BACA, MANUEL,PRESTA, LEONARD G.,WELLS, JAMES A.,LOWMAN, LEONARD G.,CHEN, YVONNE MAN-YEE
申请号：
ES10007444
公开号：
ES2380575T3
申请日:
1998.04.03
申请国别(地区):
ES
年份:
2012
代理人:
摘要：
An article of manufacture comprising a container and a label on or associated with the container, the container containing a composition comprising as active agent a humanized antibody directed against the vascular endothelial growth factor which inhibits VEGF-induced angiogenesis in vivo and / or binds human VEGF with a value of not more than 1 x 10-8 Kd and / or has an ED50 value not greater than 5 nM for inhibiting endothelial cell proliferation in vitro induced by VEGF, the antibody having a domain variable heavy chain comprising the subgroup III consensus human heavy chain framework regions as shown in SEQ ID NO: 11 and hypervariable regions CDRH1, CDRH2 and CDRH3, having the following amino acid sequences: CDRH1: GYX1X2X3X4YGX5N (SEQ ID NO: 117), wherein X1 is D, T or E, X2 is F, W or Y, X3 is T, Q, G or S, X4 is H or N and X5 is M or I CDRH2: WINTX1TGEPTYAADFKR (SEQ ID NO: 118), wherein X1 is Y or W and CDRH3: YPX1YX2X3X4X5HWYFDV (SEQ ID NO: 119), wherein X1 is H or Y, X2 is Y, R, K, I, T, E or W, X3 is G, N, A, D, Q, E , T, K or S, X4 is S, T, K, Q, N, R, A, E or G and X5 is S or G and having a variable domain of the light chain comprising the consensus subgroup I kappa light chain shown in SEQ ID NO framework regions: 12 and hypervariable regions CDRL1, CDRL2 and CDRL3, having the following sequences amino acids: CDR1: X1AX2X3X4X5SNYLN (SEQ ID NO: 121), wherein X1 is R or S, X2 is S or N, X3 is Q or E, X4 is Q or D and X5 is I or L CDRL2: FTSSLHS (SEQ ID NO: 122) CDRL3: QQYSX1X2PWT (SEQ ID NO: 123), wherein X1 is T, A or N and X2 is V or T, wherein compared to SEQ ID NO: 11, the variable domain of the heavy chain has a substitution in any one or more of the following residues of the framework consensus regions: 37H, 49H, 67H, 69H, 71H, 73H, 75H, 76H, 78H and 94H, and wherein compared to SEQ ID NO: 12, the variable domain of the light chain has either a substitution at, and only at, the rest 46L of the consensus framework or regions having substitutions in 4
