Anti-HtrA1 antibodies and methods of use

Patent metadata

Field	Value
Publication number	US-9738727-B2
Application number	US-201213651289-A
Country	US
Kind code	B2
Filing date	Oct 12, 2012
Priority date	Oct 14, 2011
Publication date	Aug 22, 2017
Grant date	Aug 22, 2017

Abstract

The invention provides anti-HtrA1 antibodies and methods of using the same.

First claim

What is claimed is:

1. An isolated monoclonal antibody that binds to HtrA1, wherein the antibody comprises the following six hypervariable regions (HVRs):
an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 4;
an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 5;
an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 6;
an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 1;
an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 2; and
an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 3.

2. The antibody of claim 1 , comprising (a) a VH sequence having at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 8; (b) a VL sequence having at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 7; or (c) a VH sequence as in (a) and a VL sequence as in (b).

3. The antibody of claim 2 , comprising (a) a VH sequence of SEQ ID NO: 8; (b) a VL sequence of SEQ ID NO: 7; or (c) a VH sequence as in (a) and a VL sequence as in (b).

4. The antibody of claim 1 , wherein the antibody is a human antibody, a humanized antibody, or a chimeric antibody.

5. The antibody of claim 1 , wherein the antibody is an antibody fragment that binds to HtrA1.

6. An immunoconjugate comprising the antibody of claim 1 and a cytotoxic agent.

7. A pharmaceutical formulation comprising the antibody of claim 1 and a pharmaceutically acceptable carrier.

8. An isolated monoclonal antibody that binds to HtrA1, wherein the antibody comprises the following six hypervariable regions (HVRs):
an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 20;
an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 5;
an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 6;
an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 1;
an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 2; and
an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 3.

9. The antibody of claim 8 , comprising (a) a VH sequence having at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 29; (b) a VL sequence having at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 7; or (c) a VH sequence as in (a) and a VL sequence as in (b).

10. The antibody of claim 9 , comprising (a) a VH sequence of SEQ ID NO: 29; (b) a VL sequence of SEQ ID NO: 7; or (c) a VH sequence as in (a) and a VL sequence as in (b).

11. The antibody of claim 8 , wherein the antibody is a human antibody, a humanized antibody, or a chimeric antibody.

12. The antibody of claim 8 , wherein the antibody is an antibody fragment that binds to HtrA1.

13. An immunoconjugate comprising the antibody of claim 8 and a cytotoxic agent.

14. A pharmaceutical formulation comprising the antibody of claim 8 and a pharmaceutically acceptable carrier.

15. An isolated monoclonal antibody that binds to HtrA1, wherein the antibody comprises the following six hypervariable regions (HVRs):
an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 20;
an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 5;
an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 6;
an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 18;
an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 2; and
an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 19.

16. The antibody of claim 15 , comprising (a) a VH sequence having at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 29; (b) a VL sequence having at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 28; or (c) a VH sequence as in (a) and a VL sequence as in (b).

17. The antibody of claim 16 , comprising (a) a VH sequence of SEQ ID NO: 29; (b) a VL sequence of SEQ ID NO: 28; or (c) a VH sequence as in (a) and a VL sequence as in (b).

18. The antibody of claim 15 , wherein the antibody is a human antibody, a humanized antibody, or a chimeric antibody.

19. The antibody of claim 15 , wherein the antibody is an antibody fragment that binds to HtrA1.

20. An immunoconjugate comprising the antibody of claim 15 and a cytotoxic agent.

21. A pharmaceutical formulation comprising the antibody of claim 15 and a pharmaceutically acceptable carrier.

22. An isolated monoclonal antibody that binds to HtrA1, wherein the antibody comprises the following six hypervariable regions (HVRs):
an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 20;
an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 5;
an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 6;
an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 21;
an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 2; and
an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 22.

23. The antibody of claim 22 , comprising (a) a VH sequence having at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 29; (b) a VL sequence having at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 30; or (c) a VH sequence as in (a) and a VL sequence as in (b).

24. The antibody of claim 23 , comprising (a) a VH sequence of SEQ ID NO: 29; (b) a VL sequence of SEQ ID NO: 30; or (c) a VH sequence as in (a) and a VL sequence as in (b).

25. The antibody of claim 22 , wherein the antibody is a human antibody, a humanized antibody, or a chimeric antibody.

26. The antibody of claim 22 , wherein the antibody is an antibody fragment that binds to HtrA1.

27. An immunoconjugate comprising the antibody of claim 22 and a cytotoxic agent.

28. A pharmaceutical formulation comprising the antibody of claim 22 and a pharmaceutically acceptable carrier.

29. An isolated monoclonal antibody that binds to HtrA1, wherein the antibody comprises the amino acid sequences of any one of the following sets of six HRV-H1, HVR-H2, HVR-H3, HVR-L1, HVR-L2, and HVR-L3 sequences, respectively:
SEQ ID NOs: 20, 5, 6, 1, 2, and 34;
SEQ ID NOs: 47, 5, 6, 1, 2, and 35;
SEQ ID NOs: 20, 5, 6, 1, 2, and 36;
SEQ ID NOs: 48, 5, 6, 1, 2, and 3;
SEQ ID NOs: 47, 5, 6, 1, 2, and 37;
SEQ ID NOs: 49, 5, 6, 1, 2, and 3;
SEQ ID NOs: 20, 5, 6, 1, 2, and 38;
SEQ ID NOs: 20, 5, 6, 1, 2, and 39;
SEQ ID NOs: 20, 52, 6, 1, 2, and 40;
SEQ ID NOs: 20, 5, 53, 1, 2, and 41;
SEQ ID NOs: 20, 52, 6, 1, 2, and 3;
SEQ ID NOs: 47, 5, 6, 1, 2, and 42;
SEQ ID NOs: 20, 5, 6, 33, 2, and 43;
SEQ ID NOs: 20, 5, 6, 1, 2, and 44;
SEQ ID NOs: 20, 5, 53, 1, 2, and 3;
SEQ ID NOs: 50, 5, 6, 1, 2, and 45;
SEQ ID NOs: 51, 5, 6, 1, 2, and 3; or
SEQ ID NOs: 20, 52, 6, 1, 2, and 46.

30. The antibody of claim 29 , wherein the antibody is a human antibody, a humanized antibody, or a chimeric antibody.

31. The antibody of claim 29 , wherein the antibody is an antibody fragment that binds to HtrA1.

32. An immunoconjugate comprising the antibody of claim 29 and a cytotoxic agent.

33. A pharmaceutical formulation comprising the antibody of claim 29 and a pharmaceutically acceptable carrier.

Assignees

• Genentech Inc

Inventors

• Wu Yan
• Van Lookeren-Campagne Menno
• Kirchhofer Daniel
• Lipari Michael Terry
• Katschke Jr Kenneth J
• Moran Paul M
• Stawicki Scott
• Liang Wei-Ching

Classifications

• 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

• A61P43/00

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

• A61P27/02

  Ophthalmic agents · CPC title

• A61P27/00 Primary

  Drugs for disorders of the senses · CPC title

• C07K2317/76

  Antagonist effect on antigen, e.g. neutralization or inhibition of binding · CPC title