Anti-VEGF antibodies and their uses
View Patent ↗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.
1. A monoclonal antibody or a binding fragment thereof which:
(a) specifically binds to human VEGF;
(b) comprises a heavy chain amino acid sequence having at least 95% sequence identity to SEQ ID NO:1 and a light chain amino acid sequence having at least 95% sequence identity to SEQ ID NO:2; and
(c) has at least one amino acid substitution or combination of amino acid substitutions selected from:
(i) K64S in CDR-H2;
(ii) H97E and Y98F in CDR-H3;
(iii) N31F in CDR-H1, H97D in CDR-H3, Y99D in CDR-H3, and S100aG in CDR-H3;
(iv) N31F in CDR-H1, H97P in CDR-H3, Y99D in CDR-H3, and S100aG in CDR-H3;
(v) N31F in CDR-H1, H97P in CDR-H3, and Y99E in CDR-H3;
(vi) N31F in CDR-H1, H97E in CDR-H3, and Y99E in CDR-H3;
(vii) N31F in CDR-H1, H97D in CDR-H3, and Y99E in CDR-H3;
(viii) N31F in CDR-H1, H97E in CDR-H3, Y99D in CDR-H3, and S100aG in CDR-H3;
(ix) N31F in CDR-H1, Y99D in CDR-H3, and S100aG in CDR-H3;
(x) N31F in CDR-H1, H97P in CDR-H3, and Y99D in CDR-H3;
(xi) N31F in CDR-H1, H97D in CDR-H3, and S100aG in CDR-H3;
(xii) N31F in CDR-H1 and S100aG in CDR-H3;
(xiii) N31F in CDR-H1, H97P in CDR-H3, and S100aG in CDR-H3; and
(xiv) N31F in CDR-H1;
wherein the substitutions occur at positions corresponding to Kabat numbering in the heavy chain of SEQ ID NO: 1 wherein the antibody or binding fragment thereof reduced immunogenicity or increased affinity to VEGF as compared to bevacizumab or ranibizumab.
2. The monoclonal antibody or binding fragment of claim 1 , wherein the heavy chain amino acid sequence has at least 98% sequence identity to SEQ ID NO:1 and the light chain amino acid sequence has at least 98% sequence identity to SEQ ID NO:2.
3. The monoclonal antibody or binding fragment of claim 1 , wherein the heavy chain amino acid sequence has at least 99% sequence identity to SEQ ID NO:1 and the light chain amino acid sequence has at least 99% sequence identity to SEQ ID NO:2.
4. The monoclonal antibody or binding thereof fragment of claim 1 , wherein said amino acid substitution includes the substitution K64S.
5. The monoclonal antibody or binding thereof fragment of claim 1 , wherein said amino acid substitution includes the substitution N31F.
6. The monoclonal antibody or binding thereof fragment of claim 1 , wherein said amino acid substitutions include the substitutions H97E and Y98F.
7. The monoclonal antibody or binding fragment thereof of claim 1 , wherein the antibody or binding fragment thereof is human or humanized antibody.
8. The monoclonal antibody or binding fragment thereof of claim 1 , wherein the antibody is an IgG.
9. The monoclonal antibody or binding fragment thereof of claim 1 , wherein the antibody or binding fragment thereof has the heavy chain framework sequences of the V H sequence of SEQ ID NO:1 and the light chain framework sequences of the V L sequence of SEQ ID NO:2.
10. The monoclonal antibody or binding fragment thereof of claim 1 , wherein the antibody or binding fragment thereof has the heavy chain framework sequences of the V H sequence of SEQ ID NO:9 and the light chain framework sequences of the V L sequence of SEQ ID NO:10.
11. An antibody-drug conjugate comprising the anti-VEGF antibody or anti-VEGF binding fragment according to claim 1 .