| 主权项 |
1. A method for treating a disease associated with CXCR4 overexpression or increased activity in an animal, comprising administering to an animal with said disease a therapeutically effective amount of an isolated antibody which binds to CXC chemokine receptor 4 (CXCR4) and which does not induce significant apoptosis of CXCR4 expressing cells, or an immunoconjugate thereof, wherein by the term not inducing significant apoptosis of CXCR4 expressing cells is meant that levels of apoptosis induced in the presence of an antibody are comparable to or not significantly different from levels of apoptosis induced in the absence of an antibody, and wherein said antibody comprises at least one heavy chain variable region that comprises three CDRs and at least one light chain variable region that comprises three CDRs, wherein said heavy chain variable region comprises:
(i) a variable heavy (VH) CDR1 that has the amino acid sequence of S/G Y X3 M/I H/S SEQ ID NO: 126), or X1 Y X3 M H (SEQ ID NO: 127) or S Y X3 M H (SEQ ID NO: 128); wherein X1 can be S or G, preferably S; X3 can be G or W or Y or A, preferably W; (ii) a VH CDR2 that has the amino acid sequence of X1 I X3 X4 D G S X8 X9 X10 Y A D S V K G (SEQ ID NO:129); wherein X1 can be V or R, preferably R; X3 can be S or N, preferably N; X4 can be Y or S, preferably S; X8 can be N or S, preferably S; X9 can be K or T, preferably T; and X10 can be Y or S, preferably S; or a VH CDR2 that has the amino acid sequence of X1 I X3 P X5 X6 G X8 X9 N Y A Q K F Q G (SEQ ID NO: 131); wherein X1, can be R or G, preferably R; X3 can be N or I, preferably N; X5 can be N or I, preferably N; X6 can be S or F, preferably S; X8 can be G or T, preferably G; and X9 can be T or A, preferably T;and
(iii) a VH CDR3 that has the amino acid sequence of SEQ ID NOs: 3, 9, 15 or 21. |
