Anti-vegf antibodies and their uses
AssigneeAbbVie Biotherapeutics Inc.
InventorYoshiko AKAMATSU
Life of this patent
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Abstract
The present disclosure relates to antibodies directed to vascular endothelial growth factor (“VEGF”) and uses of such antibodies, for example to treat diseases associated with the activity and/or overproduction of VEGF.
Claims87
An anti-VEGF antibody or an anti-VEGF binding fragment of an antibody which comprises a VEGF heavy chain variable region comprising CDRs having amino acid sequences corresponding to SEQ ID NO:3 (CDR-H1), SEQ ID NO:4 (CDR-H2), and SEQ ID NO:5 (CDR-H3), and a VEGF light chain variable region comprising CDRs having amino acid sequences corresponding SEQ ID NO:6 (CDR-L1), SEQ ID NO:7 (CDR-L2) and SEQ ID NO:8, wherein CDR-H1 and/or CDR-H3 comprises one or more of the substitutions in Table 21, and optionally one or more mutations or combinations of mutations selected from one or more of Tables 6, 7, 8, 9, 19, 12-1 to 12-9, 13-16, 21, or 22, wherein the six CDRs altogether have up to 17 amino acid substitutions as compared to CDR sequences of the antibody bevacizumab or the antibody ranibizumab.
A DVD-Ig comprising:
- (a) a VEGF binding portion comprising a VEGF heavy chain variable region comprising CDRs having amino acid sequences corresponding to SEQ ID NO:3 (CDR-H1), SEQ ID NO:4 (CDR-H2), and SEQ ID NO:5 (CDR-H3) and a VEGF light chain variable region comprising CDRs having amino acid sequences corresponding SEQ ID NO:6 (CDR-L1), SEQ ID NO:7 (CDR-L2) and SEQ ID NO:8, wherein CDRs of the VEGF binding portion include one or more substitutions as compared to bevacizumab or ranibizumab selected from N31F in CDR-H1;
- K64S in CDR-H2;
- K64Q in CDR-H2;
- Y53F in CDR-H2;
- H97E in CDR-H3;
- H97D in CDR-H3;
- H97P in CDR-H3;
- Y98F in CDR-H3;
- Y99E in CDR-H3;
- Y99D in CDR-H3;
- S100aG in CDR-H3;
- and T51A in CDR-L2, wherein the anti-VEGF binding portion optionally has one or more additional mutations or combinations of mutations selected from one or more of Tables 6, 7, 8, 9, 10, 11, 12-1 to 12-9, 13-16, or 21-22, wherein the six CDRs of the VEGF binding portion altogether have up to 17 amino acid substitutions as compared to CDR sequences of the antibody bevacizumab or the antibody ranibizumab;
- and
- (b) a second binding portion comprising second heavy and light chain variable regions which together bind to a second target.
Dependencies are inferred from the claim text.