Anti-VEGF antibodies

Patent metadata

Field	Value
Publication number	US-9353177-B2
Application number	US-201514636782-A
Country	US
Kind code	B2
Filing date	Mar 3, 2015
Priority date	Aug 1, 2003
Publication date	May 31, 2016
Grant date	May 31, 2016

Abstract

Anti-VEGF antibodies and variants thereof, including those having high affinity for binding to VEGF, are disclosed. Also provided are methods of using phage display technology with naïve libraries to generate and select the anti-VEGF antibodies with desired binding and other biological activities. Further contemplated are uses of the antibodies in research, diagnostic and therapeutic applications.

First claim

The invention claimed is:

1. A method of inhibiting angiogenesis in a human, the method comprising administering to the human an antibody capable of binding to human VEGF, wherein the antibody comprises the following complementarity determining regions (CDRs):
(a) a CDR-H1 comprising the amino acid sequence GFSISSSSIH (SEQ ID NO: 859);
(b) a CDR-H2 comprising the amino acid sequence YISPSSGSTSYADSVKG (SEQ ID NO: 860);
(c) a CDR-H3 comprising the amino acid sequence YYSSSYYYSYYYAMDY (SEQ ID NO: 861);
(d) a CDR-L1 comprising the amino acid sequence RASQSYAYAVA (SEQ ID NO: 493);
(e) a CDR-L2 comprising the amino acid sequence DASYLYS (SEQ ID NO: 494); and
(f) a CDR-L3 comprising the amino acid sequence QQSYYSPYT (SEQ ID NO: 561).

2. The method of claim 1 , wherein the human is suffering from cancer or a disease caused by ocular neovascularization.

3. The method of claim 2 , wherein the cancer is selected from the group consisting of breast cancer, colorectal cancer, non-small cell lung cancer, non-Hodgkin's lymphoma (NHL), renal cancer, prostate cancer, liver cancer, head and neck cancer, melanoma, ovarian cancer, mesothelioma, and glioblastoma.

4. The method of claim 2 , wherein the disease caused by ocular neovascularization is diabetic blindness, retinopathy, primary diabetic retinopathy or age-induced macular degeneration.

5. A method of alleviating cancer or a disease caused by ocular neovascularization in a human, the method comprising administering to the human an antibody capable of binding to human VEGF, wherein the antibody comprises the following complementarity determining regions (CDRs):
(a) a CDR-H1 comprising the amino acid sequence GFSISSSSIH (SEQ ID NO: 859);
(b) a CDR-H2 comprising the amino acid sequence YISPSSGSTSYADSVKG (SEQ ID NO: 860);
(c) a CDR-H3 comprising the amino acid sequence YYSSSYYYSYYYAMDY (SEQ ID NO: 861);
(d) a CDR-L1 comprising the amino acid sequence RASQSYAYAVA (SEQ ID NO: 493);
(e) a CDR-L2 comprising the amino acid sequence DASYLYS (SEQ ID NO: 494); and
(f) a CDR-L3 comprising the amino acid sequence QQSYYSPYT (SEQ ID NO: 561).

6. The method of claim 5 , wherein the cancer is selected from the group consisting of breast cancer, colorectal cancer, non-small cell lung cancer, non-Hodgkin's lymphoma (NHL), renal cancer, prostate cancer, liver cancer, head and neck cancer, melanoma, ovarian cancer, mesothelioma, and glioblastoma.

7. The method of claim 5 , wherein the disease caused by ocular neovascularization is diabetic blindness, retinopathy, primary diabetic retinopathy, or age-induced macular degeneration.

8. The method of claim 5 , wherein the heavy chain of the antibody comprises the sequence EVQLVESGGGLVQPGGSLRLSCAASGFSISSSSIHWVRQAPGKGLEWVAYISPSSGSTSYADSVKGRFTISA DTSKNTAYLQMNSLRAEDTAVYYCSRYYSSSYYYSYYYAMDYWGQGTL (SEQ ID NO: 942).

9. The method of claim 5 , wherein the light chain of the antibody comprises the sequence DIQMTQSPSSLSASVGDRVTITCRASQSYAYAVAWYQQKPGKAPKLLIYDASYLYSGVPSRFSGSGSGTDFT LTISSLQPEDFATYYCQQSYYSPYTFGQGTKV (SEQ ID NO: 943).

10. The method of claim 5 , wherein the antibody is selected from the group consisting of a synthetic antibody, a chimeric antibody, a humanized antibody, and an affinity matured antibody.

11. The method of claim 5 , wherein the antibody is an antigen-binding antibody fragment.

12. The method of claim 5 , wherein the antibody is capable of binding human VEGF with a Kd value of no more than about 60 nM.

13. The method of claim 1 , wherein the heavy chain of the antibody comprises the sequence EVQLVESGGGLVQPGGSLRLSCAASGFSISSSSIHWVRQAPGKGLEWVAYISPSSGSTSYADSVKGRFTISA DTSKNTAYLQMNSLRAEDTAVYYCSRYYSSSYYYSYYYAMDYWGQGTL (SEQ ID NO: 942).

14. The method of claim 1 , wherein the light chain of the antibody comprises the sequence DIQMTQSPSSLSASVGDRVTITCRASQSYAYAVAWYQQKPGKAPKLLIYDASYLYSGVPSRFSGSGSGTDFT LTISSLQPEDFATYYCQQSYYSPYTFGQGTKV (SEQ ID NO: 943).

15. The method of claim 1 , wherein the antibody is selected from the group consisting of a synthetic antibody, a chimeric antibody, a humanized antibody, and an affinity matured antibody.

16. The method of claim 1 , wherein the antibody is an antigen-binding antibody fragment.

17. The method of claim 1 , wherein the antibody is capable of binding human VEGF with a Kd value of no more than about 60 nM.

18. A method of inhibiting angiogenesis in a human, the method comprising administering to the human a bispecific antibody capable of binding to human VEGF, wherein the bispecific antibody comprises the following complementarity determining regions (CDRs):
(a) a CDR-H1 comprising the amino acid sequence GFSISSSSIH (SEQ ID NO: 859);
(b) a CDR-H2 comprising the amino acid sequence YISPSSGSTSYADSVKG (SEQ ID NO: 860);
(c) a CDR-H3 comprising the amino acid sequence YYSSSYYYSYYYAMDY (SEQ ID NO: 861);
(d) a CDR-L1 comprising the amino acid sequence RASQSYAYAVA (SEQ ID NO: 493);
(e) a CDR-L2 comprising the amino acid sequence DASYLYS (SEQ ID NO: 494); and
(f) a CDR-L3 comprising the amino acid sequence QQSYYSPYT (SEQ ID NO: 561).

19. A method of alleviating cancer or a disease caused by ocular neovascularization in a human, the method comprising administering to the human a bispecific antibody capable of binding to human VEGF, wherein the bispecific antibody comprises the following complementarity determining regions (CDRs):
(a) a CDR-H1 comprising the amino acid sequence GFSISSSSIH (SEQ ID NO: 859);
(b) a CDR-H2 comprising the amino acid sequence YISPSSGSTSYADSVKG (SEQ ID NO: 860);
(c) a CDR-H3 comprising the amino acid sequence YYSSSYYYSYYYAMDY (SEQ ID NO: 861);
(d) a CDR-L1 comprising the amino acid sequence RASQSYAYAVA (SEQ ID NO: 493);
(e) a CDR-L2 comprising the amino acid sequence DASYLYS (SEQ ID NO: 494); and
(f) a CDR-L3 comprising the amino acid sequence QQSYYSPYT (SEQ ID NO: 561).

Assignees

• Genentech Inc

Inventors

• Fuh Germaine
• Gerber Hans-Peter
• Liang Wei-Ching
• Fellouse Frederic
• Sidhu Sachdev S
• Wiesmann Christian

Classifications

• A61P37/02

  Immunomodulators · CPC title

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A61P9/10

  for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis · CPC title

• A61P37/06

  Immunosuppressants, e.g. drugs for graft rejection · CPC title

• A61P31/04

  Antibacterial agents · CPC title