LISTADO DE SECUENCIAS <110> F. Hoffmann-La Roche AG <120> Anticuerpo que se une a VEGF y a IL-1beta y métodos de utilización <130> P35223 (MME) <150> EP18215023.5 <151> 21-12-2018 <160> 27 <170> PatentIn versión 3.5 <210> 1 <211> 115 <212> PRT <213> Secuencia artificial <220> <223> dominio VH de 1HVL2.3 <400> 1 Glu Gln Leu Val Glu Ser Gly Gly Gly Leu Val Lys Pro Gly Gly Ser 1 5 10 15 Leu Arg Leu Ser Cys Ala Ala Ser Gly Met Val Phe Ser Trp Asn Ala 20 25 30 Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Gly 35 40 45 Ser Ile Ser Pro Lys Gly Asp His Lys Tyr Leu Asn Thr Lys Phe Ile 50 55 60 Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr Leu 65 70 75 80 Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala 85 90 95 Lys Asp Ile Gly Phe Phe Asp Val Trp Gly Gln Gly Thr Leu Val Thr 100 105 110 Val Ser Ser 115 <210> 2 <211> 108 <212> PRT <213> Secuencia artificial <220> <223> dominio VL de 1HVL2.3 <400> 2 Ala Ile Tyr Met His Gln Glu Pro Ser Ser Leu Ser Ala Ser Val Gly 1 5 10 15 Asp Arg Val Thr Ile Thr Cys His Gly Ser Tyr Trp Leu Ser Asn Tyr 20 25 30 Leu Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile 35 40 45 Tyr Asp Ala Ser Tyr Arg Ile Ile Gly Val Pro Ser Arg Phe Ser Gly 50 55 60 Ser Gly Ser His Glu Asp Tyr Thr Leu Thr Ile Ser Ser Leu Gln Pro 65 70 75 80 Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Tyr Arg Tyr His Pro Tyr 85 90 95 Thr Phe Gly His Gly Thr Lys Val Glu Ile Lys Arg 100 105 <210> 3 <211> 5 <212> PRT <213> Secuencia artificial <220> <223> H-CDR1 de 1HVL2.3 <400> 3 Trp Asn Ala Met Ser 1 5 <210> 4 <211> 17 <212> PRT <213> Secuencia artificial <220> <223> H-CDR2 de 1HVL2.3 <400> 4 Ser Ile Ser Pro Lys Gly Asp His Lys Tyr Leu Asn Thr Lys Phe Ile 1 5 10 15 Gly <210> 5 <211> 7 <212> PRT <213> Secuencia artificial <220> <223> H-CDR3 de 1HVL2.3 <400> 5 Asp Ile Gly Phe Phe Asp Val 1 5 <210> 6 <211> 11 <212> PRT <213> Secuencia artificial <220> <223> L-CDR1 de 1HVL2.3 <400> 6 His Gly Ser Tyr Trp Leu Ser Asn Tyr Leu Ala 1 5 10 <210> 7 <211> 7 <212> PRT <213> Secuencia artificial <220> <223> L-CDR2 de 1HVL2.3 <400> 7 Asp Ala Ser Tyr Arg Ile Ile 1 5 <210> 8 <211> 9 <212> PRT <213> Secuencia artificial <220> <223> L-CDR3 de 1HVL2.3, 1HVL12.85, 1HVL5.15 y RO7200394 <400> 8 Gln Gln Tyr Arg Tyr His Pro Tyr Thr 1 5 <210> 9 <211> 223 <212> PRT <213> Secuencia artificial <220> <223> cadena pesada de fragmento Fab de 1HVL2.3 <400> 9 Glu Gln Leu Val Glu Ser Gly Gly Gly Leu Val Lys Pro Gly Gly Ser 1 5 10 15 Leu Arg Leu Ser Cys Ala Ala Ser Gly Met Val Phe Ser Trp Asn Ala 20 25 30 Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Gly 35 40 45 Ser Ile Ser Pro Lys Gly Asp His Lys Tyr Leu Asn Thr Lys Phe Ile 50 55 60 Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr Leu 65 70 75 80 Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala 85 90 95 Lys Asp Ile Gly Phe Phe Asp Val 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 Lys 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 210 215 220 <210> 10 <211> 214 <212> PRT <213> Secuencia artificial <220> <223> cadena ligera de fragmento Fab de 1HVL2.3 <400> 10 Ala Ile Tyr Met His Gln Glu Pro Ser Ser Leu Ser Ala Ser Val Gly 1 5 10 15 Asp Arg Val Thr Ile Thr Cys His Gly Ser Tyr Trp Leu Ser Asn Tyr 20 25 30 Leu Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile 35 40 45 Tyr Asp Ala Ser Tyr Arg Ile Ile Gly Val Pro Ser Arg Phe Ser Gly 50 55 60 Ser Gly Ser His Glu Asp Tyr Thr Leu Thr Ile Ser Ser Leu Gln Pro 65 70 75 80 Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Tyr Arg Tyr His Pro Tyr 85 90 95 Thr Phe Gly His Gly Thr Lys Val Glu Ile Lys Arg Thr Val Ala Ala 100 105 110 Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly 115 120 125 Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala 130 135 140 Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln 145 150 155 160 Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser 165 170 175 Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr 180 185 190 Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser 195 200 205 Phe Asn Arg Gly Glu Cys 210 <210> 11 <211> 116 <212> PRT <213> Secuencia artificial <220> <223> dominio VH de 1HVL12.85 y RO7200394 <400> 11 Asp Glu Gln Leu Val Glu Ser Gly Gly Gly Leu Val Lys Pro Gly Gly 1 5 10 15 Ser Leu Arg Leu Ser Cys Ala Ala Glu Gly Met Val Phe Lys Trp Asn 20 25 30 Asp Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45 Gly Ser Ile Ser Lys Lys Gly Asp His Lys Tyr Leu Asn Thr Lys Phe 50 55 60 Ile Gly Arg Phe Thr Ile Ser Arg Asp Asn Glu Lys Asp 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 Asp Val Gly Phe Phe Asp Ile Trp Gly Gln Gly Thr Leu Val 100 105 110 Thr Val Ser Ser 115 <210> 12 <211> 107 <212> PRT <213> Secuencia artificial <220> <223> dominio VL de 1HVL12.85 y RO7200394 <400> 12 Ala Ile Tyr Met His Gln Glu Pro Ser Ser Leu Ser Ala Ser Val Gly 1 5 10 15 Asp Arg Val Thr Ile Thr Cys His Gly Ser Tyr Trp Leu Ser Ser Leu 20 25 30 Val Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile 35 40 45 Tyr Asp Ala Lys Tyr Lys His Leu Gly Val Pro Ser Arg Phe Ser Gly 50 55 60 Ser Lys Glu Asp Gln Glu Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro 65 70 75 80 Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Tyr Arg Tyr His Pro Tyr 85 90 95 Thr Phe Gly His Gly Thr Lys Val Glu Ile Lys 100 105 <210> 13 <211> 5 <212> PRT <213> Secuencia artificial <220> <223> H-CDR1 de 1HVL12.85, 1HVL5.15 y RO7200394 <400> 13 Trp Asn Asp Met Ser 1 5 <210> 14 <211> 17 <212> PRT <213> Secuencia artificial <220> <223> H-CDR2 de 1HVL12.85, 1HVL5.15 y RO7200394 <400> 14 Ser Ile Ser Lys Lys Gly Asp His Lys Tyr Leu Asn Thr Lys Phe Ile 1 5 10 15 Gly <210> 15 <211> 7 <212> PRT <213> Secuencia artificial <220> <223> H-CDR3 de 1HVL12.85, 1HVL5.15 y RO7200394 <400> 15 Asp Val Gly Phe Phe Asp Ile 1 5 <210> 16 <211> 11 <212> PRT <213> Secuencia artificial <220> <223> L-CDR1 de 1HVL12.85 y RO7200394 <400> 16 His Gly Ser Tyr Trp Leu Ser Ser Leu Val Ala 1 5 10 <210> 17 <211> 7 <212> PRT <213> Secuencia artificial <220> <223> L-CDR2 de 1HVL12.85, 1HVL5.15 y RO7200394 <400> 17 Asp Ala Lys Tyr Lys His Leu 1 5 <210> 18 <211> 224 <212> PRT <213> Secuencia artificial <220> <223> cadena pesada de fragmento Fab de 1HVL12.85 <400> 18 Asp Glu Gln Leu Val Glu Ser Gly Gly Gly Leu Val Lys Pro Gly Gly 1 5 10 15 Ser Leu Arg Leu Ser Cys Ala Ala Glu Gly Met Val Phe Lys Trp Asn 20 25 30 Asp Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45 Gly Ser Ile Ser Lys Lys Gly Asp His Lys Tyr Leu Asn Thr Lys Phe 50 55 60 Ile Gly Arg Phe Thr Ile Ser Arg Asp Asn Glu Lys Asp 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 Asp Val Gly Phe Phe Asp Ile Trp Gly Gln Gly Thr Leu Val 100 105 110 Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala 115 120 125 Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu 130 135 140 Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly 145 150 155 160 Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser 165 170 175 Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu 180 185 190 Gly Thr Lys Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr 195 200 205 Lys Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr 210 215 220 <210> 19 <211> 214 <212> PRT <213> Secuencia artificial <220> <223> cadena ligera de 1HVL12.85 y fragmento Fab de RO7200394 <400> 19 Ala Ile Tyr Met His Gln Glu Pro Ser Ser Leu Ser Ala Ser Val Gly 1 5 10 15 Asp Arg Val Thr Ile Thr Cys His Gly Ser Tyr Trp Leu Ser Ser Leu 20 25 30 Val Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile 35 40 45 Tyr Asp Ala Lys Tyr Lys His Leu Gly Val Pro Ser Arg Phe Ser Gly 50 55 60 Ser Lys Glu Asp Gln Glu Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro 65 70 75 80 Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Tyr Arg Tyr His Pro Tyr 85 90 95 Thr Phe Gly His Gly Thr Lys Val Glu Ile Lys Arg Thr Val Ala Ala 100 105 110 Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly 115 120 125 Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala 130 135 140 Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln 145 150 155 160 Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser 165 170 175 Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr 180 185 190 Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser 195 200 205 Phe Asn Arg Gly Glu Cys 210 <210> 20 <211> 224 <212> PRT <213> Secuencia artificial <220> <223> cadena pesada de fragmento Fab de RO7200394 (SEC ID nº 19 con mutación K196Q) <400> 20 Asp Glu Gln Leu Val Glu Ser Gly Gly Gly Leu Val Lys Pro Gly Gly 1 5 10 15 Ser Leu Arg Leu Ser Cys Ala Ala Glu Gly Met Val Phe Lys Trp Asn 20 25 30 Asp Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45 Gly Ser Ile Ser Lys Lys Gly Asp His Lys Tyr Leu Asn Thr Lys Phe 50 55 60 Ile Gly Arg Phe Thr Ile Ser Arg Asp Asn Glu Lys Asp 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 Asp Val Gly Phe Phe Asp Ile Trp Gly Gln Gly Thr Leu Val 100 105 110 Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala 115 120 125 Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu 130 135 140 Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly 145 150 155 160 Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser 165 170 175 Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu 180 185 190 Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr 195 200 205 Lys Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr 210 215 220 <210> 21 <211> 116 <212> PRT <213> Secuencia artificial <220> <223> dominio VH de 1HVL5.15 <400> 21 Asp Glu Thr Leu Val Glu Ser Gly Gly Gly Leu Val Lys Pro Gly Gly 1 5 10 15 Ser Leu Arg Leu Ser Cys Ala Ala Glu Gly Met Val Phe Lys Trp Asn 20 25 30 Asp Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45 Gly Ser Ile Ser Lys Lys Gly Asp His Lys Tyr Leu Asn Thr Lys Phe 50 55 60 Ile Gly Arg Phe Thr Ile Ser Arg Asp Asn Glu Lys Asp 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 Asp Val Gly Phe Phe Asp Ile Trp Gly Gln Gly Thr Leu Val 100 105 110 Thr Val Ser Ser 115 <210> 22 <211> 107 <212> PRT <213> Secuencia artificial <220> <223> dominio VL de 1HVL5.15 <400> 22 Ala Ile Tyr Met His Gln Glu Pro Ser Ser Leu Ser Ala Ser Val Gly 1 5 10 15 Asp Arg Val Thr Ile Thr Cys His Gly Ser Tyr Trp Leu Ser Ser Leu 20 25 30 Met Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile 35 40 45 Tyr Asp Ala Lys Tyr Lys His Leu Gly Val Pro Ser Arg Phe Ser Gly 50 55 60 Ser Gly Ser His Glu Asp Tyr Thr Leu Thr Ile Ser Ser Leu Gln Pro 65 70 75 80 Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Tyr Arg Tyr His Pro Tyr 85 90 95 Thr Phe Gly His Gly Thr Lys Val Glu Ile Lys 100 105 <210> 23 <211> 11 <212> PRT <213> Secuencia artificial <220> <223> L-CDR1 de 1HVL5.15 <400> 23 His Gly Ser Tyr Trp Leu Ser Ser Leu Met Ala 1 5 10 <210> 24 <211> 224 <212> PRT <213> Secuencia artificial <220> <223> cadena pesada de fragmento Fab de 1HVL5.15 <400> 24 Asp Glu Thr Leu Val Glu Ser Gly Gly Gly Leu Val Lys Pro Gly Gly 1 5 10 15 Ser Leu Arg Leu Ser Cys Ala Ala Glu Gly Met Val Phe Lys Trp Asn 20 25 30 Asp Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45 Gly Ser Ile Ser Lys Lys Gly Asp His Lys Tyr Leu Asn Thr Lys Phe 50 55 60 Ile Gly Arg Phe Thr Ile Ser Arg Asp Asn Glu Lys Asp 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 Asp Val Gly Phe Phe Asp Ile Trp Gly Gln Gly Thr Leu Val 100 105 110 Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala 115 120 125 Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu 130 135 140 Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly 145 150 155 160 Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser 165 170 175 Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu 180 185 190 Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr 195 200 205 Lys Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr 210 215 220 <210> 25 <211> 214 <212> PRT <213> Secuencia artificial <220> <223> cadena ligera de fragmento Fab de 1HVL5.15 <400> 25 Ala Ile Tyr Met His Gln Glu Pro Ser Ser Leu Ser Ala Ser Val Gly 1 5 10 15 Asp Arg Val Thr Ile Thr Cys His Gly Ser Tyr Trp Leu Ser Ser Leu 20 25 30 Met Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile 35 40 45 Tyr Asp Ala Lys Tyr Lys His Leu Gly Val Pro Ser Arg Phe Ser Gly 50 55 60 Ser Gly Ser His Glu Asp Tyr Thr Leu Thr Ile Ser Ser Leu Gln Pro 65 70 75 80 Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Tyr Arg Tyr His Pro Tyr 85 90 95 Thr Phe Gly His Gly Thr Lys Val Glu Ile Lys Arg Thr Val Ala Ala 100 105 110 Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly 115 120 125 Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala 130 135 140 Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln 145 150 155 160 Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser 165 170 175 Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr 180 185 190 Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser 195 200 205 Phe Asn Arg Gly Glu Cys 210 <210> 26 <211> 232 <212> PRT <213> Homo sapiens <400> 26 Met Asn Phe Leu Leu Ser Trp Val His Trp Ser Leu Ala Leu Leu Leu 1 5 10 15 Tyr Leu His His Ala Lys Trp Ser Gln Ala Ala Pro Met Ala Glu Gly 20 25 30 Gly Gly Gln Asn His His Glu Val Val Lys Phe Met Asp Val Tyr Gln 35 40 45 Arg Ser Tyr Cys His Pro Ile Glu Thr Leu Val Asp Ile Phe Gln Glu 50 55 60 Tyr Pro Asp Glu Ile Glu Tyr Ile Phe Lys Pro Ser Cys Val Pro Leu 65 70 75 80 Met Arg Cys Gly Gly Cys Cys Asn Asp Glu Gly Leu Glu Cys Val Pro 85 90 95 Thr Glu Glu Ser Asn Ile Thr Met Gln Ile Met Arg Ile Lys Pro His 100 105 110 Gln Gly Gln His Ile Gly Glu Met Ser Phe Leu Gln His Asn Lys Cys 115 120 125 Glu Cys Arg Pro Lys Lys Asp Arg Ala Arg Gln Glu Lys Lys Ser Val 130 135 140 Arg Gly Lys Gly Lys Gly Gln Lys Arg Lys Arg Lys Lys Ser Arg Tyr 145 150 155 160 Lys Ser Trp Ser Val Tyr Val Gly Ala Arg Cys Cys Leu Met Pro Trp 165 170 175 Ser Leu Pro Gly Pro His Pro Cys Gly Pro Cys Ser Glu Arg Arg Lys 180 185 190 His Leu Phe Val Gln Asp Pro Gln Thr Cys Lys Cys Ser Cys Lys Asn 195 200 205 Thr Asp Ser Arg Cys Lys Ala Arg Gln Leu Glu Leu Asn Glu Arg Thr 210 215 220 Cys Arg Cys Asp Lys Pro Arg Arg 225 230 <210> 27 <211> 111 <212> PRT <213> Homo sapiens <400> 27 Met Ala Glu Val Pro Glu Leu Ala Ser Glu Met Met Ala Tyr Tyr Ser 1 5 10 15 Gly Asn Glu Asp Asp Leu Phe Phe Glu Ala Asp Gly Pro Lys Gln Met 20 25 30 Lys Cys Ser Phe Gln Asp Leu Asp Leu Cys Pro Leu Asp Gly Gly Ile 35 40 45 Gln Leu Arg Ile Ser Asp His His Tyr Ser Lys Gly Phe Arg Gln Ala 50 55 60 Ala Ser Val Val Val Ala Met Asp Lys Leu Arg Lys Met Leu Val Pro 65 70 75 80 Cys Pro Gln Thr Phe Gln Glu Asn Asp Leu Ser Thr Phe Phe Pro Phe 85 90 95 Ile Phe Glu Glu Glu Pro Ile Phe Phe Asp Thr Trp Asp Asn Glu 100 105 110