 315 320 Gly Glu Gly Ser Gly Ser Val Ser Leu Ala Leu His Leu Gln Pro Leu 325 330 335 Arg Ser Ala Ala Gly Ala Ala Ala Leu Ala Leu Thr Val Asp Leu Pro 340 345 350 Pro Ala Ser Ser Glu Ala Arg Asn Ser Ala Phe Gly Phe Gln Gly Arg 355 360 365 Leu Leu His Leu Ser Ala Gly Gln Arg Leu Gly Val His Leu His Thr 370 375 380 Glu Ala Arg Ala Arg His Ala Trp Gln Leu Thr Gln Gly Ala Thr Val 385 390 395 400 Leu Gly Leu Phe Arg Val Thr Pro Glu Ile Pro Ala Gly Leu Gly Gly 405 410 415 Gly Gly Ser Gly Gly Gly Gly Ser Arg Glu Gly Pro Glu Leu Ser Pro 420 425 430 Asp Asp Pro Ala Gly Leu Leu Asp Leu Arg Gln Gly Met Phe Ala Gln 435 440 445 Leu Val Ala Gln Asn Val Leu Leu Ile Asp Gly Pro Leu Ser Trp Tyr 450 455 460 Ser Asp Pro Gly Leu Ala Gly Val Ser Leu Thr Gly Gly Leu Ser Tyr 465 470 475 480 Lys Glu Asp Thr Lys Glu Leu Val Val Ala Lys Ala Gly Val Tyr Tyr 485 490 495 Val Phe Phe Gln Leu Glu Leu Arg Arg Val Val Ala Gly Glu Gly Ser 500 505 510 Gly Ser Val Ser Leu Ala Leu His Leu Gln Pro Leu Arg Ser Ala Ala 515 520 525 Gly Ala Ala Ala Leu Ala Leu Thr Val Asp Leu Pro Pro Ala Ser Ser 530 535 540 Glu Ala Arg Asn Ser Ala Phe Gly Phe Gln Gly Arg Leu Leu His Leu 545 550 555 560 Ser Ala Gly Gln Arg Leu Gly Val His Leu His Thr Glu Ala Arg Ala 565 570 575 Arg His Ala Trp Gln Leu Thr Gln Gly Ala Thr Val Leu Gly Leu Phe 580 585 590 Arg Val Thr Pro Glu Ile Pro Ala Gly Leu 595 600 <210> 94 <211> 288 <212> PRT <213> Homo sapiens <400> 94 Met Gln Ile Pro Gln Ala Pro Trp Pro Val Val Trp Ala Val Leu Gln 1 5 10 15 Leu Gly Trp Arg Pro Gly Trp Phe Leu Asp Ser Pro Asp Arg Pro Trp 20 25 30 Asn Pro Pro Thr Phe Ser Pro Ala Leu Leu Val Val Thr Glu Gly Asp 35 40 45 Asn Ala Thr Phe Thr Cys Ser Phe Ser Asn Thr Ser Glu Ser Phe Val 50 55 60 Leu Asn Trp Tyr Arg Met Ser Pro Ser Asn Gln Thr Asp Lys Leu Ala 65 70 75 80 Ala Phe Pro Glu Asp Arg Ser Gln Pro Gly Gln Asp Cys Arg Phe Arg 85 90 95 Val Thr Gln Leu Pro Asn Gly Arg Asp Phe His Met Ser Val Val Arg 100 105 110 Ala Arg Arg Asn Asp Ser Gly Thr Tyr Leu Cys Gly Ala Ile Ser Leu 115 120 125 Ala Pro Lys Ala Gln Ile Lys Glu Ser Leu Arg Ala Glu Leu Arg Val 130 135 140 Thr Glu Arg Arg Ala Glu Val Pro Thr Ala His Pro Ser Pro Ser Pro 145 150 155 160 Arg Pro Ala Gly Gln Phe Gln Thr Leu Val Val Gly Val Val Gly Gly 165 170 175 Leu Leu Gly Ser Leu Val Leu Leu Val Trp Val Leu Ala Val Ile Cys 180 185 190 Ser Arg Ala Ala Arg Gly Thr Ile Gly Ala Arg Arg Thr Gly Gln Pro 195 200 205 Leu Lys Glu Asp Pro Ser Ala Val Pro Val Phe Ser Val Asp Tyr Gly 210 215 220 Glu Leu Asp Phe Gln Trp Arg Glu Lys Thr Pro Glu Pro Pro Val Pro 225 230 235 240 Cys Val Pro Glu Gln Thr Glu Tyr Ala Thr Ile Val Phe Pro Ser Gly 245 250 255 Met Gly Thr Ser Ser Pro Ala Arg Arg Gly Ser Ala Asp Gly Pro Arg 260 265 270 Ser Ala Gln Pro Leu Arg Pro Glu Asp Gly His Cys Ser Trp Pro Leu 275 280 285 <210> 95 <211> 205 <212> PRT <213> Homo sapiens <400> 95 Met Thr Pro Pro Glu Arg Leu Phe Leu Pro Arg Val Cys Gly Thr Thr 1 5 10 15 Leu His Leu Leu Leu Leu Gly Leu Leu Leu Val Leu Leu Pro Gly Ala 20 25 30 Gln Gly Leu Pro Gly Val Gly Leu Thr Pro Ser Ala Ala Gln Thr Ala 35 40 45 Arg Gln His Pro Lys Met His Leu Ala His Ser Thr Leu Lys Pro Ala 50 55 60 Ala His Leu Ile Gly Asp Pro Ser Lys Gln Asn Ser Leu Leu Trp Arg 65 70 75 80 Ala Asn Thr Asp Arg Ala Phe Leu Gln Asp Gly Phe Ser Leu Ser Asn 85 90 95 Asn Ser Leu Leu Val Pro Thr Ser Gly Ile Tyr Phe Val Tyr Ser Gln 100 105 110 Val Val Phe Ser Gly Lys Ala Tyr Ser Pro Lys Ala Thr Ser Ser Pro 115 120 125 Leu Tyr Leu Ala His Glu Val Gln Leu Phe Ser Ser Gln Tyr Pro Phe 130 135 140 His Val Pro Leu Leu Ser Ser Gln Lys Met Val Tyr Pro Gly Leu Gln 145 150 155 160 Glu Pro Trp Leu His Ser Met Tyr His Gly Ala Ala Phe Gln Leu Thr 165 170 175 Gln Gly Asp Gln Leu Ser Thr His Thr Asp Gly Ile Pro His Leu Val 180 185 190 Leu Ser Pro Ser Thr Val Phe Phe Gly Ala Phe Ala Leu 195 200 205 <210> 96 <211> 233 <212> PRT <213> Homo sapiens <400> 96 Met Ser Thr Glu Ser Met Ile Arg Asp Val Glu Leu Ala Glu Glu Ala 1 5 10 15 Leu Pro Lys Lys Thr Gly Gly Pro Gln Gly Ser Arg Arg Cys Leu Phe 20 25 30 Leu Ser Leu Phe Ser Phe Leu Ile Val Ala Gly Ala Thr Thr Leu Phe 35 40 45 Cys Leu Leu His Phe Gly Val Ile Gly Pro Gln Arg Glu Glu Phe Pro 50 55 60 Arg Asp Leu Ser Leu Ile Ser Pro Leu Ala Gln Ala Val Arg Ser Ser 65 70 75 80 Ser Arg Thr Pro Ser Asp Lys Pro Val Ala His Val Val Ala Asn Pro 85 90 95 Gln Ala Glu Gly Gln Leu Gln Trp Leu Asn Arg Arg Ala Asn Ala Leu 100 105 110 Leu Ala Asn Gly Val Glu Leu Arg Asp Asn Gln Leu Val Val Pro Ser 115 120 125 Glu Gly Leu Tyr Leu Ile Tyr Ser Gln Val Leu Phe Lys Gly Gln Gly 130 135 140 Cys Pro Ser Thr His Val Leu Leu Thr His Thr Ile Ser Arg Ile Ala 145 150 155 160 Val Ser Tyr Gln Thr Lys Val Asn Leu Leu Ser Ala Ile Lys Ser Pro 165 170 175 Cys Gln Arg Glu Thr Pro Glu Gly Ala Glu Ala Lys Pro Trp Tyr Glu 180 185 190 Pro Ile Tyr Leu Gly Gly Val Phe Gln Leu Glu Lys Gly Asp Arg Leu 195 200 205 Ser Ala Glu Ile Asn Arg Pro Asp Tyr Leu Asp Phe Ala Glu Ser Gly 210 215 220 Gln Val Tyr Phe Gly Ile Ile Ala Leu 225 230 <210> 97 <211> 244 <212> PRT <213> Homo sapiens <400> 97 Met Gly Ala Leu Gly Leu Glu Gly Arg Gly Gly Arg Leu Gln Gly Arg 1 5 10 15 Gly Ser Leu Leu Leu Ala Val Ala Gly Ala Thr Ser Leu Val Thr Leu 20 25 30 Leu Leu Ala Val Pro Ile Thr Val Leu Ala Val Leu Ala Leu Val Pro 35 40 45 Gln Asp Gln Gly Gly Leu Val Thr Glu Thr Ala Asp Pro Gly Ala Gln 50 55 60 Ala Gln Gln Gly Leu Gly Phe Gln Lys Leu Pro Glu Glu Glu Pro Glu 65 70 75 80 Thr Asp Leu Ser Pro Gly Leu Pro Ala Ala His Leu Ile Gly Ala Pro 85 90 95 Leu Lys Gly Gln Gly Leu Gly Trp Glu Thr Thr Lys Glu Gln Ala Phe 100 105 110 Leu Thr Ser Gly Thr Gln Phe Ser Asp Ala Glu Gly Leu Ala Leu Pro 115 120 125 Gln Asp Gly Leu Tyr Tyr Leu Tyr Cys Leu Val Gly Tyr Arg Gly Arg 130 135 140 Ala Pro Pro Gly Gly Gly Asp Pro Gln Gly Arg Ser Val Thr Leu Arg 145 150 155 160 Ser Ser Leu Tyr Arg Ala Gly Gly Ala Tyr Gly Pro Gly Thr Pro Glu 165 170 175 Leu Leu Leu Glu Gly Ala Glu Thr Val Thr Pro Val Leu Asp Pro Ala 180 185 190 Arg Arg Gln Gly Tyr Gly Pro Leu Trp Tyr Thr Ser Val Gly Phe Gly 195 200 205 Gly Leu Val Gln Leu Arg Arg Gly Glu Arg Val Tyr Val Asn Ile Ser 210 215 220 His Pro Asp Met Val Asp Phe Ala Arg Gly Lys Thr Phe Phe Gly Ala 225 230 235 240 Val Met Val Gly <210> 98 <211> 183 <212> PRT <213> Homo sapiens <400> 98 Met Glu Arg Val Gln Pro Leu Glu Glu Asn Val Gly Asn Ala Ala Arg 1 5 10 15 Pro Arg Phe Glu Arg Asn Lys Leu Leu Leu Val Ala Ser Val Ile Gln 20 25 30 Gly Leu Gly Leu Leu Leu Cys Phe Thr Tyr Ile Cys Leu His Phe Ser 35 40 45 Ala Leu Gln Val Ser His Arg Tyr Pro Arg Ile Gln Ser Ile Lys Val 50 55 60 Gln Phe Thr Glu Tyr Lys Lys Glu Lys Gly Phe Ile Leu Thr Ser Gln 65 70 75 80 Lys Glu Asp Glu Ile Met Lys Val Gln Asn Asn Ser Val Ile Ile Asn 85 90 95 Cys Asp Gly Phe Tyr Leu Ile Ser Leu Lys Gly Tyr Phe Ser Gln Glu 100 105 110 Val Asn Ile Ser Leu His Tyr Gln Lys Asp Glu Glu Pro Leu Phe Gln 115 120 125 Leu Lys Lys Val Arg Ser Val Asn Ser Leu Met Val Ala Ser Leu Thr 130 135 140 Tyr Lys Asp Lys Val Tyr Leu Asn Val Thr Thr Asp Asn Thr Ser Leu 145 150 155 160 Asp Asp Phe His Val Asn Gly Gly Glu Leu Ile Leu Ile His Gln Asn 165 170 175 Pro Gly Glu Phe Cys Val Leu 180 <210> 99 <211> 261 <212> PRT <213> Homo sapiens <400> 99 Met Ile Glu Thr Tyr Asn Gln Thr Ser Pro Arg Ser Ala Ala Thr Gly 1 5 10 15 Leu Pro Ile Ser Met Lys Ile Phe Met Tyr Leu Leu Thr Val Phe Leu 20 25 30 Ile Thr Gln Met Ile Gly Ser Ala Leu Phe Ala Val Tyr Leu His Arg 35 40 45 Arg Leu Asp Lys Ile Glu Asp Glu Arg Asn Leu His Glu Asp Phe Val 50 55 60 Phe Met Lys Thr Ile Gln Arg Cys Asn Thr Gly Glu Arg Ser Leu Ser 65 70 75 80 Leu Leu Asn Cys Glu Glu Ile Lys Ser Gln Phe Glu Gly Phe Val Lys 85 90 95 Asp Ile Met Leu Asn Lys Glu Glu Thr Lys Lys Glu Asn Ser Phe Glu 100 105 110 Met Gln Lys Gly Asp Gln Asn Pro Gln Ile Ala Ala His Val Ile Ser 115 120 125 Glu Ala Ser Ser Lys Thr Thr Ser Val Leu Gln Trp Ala Glu Lys Gly 130 135 140 Tyr Tyr Thr Met Ser Asn Asn Leu Val Thr Leu Glu Asn Gly Lys Gln 145 150 155 160 Leu Thr Val Lys Arg Gln Gly Leu Tyr Tyr Ile Tyr Ala Gln Val Thr 165 170 175 Phe Cys Ser Asn Arg Glu Ala Ser Ser Gln Ala Pro Phe Ile Ala Ser 180 185 190 Leu Cys Leu Lys Ser Pro Gly Arg Phe Glu Arg Ile Leu Leu Arg Ala 195 200 205 Ala Asn Thr His Ser Ser Ala Lys Pro Cys Gly Gln Gln Ser Ile His 210 215 220 Leu Gly Gly Val Phe Glu Leu Gln Pro Gly Ala Ser Val Phe Val Asn 225 230 235 240 Val Thr Asp Pro Ser Gln Val Ser His Gly Thr Gly Phe Thr Ser Phe 245 250 255 Gly Leu Leu Lys Leu 260 <210> 100 <211> 281 <212> PRT <213> Homo sapiens <400> 100 Met Gln Gln Pro Phe Asn Tyr Pro Tyr Pro Gln Ile Tyr Trp Val Asp 1 5 10 15 Ser Ser Ala Ser Ser Pro Trp Ala Pro Pro Gly Thr Val Leu Pro Cys 20 25 30 Pro Thr Ser Val Pro Arg Arg Pro Gly Gln Arg Arg Pro Pro Pro Pro 35 40 45 Pro Pro Pro Pro Pro Leu Pro Pro Pro Pro Pro Pro Pro Pro Leu Pro 50 55 60 Pro Leu Pro Leu Pro Pro Leu Lys Lys Arg Gly Asn His Ser Thr Gly 65 70 75 80 Leu Cys Leu Leu Val Met Phe Phe Met Val Leu Val Ala Leu Val Gly 85 90 95 Leu Gly Leu Gly Met Phe Gln Leu Phe His Leu Gln Lys Glu Leu Ala 100 105 110 Glu Leu Arg Glu Ser Thr Ser Gln Met His Thr Ala Ser Ser Leu Glu 115 120 125 Lys Gln Ile Gly His Pro Ser Pro Pro Pro Glu Lys Lys Glu Leu Arg 130 135 140 Lys Val Ala His Leu Thr Gly Lys Ser Asn Ser Arg Ser Met Pro Leu 145 150 155 160 Glu Trp Glu Asp Thr Tyr Gly Ile Val Leu Leu Ser Gly Val Lys Tyr 165 170 175 Lys Lys Gly Gly Leu Val Ile Asn Glu Thr Gly Leu Tyr Phe Val Tyr 180 185 190 Ser Lys Val Tyr Phe Arg Gly Gln Ser Cys Asn Asn Leu Pro Leu Ser 195 200 205 His Lys Val Tyr Met Arg Asn Ser Lys Tyr Pro Gln Asp Leu Val Met 210 215 220 Met Glu Gly Lys Met Met Ser Tyr Cys Thr Thr Gly Gln Met Trp Ala 225 230 235 240 Arg Ser Ser Tyr Leu Gly Ala Val Phe Asn Leu Thr Ser Ala Asp His 245 250 255 Leu Tyr Val Asn Val Ser Glu Leu Ser Leu Val Asn Phe Glu Glu Ser 260 265 270 Gln Thr Phe Phe Gly Leu Tyr Lys Leu 275 280 <210> 101 <211> 193 <212> PRT <213> Homo sapiens <400> 101 Met Pro Glu Glu Gly Ser Gly Cys Ser Val Arg Arg Arg Pro Tyr Gly 1 5 10 15 Cys Val Leu Arg Ala Ala Leu Val Pro Leu Val Ala Gly Leu Val Ile 20 25 30 Cys Leu Val Val Cys Ile Gln Arg Phe Ala Gln Ala Gln Gln Gln Leu 35 40 45 Pro Leu Glu Ser Leu Gly Trp Asp Val Ala Glu Leu Gln Leu Asn His 50 55 60 Thr Gly Pro Gln Gln Asp Pro Arg Leu Tyr Trp Gln Gly Gly Pro Ala 65 70 75 80 Leu Gly Arg Ser Phe Leu His Gly Pro Glu Leu Asp Lys Gly Gln Leu 85 90 95 Arg Ile His Arg Asp Gly Ile Tyr Met Val His Ile Gln Val Thr Leu 100 105 110 Ala Ile Cys Ser Ser Thr Thr Ala Ser Arg His His Pro Thr Thr Leu 115 120 125 Ala Val Gly Ile Cys Ser Pro Ala Ser Arg Ser Ile Ser Leu Leu Arg 130 135 140 Leu Ser Phe His Gln Gly Cys Thr Ile Ala Ser Gln Arg Leu Thr Pro 145 150 155 160 Leu Ala Arg Gly Asp Thr Leu Cys Thr Asn Leu Thr Gly Thr Leu Leu 165 170 175 Pro Ser Arg Asn Thr Asp Glu Thr Phe Phe Gly Val Gln Trp Val Arg 180 185 190 Pro <210> 102 <211> 234 <212> PRT <213> Homo sapiens <400> 102 Met Asp Pro Gly Leu Gln Gln Ala Leu Asn Gly Met Ala Pro Pro Gly 1 5 10 15 Asp Thr Ala Met His Val Pro Ala Gly Ser Val Ala Ser His Leu Gly 20 25 30 Thr Thr Ser Arg Ser Tyr Phe Tyr Leu Thr Thr Ala Thr Leu Ala Leu 35 40 45 Cys Leu Val Phe Thr Val Ala Thr Ile Met Val Leu Val Val Gln Arg 50 55 60 Thr Asp Ser Ile Pro Asn Ser Pro Asp Asn Val Pro Leu Lys Gly Gly 65 70 75 80 Asn Cys Ser Glu Asp Leu Leu Cys Ile Leu Lys Arg Ala Pro Phe Lys 85 90 95 Lys Ser Trp Ala Tyr Leu Gln Val Ala Lys His Leu Asn Lys Thr Lys 100 105 110 Leu Ser Trp Asn Lys Asp Gly Ile Leu His Gly Val Arg Tyr Gln Asp 115 120 125 Gly Asn Leu Val Ile Gln Phe Pro Gly Leu Tyr Phe Ile Ile Cys Gln 130 135 140 Leu Gln Phe Leu Val Gln Cys Pro Asn Asn Ser Val Asp Leu Lys Leu 145 150 155 160 Glu Leu Leu Ile Asn Lys His Ile Lys Lys Gln Ala Leu Val Thr Val 165 170 175 Cys Glu Ser Gly Met Gln Thr Lys His Val Tyr Gln Asn Leu Ser Gln 180 185 190 Phe Leu Leu Asp Tyr Leu Gln Val Asn Thr Thr Ile Ser Val Asn Val 195 200 205 Asp Thr Phe Gln Tyr Ile Asp Thr Ser Thr Phe Pro Leu Glu Asn Val 210 215 220 Leu Ser Ile Phe Leu Tyr Ser Asn Ser Asp 225 230 <210> 103 <211> 254 <212> PRT <213> Homo sapiens <400> 103 Met Glu Tyr Ala Ser Asp Ala Ser Leu Asp Pro Glu Ala Pro Trp Pro 1 5 10 15 Pro Ala Pro Arg Ala Arg Ala Cys Arg Val Leu Pro Trp Ala Leu Val 20 25 30 Ala Gly Leu Leu Leu Leu Leu Leu Leu Ala Ala Ala Cys Ala Val Phe 35 40 45 Leu Ala Cys Pro Trp Ala Val Ser Gly Ala Arg Ala Ser Pro Gly Ser 50 55 60 Ala Ala Ser Pro Arg Leu Arg Glu Gly Pro Glu Leu Ser Pro Asp Asp 65 70 75 80 Pro Ala Gly Leu Leu Asp Leu Arg Gln Gly Met Phe Ala Gln Leu Val 85 90 95 Ala Gln Asn Val Leu Leu Ile Asp Gly Pro Leu Ser Trp Tyr Ser Asp 100 105 110 Pro Gly Leu Ala Gly Val Ser Leu Thr Gly Gly Leu Ser Tyr Lys Glu 115 120 125 Asp Thr Lys Glu Leu Val Val Ala Lys Ala Gly Val Tyr Tyr Val Phe 130 135 140 Phe Gln Leu Glu Leu Arg Arg Val Val Ala Gly Glu Gly Ser Gly Ser 145 150 155 160 Val Ser Leu Ala Leu His Leu Gln Pro Leu Arg Ser Ala Ala Gly Ala 165 170 175 Ala Ala Leu Ala Leu Thr Val Asp Leu Pro Pro Ala Ser Ser Glu Ala 180 185 190 Arg Asn Ser Ala Phe Gly Phe Gln Gly Arg Leu Leu His Leu Ser Ala 195 200 205 Gly Gln Arg Leu Gly Val His Leu His Thr Glu Ala Arg Ala Arg His 210 215 220 Ala Trp Gln Leu Thr Gln Gly Ala Thr Val Leu Gly Leu Phe Arg Val 225 230 235 240 Thr Pro Glu Ile Pro Ala Gly Leu Pro Ser Pro Arg Ser Glu 245 250 <210> 104 <211> 281 <212> PRT <213> Homo sapiens <400> 104 Met Ala Met Met Glu Val Gln Gly Gly Pro Ser Leu Gly Gln Thr Cys 1 5 10 15 Val Leu Ile Val Ile Phe Thr Val Leu Leu Gln Ser Leu Cys Val Ala 20 25 30 Val Thr Tyr Val Tyr Phe Thr Asn Glu Leu Lys Gln Met Gln Asp Lys 35 40 45 Tyr Ser Lys Ser Gly Ile Ala Cys Phe Leu Lys Glu Asp Asp Ser Tyr 50 55 60 Trp Asp Pro Asn Asp Glu Glu Ser Met Asn Ser Pro Cys Trp Gln Val 65 70 75 80 Lys Trp Gln Leu Arg Gln Leu Val Arg Lys Met Ile Leu Arg Thr Ser 85 90 95 Glu Glu Thr Ile Ser Thr Val Gln Glu Lys Gln Gln Asn Ile Ser Pro 100 105 110 Leu Val Arg Glu Arg Gly Pro Gln Arg Val Ala Ala His Ile Thr Gly 115 120 125 Thr Arg Gly Arg Ser Asn Thr Leu Ser Ser Pro Asn Ser Lys Asn Glu 130 135 140 Lys Ala Leu Gly Arg Lys Ile Asn Ser Trp Glu Ser Ser Arg Ser Gly 145 150 155 160 His Ser Phe Leu Ser Asn Leu His Leu Arg Asn Gly Glu Leu Val Ile 165 170 175 His Glu Lys Gly Phe Tyr Tyr Ile Tyr Ser Gln Thr Tyr Phe Arg Phe 180 185 190 Gln Glu Glu Ile Lys Glu Asn Thr Lys Asn Asp Lys Gln Met Val Gln 195 200 205 Tyr Ile Tyr Lys Tyr Thr Ser Tyr Pro Asp Pro Ile Leu Leu Met Lys 210 215 220 Ser Ala Arg Asn Ser Cys Trp Ser Lys Asp Ala Glu Tyr Gly Leu Tyr 225 230 235 240 Ser Ile Tyr Gln Gly Gly Ile Phe Glu Leu Lys Glu Asn Asp Arg Ile 245 250 255 Phe Val Ser Val Thr Asn Glu His Leu Ile Asp Met Asp His Glu Ala 260 265 270 Ser Phe Phe Gly Ala Phe Leu Val Gly 275 280 <210> 105 <211> 317 <212> PRT <213> Homo sapiens <400> 105 Met Arg Arg Ala Ser Arg Asp Tyr Thr Lys Tyr Leu Arg Gly Ser Glu 1 5 10 15 Glu Met Gly Gly Gly Pro Gly Ala Pro His Glu Gly Pro Leu His Ala 20 25 30 Pro Pro Pro Pro Ala Pro His Gln Pro Pro Ala Ala Ser Arg Ser Met 35 40 45 Phe Val Ala Leu Leu Gly Leu Gly Leu Gly Gln Val Val Cys Ser Val 50 55 60 Ala Leu Phe Phe Tyr Phe Arg Ala Gln Met Asp Pro Asn Arg Ile Ser 65 70 75 80 Glu Asp Gly Thr His Cys Ile Tyr Arg Ile Leu Arg Leu His Glu Asn 85 90 95 Ala Asp Phe Gln Asp Thr Thr Leu Glu Ser Gln Asp Thr Lys Leu Ile 100 105 110 Pro Asp Ser Cys Arg Arg Ile Lys Gln Ala Phe Gln Gly Ala Val Gln 115 120 125 Lys Glu Leu Gln His Ile Val Gly Ser Gln His Ile Arg Ala Glu Lys 130 135 140 Ala Met Val Asp Gly Ser Trp Leu Asp Leu Ala Lys Arg Ser Lys Leu 145 150 155 160 Glu Ala Gln Pro Phe Ala His Leu Thr Ile Asn Ala Thr Asp Ile Pro 165 170 175 Ser Gly Ser His Lys Val Ser Leu Ser Ser Trp Tyr His Asp Arg Gly 180 185 190 Trp Ala Lys Ile Ser Asn Met Thr Phe Ser Asn Gly Lys Leu Ile Val 195 200 205 Asn Gln Asp Gly Phe Tyr Tyr Leu Tyr Ala Asn Ile Cys Phe Arg His 210 215 220 His Glu Thr Ser Gly Asp Leu Ala Thr Glu Tyr Leu Gln Leu Met Val 225 230 235 240 Tyr Val Thr Lys Thr Ser Ile Lys Ile Pro Ser Ser His Thr Leu Met 245 250 255 Lys Gly Gly Ser Thr Lys Tyr Trp Ser Gly Asn Ser Glu Phe His Phe 260 265 270 Tyr Ser Ile Asn Val Gly Gly Phe Phe Lys Leu Arg Ser Gly Glu Glu 275 280 285 Ile Ser Ile Glu Val Ser Asn Pro Ser Leu Leu Asp Pro Asp Gln Asp 290 295 300 Ala Thr Tyr Phe Gly Ala Phe Lys Val Arg Asp Ile Asp 305 310 315 <210> 106 <211> 249 <212> PRT <213> Homo sapiens <400> 106 Met Ala Ala Arg Arg Ser Gln Arg Arg Arg Gly Arg Arg Gly Glu Pro 1 5 10 15 Gly Thr Ala Leu Leu Val Pro Leu Ala Leu Gly Leu Gly Leu Ala Leu 20 25 30 Ala Cys Leu Gly Leu Leu Leu Ala Val Val Ser Leu Gly Ser Arg Ala 35 40 45 Ser Leu Ser Ala Gln Glu Pro Ala Gln Glu Glu Leu Val Ala Glu Glu 50 55 60 Asp Gln Asp Pro Ser Glu Leu Asn Pro Gln Thr Glu Glu Ser Gln Asp 65 70 75 80 Pro Ala Pro Phe Leu Asn Arg Leu Val Arg Pro Arg Arg Ser Ala Pro 85 90 95 Lys Gly Arg Lys Thr Arg Ala Arg Arg Ala Ile Ala Ala His Tyr Glu 100 105 110 Val His Pro Arg Pro Gly Gln Asp Gly Ala Gln Ala Gly Val Asp Gly 115 120 125 Thr Val Ser Gly Trp Glu Glu Ala Arg Ile Asn Ser Ser Ser Pro Leu 130 135 140 Arg Tyr Asn Arg Gln Ile Gly Glu Phe Ile Val Thr Arg Ala Gly Leu 145 150 155 160 Tyr Tyr Leu Tyr Cys Gln Val His Phe Asp Glu Gly Lys Ala Val Tyr 165 170 175 Leu Lys Leu Asp Leu Leu Val Asp Gly Val Leu Ala Leu Arg Cys Leu 180 185 190 Glu Glu Phe Ser Ala Thr Ala Ala Ser Ser Leu Gly Pro Gln Leu Arg 195 200 205 Leu Cys Gln Val Ser Gly Leu Leu Ala Leu Arg Pro Gly Ser Ser Leu 210 215 220 Arg Ile Arg Thr Leu Pro Trp Ala His Leu Lys Ala Ala Pro Phe Leu 225 230 235 240 Thr Tyr Phe Gly Leu Phe Gln Val His 245 <210> 107 <211> 250 <212> PRT <213> Homo sapiens <400> 107 Met Pro Ala Ser Ser Pro Phe Leu Leu Ala Pro Lys Gly Pro Pro Gly 1 5 10 15 Asn Met Gly Gly Pro Val Arg Glu Pro Ala Leu Ser Val Ala Leu Trp 20 25 30 Leu Ser Trp Gly Ala Ala Leu Gly Ala Val Ala Cys Ala Met Ala Leu 35 40 45 Leu Thr Gln Gln Thr Glu Leu Gln Ser Leu Arg Arg Glu Val Ser Arg 50 55 60 Leu Gln Gly Thr Gly Gly Pro Ser Gln Asn Gly Glu Gly Tyr Pro Trp 65 70 75 80 Gln Ser Leu Pro Glu Gln Ser Ser Asp Ala Leu Glu Ala Trp Glu Asn 85 90 95 Gly Glu Arg Ser Arg Lys Arg Arg Ala Val Leu Thr Gln Lys Gln Lys 100 105 110 Lys Gln His Ser Val Leu His Leu Val Pro Ile Asn Ala Thr Ser Lys 115 120 125 Asp Asp Ser Asp Val Thr Glu Val Met Trp Gln Pro Ala Leu Arg Arg 130 135 140 Gly Arg Gly Leu Gln Ala Gln Gly Tyr Gly Val Arg Ile Gln Asp Ala 145 150 155 160 Gly Val Tyr Leu Leu Tyr Ser Gln Val Leu Phe Gln Asp Val Thr Phe 165 170 175 Thr Met Gly Gln Val Val Ser Arg Glu Gly Gln Gly Arg Gln Glu Thr 180 185 190 Leu Phe Arg Cys Ile Arg Ser Met Pro Ser His Pro Asp Arg Ala Tyr 195 200 205 Asn Ser Cys Tyr Ser Ala Gly Val Phe His Leu His Gln Gly Asp Ile 210 215 220 Leu Ser Val Ile Ile Pro Arg Ala Arg Ala Lys Leu Asn Leu Ser Pro 225 230 235 240 His Gly Thr Phe Leu Gly Phe Val Lys Leu 245 250 <210> 108 <211> 285 <212> PRT <213> Homo sapiens <400> 108 Met Asp Asp Ser Thr Glu Arg Glu Gln Ser Arg Leu Thr Ser Cys Leu 1 5 10 15 Lys Lys Arg Glu Glu Met Lys Leu Lys Glu Cys Val Ser Ile Leu Pro 20 25 30 Arg Lys Glu Ser Pro Ser Val Arg Ser Ser Lys Asp Gly Lys Leu Leu 35 40 45 Ala Ala Thr Leu Leu Leu Ala Leu Leu Ser Cys Cys Leu Thr Val Val 50 55 60 Ser Phe Tyr Gln Val Ala Ala Leu Gln Gly Asp Leu Ala Ser Leu Arg 65 70 75 80 Ala Glu Leu Gln Gly His His Ala Glu Lys Leu Pro Ala Gly Ala Gly 85 90 95 Ala Pro Lys Ala Gly Leu Glu Glu Ala Pro Ala Val Thr Ala Gly Leu 100 105 110 Lys Ile Phe Glu Pro Pro Ala Pro Gly Glu Gly Asn Ser Ser Gln Asn 115 120 125 Ser Arg Asn Lys Arg Ala Val Gln Gly Pro Glu Glu Thr Val Thr Gln 130 135 140 Asp Cys Leu Gln Leu Ile Ala Asp Ser Glu Thr Pro Thr Ile Gln Lys 145 150 155 160 Gly Ser Tyr Thr Phe Val Pro Trp Leu Leu Ser Phe Lys Arg Gly Ser 165 170 175 Ala Leu Glu Glu Lys Glu Asn Lys Ile Leu Val Lys Glu Thr Gly Tyr 180 185 190 Phe Phe Ile Tyr Gly Gln Val Leu Tyr Thr Asp Lys Thr Tyr Ala Met 195 200 205 Gly His Leu Ile Gln Arg Lys Lys Val His Val Phe Gly Asp Glu Leu 210 215 220 Ser Leu Val Thr Leu Phe Arg Cys Ile Gln Asn Met Pro Glu Thr Leu 225 230 235 240 Pro Asn Asn Ser Cys Tyr Ser Ala Gly Ile Ala Lys Leu Glu Glu Gly 245 250 255 Asp Glu Leu Gln Leu Ala Ile Pro Arg Glu Asn Ala Gln Ile Ser Leu 260 265 270 Asp Gly Asp Val Thr Phe Phe Gly Ala Leu Lys Leu Leu 275 280 285 <210> 109 <211> 240 <212> PRT <213> Homo sapiens <400> 109 Met Glu Glu Ser Val Val Arg Pro Ser Val Phe Val Val Asp Gly Gln 1 5 10 15 Thr Asp Ile Pro Phe Thr Arg Leu Gly Arg Ser His Arg Arg Gln Ser 20 25 30 Cys Ser Val Ala Arg Val Gly Leu Gly Leu Leu Leu Leu Leu Met Gly 35 40 45 Ala Gly Leu Ala Val Gln Gly Trp Phe Leu Leu Gln Leu His Trp Arg 50 55 60 Leu Gly Glu Met Val Thr Arg Leu Pro Asp Gly Pro Ala Gly Ser Trp 65 70 75 80 Glu Gln Leu Ile Gln Glu Arg Arg Ser His Glu Val Asn Pro Ala Ala 85 90 95 His Leu Thr Gly Ala Asn Ser Ser Leu Thr Gly Ser Gly Gly Pro Leu 100 105 110 Leu Trp Glu Thr Gln Leu Gly Leu Ala Phe Leu Arg Gly Leu Ser Tyr 115 120 125 His Asp Gly Ala Leu Val Val Thr Lys Ala Gly Tyr Tyr Tyr Ile Tyr 130 135 140 Ser Lys Val Gln Leu Gly Gly Val Gly Cys Pro Leu Gly Leu Ala Ser 145 150 155 160 Thr Ile Thr His Gly Leu Tyr Lys Arg Thr Pro Arg Tyr Pro Glu Glu 165 170 175 Leu Glu Leu Leu Val Ser Gln Gln Ser Pro Cys Gly Arg Ala Thr Ser 180 185 190 Ser Ser Arg Val Trp Trp Asp Ser Ser Phe Leu Gly Gly Val Val His 195 200 205 Leu Glu Ala Gly Glu Lys Val Val Val Arg Val Leu Asp Glu Arg Leu 210 215 220 Val Arg Leu Arg Asp Gly Thr Arg Ser Tyr Phe Gly Ala Phe Met Val 225 230 235 240 <210> 110 <211> 251 <212> PRT <213> Homo sapiens <400> 110 Met Ala Glu Asp Leu Gly Leu Ser Phe Gly Glu Thr Ala Ser Val Glu 1 5 10 15 Met Leu Pro Glu His Gly Ser Cys Arg Pro Lys Ala Arg Ser Ser Ser 20 25 30 Ala Arg Trp Ala Leu Thr Cys Cys Leu Val Leu Leu Pro Phe Leu Ala 35 40 45 Gly Leu Thr Thr Tyr Leu Leu Val Ser Gln Leu Arg Ala Gln Gly Glu 50 55 60 Ala Cys Val Gln Phe Gln Ala Leu Lys Gly Gln Glu Phe Ala Pro Ser 65 70 75 80 His Gln Gln Val Tyr Ala Pro Leu Arg Ala Asp Gly Asp Lys Pro Arg 85 90 95 Ala His Leu Thr Val Val Arg Gln Thr Pro Thr Gln His Phe Lys Asn 100 105 110 Gln Phe Pro Ala Leu His Trp Glu His Glu Leu Gly Leu Ala Phe Thr 115 120 125 Lys Asn Arg Met Asn Tyr Thr Asn Lys Phe Leu Leu Ile Pro Glu Ser 130 135 140 Gly Asp Tyr Phe Ile Tyr Ser Gln Val Thr Phe Arg Gly Met Thr Ser 145 150 155 160 Glu Cys Ser Glu Ile Arg Gln Ala Gly Arg Pro Asn Lys Pro Asp Ser 165 170 175 Ile Thr Val Val Ile Thr Lys Val Thr Asp Ser Tyr Pro Glu Pro Thr 180 185 190 Gln Leu Leu Met Gly Thr Lys Ser Val Cys Glu Val Gly Ser Asn Trp 195 200 205 Phe Gln Pro Ile Tyr Leu Gly Ala Met Phe Ser Leu Gln Glu Gly Asp 210 215 220 Lys Leu Met Val Asn Val Ser Asp Ile Ser Leu Val Asp Tyr Thr Lys 225 230 235 240 Glu Asp Lys Thr Phe Phe Gly Ala Phe Leu Leu 245 250 <210> 111 <211> 199 <212> PRT <213> Homo sapiens <400> 111 Met Thr Leu His Pro Ser Pro Ile Thr Cys Glu Phe Leu Phe Ser Thr 1 5 10 15 Ala Leu Ile Ser Pro Lys Met Cys Leu Ser His Leu Glu Asn Met Pro 20 25 30 Leu Ser His Ser Arg Thr Gln Gly Ala Gln Arg Ser Ser Trp Lys Leu 35 40 45 Trp Leu Phe Cys Ser Ile Val Met Leu Leu Phe Leu Cys Ser Phe Ser 50 55 60 Trp Leu Ile Phe Ile Phe Leu Gln Leu Glu Thr Ala Lys Glu Pro Cys 65 70 75 80 Met Ala Lys Phe Gly Pro Leu Pro Ser Lys Trp Gln Met Ala Ser Ser 85 90 95 Glu Pro Pro Cys Val Asn Lys Val Ser Asp Trp Lys Leu Glu Ile Leu 100 105 110 Gln Asn Gly Leu Tyr Leu Ile Tyr Gly Gln Val Ala Pro Asn Ala Asn 115 120 125 Tyr Asn Asp Val Ala Pro Phe Glu Val Arg Leu Tyr Lys Asn Lys Asp 130 135 140 Met Ile Gln Thr Leu Thr Asn Lys Ser Lys Ile Gln Asn Val Gly Gly 145 150 155 160 Thr Tyr Glu Leu His Val Gly Asp Thr Ile Asp Leu Ile Phe Asn Ser 165 170 175 Glu His Gln Val Leu Lys Asn Asn Thr Tyr Trp Gly Ile Ile Leu Leu 180 185 190 Ala Asn Pro Gln Phe Ile Ser 195 <210> 112 <211> 391 <212> PRT <213> Homo sapiens <400> 112 Met Gly Tyr Pro Glu Val Glu Arg Arg Glu Leu Leu Pro Ala Ala Ala 1 5 10 15 Pro Arg Glu Arg Gly Ser Gln Gly Cys Gly Cys Gly Gly Ala Pro Ala 20 25 30 Arg Ala Gly Glu Gly Asn Ser Cys Leu Leu Phe Leu Gly Phe Phe Gly 35 40 45 Leu Ser Leu Ala Leu His Leu Leu Thr Leu Cys Cys Tyr Leu Glu Leu 50 55 60 Arg Ser Glu Leu Arg Arg Glu Arg Gly Ala Glu Ser Arg Leu Gly Gly 65 70 75 80 Ser Gly Thr Pro Gly Thr Ser Gly Thr Leu Ser Ser Leu Gly Gly Leu 85 90 95 Asp Pro Asp Ser Pro Ile Thr Ser His Leu Gly Gln Pro Ser Pro Lys 100 105 110 Gln Gln Pro Leu Glu Pro Gly Glu Ala Ala Leu His Ser Asp Ser Gln 115 120 125 Asp Gly His Gln Met Ala Leu Leu Asn Phe Phe Phe Pro Asp Glu Lys 130 135 140 Pro Tyr Ser Glu Glu Glu Ser Arg Arg Val Arg Arg Asn Lys Arg Ser 145 150 155 160 Lys Ser Asn Glu Gly Ala Asp Gly Pro Val Lys Asn Lys Lys Lys Gly 165 170 175 Lys Lys Ala Gly Pro Pro Gly Pro Asn Gly Pro Pro Gly Pro Pro Gly 180 185 190 Pro Pro Gly Pro Gln Gly Pro Pro Gly Ile Pro Gly Ile Pro Gly Ile 195 200 205 Pro Gly Thr Thr Val Met Gly Pro Pro Gly Pro Pro Gly Pro Pro Gly 210 215 220 Pro Gln Gly Pro Pro Gly Leu Gln Gly Pro Ser Gly Ala Ala Asp Lys 225 230 235 240 Ala Gly Thr Arg Glu Asn Gln Pro Ala Val Val His Leu Gln Gly Gln 245 250 255 Gly Ser Ala Ile Gln Val Lys Asn Asp Leu Ser Gly Gly Val Leu Asn 260 265 270 Asp Trp Ser Arg Ile Thr Met Asn Pro Lys Val Phe Lys Leu His Pro 275 280 285 Arg Ser Gly Glu Leu Glu Val Leu Val Asp Gly Thr Tyr Phe Ile Tyr 290 295 300 Ser Gln Val Glu Val Tyr Tyr Ile Asn Phe Thr Asp Phe Ala Ser Tyr 305 310 315 320 Glu Val Val Val Asp Glu Lys Pro Phe Leu Gln Cys Thr Arg Ser Ile 325 330 335 Glu Thr Gly Lys Thr Asn Tyr Asn Thr Cys Tyr Thr Ala Gly Val Cys 340 345 350 Leu Leu Lys Ala Arg Gln Lys Ile Ala Val Lys Met Val His Ala Asp 355 360 365 Ile Ser Ile Asn Met Ser Lys His Thr Thr Phe Phe Gly Ala Ile Arg 370 375 380 Leu Gly Glu Ala Pro Ala Ser 385 390 <210> 113 <211> 205 <212> PRT <213> Homo sapiens <400> 113 Ala Cys Pro Trp Ala Val Ser Gly Ala Arg Ala Ser Pro Gly Ser Ala 1 5 10 15 Ala Ser Pro Arg Leu Arg Glu Gly Pro Glu Leu Ser Pro Asp Asp Pro 20 25 30 Ala Gly Leu Leu Asp Leu Arg Gln Gly Met Phe Ala Gln Leu Val Ala 35 40 45 Gln Asn Val Leu Leu Ile Asp Gly Pro Leu Ser Trp Tyr Ser Asp Pro 50 55 60 Gly Leu Ala Gly Val Ser Leu Thr Gly Gly Leu Ser Tyr Lys Glu Asp 65 70 75 80 Thr Lys Glu Leu Val Val Ala Lys Ala Gly Val Tyr Tyr Val Phe Phe 85 90 95 Gln Leu Glu Leu Arg Arg Val Val Ala Gly Glu Gly Ser Gly Ser Val 100 105 110 Ser Leu Ala Leu His Leu Gln Pro Leu Arg Ser Ala Ala Gly Ala Ala 115 120 125 Ala Leu Ala Leu Thr Val Asp Leu Pro Pro Ala Ser Ser Glu Ala Arg 130 135 140 Asn Ser Ala Phe Gly Phe Gln Gly Arg Leu Leu His Leu Ser Ala Gly 145 150 155 160 Gln Arg Leu Gly Val His Leu His Thr Glu Ala Arg Ala Arg His Ala 165 170 175 Trp Gln Leu Thr Gln Gly Ala Thr Val Leu Gly Leu Phe Arg Val Thr 180 185 190 Pro Glu Ile Pro Ala Gly Leu Pro Ser Pro Arg Ser Glu 195 200 205 <210> 114 <211> 133 <212> PRT <213> Homo sapiens <400> 114 Gln Val Ser His Arg Tyr Pro Arg Ile Gln Ser Ile Lys Val Gln Phe 1 5 10 15 Thr Glu Tyr Lys Lys Glu Lys Gly Phe Ile Leu Thr Ser Gln Lys Glu 20 25 30 Asp Glu Ile Met Lys Val Gln Asn Asn Ser Val Ile Ile Asn Cys Asp 35 40 45 Gly Phe Tyr Leu Ile Ser Leu Lys Gly Tyr Phe Ser Gln Glu Val Asn 50 55 60 Ile Ser Leu His Tyr Gln Lys Asp Glu Glu Pro Leu Phe Gln Leu Lys 65 70 75 80 Lys Val Arg Ser Val Asn Ser Leu Met Val Ala Ser Leu Thr Tyr Lys 85 90 95 Asp Lys Val Tyr Leu Asn Val Thr Thr Asp Asn Thr Ser Leu Asp Asp 100 105 110 Phe His Val Asn Gly Gly Glu Leu Ile Leu Ile His Gln Asn Pro Gly 115 120 125 Glu Phe Cys Val Leu 130 <210> 115 <211> 132 <212> PRT <213> Homo sapiens <400> 115 Val Ser His Arg Tyr Pro Arg Ile Gln Ser Ile Lys Val Gln Phe Thr 1 5 10 15 Glu Tyr Lys Lys Glu Lys Gly Phe Ile Leu Thr Ser Gln Lys Glu Asp 20 25 30 Glu Ile Met Lys Val Gln Asn Asn Ser Val Ile Ile Asn Cys Asp Gly 35 40 45 Phe Tyr Leu Ile Ser Leu Lys Gly Tyr Phe Ser Gln Glu Val Asn Ile 50 55 60 Ser Leu His Tyr Gln Lys Asp Glu Glu Pro Leu Phe Gln Leu Lys Lys 65 70 75 80 Val Arg Ser Val Asn Ser Leu Met Val Ala Ser Leu Thr Tyr Lys Asp 85 90 95 Lys Val Tyr Leu Asn Val Thr Thr Asp Asn Thr Ser Leu Asp Asp Phe 100 105 110 His Val Asn Gly Gly Glu Leu Ile Leu Ile His Gln Asn Pro Gly Glu 115 120 125 Phe Cys Val Leu 130 <210> 116 <211> 5 <212> PRT <213> Secuencia artificial <220> <223> Enlazador peptídico G4S <400> 116 Gly Gly Gly Gly Ser 1 5 <210> 117 <211> 10 <212> PRT <213> Secuencia artificial <220> <223> Enlazador peptídico (G4S)2 <400> 117 Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser 1 5 10 <210> 118 <211> 10 <212> PRT <213> Secuencia artificial <220> <223> Enlazador peptídico (SG4)2 <400> 118 Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly 1 5 10 <210> 119 <211> 15 <212> PRT <213> Secuencia artificial <220> <223> Enlazador peptídico (G4S)3 <400> 119 Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser 1 5 10 15 <210> 120 <211> 14 <212> PRT <213> Secuencia artificial <220> <223> Enlazador peptídico G4(SG4)2 <400> 120 Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly 1 5 10 <210> 121 <211> 20 <212> PRT <213> Secuencia artificial <220> <223> Enlazador peptídico (G4S)4 <400> 121 Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly 1 5 10 15 Gly Gly Gly Ser 20 <210> 122 <211> 10 <212> PRT <213> Secuencia artificial <220> <223> Enlazador peptídico GSPGSSSSGS <400> 122 Gly Ser Pro Gly Ser Ser Ser Ser Gly Ser 1 5 10 <210> 123 <211> 8 <212> PRT <213> Secuencia artificial <220> <223> Enlazador peptídico GSGSGSGS <400> 123 Gly Ser Gly Ser Gly Ser Gly Ser 1 5 <210> 124 <211> 8 <212> PRT <213> Secuencia artificial <220> <223> Enlazador peptídico GSGSGNGS <400> 124 Gly Ser Gly Ser Gly Asn Gly Ser 1 5 <210> 125 <211> 8 <212> PRT <213> Secuencia artificial <220> <223> Enlazador peptídico GGSGSGSG <400> 125 Gly Gly Ser Gly Ser Gly Ser Gly 1 5 <210> 126 <211> 6 <212> PRT <213> Secuencia artificial <220> <223> Enlazador peptídico GGSGSG <400> 126 Gly Gly Ser Gly Ser Gly 1 5 <210> 127 <211> 4 <212> PRT <213> Secuencia artificial <220> <223> Enlazador peptídico GGSG <400> 127 Gly Gly Ser Gly 1 <210> 128 <211> 8 <212> PRT <213> Secuencia artificial <220> <223> GGSGNGSG <400> 128 Gly Gly Ser Gly Asn Gly Ser Gly 1 5 <210> 129 <211> 8 <212> PRT <213> Secuencia artificial <220> <223> Enlazador peptídico GGNGSGSG <400> 129 Gly Gly Asn Gly Ser Gly Ser Gly 1 5 <210> 130 <211> 6 <212> PRT <213> Secuencia artificial <220> <223> Enlazador peptídico GGNGSG <400> 130 Gly Gly Asn Gly Ser Gly 1 5 <210> 131 <211> 2166 <212> ADN <213> Secuencia artificial <220> <223> Secuencia de nucleótidos de 4-1BBL hu dimérico (71-254) - CL cadena pomo * Fc chain <400> 131 agagagggcc ctgagctgag ccccgatgat cctgctggac tgctggacct gcggcagggc 60 atgtttgctc agctggtggc ccagaacgtg ctgctgatcg atggccccct gtcctggtac 120 agcgatcctg gactggctgg cgtgtcactg acaggcggcc tgagctacaa agaggacacc 180 aaagaactgg tggtggccaa ggccggcgtg tactacgtgt tctttcagct ggaactgcgg 240 agagtggtgg ccggcgaagg atctggctct gtgtctctgg ccctgcatct gcagcctctg 300 agaagcgctg ctggcgctgc agctctggca ctgacagtgg atctgcctcc tgccagctcc 360 gaggcccgga atagcgcatt tgggtttcaa ggcaggctgc tgcacctgtc tgccggccag 420 aggctgggag tgcatctgca cacagaggcc agggctagac acgcctggca gctgacacag 480 ggcgctacag tgctgggcct gttcagagtg acccccgaga ttccagccgg cctgccttct 540 ccaagaagcg aaggcggagg cggatctggc ggcggaggat ctagagaggg acccgaactg 600 tcccctgacg atccagccgg gctgctggat ctgagacagg gaatgttcgc ccagctggtg 660 gctcagaatg tgctgctgat tgacggacct ctgagctggt actccgaccc agggctggca 720 ggggtgtccc tgactggggg actgtcctac aaagaagata caaaagaact ggtggtggct 780 aaagctgggg tgtactatgt gttttttcag ctggaactga ggcgggtggt ggctggggag 840 ggctcaggat ctgtgtccct ggctctgcat ctgcagccac tgcgctctgc tgctggcgca 900 gctgcactgg ctctgactgt ggacctgcca ccagcctcta gcgaggccag aaacagcgcc 960 ttcgggttcc aaggacgcct gctgcatctg agcgccggac agcgcctggg agtgcatctg 1020 catactgaag ccagagcccg gcatgcttgg cagctgactc agggggcaac tgtgctggga 1080 ctgtttcgcg tgacacctga gatccctgcc ggactgccaa gccctagatc agaagggggc 1140 ggaggttccg gagggggagg atctcgtacg gtggctgcac catctgtctt tatcttccca 1200 cccagcgacc ggaagctgaa gtctggcaca gccagcgtcg tgtgcctgct gaataacttc 1260 tacccccgcg aggccaaggt gcagtggaag gtggacaatg ccctgcagag cggcaacagc 1320 caggaaagcg tgaccgagca ggacagcaag gactccacct acagcctgag cagcaccctg 1380 accctgagca aggccgacta cgagaagcac aaggtgtacg cctgcgaagt gacccaccag 1440 ggcctgtcta gccccgtgac caagagcttc aaccggggcg agtgcgacaa gacccacacc 1500 tgtcctccat gccctgcccc tgaagctgct ggcggcccta gcgtgttcct gttcccccca 1560 aagcccaagg acaccctgat gatcagccgg acccctgaag tgacctgcgt ggtggtggat 1620 gtgtcccacg aggaccctga agtgaagttc aattggtacg tggacggcgt ggaagtgcac 1680 aatgccaaga ccaagccgcg ggaggagcag tacaacagca cgtaccgtgt ggtcagcgtc 1740 ctcaccgtcc tgcaccagga ctggctgaat ggcaaggagt acaagtgcaa ggtctccaac 1800 aaagccctcg gcgcccccat cgagaaaacc atctccaaag ccaaagggca gccccgagaa 1860 ccacaggtgt acaccctgcc cccatgccgg gatgagctga ccaagaacca ggtcagcctg 1920 tggtgcctgg tcaaaggctt ctatcccagc gacatcgccg tggagtggga gagcaatggg 1980 cagccggaga acaactacaa gaccacgcct cccgtgctgg actccgacgg ctccttcttc 2040 ctctacagca agctcaccgt ggacaagagc aggtggcagc aggggaacgt cttctcatgc 2100 tccgtgatgc atgaggctct gcacaaccac tacacgcaga agagcctctc cctgtctccg 2160 ggtaaa 2166 <210> 132 <211> 891 <212> ADN <213> Secuencia artificial <220> <223> secuencia de nucleótidos de 4-1BBL hu monomérico (71-254) - CH1* <400> 132 agagagggcc ctgagctgag ccccgatgat cctgctggac tgctggacct gcggcagggc 60 atgtttgctc agctggtggc ccagaacgtg ctgctgatcg atggccccct gtcctggtac 120 agcgatcctg gactggctgg cgtgtcactg acaggcggcc tgagctacaa agaggacacc 180 aaagaactgg tggtggccaa ggccggcgtg tactacgtgt tctttcagct ggaactgcgg 240 agagtggtgg ccggcgaagg atctggctct gtgtctctgg ccctgcatct gcagcctctg 300 agaagcgctg ctggcgctgc agctctggct ctgacagtgg atctgcctcc tgccagctcc 360 gaggcccgga atagcgcatt tgggtttcaa ggccggctgc tgcacctgtc tgccggccag 420 agactgggag tgcatctgca cacagaggcc agagccaggc acgcctggca gctgacacag 480 ggcgctacag tgctgggcct gttcagagtg acccccgaga ttcctgccgg cctgcctagc 540 cctagatctg aaggcggcgg aggttccgga ggcggaggat ctgctagcac aaagggcccc 600 agcgtgttcc ctctggcccc tagcagcaag agcacatctg gcggaacagc cgccctgggc 660 tgcctggtgg aagattactt ccccgagccc gtgaccgtgt cctggaattc tggcgccctg 720 acaagcggcg tgcacacctt tccagccgtg ctgcagagca gcggcctgta ctctctgagc 780 agcgtcgtga cagtgcccag cagctctctg ggcacccaga cctacatctg caacgtgaac 840 cacaagccca gcaacaccaa ggtggacgag aaggtggaac ccaagtcctg c 891 <210> 133 <211> 1350 <212> ADN <213> Secuencia artificial <220> <223> secuencia de nucleótidos de cadena pomo Fc de anti-PD1 (0314) <400> 133 gaagtgcagc tgctcgaaag cggcggggga ctggtccagc ccggcggttc cctgaggctg 60 tcttgcgccg cttcagggtt cagcttttcc tcttacacca tgagttgggt cagacaggca 120 cctggcaagg gactggagtg ggtcgccaca atcagcggtg gcgggcgcga catttattac 180 ccagattccg tgaaaggacg gttcaccatc tctagggaca actcaaagaa tactctgtat 240 ttgcagatga acagcctgag agctgaggat acagcagttt actactgtgt gctcctgacc 300 ggccgcgtct attttgccct tgactcctgg ggacaaggca ctctggtgac cgtatctagt 360 gctagcacca agggcccctc cgtgttcccc ctggccccca gcagcaagag caccagcggc 420 ggcacagccg ctctgggctg cctggtcaag gactacttcc ccgagcccgt gaccgtgtcc 480 tggaacagcg gagccctgac ctccggcgtg cacaccttcc ccgccgtgct gcagagttct 540 ggcctgtata gcctgagcag cgtggtcacc gtgccttcta gcagcctggg cacccagacc 600 tacatctgca acgtgaacca caagcccagc aacaccaagg tggacaagaa ggtggagccc 660 aagagctgcg acaaaactca cacatgccca ccgtgcccag cacctgaagc tgcaggggga 720 ccgtcagtct tcctcttccc cccaaaaccc aaggacaccc tcatgatctc ccggacccct 780 gaggtcacat gcgtggtggt ggacgtgagc cacgaagacc ctgaggtcaa gttcaactgg 840 tacgtggacg gcgtggaggt gcataatgcc aagacaaagc cgcgggagga gcagtacaac 900 agcacgtacc gtgtggtcag cgtcctcacc gtcctgcacc aggactggct gaatggcaag 960 gagtacaagt gcaaggtctc caacaaagcc ctcggcgccc ccatcgagaa aaccatctcc 1020 aaagccaaag ggcagccccg agaaccacag gtgtgcaccc tgcccccatc ccgggatgag 1080 ctgaccaaga accaggtcag cctctcgtgc gcagtcaaag gcttctatcc cagcgacatc 1140 gccgtggagt gggagagcaa tgggcagccg gagaacaact acaagaccac gcctcccgtg 1200 ctggactccg acggctcctt cttcctcgtg agcaagctca ccgtggacaa gagcaggtgg 1260 cagcagggga acgtcttctc atgctccgtg atgcatgagg ctctgcacaa ccactacacg 1320 cagaagagcc tctccctgtc tccgggtaaa 1350 <210> 134 <211> 654 <212> ADN <213> Secuencia artificial <220> <223> secuencia de nucleótidos de cadena ligera de anti-PD1 (0314) <400> 134 gagatcgtgc tgacccagag ccccgccaca ctctccctgt ctcctggcga aagggctacc 60 ctttcatgca gagcaagcga gtccgtggac acttctgata acagtttcat tcactggtat 120 cagcagaagc cagggcagag cccccgcctg ctcatctatc ggtcctctac actggagtca 180 gggattcctg ccaggtttag cggctccggt tctgggaccg acttcacttt gaccatcagt 240 agcctggaac cagaggattt tgctgtgtac tattgtcaac agaattacga cgtcccctgg 300 acattcggcc agggaaccaa agtggagata aagcgtacgg tggctgcacc atctgtcttc 360 atcttcccgc catctgatga gcagttgaaa tctggaactg cctctgttgt gtgcctgctg 420 aataacttct atcccagaga ggccaaagta cagtggaagg tggataacgc cctccaatcg 480 ggtaactccc aggagagtgt cacagagcag gacagcaagg acagcaccta cagcctcagc 540 agcaccctga cgctgagcaa agcagactac gagaaacaca aagtctacgc ctgcgaagtc 600 acccatcagg gcctgagctc gcccgtcaca aagagcttca acaggggaga gtgt 654 <210> 135 <211> 2166 <212> ADN <213> Secuencia artificial <220> <223> Secuencia de nucleótidos de 4-1BBL hu dimérico (71-254) - CL cadena pomo Fc chain <400> 135 agagagggcc ctgagctgag ccccgatgat cctgctggac tgctggacct gcggcagggc 60 atgtttgctc agctggtggc ccagaacgtg ctgctgatcg atggccccct gtcctggtac 120 agcgatcctg gactggctgg cgtgtcactg acaggcggcc tgagctacaa agaggacacc 180 aaagaactgg tggtggccaa ggccggcgtg tactacgtgt tctttcagct ggaactgcgg 240 agagtggtgg ccggcgaagg atctggctct gtgtctctgg ccctgcatct gcagcctctg 300 agaagcgctg ctggcgctgc agctctggca ctgacagtgg atctgcctcc tgccagctcc 360 gaggcccgga atagcgcatt tgggtttcaa ggcaggctgc tgcacctgtc tgccggccag 420 aggctgggag tgcatctgca cacagaggcc agggctagac acgcctggca gctgacacag 480 ggcgctacag tgctgggcct gttcagagtg acccccgaga ttccagccgg cctgccttct 540 ccaagaagcg aaggcggagg cggatctggc ggcggaggat ctagagaggg acccgaactg 600 tcccctgacg atccagccgg gctgctggat ctgagacagg gaatgttcgc ccagctggtg 660 gctcagaatg tgctgctgat tgacggacct ctgagctggt actccgaccc agggctggca 720 ggggtgtccc tgactggggg actgtcctac aaagaagata caaaagaact ggtggtggct 780 aaagctgggg tgtactatgt gttttttcag ctggaactga ggcgggtggt ggctggggag 840 ggctcaggat ctgtgtccct ggctctgcat ctgcagccac tgcgctctgc tgctggcgca 900 gctgcactgg ctctgactgt ggacctgcca ccagcctcta gcgaggccag aaacagcgcc 960 ttcgggttcc aaggacgcct gctgcatctg agcgccggac agcgcctggg agtgcatctg 1020 catactgaag ccagagcccg gcatgcttgg cagctgactc agggggcaac tgtgctggga 1080 ctgtttcgcg tgacacctga gatccctgcc ggactgccaa gccctagatc agaagggggc 1140 ggaggttccg gagggggagg atctcgtacg gtggccgctc cctccgtgtt tatctttccc 1200 ccatccgatg aacagctgaa aagcggcacc gcctccgtcg tgtgtctgct gaacaatttt 1260 taccctaggg aagctaaagt gcagtggaaa gtggataacg cactgcagtc cggcaactcc 1320 caggaatctg tgacagaaca ggactccaag gacagcacct actccctgtc ctccaccctg 1380 acactgtcta aggctgatta tgagaaacac aaagtctacg cctgcgaagt cacccatcag 1440 ggcctgagct cgcccgtcac aaagagcttc aacaggggag agtgtgacaa gacccacacc 1500 tgtccccctt gtcctgcccc tgaagctgct ggcggccctt ctgtgttcct gttcccccca 1560 aagcccaagg acaccctgat gatcagccgg acccccgaag tgacctgcgt ggtggtggat 1620 gtgtcccacg aggaccctga agtgaagttc aattggtacg tggacggcgt ggaagtgcac 1680 aatgccaaga ccaagccgcg ggaggagcag tacaacagca cgtaccgtgt ggtcagcgtc 1740 ctcaccgtcc tgcaccagga ctggctgaat ggcaaggagt acaagtgcaa ggtctccaac 1800 aaagccctcg gcgcccccat cgagaaaacc atctccaaag ccaaagggca gccccgagaa 1860 ccacaggtgt acaccctgcc cccatgccgg gatgagctga ccaagaacca ggtcagcctg 1920 tggtgcctgg tcaaaggctt ctatcccagc gacatcgccg tggagtggga gagcaatggg 1980 cagccggaga acaactacaa gaccacgcct cccgtgctgg actccgacgg ctccttcttc 2040 ctctacagca agctcaccgt ggacaagagc aggtggcagc aggggaacgt cttctcatgc 2100 tccgtgatgc atgaggctct gcacaaccac tacacgcaga agagcctctc cctgtctccg 2160 ggtaaa 2166 <210> 136 <211> 891 <212> ADN <213> Secuencia artificial <220> <223> secuencia de nucleótidos de 4-1BBL hu monomérico (71-254) - CH1 <400> 136 agagagggcc ctgagctgag ccccgatgat cctgctggac tgctggacct gcggcagggc 60 atgtttgctc agctggtggc ccagaacgtg ctgctgatcg atggccccct gtcctggtac 120 agcgatcctg gactggctgg cgtgtcactg acaggcggcc tgagctacaa agaggacacc 180 aaagaactgg tggtggccaa ggccggcgtg tactacgtgt tctttcagct ggaactgcgg 240 agagtggtgg ccggcgaagg atctggctct gtgtctctgg ccctgcatct gcagcctctg 300 agaagcgctg ctggcgctgc agctctggct ctgacagtgg atctgcctcc tgccagctcc 360 gaggcccgga atagcgcatt tgggtttcaa ggccggctgc tgcacctgtc tgccggccag 420 agactgggag tgcatctgca cacagaggcc agagccaggc acgcctggca gctgacacag 480 ggcgctacag tgctgggcct gttcagagtg acccccgaga ttcctgccgg cctgcctagc 540 cctagatctg aaggcggcgg aggttccgga ggcggaggat ctgctagcac caaaggccct 600 tccgtgtttc ctctggctcc tagctccaag tccacctctg gaggcaccgc tgctctcgga 660 tgcctcgtga aggattattt tcctgagcct gtgacagtgt cctggaatag cggagcactg 720 acctctggag tgcatacttt ccccgctgtg ctgcagtcct ctggactgta cagcctgagc 780 agcgtggtga cagtgcccag cagcagcctg ggcacccaga cctacatctg caacgtgaac 840 cacaagccca gcaacaccaa ggtggacaag aaggtggaac ccaagtcttg t 891 <210> 137 <211> 2511 <212> ADN <213> Secuencia artificial <220> <223> secuencia de nucleótidos de cadena agujero Fc de anti-PD1 (0314) condensada a 4-1BBL hu dimérico (71-254) <400> 137 gaagtgcagc tgctcgaaag cggcggggga ctggtccagc ccggcggttc cctgaggctg 60 tcttgcgccg cttcagggtt cagcttttcc tcttacacca tgagttgggt cagacaggca 120 cctggcaagg gactggagtg ggtcgccaca atcagcggtg gcgggcgcga catttattac 180 ccagattccg tgaaaggacg gttcaccatc tctagggaca actcaaagaa tactctgtat 240 ttgcagatga acagcctgag agctgaggat acagcagttt actactgtgt gctcctgacc 300 ggccgcgtct attttgccct tgactcctgg ggacaaggca ctctggtgac cgtatctagt 360 gctagcacca agggcccctc cgtgttcccc ctggccccca gcagcaagag caccagcggc 420 ggcacagccg ctctgggctg cctggtcaag gactacttcc ccgagcccgt gaccgtgtcc 480 tggaacagcg gagccctgac ctccggcgtg cacaccttcc ccgccgtgct gcagagttct 540 ggcctgtata gcctgagcag cgtggtcacc gtgccttcta gcagcctggg cacccagacc 600 tacatctgca acgtgaacca caagcccagc aacaccaagg tggacaagaa ggtggagccc 660 aagagctgcg acaaaactca cacatgccca ccgtgcccag cacctgaagc tgcaggggga 720 ccgtcagtct tcctcttccc cccaaaaccc aaggacaccc tcatgatctc ccggacccct 780 gaggtcacat gcgtggtggt ggacgtgagc cacgaagacc ctgaggtcaa gttcaactgg 840 tacgtggacg gcgtggaggt gcataatgcc aagacaaagc cgcgggagga gcagtacaac 900 agcacgtacc gtgtggtcag cgtcctcacc gtcctgcacc aggactggct gaatggcaag 960 gagtacaagt gcaaggtctc caacaaagcc ctcggcgccc ccatcgagaa aaccatctcc 1020 aaagccaaag ggcagccccg agaaccacag gtgtgcaccc tgcccccatc ccgggatgag 1080 ctgaccaaga accaggtcag cctctcgtgc gcagtcaaag gcttctatcc cagcgacatc 1140 gccgtggagt gggagagcaa tgggcagccg gagaacaact acaagaccac gcctcccgtg 1200 ctggactccg acggctcctt cttcctcgtg agcaagctca ccgtggacaa gagcaggtgg 1260 cagcagggga acgtcttctc atgctccgtg atgcatgagg ctctgcacaa ccactacacg 1320 cagaagagcc tctccctgtc tccgggtgga ggcggcggaa gcggaggagg aggatccaga 1380 gagggccctg agctgagccc cgatgatcct gctggactgc tggacctgcg gcagggcatg 1440 tttgctcagc tggtggccca gaacgtgctg ctgatcgatg gccccctgtc ctggtacagc 1500 gatcctggac tggctggcgt gtcactgaca ggcggcctga gctacaaaga ggacaccaaa 1560 gaactggtgg tggccaaggc cggcgtgtac tacgtgttct ttcagctgga actgcggaga 1620 gtggtggccg gcgaaggatc tggctctgtg tctctggccc tgcatctgca gcctctgaga 1680 agcgctgctg gcgctgcagc tctggcactg acagtggatc tgcctcctgc cagctccgag 1740 gcccggaata gcgcatttgg gtttcaaggc aggctgctgc acctgtctgc cggccagagg 1800 ctgggagtgc atctgcacac agaggccagg gctagacacg cctggcagct gacacagggc 1860 gctacagtgc tgggcctgtt cagagtgacc cccgagattc cagccggcct gccttctcca 1920 agaagcgaag gcggaggcgg atctggcggc ggaggatcta gagagggacc cgaactgtcc 1980 cctgacgatc cagccgggct gctggatctg agacagggaa tgttcgccca gctggtggct 2040 cagaatgtgc tgctgattga cggacctctg agctggtact ccgacccagg gctggcaggg 2100 gtgtccctga ctgggggact gtcctacaaa gaagatacaa aagaactggt ggtggctaaa 2160 gctggggtgt actatgtgtt ttttcagctg gaactgaggc gggtggtggc tggggagggc 2220 tcaggatctg tgtccctggc tctgcatctg cagccactgc gctctgctgc tggcgcagct 2280 gcactggctc tgactgtgga cctgccacca gcctctagcg aggccagaaa cagcgccttc 2340 gggttccaag gacgcctgct gcatctgagc gccggacagc gcctgggagt gcatctgcat 2400 actgaagcca gagcccggca tgcttggcag ctgactcagg gggcaactgt gctgggactg 2460 tttcgcgtga cacctgagat ccctgccgga ctgccaagcc ctagatcaga a 2511 <210> 138 <211> 1929 <212> ADN <213> Secuencia artificial <220> <223> secuencia de nucleótidos de cadena pomo Fc de anti-PD1 (0314) condensada a 4-1BBL hu monomérico (71-254) <400> 138 gaagtgcagc tgctcgaaag cggcggggga ctggtccagc ccggcggttc cctgaggctg 60 tcttgcgccg cttcagggtt cagcttttcc tcttacacca tgagttgggt cagacaggca 120 cctggcaagg gactggagtg ggtcgccaca atcagcggtg gcgggcgcga catttattac 180 ccagattccg tgaaaggacg gttcaccatc tctagggaca actcaaagaa tactctgtat 240 ttgcagatga acagcctgag agctgaggat acagcagttt actactgtgt gctcctgacc 300 ggccgcgtct attttgccct tgactcctgg ggacaaggca ctctggtgac cgtatctagt 360 gctagcacca agggcccatc ggtcttcccc ctggcaccct cctccaagag cacctctggg 420 ggcacagcgg ccctgggctg cctggtcaag gactacttcc ccgaaccggt gacggtgtcg 480 tggaactcag gcgccctgac cagcggcgtg cacaccttcc cggctgtcct acagtcctca 540 ggactctact ccctcagcag cgtggtgacc gtgccctcca gcagcttggg cacccagacc 600 tacatctgca acgtgaatca caagcccagc aacaccaagg tggacaagaa agttgagccc 660 aaatcttgtg acaaaactca cacatgccca ccgtgcccag cacctgaagc tgcaggggga 720 ccgtcagtct tcctcttccc cccaaaaccc aaggacaccc tcatgatctc ccggacccct 780 gaggtcacat gcgtggtggt ggacgtgagc cacgaagacc ctgaggtcaa gttcaactgg 840 tacgtggacg gcgtggaggt gcataatgcc aagacaaagc cgcgggagga gcagtacaac 900 agcacgtacc gtgtggtcag cgtcctcacc gtcctgcacc aggactggct gaatggcaag 960 gagtacaagt gcaaggtctc caacaaagcc ctcggcgccc ccatcgagaa aaccatctcc 1020 aaagccaaag ggcagccccg agaaccacag gtgtacaccc tgcccccctg cagagatgag 1080 ctgaccaaga accaggtgtc cctgtggtgt ctggtcaagg gcttctaccc cagcgatatc 1140 gccgtggagt gggagagcaa cggccagcct gagaacaact acaagaccac cccccctgtg 1200 ctggacagcg acggcagctt cttcctgtac tccaaactga ccgtggacaa gagccggtgg 1260 cagcagggca acgtgttcag ctgcagcgtg atgcacgagg ccctgcacaa ccactacacc 1320 cagaagtccc tgagcctgag ccccggcgga ggcggcggaa gcggaggagg aggatccaga 1380 gagggccctg agctgagccc cgatgatcct gctggactgc tggacctgcg gcagggcatg 1440 tttgctcagc tggtggccca gaacgtgctg ctgatcgatg gccccctgtc ctggtacagc 1500 gatcctggac tggctggcgt gtcactgaca ggcggcctga gctacaaaga ggacaccaaa 1560 gaactggtgg tggccaaggc cggcgtgtac tacgtgttct ttcagctgga actgcggaga 1620 gtggtggccg gcgaaggatc tggctctgtg tctctggccc tgcatctgca gcctctgaga 1680 agcgctgctg gcgctgcagc tctggcactg acagtggatc tgcctcctgc cagctccgag 1740 gcccggaata gcgcatttgg gtttcaaggc aggctgctgc acctgtctgc cggccagagg 1800 ctgggagtgc atctgcacac agaggccagg gctagacacg cctggcagct gacacagggc 1860 gctacagtgc tgggcctgtt cagagtgacc cccgagattc cagccggcct gccttctcca 1920 agaagcgaa 1929 <210> 139 <211> 2130 <212> ADN <213> Secuencia artificial <220> <223> Secuencia de nucleótidos de 4-1BBL hu dimérico (71-248) - CL cadena pomo * Fc chain <400> 139 agagagggcc ctgagctgag ccccgatgat cctgctggac tgctggacct gcggcagggc 60 atgtttgctc agctggtggc ccagaacgtg ctgctgatcg atggccccct gtcctggtac 120 agcgatcctg gactggctgg cgtgtcactg acaggcggcc tgagctacaa agaggacacc 180 aaagaactgg tggtggccaa ggccggcgtg tactacgtgt tctttcagct ggaactgcgg 240 agagtggtgg ccggcgaagg atctggctct gtgtctctgg ccctgcatct gcagcctctg 300 agatctgctg ctggcgccgc tgctctggca ctgacagtgg atctgcctcc tgccagcagc 360 gaggcccgga atagcgcatt tgggtttcaa ggcaggctgc tgcacctgtc tgccggccag 420 aggctgggag tgcatctgca cacagaggcc agggctagac acgcctggca gctgacacag 480 ggcgctacag tgctgggcct gttcagagtg acccccgaga ttccagccgg actgggaggc 540 ggcggatctg gcggcggagg atctagagaa ggacccgagc tgtcccctga cgatccagcc 600 gggctgctgg atctgagaca gggaatgttc gcccagctgg tggctcagaa tgtgctgctg 660 attgacggac ctctgagctg gtactccgac ccagggctgg caggggtgtc cctgactggg 720 ggactgtcct acaaagaaga tacaaaagaa ctggtggtgg ctaaagctgg ggtgtactat 780 gtgttttttc agctggaact gaggcgggtg gtggctgggg agggctcagg atctgtgtcc 840 ctggctctgc atctgcagcc actgcgctct gcagcagggg ctgcagcact ggccctgact 900 gtggacctgc ccccagcttc ttccgaggcc agaaacagcg ccttcgggtt ccaaggacgc 960 ctgctgcatc tgagcgccgg acagcgcctg ggagtgcatc tgcatactga agccagagcc 1020 cggcatgctt ggcagctgac tcagggggca actgtgctgg gactgtttcg cgtgacacct 1080 gagatccccg ctggactggg cggaggcggt tccggagggg gaggatctcg tacggtggct 1140 gcaccatctg tctttatctt cccacccagc gaccggaagc tgaagtctgg cacagccagc 1200 gtcgtgtgcc tgctgaataa cttctacccc cgcgaggcca aggtgcagtg gaaggtggac 1260 aatgccctgc agagcggcaa cagccaggaa agcgtgaccg agcaggacag caaggactcc 1320 acctacagcc tgagcagcac cctgaccctg agcaaggccg actacgagaa gcacaaggtg 1380 tacgcctgcg aagtgaccca ccagggcctg tctagccccg tgaccaagag cttcaaccgg 1440 ggcgagtgcg acaagaccca cacctgtcct ccatgccctg cccctgaagc tgctggcggc 1500 cctagcgtgt tcctgttccc cccaaagccc aaggacaccc tgatgatcag ccggacccct 1560 gaagtgacct gcgtggtggt ggatgtgtcc cacgaggacc ctgaagtgaa gttcaattgg 1620 tacgtggacg gcgtggaagt gcacaatgcc aagaccaagc cgcgggagga gcagtacaac 1680 agcacgtacc gtgtggtcag cgtcctcacc gtcctgcacc aggactggct gaatggcaag 1740 gagtacaagt gcaaggtctc caacaaagcc ctcggcgccc ccatcgagaa aaccatctcc 1800 aaagccaaag ggcagccccg agaaccacag gtgtacaccc tgcccccatg ccgggatgag 1860 ctgaccaaga accaggtcag cctgtggtgc ctggtcaaag gcttctatcc cagcgacatc 1920 gccgtggagt gggagagcaa tgggcagccg gagaacaact acaagaccac gcctcccgtg 1980 ctggactccg acggctcctt cttcctctac agcaagctca ccgtggacaa gagcaggtgg 2040 cagcagggga acgtcttctc atgctccgtg atgcatgagg ctctgcacaa ccactacacg 2100 cagaagagcc tctccctgtc tccgggtaaa 2130 <210> 140 <211> 873 <212> ADN <213> Secuencia artificial <220> <223> secuencia de nucleótidos de 4-1BBL hu monomérico (71-248) - CH1* <400> 140 agagagggcc ctgagctgag ccccgatgat cctgctggac tgctggacct gcggcagggc 60 atgtttgctc agctggtggc ccagaacgtg ctgctgatcg atggccccct gtcctggtac 120 agcgatcctg gactggctgg cgtgtcactg acaggcggcc tgagctacaa agaggacacc 180 aaagaactgg tggtggccaa ggccggcgtg tactacgtgt tctttcagct ggaactgcgg 240 agagtggtgg ccggcgaagg atctggctct gtgtctctgg ccctgcatct gcagcctctg 300 agatctgctg ctggcgccgc tgctctggca ctgacagtgg atctgcctcc tgccagcagc 360 gaggcccgga atagcgcatt tgggtttcaa ggcaggctgc tgcacctgtc tgccggccag 420 aggctgggag tgcatctgca cacagaggcc agggctagac acgcctggca gctgacacag 480 ggcgctacag tgctgggcct gttcagagtg acccccgaga ttccagccgg actgggaggc 540 ggaggttccg gaggcggagg atctgctagc acaaagggcc ccagcgtgtt ccctctggcc 600 cctagcagca agagcacatc tggcggaaca gccgccctgg gctgcctggt ggaagattac 660 ttccccgagc ccgtgaccgt gtcctggaat tctggcgccc tgacaagcgg cgtgcacacc 720 tttccagccg tgctgcagag cagcggcctg tactctctga gcagcgtcgt gacagtgccc 780 agcagctctc tgggcaccca gacctacatc tgcaacgtga accacaagcc cagcaacacc 840 aaggtggacg agaaggtgga acccaagtcc tgc 873 <210> 141 <211> 2130 <212> ADN <213> Secuencia artificial <220> <223> Secuencia de nucleótidos de 4-1BBL hu dimérico (71-248) - CL cadena pomo Fc chain <400> 141 agagagggcc ctgagctgag ccccgatgat cctgctggac tgctggacct gcggcagggc 60 atgtttgctc agctggtggc ccagaacgtg ctgctgatcg atggccccct gtcctggtac 120 agcgatcctg gactggctgg cgtgtcactg acaggcggcc tgagctacaa agaggacacc 180 aaagaactgg tggtggccaa ggccggcgtg tactacgtgt tctttcagct ggaactgcgg 240 agagtggtgg ccggcgaagg atctggctct gtgtctctgg ccctgcatct gcagcctctg 300 agatctgctg ctggcgccgc tgctctggca ctgacagtgg atctgcctcc tgccagcagc 360 gaggcccgga atagcgcatt tgggtttcaa ggcaggctgc tgcacctgtc tgccggccag 420 aggctgggag tgcatctgca cacagaggcc agggctagac acgcctggca gctgacacag 480 ggcgctacag tgctgggcct gttcagagtg acccccgaga ttccagccgg actgggaggc 540 ggcggatctg gcggcggagg atctagagaa ggacccgagc tgtcccctga cgatccagcc 600 gggctgctgg atctgagaca gggaatgttc gcccagctgg tggctcagaa tgtgctgctg 660 attgacggac ctctgagctg gtactccgac ccagggctgg caggggtgtc cctgactggg 720 ggactgtcct acaaagaaga tacaaaagaa ctggtggtgg ctaaagctgg ggtgtactat 780 gtgttttttc agctggaact gaggcgggtg gtggctgggg agggctcagg atctgtgtcc 840 ctggctctgc atctgcagcc actgcgctct gcagcagggg ctgcagcact ggccctgact 900 gtggacctgc ccccagcttc ttccgaggcc agaaacagcg ccttcgggtt ccaaggacgc 960 ctgctgcatc tgagcgccgg acagcgcctg ggagtgcatc tgcatactga agccagagcc 1020 cggcatgctt ggcagctgac tcagggggca actgtgctgg gactgtttcg cgtgacacct 1080 gagatccccg ctggactggg cggaggcggt tccggagggg gaggatctcg tacggtggcc 1140 gctccctccg tgtttatctt tcccccatcc gatgaacagc tgaaaagcgg caccgcctcc 1200 gtcgtgtgtc tgctgaacaa tttttaccct agggaagcta aagtgcagtg gaaagtggat 1260 aacgcactgc agtccggcaa ctcccaggaa tctgtgacag aacaggactc caaggacagc 1320 acctactccc tgtcctccac cctgacactg tctaaggctg attatgagaa acacaaagtc 1380 tacgcctgcg aagtcaccca tcagggcctg agctcgcccg tcacaaagag cttcaacagg 1440 ggagagtgtg acaagaccca cacctgtccc ccttgtcctg cccctgaagc tgctggcggc 1500 ccttctgtgt tcctgttccc cccaaagccc aaggacaccc tgatgatcag ccggaccccc 1560 gaagtgacct gcgtggtggt ggatgtgtcc cacgaggacc ctgaagtgaa gttcaattgg 1620 tacgtggacg gcgtggaagt gcacaatgcc aagaccaagc cgcgggagga gcagtacaac 1680 agcacgtacc gtgtggtcag cgtcctcacc gtcctgcacc aggactggct gaatggcaag 1740 gagtacaagt gcaaggtctc caacaaagcc ctcggcgccc ccatcgagaa aaccatctcc 1800 aaagccaaag ggcagccccg agaaccacag gtgtacaccc tgcccccatg ccgggatgag 1860 ctgaccaaga accaggtcag cctgtggtgc ctggtcaaag gcttctatcc cagcgacatc 1920 gccgtggagt gggagagcaa tgggcagccg gagaacaact acaagaccac gcctcccgtg 1980 ctggactccg acggctcctt cttcctctac agcaagctca ccgtggacaa gagcaggtgg 2040 cagcagggga acgtcttctc atgctccgtg atgcatgagg ctctgcacaa ccactacacg 2100 cagaagagcc tctccctgtc tccgggtaaa 2130 <210> 142 <211> 873 <212> ADN <213> Secuencia artificial <220> <223> secuencia de nucleótidos de 4-1BBL hu monomérico (71-248) - CH1 <400> 142 agagagggcc ctgagctgag ccccgatgat cctgctggac tgctggacct gcggcagggc 60 atgtttgctc agctggtggc ccagaacgtg ctgctgatcg atggccccct gtcctggtac 120 agcgatcctg gactggctgg cgtgtcactg acaggcggcc tgagctacaa agaggacacc 180 aaagaactgg tggtggccaa ggccggcgtg tactacgtgt tctttcagct ggaactgcgg 240 agagtggtgg ccggcgaagg atctggctct gtgtctctgg ccctgcatct gcagcctctg 300 agatctgctg ctggcgccgc tgctctggca ctgacagtgg atctgcctcc tgccagcagc 360 gaggcccgga atagcgcatt tgggtttcaa ggcaggctgc tgcacctgtc tgccggccag 420 aggctgggag tgcatctgca cacagaggcc agggctagac acgcctggca gctgacacag 480 ggcgctacag tgctgggcct gttcagagtg acccccgaga ttccagccgg actgggaggc 540 ggaggttccg gaggcggagg atctgctagc accaaaggcc cttccgtgtt tcctctggct 600 cctagctcca agtccacctc tggaggcacc gctgctctcg gatgcctcgt gaaggattat 660 tttcctgagc ctgtgacagt gtcctggaat agcggagcac tgacctctgg agtgcatact 720 ttccccgctg tgctgcagtc ctctggactg tacagcctga gcagcgtggt gacagtgccc 780 agcagcagcc tgggcaccca gacctacatc tgcaacgtga accacaagcc cagcaacacc 840 aaggtggaca agaaggtgga acccaagtct tgt 873 <210> 143 <211> 2475 <212> ADN <213> Secuencia artificial <220> <223> secuencia de nucleótidos de cadena agujero Fc de anti-PD1 (0314) condensada a 4-1BBL hu dimérico (71-248) <400> 143 gaagtgcagc tgctcgaaag cggcggggga ctggtccagc ccggcggttc cctgaggctg 60 tcttgcgccg cttcagggtt cagcttttcc tcttacacca tgagttgggt cagacaggca 120 cctggcaagg gactggagtg ggtcgccaca atcagcggtg gcgggcgcga catttattac 180 ccagattccg tgaaaggacg gttcaccatc tctagggaca actcaaagaa tactctgtat 240 ttgcagatga acagcctgag agctgaggat acagcagttt actactgtgt gctcctgacc 300 ggccgcgtct attttgccct tgactcctgg ggacaaggca ctctggtgac cgtatctagt 360 gctagcacca agggcccctc cgtgttcccc ctggccccca gcagcaagag caccagcggc 420 ggcacagccg ctctgggctg cctggtcaag gactacttcc ccgagcccgt gaccgtgtcc 480 tggaacagcg gagccctgac ctccggcgtg cacaccttcc ccgccgtgct gcagagttct 540 ggcctgtata gcctgagcag cgtggtcacc gtgccttcta gcagcctggg cacccagacc 600 tacatctgca acgtgaacca caagcccagc aacaccaagg tggacaagaa ggtggagccc 660 aagagctgcg acaaaactca cacatgccca ccgtgcccag cacctgaagc tgcaggggga 720 ccgtcagtct tcctcttccc cccaaaaccc aaggacaccc tcatgatctc ccggacccct 780 gaggtcacat gcgtggtggt ggacgtgagc cacgaagacc ctgaggtcaa gttcaactgg 840 tacgtggacg gcgtggaggt gcataatgcc aagacaaagc cgcgggagga gcagtacaac 900 agcacgtacc gtgtggtcag cgtcctcacc gtcctgcacc aggactggct gaatggcaag 960 gagtacaagt gcaaggtctc caacaaagcc ctcggcgccc ccatcgagaa aaccatctcc 1020 aaagccaaag ggcagccccg agaaccacag gtgtgcaccc tgcccccatc ccgggatgag 1080 ctgaccaaga accaggtcag cctctcgtgc gcagtcaaag gcttctatcc cagcgacatc 1140 gccgtggagt gggagagcaa tgggcagccg gagaacaact acaagaccac gcctcccgtg 1200 ctggactccg acggctcctt cttcctcgtg agcaagctca ccgtggacaa gagcaggtgg 1260 cagcagggga acgtcttctc atgctccgtg atgcatgagg ctctgcacaa ccactacacg 1320 cagaagagcc tctccctgtc tccgggtgga ggcggcggaa gcggaggagg aggatccaga 1380 gagggccctg agctgagccc tgatgatcct gccggactgc tggacctgcg gcagggaatg 1440 tttgcccagc tggtggccca gaacgtgctg ctgatcgatg gccccctgtc ctggtacagc 1500 gatcctggac tggctggcgt gtcactgaca ggcggcctga gctacaaaga ggacaccaaa 1560 gaactggtgg tggccaaggc cggcgtgtac tacgtgttct ttcagctgga actgcggaga 1620 gtggtggccg gcgaaggatc tggctctgtg tctctggccc tgcatctgca gcctctgaga 1680 tctgctgctg gcgccgctgc tctggcactg acagtggatc tgcctcctgc cagcagcgag 1740 gcccggaata gcgcatttgg gtttcaaggc aggctgctgc acctgtctgc cggccagagg 1800 ctgggagtgc atctgcacac agaggccagg gctagacacg cctggcagct gacacagggc 1860 gctacagtgc tgggcctgtt cagagtgacc cccgagattc cagcaggcct gggaggcggc 1920 ggatctggcg gcggaggatc tagagaagga cccgagctgt cccccgacga tcccgctggg 1980 ctgctggatc tgagacaggg catgttcgct cagctggtgg ctcagaatgt gctgctgatt 2040 gacggacctc tgagctggta ctccgaccca gggctggcag gggtgtccct gactggggga 2100 ctgtcctaca aagaagatac aaaagaactg gtggtggcta aagctggggt gtactatgtg 2160 ttttttcagc tggaactgag gcgggtggtg gctggggagg gctcaggatc tgtgtccctg 2220 gctctgcatc tgcagccact gcgctctgca gcaggggctg cagcactggc cctgactgtg 2280 gacctgcccc cagcttcttc cgaggccaga aacagcgcct tcgggttcca aggacgcctg 2340 ctgcatctga gcgccggaca gcgcctggga gtgcatctgc atactgaagc cagagcccgg 2400 catgcttggc agctgactca gggggcaact gtgctgggac tgtttcgcgt gacacctgag 2460 atcccagccg ggctc 2475 <210> 144 <211> 1911 <212> ADN <213> Secuencia artificial <220> <223> secuencia de nucleótidos de cadena pomo Fc de anti-PD1 (0314) condensada a 4-1BBL hu monomérico (71-248) <400> 144 gaagtgcagc tgctcgaaag cggcggggga ctggtccagc ccggcggttc cctgaggctg 60 tcttgcgccg cttcagggtt cagcttttcc tcttacacca tgagttgggt cagacaggca 120 cctggcaagg gactggagtg ggtcgccaca atcagcggtg gcgggcgcga catttattac 180 ccagattccg tgaaaggacg gttcaccatc tctagggaca actcaaagaa tactctgtat 240 ttgcagatga acagcctgag agctgaggat acagcagttt actactgtgt gctcctgacc 300 ggccgcgtct attttgccct tgactcctgg ggacaaggca ctctggtgac cgtatctagt 360 gctagcacca agggcccatc ggtcttcccc ctggcaccct cctccaagag cacctctggg 420 ggcacagcgg ccctgggctg cctggtcaag gactacttcc ccgaaccggt gacggtgtcg 480 tggaactcag gcgccctgac cagcggcgtg cacaccttcc cggctgtcct acagtcctca 540 ggactctact ccctcagcag cgtggtgacc gtgccctcca gcagcttggg cacccagacc 600 tacatctgca acgtgaatca caagcccagc aacaccaagg tggacaagaa agttgagccc 660 aaatcttgtg acaaaactca cacatgccca ccgtgcccag cacctgaagc tgcaggggga 720 ccgtcagtct tcctcttccc cccaaaaccc aaggacaccc tcatgatctc ccggacccct 780 gaggtcacat gcgtggtggt ggacgtgagc cacgaagacc ctgaggtcaa gttcaactgg 840 tacgtggacg gcgtggaggt gcataatgcc aagacaaagc cgcgggagga gcagtacaac 900 agcacgtacc gtgtggtcag cgtcctcacc gtcctgcacc aggactggct gaatggcaag 960 gagtacaagt gcaaggtctc caacaaagcc ctcggcgccc ccatcgagaa aaccatctcc 1020 aaagccaaag ggcagccccg agaaccacag gtgtacaccc tgcccccctg cagagatgag 1080 ctgaccaaga accaggtgtc cctgtggtgt ctggtcaagg gcttctaccc cagcgatatc 1140 gccgtggagt gggagagcaa cggccagcct gagaacaact acaagaccac cccccctgtg 1200 ctggacagcg acggcagctt cttcctgtac tccaaactga ccgtggacaa gagccggtgg 1260 cagcagggca acgtgttcag ctgcagcgtg atgcacgagg ccctgcacaa ccactacacc 1320 cagaagtccc tgagcctgag ccccggcgga ggcggcggaa gcggaggagg aggatccaga 1380 gagggccctg agctgagccc tgatgatcct gccggactgc tggacctgcg gcagggaatg 1440 tttgcccagc tggtggccca gaacgtgctg ctgatcgatg gccccctgtc ctggtacagc 1500 gatcctggac tggctggcgt gtcactgaca ggcggcctga gctacaaaga ggacaccaaa 1560 gaactggtgg tggccaaggc cggcgtgtac tacgtgttct ttcagctgga actgcggaga 1620 gtggtggccg gcgaaggatc tggctctgtg tctctggccc tgcatctgca gcctctgaga 1680 tctgctgctg gcgccgctgc tctggcactg acagtggatc tgcctcctgc cagcagcgag 1740 gcccggaata gcgcatttgg gtttcaaggc aggctgctgc acctgtctgc cggccagagg 1800 ctgggagtgc atctgcacac agaggccagg gctagacacg cctggcagct gacacagggc 1860 gctacagtgc tgggcctgtt cagagtgacc cccgagattc ctgccgggct c 1911 <210> 145 <211> 1806 <212> ADN <213> Secuencia artificial <220> <223> secuencia de nucleótidos de cadena de ligando dimérico (71-248) de Fc agujero <400> 145 gacaaaactc acacatgccc accgtgccca gcacctgaag ctgcaggggg accgtcagtc 60 ttcctcttcc ccccaaaacc caaggacacc ctcatgatct cccggacccc tgaggtcaca 120 tgcgtggtgg tggacgtgag ccacgaagac cctgaggtca agttcaactg gtacgtggac 180 ggcgtggagg tgcataatgc caagacaaag ccgcgggagg agcagtacaa cagcacgtac 240 cgtgtggtca gcgtcctcac cgtcctgcac caggactggc tgaatggcaa ggagtacaag 300 tgcaaggtct ccaacaaagc cctcggcgcc cccatcgaga aaaccatctc caaagccaaa 360 gggcagcccc gagaaccaca ggtgtgcacc ctgcccccat cccgggatga gctgaccaag 420 aaccaggtca gcctctcgtg cgcagtcaaa ggcttctatc ccagcgacat cgccgtggag 480 tgggagagca atgggcagcc ggagaacaac tacaagacca cgcctcccgt gctggactcc 540 gacggctcct tcttcctcgt gagcaagctc accgtggaca agagcaggtg gcagcagggg 600 aacgtcttct catgctccgt gatgcatgag gctctgcaca accactacac gcagaagagc 660 ctctccctgt ctccgggtgg aggcggcgga agcggaggag gaggatccag agagggccct 720 gagctgagcc ctgatgatcc tgccggactg ctggacctgc ggcagggaat gtttgcccag 780 ctggtggccc agaacgtgct gctgatcgat ggccccctgt cctggtacag cgatcctgga 840 ctggctggcg tgtcactgac aggcggcctg agctacaaag aggacaccaa agaactggtg 900 gtggccaagg ccggcgtgta ctacgtgttc tttcagctgg aactgcggag agtggtggcc 960 ggcgaaggat ctggctctgt gtctctggcc ctgcatctgc agcctctgag atctgctgct 1020 ggcgccgctg ctctggcact gacagtggat ctgcctcctg ccagcagcga ggcccggaat 1080 agcgcatttg ggtttcaagg caggctgctg cacctgtctg ccggccagag gctgggagtg 1140 catctgcaca cagaggccag ggctagacac gcctggcagc tgacacaggg cgctacagtg 1200 ctgggcctgt tcagagtgac ccccgagatt ccagcaggcc tgggaggcgg cggatctggc 1260 ggcggaggat ctagagaagg acccgagctg tcccccgacg atcccgctgg gctgctggat 1320 ctgagacagg gcatgttcgc tcagctggtg gctcagaatg tgctgctgat tgacggacct 1380 ctgagctggt actccgaccc agggctggca ggggtgtccc tgactggggg actgtcctac 1440 aaagaagata caaaagaact ggtggtggct aaagctgggg tgtactatgt gttttttcag 1500 ctggaactga ggcgggtggt ggctggggag ggctcaggat ctgtgtccct ggctctgcat 1560 ctgcagccac tgcgctctgc agcaggggct gcagcactgg ccctgactgt ggacctgccc 1620 ccagcttctt ccgaggccag aaacagcgcc ttcgggttcc aaggacgcct gctgcatctg 1680 agcgccggac agcgcctggg agtgcatctg catactgaag ccagagcccg gcatgcttgg 1740 cagctgactc agggggcaac tgtgctggga ctgtttcgcg tgacacctga gatcccagcc 1800 gggctc 1806 <210> 146 <211> 1212 <212> ADN <213> Secuencia artificial <220> <223> secuencia de nucleótidos de cadena de ligando monomérico (71-248) de Fc agujero <400> 146 gacaaaactc acacatgccc accgtgccca gcacctgaag ctgcaggggg accgtcagtc 60 ttcctcttcc ccccaaaacc caaggacacc ctcatgatct cccggacccc tgaggtcaca 120 tgcgtggtgg tggacgtgag ccacgaagac cctgaggtca agttcaactg gtacgtggac 180 ggcgtggagg tgcataatgc caagacaaag ccgcgggagg agcagtacaa cagcacgtac 240 cgtgtggtca gcgtcctcac cgtcctgcac caggactggc tgaatggcaa ggagtacaag 300 tgcaaggtct ccaacaaagc cctcggcgcc cccatcgaga aaaccatctc caaagccaaa 360 gggcagcccc gagaaccaca ggtgtgcacc ctgcccccat cccgggatga gctgaccaag 420 aaccaggtca gcctctcgtg cgcagtcaaa ggcttctatc ccagcgacat cgccgtggag 480 tgggagagca atgggcagcc ggagaacaac tacaagacca cgcctcccgt gctggactcc 540 gacggctcct tcttcctcgt gagcaagctc accgtggaca agagcaggtg gcagcagggg 600 aacgtcttct catgctccgt gatgcatgag gctctgcaca accactacac gcagaagagc 660 ctctccctgt ctccgggtag agagggccct gagctgagcc ctgatgatcc tgccggactg 720 ctggacctgc ggcagggaat gtttgcccag ctggtggccc agaacgtgct gctgatcgat 780 ggccccctgt cctggtacag cgatcctgga ctggctggcg tgtcactgac aggcggcctg 840 agctacaaag aggacaccaa agaactggtg gtggccaagg ccggcgtgta ctacgtgttc 900 tttcagctgg aactgcggag agtggtggcc ggcgaaggat ctggctctgt gtctctggcc 960 ctgcatctgc agcctctgag atctgctgct ggcgccgctg ctctggcact gacagtggat 1020 ctgcctcctg ccagcagcga ggcccggaat agcgcatttg ggtttcaagg caggctgctg 1080 cacctgtctg ccggccagag gctgggagtg catctgcaca cagaggccag ggctagacac 1140 gcctggcagc tgacacaggg cgctacagtg ctgggcctgt tcagagtgac ccccgagatt 1200 cctgccgggc tc 1212 <210> 147 <211> 2445 <212> ADN <213> Secuencia artificial <220> <223> secuencia de nucleótidos de cadena pomo Fc de anti-PD1 (0314) condensada a 4-1BBL hu dimérico (71-248) <400> 147 gaagtgcagc tgctcgaaag cggcggggga ctggtccagc ccggcggttc cctgaggctg 60 tcttgcgccg cttcagggtt cagcttttcc tcttacacca tgagttgggt cagacaggca 120 cctggcaagg gactggagtg ggtcgccaca atcagcggtg gcgggcgcga catttattac 180 ccagattccg tgaaaggacg gttcaccatc tctagggaca actcaaagaa tactctgtat 240 ttgcagatga acagcctgag agctgaggat acagcagttt actactgtgt gctcctgacc 300 ggccgcgtct attttgccct tgactcctgg ggacaaggca ctctggtgac cgtatctagt 360 gctagcacca agggcccatc ggtcttcccc ctggcaccct cctccaagag cacctctggg 420 ggcacagcgg ccctgggctg cctggtcaag gactacttcc ccgaaccggt gacggtgtcg 480 tggaactcag gcgccctgac cagcggcgtg cacaccttcc cggctgtcct acagtcctca 540 ggactctact ccctcagcag cgtggtgacc gtgccctcca gcagcttggg cacccagacc 600 tacatctgca acgtgaatca caagcccagc aacaccaagg tggacaagaa agttgagccc 660 aaatcttgtg acaaaactca cacatgccca ccgtgcccag cacctgaagc tgcaggggga 720 ccgtcagtct tcctcttccc cccaaaaccc aaggacaccc tcatgatctc ccggacccct 780 gaggtcacat gcgtggtggt ggacgtgagc cacgaagacc ctgaggtcaa gttcaactgg 840 tacgtggacg gcgtggaggt gcataatgcc aagacaaagc cgcgggagga gcagtacaac 900 agcacgtacc gtgtggtcag cgtcctcacc gtcctgcacc aggactggct gaatggcaag 960 gagtacaagt gcaaggtctc caacaaagcc ctcggcgccc ccatcgagaa aaccatctcc 1020 aaagccaaag ggcagccccg agaaccacag gtgtacaccc tgcccccctg cagagatgag 1080 ctgaccaaga accaggtgtc cctgtggtgt ctggtcaagg gcttctaccc cagcgatatc 1140 gccgtggagt gggagagcaa cggccagcct gagaacaact acaagaccac cccccctgtg 1200 ctggacagcg acggcagctt cttcctgtac tccaaactga ccgtggacaa gagccggtgg 1260 cagcagggca acgtgttcag ctgcagcgtg atgcacgagg ccctgcacaa ccactacacc 1320 cagaagtccc tgagcctgag ccccggcaga gagggccctg agctgagccc tgatgatcct 1380 gccggactgc tggacctgcg gcagggaatg tttgcccagc tggtggccca gaacgtgctg 1440 ctgatcgatg gccccctgtc ctggtacagc gatcctggac tggctggcgt gtcactgaca 1500 ggcggcctga gctacaaaga ggacaccaaa gaactggtgg tggccaaggc cggcgtgtac 1560 tacgtgttct ttcagctgga actgcggaga gtggtggccg gcgaaggatc tggctctgtg 1620 tctctggccc tgcatctgca gcctctgaga tctgctgctg gcgccgctgc tctggcactg 1680 acagtggatc tgcctcctgc cagcagcgag gcccggaata gcgcatttgg gtttcaaggc 1740 aggctgctgc acctgtctgc cggccagagg ctgggagtgc atctgcacac agaggccagg 1800 gctagacacg cctggcagct gacacagggc gctacagtgc tgggcctgtt cagagtgacc 1860 cccgagattc cagcaggcct gggaggcggc ggatctggcg gcggaggatc tagagaagga 1920 cccgagctgt cccccgacga tcccgctggg ctgctggatc tgagacaggg catgttcgct 1980 cagctggtgg ctcagaatgt gctgctgatt gacggacctc tgagctggta ctccgaccca 2040 gggctggcag gggtgtccct gactggggga ctgtcctaca aagaagatac aaaagaactg 2100 gtggtggcta aagctggggt gtactatgtg ttttttcagc tggaactgag gcgggtggtg 2160 gctggggagg gctcaggatc tgtgtccctg gctctgcatc tgcagccact gcgctctgca 2220 gcaggggctg cagcactggc cctgactgtg gacctgcccc cagcttcttc cgaggccaga 2280 aacagcgcct tcgggttcca aggacgcctg ctgcatctga gcgccggaca gcgcctggga 2340 gtgcatctgc atactgaagc cagagcccgg catgcttggc agctgactca gggggcaact 2400 gtgctgggac tgtttcgcgt gacacctgag atcccagccg ggctc 2445 <210> 148 <211> 1242 <212> ADN <213> Secuencia artificial <220> <223> secuencia de nucleótidos de cadena pomo Fc fusionada a 4-1BBL hu monomérico (71-248) <400> 148 gacaaaactc acacatgccc accgtgccca gcacctgaag ctgcaggggg accgtcagtc 60 ttcctcttcc ccccaaaacc caaggacacc ctcatgatct cccggacccc tgaggtcaca 120 tgcgtggtgg tggacgtgag ccacgaagac cctgaggtca agttcaactg gtacgtggac 180 ggcgtggagg tgcataatgc caagacaaag ccgcgggagg agcagtacaa cagcacgtac 240 cgtgtggtca gcgtcctcac cgtcctgcac caggactggc tgaatggcaa ggagtacaag 300 tgcaaggtct ccaacaaagc cctcggcgcc cccatcgaga aaaccatctc caaagccaaa 360 gggcagcccc gagaaccaca ggtgtacacc ctgcccccct gcagagatga gctgaccaag 420 aaccaggtgt ccctgtggtg tctggtcaag ggcttctacc ccagcgatat cgccgtggag 480 tgggagagca acggccagcc tgagaacaac tacaagacca ccccccctgt gctggacagc 540 gacggcagct tcttcctgta ctccaaactg accgtggaca agagccggtg gcagcagggc 600 aacgtgttca gctgcagcgt gatgcacgag gccctgcaca accactacac ccagaagtcc 660 ctgagcctga gccccggcgg aggcggcgga agcggaggag gaggatccag agagggccct 720 gagctgagcc ctgatgatcc tgccggactg ctggacctgc ggcagggaat gtttgcccag 780 ctggtggccc agaacgtgct gctgatcgat ggccccctgt cctggtacag cgatcctgga 840 ctggctggcg tgtcactgac aggcggcctg agctacaaag aggacaccaa agaactggtg 900 gtggccaagg ccggcgtgta ctacgtgttc tttcagctgg aactgcggag agtggtggcc 960 ggcgaaggat ctggctctgt gtctctggcc ctgcatctgc agcctctgag atctgctgct 1020 ggcgccgctg ctctggcact gacagtggat ctgcctcctg ccagcagcga ggcccggaat 1080 agcgcatttg ggtttcaagg caggctgctg cacctgtctg ccggccagag gctgggagtg 1140 catctgcaca cagaggccag ggctagacac gcctggcagc tgacacaggg cgctacagtg 1200 ctgggcctgt tcagagtgac ccccgagatt cctgccgggc tc 1242 <210> 149 <211> 1911 <212> ADN <213> Secuencia artificial <220> <223> secuencia de nucleótidos de cadena pomo (71-248) Fc de ligando monomérico de anti-PD1 (0314) (71-248) chain <400> 149 gaagtgcagc tgctcgaaag cggcggggga ctggtccagc ccggcggttc cctgaggctg 60 tcttgcgccg cttcagggtt cagcttttcc tcttacacca tgagttgggt cagacaggca 120 cctggcaagg gactggagtg ggtcgccaca atcagcggtg gcgggcgcga catttattac 180 ccagattccg tgaaaggacg gttcaccatc tctagggaca actcaaagaa tactctgtat 240 ttgcagatga acagcctgag agctgaggat acagcagttt actactgtgt gctcctgacc 300 ggccgcgtct attttgccct tgactcctgg ggacaaggca ctctggtgac cgtatctagt 360 gctagcacca agggcccctc cgtgttcccc ctggccccca gcagcaagag caccagcggc 420 ggcacagccg ctctgggctg cctggtcaag gactacttcc ccgagcccgt gaccgtgtcc 480 tggaacagcg gagccctgac ctccggcgtg cacaccttcc ccgccgtgct gcagagttct 540 ggcctgtata gcctgagcag cgtggtcacc gtgccttcta gcagcctggg cacccagacc 600 tacatctgca acgtgaacca caagcccagc aacaccaagg tggacaagaa ggtggagccc 660 aagagctgcg acaaaactca cacatgccca ccgtgcccag cacctgaagc tgcaggggga 720 ccgtcagtct tcctcttccc cccaaaaccc aaggacaccc tcatgatctc ccggacccct 780 gaggtcacat gcgtggtggt ggacgtgagc cacgaagacc ctgaggtcaa gttcaactgg 840 tacgtggacg gcgtggaggt gcataatgcc aagacaaagc cgcgggagga gcagtacaac 900 agcacgtacc gtgtggtcag cgtcctcacc gtcctgcacc aggactggct gaatggcaag 960 gagtacaagt gcaaggtctc caacaaagcc ctcggcgccc ccatcgagaa aaccatctcc 1020 aaagccaaag ggcagccccg agaaccacag gtgtgcaccc tgcccccatc ccgggatgag 1080 ctgaccaaga accaggtcag cctctcgtgc gcagtcaaag gcttctatcc cagcgacatc 1140 gccgtggagt gggagagcaa tgggcagccg gagaacaact acaagaccac gcctcccgtg 1200 ctggactccg acggctcctt cttcctcgtg agcaagctca ccgtggacaa gagcaggtgg 1260 cagcagggga acgtcttctc atgctccgtg atgcatgagg ctctgcacaa ccactacacg 1320 cagaagagcc tctccctgtc tccgggtgga ggcggcggaa gcggaggagg aggatccaga 1380 gagggccctg agctgagccc tgatgatcct gccggactgc tggacctgcg gcagggaatg 1440 tttgcccagc tggtggccca gaacgtgctg ctgatcgatg gccccctgtc ctggtacagc 1500 gatcctggac tggctggcgt gtcactgaca ggcggcctga gctacaaaga ggacaccaaa 1560 gaactggtgg tggccaaggc cggcgtgtac tacgtgttct ttcagctgga actgcggaga 1620 gtggtggccg gcgaaggatc tggctctgtg tctctggccc tgcatctgca gcctctgaga 1680 tctgctgctg gcgccgctgc tctggcactg acagtggatc tgcctcctgc cagcagcgag 1740 gcccggaata gcgcatttgg gtttcaaggc aggctgctgc acctgtctgc cggccagagg 1800 ctgggagtgc atctgcacac agaggccagg gctagacacg cctggcagct gacacagggc 1860 gctacagtgc tgggcctgtt cagagtgacc cccgagattc ctgccgggct c 1911 <210> 150 <211> 1806 <212> ADN <213> Secuencia artificial <220> <223> secuencia de nucleótidos de cadena pomo Fc fusionada a 4-1BBL hu dimérico (71-248) <400> 150 gacaaaactc acacatgccc accgtgccca gcacctgaag ctgcaggggg accgtcagtc 60 ttcctcttcc ccccaaaacc caaggacacc ctcatgatct cccggacccc tgaggtcaca 120 tgcgtggtgg tggacgtgag ccacgaagac cctgaggtca agttcaactg gtacgtggac 180 ggcgtggagg tgcataatgc caagacaaag ccgcgggagg agcagtacaa cagcacgtac 240 cgtgtggtca gcgtcctcac cgtcctgcac caggactggc tgaatggcaa ggagtacaag 300 tgcaaggtct ccaacaaagc cctcggcgcc cccatcgaga aaaccatctc caaagccaaa 360 gggcagcccc gagaaccaca ggtgtacacc ctgcccccct gcagagatga gctgaccaag 420 aaccaggtgt ccctgtggtg tctggtcaag ggcttctacc ccagcgatat cgccgtggag 480 tgggagagca acggccagcc tgagaacaac tacaagacca ccccccctgt gctggacagc 540 gacggcagct tcttcctgta ctccaaactg accgtggaca agagccggtg gcagcagggc 600 aacgtgttca gctgcagcgt gatgcacgag gccctgcaca accactacac ccagaagtcc 660 ctgagcctga gccccggcgg aggcggcgga agcggaggag gaggatccag agagggccct 720 gagctgagcc ctgatgatcc tgccggactg ctggacctgc ggcagggaat gtttgcccag 780 ctggtggccc agaacgtgct gctgatcgat ggccccctgt cctggtacag cgatcctgga 840 ctggctggcg tgtcactgac aggcggcctg agctacaaag aggacaccaa agaactggtg 900 gtggccaagg ccggcgtgta ctacgtgttc tttcagctgg aactgcggag agtggtggcc 960 ggcgaaggat ctggctctgt gtctctggcc ctgcatctgc agcctctgag atctgctgct 1020 ggcgccgctg ctctggcact gacagtggat ctgcctcctg ccagcagcga ggcccggaat 1080 agcgcatttg ggtttcaagg caggctgctg cacctgtctg ccggccagag gctgggagtg 1140 catctgcaca cagaggccag ggctagacac gcctggcagc tgacacaggg cgctacagtg 1200 ctgggcctgt tcagagtgac ccccgagatt ccagcaggcc tgggaggcgg cggatctggc 1260 ggcggaggat ctagagaagg acccgagctg tcccccgacg atcccgctgg gctgctggat 1320 ctgagacagg gcatgttcgc tcagctggtg gctcagaatg tgctgctgat tgacggacct 1380 ctgagctggt actccgaccc agggctggca ggggtgtccc tgactggggg actgtcctac 1440 aaagaagata caaaagaact ggtggtggct aaagctgggg tgtactatgt gttttttcag 1500 ctggaactga ggcgggtggt ggctggggag ggctcaggat ctgtgtccct ggctctgcat 1560 ctgcagccac tgcgctctgc agcaggggct gcagcactgg ccctgactgt ggacctgccc 1620 ccagcttctt ccgaggccag aaacagcgcc ttcgggttcc aaggacgcct gctgcatctg 1680 agcgccggac agcgcctggg agtgcatctg catactgaag ccagagcccg gcatgcttgg 1740 cagctgactc agggggcaac tgtgctggga ctgtttcgcg tgacacctga gatcccagcc 1800 gggctc 1806 <210> 151 <211> 1335 <212> ADN <213> Secuencia artificial <220> <223> secuencia de nucleótidos de cadena agujero Fc de DP47 <400> 151 gaggtgcaat tgttggagtc tgggggaggc ttggtacagc ctggggggtc cctgagactc 60 tcctgtgcag cctccggatt cacctttagc agttatgcca tgagctgggt ccgccaggct 120 ccagggaagg ggctggagtg ggtctcagct attagtggta gtggtggtag cacatactac 180 gcagactccg tgaagggccg gttcaccatc tccagagaca attccaagaa cacgctgtat 240 ctgcagatga acagcctgag agccgaggac acggccgtat attactgtgc gaaaggcagc 300 ggatttgact actggggcca aggaaccctg gtcaccgtct cgagtgctag caccaagggc 360 ccatcggtct tccccctggc accctcctcc aagagcacct ctgggggcac agcggccctg 420 ggctgcctgg tcaaggacta cttccccgaa ccggtgacgg tgtcgtggaa ctcaggcgcc 480 ctgaccagcg gcgtgcacac cttcccggct gtcctacagt cctcaggact ctactccctc 540 agcagcgtgg tgaccgtgcc ctccagcagc ttgggcaccc agacctacat ctgcaacgtg 600 aatcacaagc ccagcaacac caaggtggac aagaaagttg agcccaaatc ttgtgacaaa 660 actcacacat gcccaccgtg cccagcacct gaagctgcag ggggaccgtc agtcttcctc 720 ttccccccaa aacccaagga caccctcatg atctcccgga cccctgaggt cacatgcgtg 780 gtggtggacg tgagccacga agaccctgag gtcaagttca actggtacgt ggacggcgtg 840 gaggtgcata atgccaagac aaagccgcgg gaggagcagt acaacagcac gtaccgtgtg 900 gtcagcgtcc tcaccgtcct gcaccaggac tggctgaatg gcaaggagta caagtgcaag 960 gtctccaaca aagccctcgg cgcccccatc gagaaaacca tctccaaagc caaagggcag 1020 ccccgagaac cacaggtgtg caccctgccc ccatcccggg atgagctgac caagaaccag 1080 gtcagcctct cgtgcgcagt caaaggcttc tatcccagcg acatcgccgt ggagtgggag 1140 agcaatgggc agccggagaa caactacaag accacgcctc ccgtgctgga ctccgacggc 1200 tccttcttcc tcgtgagcaa gctcaccgtg gacaagagca ggtggcagca ggggaacgtc 1260 ttctcatgct ccgtgatgca tgaggctctg cacaaccact acacgcagaa gagcctctcc 1320 ctgtctccgg gtaaa 1335 <210> 152 <211> 645 <212> ADN <213> Secuencia artificial <220> <223> secuencia de nucleótidos de cadena ligera de DP47 <400> 152 gaaatcgtgt taacgcagtc tccaggcacc ctgtctttgt ctccagggga aagagccacc 60 ctctcttgca gggccagtca gagtgttagc agcagctact tagcctggta ccagcagaaa 120 cctggccagg ctcccaggct cctcatctat ggagcatcca gcagggccac tggcatccca 180 gacaggttca gtggcagtgg atccgggaca gacttcactc tcaccatcag cagactggag 240 cctgaagatt ttgcagtgta ttactgtcag cagtatggta gctcaccgct gacgttcggc 300 caggggacca aagtggaaat caaacgtacg gtggctgcac catctgtctt catcttcccg 360 ccatctgatg agcagttgaa atctggaact gcctctgttg tgtgcctgct gaataacttc 420 tatcccagag aggccaaagt acagtggaag gtggataacg ccctccaatc gggtaactcc 480 caggagagtg tcacagagca ggacagcaag gacagcacct acagcctcag cagcaccctg 540 acgctgagca aagcagacta cgagaaacac aaagtctacg cctgcgaagt cacccatcag 600 ggcctgagct cgcccgtcac aaagagcttc aacaggggag agtgt 645 <210> 153 <211> 445 <212> PRT <213> Secuencia artificial <220> <223> cadena agujero Fc de DP47 <400> 153 Glu Val Gln Leu Leu Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 1 5 10 15 Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Ser Tyr 20 25 30 Ala Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45 Ser Ala Ile Ser Gly Ser Gly Gly Ser Thr Tyr Tyr Ala Asp Ser Val 50 55 60 Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 65 70 75 80 Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Ala Lys Gly Ser Gly Phe Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr 100 105 110 Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro 115 120 125 Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val 130 135 140 Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala 145 150 155 160 Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly 165 170 175 Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly 180 185 190 Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys 195 200 205 Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys 210 215 220 Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu 225 230 235 240 Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu 245 250 255 Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys 260 265 270 Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys 275 280 285 Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu 290 295 300 Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys 305 310 315 320 Val Ser Asn Lys Ala Leu Gly Ala Pro Ile Glu Lys Thr Ile Ser Lys 325 330 335 Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Cys Thr Leu Pro Pro Ser 340 345 350 Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Ser Cys Ala Val Lys 355 360 365 Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln 370 375 380 Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly 385 390 395 400 Ser Phe Phe Leu Val Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln 405 410 415 Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn 420 425 430 His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys 435 440 445 <210> 154 <211> 215 <212> PRT <213> Secuencia artificial <220> <223> cadena ligera de DP47 <400> 154 Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly 1 5 10 15 Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Ser Ser 20 25 30 Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu 35 40 45 Ile Tyr Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser 50 55 60 Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu 65 70 75 80 Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Gly Ser Ser Pro 85 90 95 Leu Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Arg Thr Val Ala 100 105 110 Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser 115 120 125 Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu 130 135 140 Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser 145 150 155 160 Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu 165 170 175 Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val 180 185 190 Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys 195 200 205 Ser Phe Asn Arg Gly Glu Cys 210 215 <210> 155 <211> 2496 <212> ADN <213> Secuencia artificial <220> <223> secuencia de nucleótidos de cadena agujero Fc de DP47 fusionada a 4-1BBL hu dimérico (71-254) <400> 155 gaggtgcaat tgttggagtc tgggggaggc ttggtacagc ctggggggtc cctgagactc 60 tcctgtgcag cctccggatt cacctttagc agttatgcca tgagctgggt ccgccaggct 120 ccagggaagg ggctggagtg ggtctcagct attagtggta gtggtggtag cacatactac 180 gcagactccg tgaagggccg gttcaccatc tccagagaca attccaagaa cacgctgtat 240 ctgcagatga acagcctgag agccgaggac acggccgtat attactgtgc gaaaggcagc 300 ggatttgact actggggcca aggaaccctg gtcaccgtct cgagtgctag caccaagggc 360 ccctccgtgt tccccctggc ccccagcagc aagagcacca gcggcggcac agccgctctg 420 ggctgcctgg tcaaggacta cttccccgag cccgtgaccg tgtcctggaa cagcggagcc 480 ctgacctccg gcgtgcacac cttccccgcc gtgctgcaga gttctggcct gtatagcctg 540 agcagcgtgg tcaccgtgcc ttctagcagc ctgggcaccc agacctacat ctgcaacgtg 600 aaccacaagc ccagcaacac caaggtggac aagaaggtgg agcccaagag ctgcgacaaa 660 actcacacat gcccaccgtg cccagcacct gaagctgcag ggggaccgtc agtcttcctc 720 ttccccccaa aacccaagga caccctcatg atctcccgga cccctgaggt cacatgcgtg 780 gtggtggacg tgagccacga agaccctgag gtcaagttca actggtacgt ggacggcgtg 840 gaggtgcata atgccaagac aaagccgcgg gaggagcagt acaacagcac gtaccgtgtg 900 gtcagcgtcc tcaccgtcct gcaccaggac tggctgaatg gcaaggagta caagtgcaag 960 gtctccaaca aagccctcgg cgcccccatc gagaaaacca tctccaaagc caaagggcag 1020 ccccgagaac cacaggtgtg caccctgccc ccatcccggg atgagctgac caagaaccag 1080 gtcagcctct cgtgcgcagt caaaggcttc tatcccagcg acatcgccgt ggagtgggag 1140 agcaatgggc agccggagaa caactacaag accacgcctc ccgtgctgga ctccgacggc 1200 tccttcttcc tcgtgagcaa gctcaccgtg gacaagagca ggtggcagca ggggaacgtc 1260 ttctcatgct ccgtgatgca tgaggctctg cacaaccact acacgcagaa gagcctctcc 1320 ctgtctccgg gtggaggcgg cggaagcgga ggaggaggat ccagagaggg ccctgagctg 1380 agccccgatg atcctgctgg actgctggac ctgcggcagg gcatgtttgc tcagctggtg 1440 gcccagaacg tgctgctgat cgatggcccc ctgtcctggt acagcgatcc tggactggct 1500 ggcgtgtcac tgacaggcgg cctgagctac aaagaggaca ccaaagaact ggtggtggcc 1560 aaggccggcg tgtactacgt gttctttcag ctggaactgc ggagagtggt ggccggcgaa 1620 ggatctggct ctgtgtctct ggccctgcat ctgcagcctc tgagaagcgc tgctggcgct 1680 gcagctctgg cactgacagt ggatctgcct cctgccagct ccgaggcccg gaatagcgca 1740 tttgggtttc aaggcaggct gctgcacctg tctgccggcc agaggctggg agtgcatctg 1800 cacacagagg ccagggctag acacgcctgg cagctgacac agggcgctac agtgctgggc 1860 ctgttcagag tgacccccga gattccagcc ggcctgcctt ctccaagaag cgaaggcgga 1920 ggcggatctg gcggcggagg atctagagag ggacccgaac tgtcccctga cgatccagcc 1980 gggctgctgg atctgagaca gggaatgttc gcccagctgg tggctcagaa tgtgctgctg 2040 attgacggac ctctgagctg gtactccgac ccagggctgg caggggtgtc cctgactggg 2100 ggactgtcct acaaagaaga tacaaaagaa ctggtggtgg ctaaagctgg ggtgtactat 2160 gtgttttttc agctggaact gaggcgggtg gtggctgggg agggctcagg atctgtgtcc 2220 ctggctctgc atctgcagcc actgcgctct gctgctggcg cagctgcact ggctctgact 2280 gtggacctgc caccagcctc tagcgaggcc agaaacagcg ccttcgggtt ccaaggacgc 2340 ctgctgcatc tgagcgccgg acagcgcctg ggagtgcatc tgcatactga agccagagcc 2400 cggcatgctt ggcagctgac tcagggggca actgtgctgg gactgtttcg cgtgacacct 2460 gagatccctg ccggactgcc aagccctaga tcagaa 2496 <210> 156 <211> 1914 <212> ADN <213> Secuencia artificial <220> <223> secuencia de nucleótidos de cadena pomo Fc de DP47 fusionada a 4-1BBL hu monomérico (71-254) <400> 156 gaggtgcaat tgttggagtc tgggggaggc ttggtacagc ctggggggtc cctgagactc 60 tcctgtgcag cctccggatt cacctttagc agttatgcca tgagctgggt ccgccaggct 120 ccagggaagg ggctggagtg ggtctcagct attagtggta gtggtggtag cacatactac 180 gcagactccg tgaagggccg gttcaccatc tccagagaca attccaagaa cacgctgtat 240 ctgcagatga acagcctgag agccgaggac acggccgtat attactgtgc gaaaggcagc 300 ggatttgact actggggcca aggaaccctg gtcaccgtct cgagtgctag caccaagggc 360 ccatcggtct tccccctggc accctcctcc aagagcacct ctgggggcac agcggccctg 420 ggctgcctgg tcaaggacta cttccccgaa ccggtgacgg tgtcgtggaa ctcaggcgcc 480 ctgaccagcg gcgtgcacac cttcccggct gtcctacagt cctcaggact ctactccctc 540 agcagcgtgg tgaccgtgcc ctccagcagc ttgggcaccc agacctacat ctgcaacgtg 600 aatcacaagc ccagcaacac caaggtggac aagaaagttg agcccaaatc ttgtgacaaa 660 actcacacat gcccaccgtg cccagcacct gaagctgcag ggggaccgtc agtcttcctc 720 ttccccccaa aacccaagga caccctcatg atctcccgga cccctgaggt cacatgcgtg 780 gtggtggacg tgagccacga agaccctgag gtcaagttca actggtacgt ggacggcgtg 840 gaggtgcata atgccaagac aaagccgcgg gaggagcagt acaacagcac gtaccgtgtg 900 gtcagcgtcc tcaccgtcct gcaccaggac tggctgaatg gcaaggagta caagtgcaag 960 gtctccaaca aagccctcgg cgcccccatc gagaaaacca tctccaaagc caaagggcag 1020 ccccgagaac cacaggtgta caccctgccc ccctgcagag atgagctgac caagaaccag 1080 gtgtccctgt ggtgtctggt caagggcttc taccccagcg atatcgccgt ggagtgggag 1140 agcaacggcc agcctgagaa caactacaag accacccccc ctgtgctgga cagcgacggc 1200 agcttcttcc tgtactccaa actgaccgtg gacaagagcc ggtggcagca gggcaacgtg 1260 ttcagctgca gcgtgatgca cgaggccctg cacaaccact acacccagaa gtccctgagc 1320 ctgagccccg gcggaggcgg cggaagcgga ggaggaggat ccagagaggg ccctgagctg 1380 agccccgatg atcctgctgg actgctggac ctgcggcagg gcatgtttgc tcagctggtg 1440 gcccagaacg tgctgctgat cgatggcccc ctgtcctggt acagcgatcc tggactggct 1500 ggcgtgtcac tgacaggcgg cctgagctac aaagaggaca ccaaagaact ggtggtggcc 1560 aaggccggcg tgtactacgt gttctttcag ctggaactgc ggagagtggt ggccggcgaa 1620 ggatctggct ctgtgtctct ggccctgcat ctgcagcctc tgagaagcgc tgctggcgct 1680 gcagctctgg cactgacagt ggatctgcct cctgccagct ccgaggcccg gaatagcgca 1740 tttgggtttc aaggcaggct gctgcacctg tctgccggcc agaggctggg agtgcatctg 1800 cacacagagg ccagggctag acacgcctgg cagctgacac agggcgctac agtgctgggc 1860 ctgttcagag tgacccccga gattccagcc ggcctgcctt ctccaagaag cgaa 1914 <210> 157 <211> 832 <212> PRT <213> Secuencia artificial <220> <223> cadena agujero Fc de DP47 fusionada a 4-1BBL hu dimérico (71-254) <400> 157 Glu Val Gln Leu Leu Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 1 5 10 15 Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Ser Tyr 20 25 30 Ala Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45 Ser Ala Ile Ser Gly Ser Gly Gly Ser Thr Tyr Tyr Ala Asp Ser Val 50 55 60 Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 65 70 75 80 Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Ala Lys Gly Ser Gly Phe Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr 100 105 110 Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro 115 120 125 Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val 130 135 140 Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala 145 150 155 160 Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly 165 170 175 Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly 180 185 190 Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys 195 200 205 Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys 210 215 220 Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu 225 230 235 240 Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu 245 250 255 Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys 260 265 270 Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys 275 280 285 Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu 290 295 300 Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys 305 310 315 320 Val Ser Asn Lys Ala Leu Gly Ala Pro Ile Glu Lys Thr Ile Ser Lys 325 330 335 Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Cys Thr Leu Pro Pro Ser 340 345 350 Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Ser Cys Ala Val Lys 355 360 365 Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln 370 375 380 Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly 385 390 395 400 Ser Phe Phe Leu Val Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln 405 410 415 Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn 420 425 430 His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Gly Gly Gly Gly 435 440 445 Ser Gly Gly Gly Gly Ser Arg Glu Gly Pro Glu Leu Ser Pro Asp Asp 450 455 460 Pro Ala Gly Leu Leu Asp Leu Arg Gln Gly Met Phe Ala Gln Leu Val 465 470 475 480 Ala Gln Asn Val Leu Leu Ile Asp Gly Pro Leu Ser Trp Tyr Ser Asp 485 490 495 Pro Gly Leu Ala Gly Val Ser Leu Thr Gly Gly Leu Ser Tyr Lys Glu 500 505 510 Asp Thr Lys Glu Leu Val Val Ala Lys Ala Gly Val Tyr Tyr Val Phe 515 520 525 Phe Gln Leu Glu Leu Arg Arg Val Val Ala Gly Glu Gly Ser Gly Ser 530 535 540 Val Ser Leu Ala Leu His Leu Gln Pro Leu Arg Ser Ala Ala Gly Ala 545 550 555 560 Ala Ala Leu Ala Leu Thr Val Asp Leu Pro Pro Ala Ser Ser Glu Ala 565 570 575 Arg Asn Ser Ala Phe Gly Phe Gln Gly Arg Leu Leu His Leu Ser Ala 580 585 590 Gly Gln Arg Leu Gly Val His Leu His Thr Glu Ala Arg Ala Arg His 595 600 605 Ala Trp Gln Leu Thr Gln Gly Ala Thr Val Leu Gly Leu Phe Arg Val 610 615 620 Thr Pro Glu Ile Pro Ala Gly Leu Pro Ser Pro Arg Ser Glu Gly Gly 625 630 635 640 Gly Gly Ser Gly Gly Gly Gly Ser Arg Glu Gly Pro Glu Leu Ser Pro 645 650 655 Asp Asp Pro Ala Gly Leu Leu Asp Leu Arg Gln Gly Met Phe Ala Gln 660 665 670 Leu Val Ala Gln Asn Val Leu Leu Ile Asp Gly Pro Leu Ser Trp Tyr 675 680 685 Ser Asp Pro Gly Leu Ala Gly Val Ser Leu Thr Gly Gly Leu Ser Tyr 690 695 700 Lys Glu Asp Thr Lys Glu Leu Val Val Ala Lys Ala Gly Val Tyr Tyr 705 710 715 720 Val Phe Phe Gln Leu Glu Leu Arg Arg Val Val Ala Gly Glu Gly Ser 725 730 735 Gly Ser Val Ser Leu Ala Leu His Leu Gln Pro Leu Arg Ser Ala Ala 740 745 750 Gly Ala Ala Ala Leu Ala Leu Thr Val Asp Leu Pro Pro Ala Ser Ser 755 760 765 Glu Ala Arg Asn Ser Ala Phe Gly Phe Gln Gly Arg Leu Leu His Leu 770 775 780 Ser Ala Gly Gln Arg Leu Gly Val His Leu His Thr Glu Ala Arg Ala 785 790 795 800 Arg His Ala Trp Gln Leu Thr Gln Gly Ala Thr Val Leu Gly Leu Phe 805 810 815 Arg Val Thr Pro Glu Ile Pro Ala Gly Leu Pro Ser Pro Arg Ser Glu 820 825 830 <210> 158 <211> 638 <212> PRT <213> Secuencia artificial <220> <223> cadena pomo Fc de DP47 fusionada a 4-1BBL hu monomérico (71-254) <400> 158 Glu Val Gln Leu Leu Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 1 5 10 15 Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Ser Tyr 20 25 30 Ala Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45 Ser Ala Ile Ser Gly Ser Gly Gly Ser Thr Tyr Tyr Ala Asp Ser Val 50 55 60 Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 65 70 75 80 Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Ala Lys Gly Ser Gly Phe Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr 100 105 110 Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro 115 120 125 Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val 130 135 140 Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala 145 150 155 160 Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly 165 170 175 Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly 180 185 190 Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys 195 200 205 Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys 210 215 220 Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu 225 230 235 240 Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu 245 250 255 Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys 260 265 270 Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys 275 280 285 Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu 290 295 300 Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys 305 310 315 320 Val Ser Asn Lys Ala Leu Gly Ala Pro Ile Glu Lys Thr Ile Ser Lys 325 330 335 Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Cys 340 345 350 Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Trp Cys Leu Val Lys 355 360 365 Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln 370 375 380 Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly 385 390 395 400 Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln 405 410 415 Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn 420 425 430 His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Gly Gly Gly Gly 435 440 445 Ser Gly Gly Gly Gly Ser Arg Glu Gly Pro Glu Leu Ser Pro Asp Asp 450 455 460 Pro Ala Gly Leu Leu Asp Leu Arg Gln Gly Met Phe Ala Gln Leu Val 465 470 475 480 Ala Gln Asn Val Leu Leu Ile Asp Gly Pro Leu Ser Trp Tyr Ser Asp 485 490 495 Pro Gly Leu Ala Gly Val Ser Leu Thr Gly Gly Leu Ser Tyr Lys Glu 500 505 510 Asp Thr Lys Glu Leu Val Val Ala Lys Ala Gly Val Tyr Tyr Val Phe 515 520 525 Phe Gln Leu Glu Leu Arg Arg Val Val Ala Gly Glu Gly Ser Gly Ser 530 535 540 Val Ser Leu Ala Leu His Leu Gln Pro Leu Arg Ser Ala Ala Gly Ala 545 550 555 560 Ala Ala Leu Ala Leu Thr Val Asp Leu Pro Pro Ala Ser Ser Glu Ala 565 570 575 Arg Asn Ser Ala Phe Gly Phe Gln Gly Arg Leu Leu His Leu Ser Ala 580 585 590 Gly Gln Arg Leu Gly Val His Leu His Thr Glu Ala Arg Ala Arg His 595 600 605 Ala Trp Gln Leu Thr Gln Gly Ala Thr Val Leu Gly Leu Phe Arg Val 610 615 620 Thr Pro Glu Ile Pro Ala Gly Leu Pro Ser Pro Arg Ser Glu 625 630 635 <210> 159 <211> 1335 <212> ADN <213> Secuencia artificial <220> <223> secuencia de nucleótidos de cadena pesada de DP47 (IgG1 hu PGLALA) <400> 159 gaggtgcaat tgttggagtc tgggggaggc ttggtacagc ctggggggtc cctgagactc 60 tcctgtgcag cctccggatt cacctttagc agttatgcca tgagctgggt ccgccaggct 120 ccagggaagg ggctggagtg ggtctcagct attagtggta gtggtggtag cacatactac 180 gcagactccg tgaagggccg gttcaccatc tccagagaca attccaagaa cacgctgtat 240 ctgcagatga acagcctgag agccgaggac acggccgtat attactgtgc gaaaggcagc 300 ggatttgact actggggcca aggaaccctg gtcaccgtct cgagtgctag caccaagggc 360 ccatcggtct tccccctggc accctcctcc aagagcacct ctgggggcac agcggccctg 420 ggctgcctgg tcaaggacta cttccccgaa ccggtgacgg tgtcgtggaa ctcaggcgcc 480 ctgaccagcg gcgtgcacac cttcccggct gtcctacagt cctcaggact ctactccctc 540 agcagcgtgg tgaccgtgcc ctccagcagc ttgggcaccc agacctacat ctgcaacgtg 600 aatcacaagc ccagcaacac caaggtggac aagaaagttg agcccaaatc ttgtgacaaa 660 actcacacat gcccaccgtg cccagcacct gaagctgcag ggggaccgtc agtcttcctc 720 ttccccccaa aacccaagga caccctcatg atctcccgga cccctgaggt cacatgcgtg 780 gtggtggacg tgagccacga agaccctgag gtcaagttca actggtacgt ggacggcgtg 840 gaggtgcata atgccaagac aaagccgcgg gaggagcagt acaacagcac gtaccgtgtg 900 gtcagcgtcc tcaccgtcct gcaccaggac tggctgaatg gcaaggagta caagtgcaag 960 gtctccaaca aagccctcgg cgcccccatc gagaaaacca tctccaaagc caaagggcag 1020 ccccgagaac cacaggtgta caccctgccc ccatcccggg atgagctgac caagaaccag 1080 gtcagcctga cctgcctggt caaaggcttc tatcccagcg acatcgccgt ggagtgggag 1140 agcaatgggc agccggagaa caactacaag accacgcctc ccgtgctgga ctccgacggc 1200 tccttcttcc tctacagcaa gctcaccgtg gacaagagca ggtggcagca ggggaacgtc 1260 ttctcatgct ccgtgatgca tgaggctctg cacaaccact acacgcagaa gagcctctcc 1320 ctgtctccgg gtaaa 1335 <210> 160 <211> 445 <212> PRT <213> Secuencia artificial <220> <223> cadena pesada de DP47 (IgG1 hu PGLALA) <400> 160 Glu Val Gln Leu Leu Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 1 5 10 15 Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Ser Tyr 20 25 30 Ala Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45 Ser Ala Ile Ser Gly Ser Gly Gly Ser Thr Tyr Tyr Ala Asp Ser Val 50 55 60 Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 65 70 75 80 Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Ala Lys Gly Ser Gly Phe Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr 100 105 110 Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro 115 120 125 Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val 130 135 140 Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala 145 150 155 160 Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly 165 170 175 Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly 180 185 190 Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys 195 200 205 Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys 210 215 220 Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu 225 230 235 240 Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu 245 250 255 Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys 260 265 270 Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys 275 280 285 Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu 290 295 300 Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys 305 310 315 320 Val Ser Asn Lys Ala Leu Gly Ala Pro Ile Glu Lys Thr Ile Ser Lys 325 330 335 Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser 340 345 350 Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys 355 360 365 Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln 370 375 380 Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly 385 390 395 400 Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln 405 410 415 Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn 420 425 430 His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys 435 440 445 <210> 161 <211> 1350 <212> ADN <213> Secuencia artificial <220> <223> secuencia de nucleótidos de cadena pesada de PD1(0314) (IgG1 hu PGLALA) <400> 161 gaagtgcagc tgctcgaaag cggcggggga ctggtccagc ccggcggttc cctgaggctg 60 tcttgcgccg cttcagggtt cagcttttcc tcttacacca tgagttgggt cagacaggca 120 cctggcaagg gactggagtg ggtcgccaca atcagcggtg gcgggcgcga catttattac 180 ccagattccg tgaaaggacg gttcaccatc tctagggaca actcaaagaa tactctgtat 240 ttgcagatga acagcctgag agctgaggat acagcagttt actactgtgt gctcctgacc 300 ggccgcgtct attttgccct tgactcctgg ggacaaggca ctctggtgac cgtatctagt 360 gctagcacca agggcccatc ggtcttcccc ctggcaccct cctccaagag cacctctggg 420 ggcacagcgg ccctgggctg cctggtcaag gactacttcc ccgaaccggt gacggtgtcg 480 tggaactcag gcgccctgac cagcggcgtg cacaccttcc cggctgtcct acagtcctca 540 ggactctact ccctcagcag cgtggtgacc gtgccctcca gcagcttggg cacccagacc 600 tacatctgca acgtgaatca caagcccagc aacaccaagg tggacaagaa agttgagccc 660 aaatcttgtg acaaaactca cacatgccca ccgtgcccag cacctgaagc tgcaggggga 720 ccgtcagtct tcctcttccc cccaaaaccc aaggacaccc tcatgatctc ccggacccct 780 gaggtcacat gcgtggtggt ggacgtgagc cacgaagacc ctgaggtcaa gttcaactgg 840 tacgtggacg gcgtggaggt gcataatgcc aagacaaagc cgcgggagga gcagtacaac 900 agcacgtacc gtgtggtcag cgtcctcacc gtcctgcacc aggactggct gaatggcaag 960 gagtacaagt gcaaggtctc caacaaagcc ctcggcgccc ccatcgagaa aaccatctcc 1020 aaagccaaag ggcagccccg agaaccacag gtgtacaccc tgcccccatc ccgggatgag 1080 ctgaccaaga accaggtcag cctgacctgc ctggtcaaag gcttctatcc cagcgacatc 1140 gccgtggagt gggagagcaa tgggcagccg gagaacaact acaagaccac gcctcccgtg 1200 ctggactccg acggctcctt cttcctctac agcaagctca ccgtggacaa gagcaggtgg 1260 cagcagggga acgtcttctc atgctccgtg atgcatgagg ctctgcacaa ccactacacg 1320 cagaagagcc tctccctgtc tccgggtaaa 1350 <210> 162 <211> 450 <212> PRT <213> Secuencia artificial <220> <223> cadena pesada de PD1(0314) (IgG1 hu PGLALA) <400> 162 Glu Val Gln Leu Leu Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 1 5 10 15 Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Ser Phe Ser Ser Tyr 20 25 30 Thr Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45 Ala Thr Ile Ser Gly Gly Gly Arg Asp Ile Tyr Tyr Pro Asp Ser Val 50 55 60 Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 65 70 75 80 Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Val Leu Leu Thr Gly Arg Val Tyr Phe Ala Leu Asp Ser Trp Gly Gln 100 105 110 Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val 115 120 125 Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala 130 135 140 Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser 145 150 155 160 Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val 165 170 175 Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro 180 185 190 Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys 195 200 205 Pro Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp 210 215 220 Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly Gly 225 230 235 240 Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile 245 250 255 Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu 260 265 270 Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His 275 280 285 Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg 290 295 300 Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys 305 310 315 320 Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Gly Ala Pro Ile Glu 325 330 335 Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr 340 345 350 Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu 355 360 365 Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp 370 375 380 Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val 385 390 395 400 Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp 405 410 415 Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His 420 425 430 Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro 435 440 445 Gly Lys 450 <210> 163 <211> 163 <212> PRT <213> Homo sapiens <400> 163 Leu Gln Asp Pro Cys Ser Asn Cys Pro Ala Gly Thr Phe Cys Asp Asn 1 5 10 15 Asn Arg Asn Gln Ile Cys Ser Pro Cys Pro Pro Asn Ser Phe Ser Ser 20 25 30 Ala Gly Gly Gln Arg Thr Cys Asp Ile Cys Arg Gln Cys Lys Gly Val 35 40 45 Phe Arg Thr Arg Lys Glu Cys Ser Ser Thr Ser Asn Ala Glu Cys Asp 50 55 60 Cys Thr Pro Gly Phe His Cys Leu Gly Ala Gly Cys Ser Met Cys Glu 65 70 75 80 Gln Asp Cys Lys Gln Gly Gln Glu Leu Thr Lys Lys Gly Cys Lys Asp 85 90 95 Cys Cys Phe Gly Thr Phe Asn Asp Gln Lys Arg Gly Ile Cys Arg Pro 100 105 110 Trp Thr Asn Cys Ser Leu Asp Gly Lys Ser Val Leu Val Asn Gly Thr 115 120 125 Lys Glu Arg Asp Val Val Cys Gly Pro Ser Pro Ala Asp Leu Ser Pro 130 135 140 Gly Ala Ser Ser Val Thr Pro Pro Ala Pro Ala Arg Glu Pro Gly His 145 150 155 160 Ser Pro Gln <210> 164 <211> 681 <212> ADN <213> Secuencia artificial <220> <223> secuencia de nucleótidos de cadena agujero Fc <400> 164 gacaaaactc acacatgccc accgtgccca gcacctgaac tcctgggggg accgtcagtc 60 ttcctcttcc ccccaaaacc caaggacacc ctcatgatct cccggacccc tgaggtcaca 120 tgcgtggtgg tggacgtgag ccacgaagac cctgaggtca agttcaactg gtacgtggac 180 ggcgtggagg tgcataatgc caagacaaag ccgcgggagg agcagtacaa cagcacgtac 240 cgtgtggtca gcgtcctcac cgtcctgcac caggactggc tgaatggcaa ggagtacaag 300 tgcaaggtct ccaacaaagc cctcccagcc cccatcgaga aaaccatctc caaagccaaa 360 gggcagcccc gagaaccaca ggtgtgcacc ctgcccccat cccgggatga gctgaccaag 420 aaccaggtca gcctctcgtg cgcagtcaaa ggcttctatc ccagcgacat cgccgtggag 480 tgggagagca atgggcagcc ggagaacaac tacaagacca cgcctcccgt gctggactcc 540 gacggctcct tcttcctcgt gagcaagctc accgtggaca agagcaggtg gcagcagggg 600 aacgtcttct catgctccgt gatgcatgag gctctgcaca accactacac gcagaagagc 660 ctctccctgt ctccgggtaa a 681 <210> 165 <211> 1266 <212> ADN <213> Secuencia artificial <220> <223> Secuencia de nucleótidos de cadena pomo Fc de antígeno 4-1BB humano <400> 165 ctgcaggacc cctgcagcaa ctgccctgcc ggcaccttct gcgacaacaa ccggaaccag 60 atctgcagcc cctgcccccc caacagcttc agctctgccg gcggacagcg gacctgcgac 120 atctgcagac agtgcaaggg cgtgttcaga acccggaaag agtgcagcag caccagcaac 180 gccgagtgcg actgcacccc cggcttccat tgtctgggag ccggctgcag catgtgcgag 240 caggactgca agcagggcca ggaactgacc aagaagggct gcaaggactg ctgcttcggc 300 accttcaacg accagaagcg gggcatctgc cggccctgga ccaactgtag cctggacggc 360 aagagcgtgc tggtcaacgg caccaaagaa cgggacgtcg tgtgcggccc cagccctgct 420 gatctgtctc ctggggccag cagcgtgacc cctcctgccc ctgccagaga gcctggccac 480 tctcctcagg tcgacgaaca gttatatttt cagggcggct cacccaaatc tgcagacaaa 540 actcacacat gcccaccgtg cccagcacct gaactcctgg ggggaccgtc agtcttcctc 600 ttccccccaa aacccaagga caccctcatg atctcccgga cccctgaggt cacatgcgtg 660 gtggtggacg tgagccacga agaccctgag gtcaagttca actggtacgt ggacggcgtg 720 gaggtgcata atgccaagac aaagccgcgg gaggagcagt acaacagcac gtaccgtgtg 780 gtcagcgtcc tcaccgtcct gcaccaggac tggctgaatg gcaaggagta caagtgcaag 840 gtctccaaca aagccctccc agcccccatc gagaaaacca tctccaaagc caaagggcag 900 ccccgagaac cacaggtgta caccctgccc ccatgccggg atgagctgac caagaaccag 960 gtcagcctgt ggtgcctggt caaaggcttc tatcccagcg acatcgccgt ggagtgggag 1020 agcaatgggc agccggagaa caactacaag accacgcctc ccgtgctgga ctccgacggc 1080 tccttcttcc tctacagcaa gctcaccgtg gacaagagca ggtggcagca ggggaacgtc 1140 ttctcatgct ccgtgatgca tgaggctctg cacaaccact acacgcagaa gagcctctcc 1200 ctgtctccgg gtaaatccgg aggcctgaac gacatcttcg aggcccagaa gattgaatgg 1260 cacgag 1266 <210> 166 <211> 227 <212> PRT <213> Secuencia artificial <220> <223> cadena Fc agujero <400> 166 Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly 1 5 10 15 Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met 20 25 30 Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His 35 40 45 Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val 50 55 60 His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr 65 70 75 80 Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly 85 90 95 Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile 100 105 110 Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val 115 120 125 Cys Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser 130 135 140 Leu Ser Cys Ala Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu 145 150 155 160 Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro 165 170 175 Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Val Ser Lys Leu Thr Val 180 185 190 Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met 195 200 205 His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser 210 215 220 Pro Gly Lys 225 <210> 167 <211> 422 <212> PRT <213> Secuencia artificial <220> <223> cadena pomo Fc de antígeno 4-1BB humano <400> 167 Leu Gln Asp Pro Cys Ser Asn Cys Pro Ala Gly Thr Phe Cys Asp Asn 1 5 10 15 Asn Arg Asn Gln Ile Cys Ser Pro Cys Pro Pro Asn Ser Phe Ser Ser 20 25 30 Ala Gly Gly Gln Arg Thr Cys Asp Ile Cys Arg Gln Cys Lys Gly Val 35 40 45 Phe Arg Thr Arg Lys Glu Cys Ser Ser Thr Ser Asn Ala Glu Cys Asp 50 55 60 Cys Thr Pro Gly Phe His Cys Leu Gly Ala Gly Cys Ser Met Cys Glu 65 70 75 80 Gln Asp Cys Lys Gln Gly Gln Glu Leu Thr Lys Lys Gly Cys Lys Asp 85 90 95 Cys Cys Phe Gly Thr Phe Asn Asp Gln Lys Arg Gly Ile Cys Arg Pro 100 105 110 Trp Thr Asn Cys Ser Leu Asp Gly Lys Ser Val Leu Val Asn Gly Thr 115 120 125 Lys Glu Arg Asp Val Val Cys Gly Pro Ser Pro Ala Asp Leu Ser Pro 130 135 140 Gly Ala Ser Ser Val Thr Pro Pro Ala Pro Ala Arg Glu Pro Gly His 145 150 155 160 Ser Pro Gln Val Asp Glu Gln Leu Tyr Phe Gln Gly Gly Ser Pro Lys 165 170 175 Ser Ala Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu 180 185 190 Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr 195 200 205 Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val 210 215 220 Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val 225 230 235 240 Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser 245 250 255 Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu 260 265 270 Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala 275 280 285 Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro 290 295 300 Gln Val Tyr Thr Leu Pro Pro Cys Arg Asp Glu Leu Thr Lys Asn Gln 305 310 315 320 Val Ser Leu Trp Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala 325 330 335 Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr 340 345 350 Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu 355 360 365 Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser 370 375 380 Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser 385 390 395 400 Leu Ser Pro Gly Lys Ser Gly Gly Leu Asn Asp Ile Phe Glu Ala Gln 405 410 415 Lys Ile Glu Trp His Glu 420 <210> 168 <211> 15 <212> PRT <213> Secuencia artificial <220> <223> etiqueta avi <400> 168 Gly Leu Asn Asp Ile Phe Glu Ala Gln Lys Ile Glu Trp His Glu 1 5 10 15 <210> 169 <211> 594 <212> ADN <213> Secuencia artificial <220> <223> secuencia de nucleótidos de 4-1BB His humano <400> 169 ctgcaggacc cctgcagcaa ctgccctgcc ggcaccttct gcgacaacaa ccggaaccag 60 atctgcagcc cctgcccccc caacagcttc agctctgccg gcggacagcg gacctgcgac 120 atctgcagac agtgcaaggg cgtgttcaga acccggaaag agtgcagcag caccagcaac 180 gccgagtgcg actgcacccc cggcttccat tgtctgggag ccggctgcag catgtgcgag 240 caggactgca agcagggcca ggaactgacc aagaagggct gcaaggactg ctgcttcggc 300 accttcaacg accagaagcg gggcatctgc cggccctgga ccaactgtag cctggacggc 360 aagagcgtgc tggtcaacgg caccaaagaa cgggacgtcg tgtgcggccc cagccctgct 420 gatctgtctc ctggggccag cagcgtgacc cctcctgccc ctgccagaga gcctggccac 480 tctcctcagg tcgacgaaca gttatatttt cagggcggct caggcctgaa cgacatcttc 540 gaggcccaga agatcgagtg gcacgaggct cgagctcacc accatcacca tcac 594 <210> 170 <211> 198 <212> PRT <213> Secuencia artificial <220> <223> 4-1BB His humano <400> 170 Leu Gln Asp Pro Cys Ser Asn Cys Pro Ala Gly Thr Phe Cys Asp Asn 1 5 10 15 Asn Arg Asn Gln Ile Cys Ser Pro Cys Pro Pro Asn Ser Phe Ser Ser 20 25 30 Ala Gly Gly Gln Arg Thr Cys Asp Ile Cys Arg Gln Cys Lys Gly Val 35 40 45 Phe Arg Thr Arg Lys Glu Cys Ser Ser Thr Ser Asn Ala Glu Cys Asp 50 55 60 Cys Thr Pro Gly Phe His Cys Leu Gly Ala Gly Cys Ser Met Cys Glu 65 70 75 80 Gln Asp Cys Lys Gln Gly Gln Glu Leu Thr Lys Lys Gly Cys Lys Asp 85 90 95 Cys Cys Phe Gly Thr Phe Asn Asp Gln Lys Arg Gly Ile Cys Arg Pro 100 105 110 Trp Thr Asn Cys Ser Leu Asp Gly Lys Ser Val Leu Val Asn Gly Thr 115 120 125 Lys Glu Arg Asp Val Val Cys Gly Pro Ser Pro Ala Asp Leu Ser Pro 130 135 140 Gly Ala Ser Ser Val Thr Pro Pro Ala Pro Ala Arg Glu Pro Gly His 145 150 155 160 Ser Pro Gln Val Asp Glu Gln Leu Tyr Phe Gln Gly Gly Ser Gly Leu 165 170 175 Asn Asp Ile Phe Glu Ala Gln Lys Ile Glu Trp His Glu Ala Arg Ala 180 185 190 His His His His His His 195 <210> 171 <211> 218 <212> PRT <213> Secuencia artificial <220> <223> cadena ligera de anti-PD1 (0312) <400> 171 Asp Ile Val Met Thr Gln Ser Pro Asp Ser Leu Ala Val Ser Leu Gly 1 5 10 15 Glu Arg Ala Thr Ile Asn Cys Lys Ala Ser Glu Ser Val Asp Thr Ser 20 25 30 Asp Asn Ser Phe Ile His Trp Tyr Gln Gln Lys Pro Gly Gln Ser Pro 35 40 45 Lys Leu Leu Ile Tyr Arg Ser Ser Thr Leu Glu Ser Gly Val Pro Asp 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 Gln Ala Glu Asp Val Ala Val Tyr Tyr Cys Gln Gln Asn Tyr 85 90 95 Asp Val Pro Trp Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Arg 100 105 110 Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln 115 120 125 Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr 130 135 140 Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser 145 150 155 160 Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr 165 170 175 Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys 180 185 190 His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro 195 200 205 Val Thr Lys Ser Phe Asn Arg Gly Glu Cys 210 215