IP Library › Granted Patent US 10,544,219
Granted Patent B2
US 10,544,219 · App. 16/138,418 · Granted Jan 28, 2020

TIGIT-binding agents and uses thereof

Inventors: Austin L. Gurney (San Francisco, CA); Ming-Hong Xie (Foster City, CA)
Assignee: ONCOMED PHARMACEUTICALS, INC.
C07K16/2803A61K39/39558C07K16/28C07K16/2818C07K16/2827A61K2039/505A61K2039/507C07K2317/24C07K2317/31C07K2317/32C07K2317/41C07K2317/56C07K2317/565C07K2317/732C07K2317/76C07K2317/92C07K2317/94Y02A50/466
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Quick Facts
Patent No.
US 10,544,219
App. No.
16/138,418
Granted
Jan 28, 2020
Kind
B2
Abstract

Agents that specifically bind TIGIT are disclosed. The TIGIT-binding agents may include polypeptides, antibodies, and/or bispecific agents. Also disclosed are methods of using the agents for enhancing the immune response and/or treatment of diseases such as cancer.

Claims (64)

1. A method of inducing, activating, promoting, increasing, enhancing, or prolonging an immune response in a subject, comprising administering to the subject a therapeutically effective amount of an antibody that specifically binds the extracellular domain of TIGIT, wherein the antibody comprises:

(a) a heavy chain CDR1 comprising GSSLSSSYMS (SEQ ID NO:7), a heavy chain CDR2 comprising IIGSNGNTYYANWAKG (SEQ ID NO:8), a heavy chain CDR3 comprising GGYRTSGMDP (SEQ ID NO:9), a light chain CDR1 comprising QASQSISSYLNW (SEQ ID NO: 10), a light chain CDR2 comprising DALKLAS (SEQ ID NO: 11), and a light chain CDR3 comprising QQEHSVGNVDN (SEQ ID NO: 12);

(b) a heavy chain CDR1 comprising GFSLSSSYMS (SEQ ID NO:13), a heavy chain CDR2 comprising IIGSNGNTYYANWAKG (SEQ ID NO:8), a heavy chain CDR3 comprising GGYRTSGMDP (SEQ ID NO:9), a light chain CDR1 comprising QASQNIYSDLAW (SEQ ID NO:81), a light chain CDR2 comprising RASTLAS (SEQ ID NO:15), and a light chain CDR3 comprising QQEHLVAWIYN (SEQ ID NO: 16); or

(c) a heavy chain CDR1 comprising TSDYAWN (SEQ ID NO:57), a heavy chain CDR2 comprising YISYSGSTSYNPSLRS (SEQ ID NO:58), a heavy chain CDR3 comprising ARRQVGLGFAY (SEQ ID NO:59), a light chain CDR1 comprising KASQDVSTAVA (SEQ ID NO:60), a light chain CDR2 comprising SASYRYT (SEQ ID NO:61), and a light chain CDR3 comprising QQHYSTP (SEQ ID NO:62).

2. The method of claim 1 , wherein the antibody comprises:

(a) a heavy chain variable region having at least 90% sequence identity to SEQ ID NO: 17 and a light chain variable region having at least 90% sequence identity to SEQ ID NO: 18;

(b) a heavy chain variable region having at least 90% sequence identity to SEQ ID NO: 19 and a light chain variable region having at least 90% sequence identity to SEQ ID NO:20;

(c) a heavy chain variable region having at least 90% sequence identity to SEQ ID NO:32 and a light chain variable region having at least 90% sequence identity to SEQ ID NO:20;

(d) a heavy chain variable region having at least 95% sequence identity to SEQ ID NO:63 and a light chain variable region having at least 95% sequence identity to SEQ ID NO:64; or

(e) a heavy chain variable region having at least 95% sequence identity to SEQ ID NO:67 and a light chain variable region having at least 95% sequence identity to SEQ ID NO:68.

3. The method of claim 1 , wherein the antibody comprises:

(a) a heavy chain amino acid sequence of SEQ ID NO:26 and a light chain amino acid sequence of SEQ ID NO:28;

(b) a heavy chain amino acid sequence of SEQ ID NO:27 and a light chain amino acid sequence of SEQ ID NO:28;

(c) a heavy chain amino acid sequence of SEQ ID NO:29 and a light chain amino acid sequence of SEQ ID NO:30;

(d) a heavy chain amino acid sequence of SEQ ID NO:34 and a light chain amino acid sequence of SEQ ID NO:30;

(e) a heavy chain amino acid sequence of SEQ ID NO:56 and a light chain amino acid sequence of SEQ ID NO:30; or

(f) a heavy chain amino acid sequence of SEQ ID NO:70 and a light chain amino acid sequence of SEQ ID NO:72.

4. The method of claim 1 , wherein the antibody is an antibody fragment comprising an antigen binding site.

5. The method of claim 1 , wherein the immune response is against a tumor or cancer.

6. A method of inhibiting growth of a tumor in a subject, comprising administering to the subject a therapeutically effective amount of an antibody that specifically binds the extracellular domain of TIGIT, wherein the antibody comprises:

(a) a heavy chain CDR1 comprising GSSLSSSYMS (SEQ ID NO:7), a heavy chain CDR2 comprising IIGSNGNTYYANWAKG (SEQ ID NO:8), a heavy chain CDR3 comprising GGYRTSGMDP (SEQ ID NO:9), a light chain CDR1 comprising QASQSISSYLNW (SEQ ID NO:10), a light chain CDR2 comprising DALKLAS (SEQ ID NO:11), and a light chain CDR3 comprising QQEHSVGNVDN (SEQ ID NO:12);

(b) a heavy chain CDR1 comprising GFSLSSSYMS (SEQ ID NO:13), a heavy chain CDR2 comprising IIGSNGNTYYANWAKG (SEQ ID NO:8), a heavy chain CDR3 comprising GGYRTSGMDP (SEQ ID NO:9), a light chain CDR1 comprising QASQNIYSDLAW (SEQ ID NO:81), a light chain CDR2 comprising RASTLAS (SEQ ID NO: 15), and a light chain CDR3 comprising QQEHLVAWIYN (SEQ ID NO: 16); or

(c) a heavy chain CDR1 comprising TSDYAWN (SEQ ID NO:57), a heavy chain CDR2 comprising YISYSGSTSYNPSLRS (SEQ ID NO:58), a heavy chain CDR3 comprising ARRQVGLGFAY (SEQ ID NO:59), a light chain CDR1 comprising KASQDVSTAVA (SEQ ID NO:60), a light chain CDR2 comprising SASYRYT (SEQ ID NO:61), and a light chain CDR3 comprising QQHYSTP (SEQ ID NO:62).

7. The method of claim 6 , wherein the antibody comprises:

(a) a heavy chain variable region having at least 90% sequence identity to SEQ ID NO: 17 and a light chain variable region having at least 90% sequence identity to SEQ ID NO: 18;

(b) a heavy chain variable region having at least 90% sequence identity to SEQ ID NO: 19 and a light chain variable region having at least 90% sequence identity to SEQ ID NO:20;

(c) a heavy chain variable region having at least 90% sequence identity to SEQ ID NO:32 and a light chain variable region having at least 90% sequence identity to SEQ ID NO:20;

(d) a heavy chain variable region having at least 95% sequence identity to SEQ ID NO:63 and a light chain variable region having at least 95% sequence identity to SEQ ID NO:64; or

(e) a heavy chain variable region having at least 95% sequence identity to SEQ ID NO:67 and a light chain variable region having at least 95% sequence identity to SEQ ID NO:68.

8. The method of claim 6 , wherein the antibody comprises:

(a) a heavy chain amino acid sequence of SEQ ID NO:26 and a light chain amino acid sequence of SEQ ID NO:28;

(b) a heavy chain amino acid sequence of SEQ ID NO:27 and a light chain amino acid sequence of SEQ ID NO:28;

(c) a heavy chain amino acid sequence of SEQ ID NO:29 and a light chain amino acid sequence of SEQ ID NO:30;

(d) a heavy chain amino acid sequence of SEQ ID NO:34 and a light chain amino acid sequence of SEQ ID NO:30;

(e) a heavy chain amino acid sequence of SEQ ID NO:56 and a light chain amino acid sequence of SEQ ID NO:30; or

(f) a heavy chain amino acid sequence of SEQ ID NO:70 and a light chain amino acid sequence of SEQ ID NO:72.

9. The method of claim 6 , wherein the antibody is an antibody fragment comprising an antigen binding site.

10. The method of claim 6 , wherein the tumor is a colorectal tumor or an ovarian tumor.

11. The method of claim 6 , further comprising administering to the subject a therapeutically effective amount of an anti-PD-1 antibody, an anti-PD-L1 antibody, an anti-CTLA4 antibody, an anti-LAG-3 antibody, or an anti-TIM-3 antibody.

12. The method of claim 6 , further comprising administering to the subject a therapeutically effective amount of GM-CSF, M-CSF, G-CSF, IL-2, IL-3, IL-12, IL-15, B7-1 (CD80), B7-2 (CD86), 4-1BB ligand, GITRL, OX-40 ligand, an anti-CD3 antibody, an anti-GITR antibody, or an anti-OX-40 antibody.

13. The method of claim 6 , wherein the subject is human.

14. A method of treating cancer in a subject, comprising administering to the subject a therapeutically effective amount of an antibody that specifically binds the extracellular domain of TIGIT, wherein the antibody comprises:

(a) a heavy chain CDR1 comprising GSSLSSSYMS (SEQ ID NO:7), a heavy chain CDR2 comprising IIGSNGNTYYANWAKG (SEQ ID NO:8), a heavy chain CDR3 comprising GGYRTSGMDP (SEQ ID NO:9), a light chain CDR1 comprising QASQSISSYLNW (SEQ ID NO:10), a light chain CDR2 comprising DALKLAS (SEQ ID NO:11), and a light chain CDR3 comprising QQEHSVGNVDN (SEQ ID NO: 12),

(b) a heavy chain CDR1 comprising GFSLSSSYMS (SEQ ID NO:13), a heavy chain CDR2 comprising IIGSNGNTYYANWAKG (SEQ ID NO:8), a heavy chain CDR3 comprising GGYRTSGMDP (SEQ ID NO:9), a light chain CDR1 comprising QASQNIYSDLAW (SEQ ID NO:81), a light chain CDR2 comprising RASTLAS (SEQ ID NO: 15), and a light chain CDR3 comprising QQEHLVAWIYN (SEQ ID NO: 16); or

(c) a heavy chain CDR1 comprising TSDYAWN (SEQ ID NO:57), a heavy chain CDR2 comprising YISYSGSTSYNPSLRS (SEQ ID NO:58), a heavy chain CDR3 comprising ARRQVGLGFAY (SEQ ID NO:59), a light chain CDR1 comprising KASQDVSTAVA (SEQ ID NO:60), a light chain CDR2 comprising SASYRYT (SEQ ID NO:61), and a light chain CDR3 comprising QQHYSTP (SEQ ID NO:62).

15. The method of claim 14 , wherein the antibody comprises:

(a) a heavy chain variable region having at least 90% sequence identity to SEQ ID NO: 17 and a light chain variable region having at least 90% sequence identity to SEQ ID NO:18;

(b) a heavy chain variable region having at least 90% sequence identity to SEQ ID NO: 19 and a light chain variable region having at least 90% sequence identity to SEQ ID NO:20;

(c) a heavy chain variable region having at least 90% sequence identity to SEQ ID NO:32 and a light chain variable region having at least 90% sequence identity to SEQ ID NO:20;

(d) a heavy chain variable region having at least 95% sequence identity to SEQ ID NO:63 and a light chain variable region having at least 95% sequence identity to SEQ ID NO:64; or

(e) a heavy chain variable region having at least 95% sequence identity to SEQ ID NO:67 and a light chain variable region having at least 95% sequence identity to SEQ ID NO:68.

16. The method of claim 14 , wherein the antibody comprises:

(a) a heavy chain amino acid sequence of SEQ ID NO:26 and a light chain amino acid sequence of SEQ ID NO:28;

(b) a heavy chain amino acid sequence of SEQ ID NO:27 and a light chain amino acid sequence of SEQ ID NO:28;

(c) a heavy chain amino acid sequence of SEQ ID NO:29 and a light chain amino acid sequence of SEQ ID NO:30;

(d) a heavy chain amino acid sequence of SEQ ID NO:34 and a light chain amino acid sequence of SEQ ID NO:30;

(e) a heavy chain amino acid sequence of SEQ ID NO:56 and a light chain amino acid sequence of SEQ ID NO:30; or

(f) a heavy chain amino acid sequence of SEQ ID NO:70 and a light chain amino acid sequence of SEQ ID NO:72.

17. The method of claim 14 , wherein the antibody is an antibody fragment comprising an antigen binding site.

18. The method of claim 14 , wherein the cancer is colorectal cancer or ovarian cancer.

19. The method of claim 14 , further comprising administering to the subject a therapeutically effective amount of an anti-PD-1 antibody, an anti-PD-L1 antibody, an anti-CTLA4 antibody, an anti-LAG-3 antibody, or an anti-TIM-3 antibody.

20. The method of claim 14 , further comprising administering to the subject a therapeutically effective amount of GM-CSF, M-CSF, G-CSF, IL-2, IL-3, IL-12, IL-15, B7-1 (CD80), B7-2 (CD86), 4-1BB ligand, GITRL, OX-40 ligand, an anti-CD3 antibody, an anti-GITR antibody, or an anti-OX-40 antibody.

21. The method of claim 14 , wherein the subject is human.

22. A plasmid deposited with the ATCC and assigned designation number PTA-122346 or PTA-122347.

Assignments (2)
CHANGE OF NAME Recorded Sep 23, 2020
From: ONCOMED PHARMACEUTICALS, INC.
To: MEREO BIOPHARMA 5, INC.
Reel/Frame 053859/0175 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Sep 19, 2019
From: GURNEY, AUSTIN L; XIE, MING-HONG
To: ONCOMED PHARMACEUTICALS, INC.
Reel/Frame 050427/0167 →
Continuity (5)
Division 15167166 · May 27, 2016
Provisional Application 62313487 · Mar 25, 2016
Provisional Application 62205279 · Aug 14, 2015
Provisional Application 62167582 · May 28, 2015
Related Publication 20190077864A1 · Mar 14, 2019