IP Library › Granted Patent US 9,738,727
Granted Patent B2
US 9,738,727 · App. 13/651,289 · Granted Aug 22, 2017

Anti-HtrA1 antibodies and methods of use

Inventors: Yan Wu (Foster City, CA); Menno van Lookeren-Campagne (San Francisco, CA); Daniel Kirchhofer (Los Altos, CA); Michael Terry Lipari (Santa Clara, CA); Kenneth J. Katschke, Jr. (Fairfield, CA); Paul M. Moran (El Cerrito, CA); Scott Stawicki (San Francisco, CA); Wei-Ching Liang (Foster City, CA)
Assignee: Genentech, Inc.
C07K16/40C07K2317/34C07K2317/76C07K2317/92
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Quick Facts
Patent No.
US 9,738,727
App. No.
13/651,289
Granted
Aug 22, 2017
Kind
B2
Abstract

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

Claims (75)

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.

Assignments (2)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jul 2, 2013
From: GENENTECH, INC.
To: F. HOFFMANN-LA ROCHE AG
Reel/Frame 030726/0514 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Dec 7, 2012
From: WU, YAN; VAN LOOKEREN-CAMPAGNE, MENNO; KIRCHHOFER, DANIEL; LIPARI, MICHAEL TERRY; KATSCHKE JR., KENNETH J.; MORAN, PAUL M.; STAWICKI, SCOTT; LIANG, WEI-CHING
To: GENENTECH, INC.
Reel/Frame 029428/0719 →
Continuity (2)
Provisional Application 61547649 · Oct 14, 2011
Related Publication 20130129743A1 · May 23, 2013