Anti-TIGIT antibodies and methods of use

Patent metadata

Field	Value
Publication number	US-10047158-B2
Application number	US-201815895741-A
Country	US
Kind code	B2
Filing date	Feb 13, 2018
Priority date	Sep 25, 2015
Publication date	Aug 14, 2018
Grant date	Aug 14, 2018

Abstract

The invention provides anti-TIGIT (T-cell immunoreceptor with Ig and ITIM domains) antibodies and methods of using the same.

First claim

What is claimed is:

1. An antibody that specifically binds to human TIGIT, wherein the antibody comprises the following six hypervariable regions (HVRs):
an HVR-H1 comprising the amino acid sequence of SNSAAWN (SEQ ID NO: 1);
an HVR-H2 comprising the amino acid sequence of KTYYRFKWYSDYAVSVKG (SEQ ID NO: 2);
an HVR-H3 comprising the amino acid sequence of ESTTYDLLAGPFDY (SEQ ID NO: 3);
an HVR-L1 comprising the amino acid sequence of KSSQTVLYSSNNKKYLA (SEQ ID NO: 4);
an HVR-L2 comprising the amino acid sequence of WASTRES (SEQ ID NO: 5); and
an HVR-L3 comprising the amino acid sequence of QQYYSTPFT (SEQ ID NO: 6).

2. The antibody of claim 1 , wherein the antibody further comprises the following light chain variable region framework regions (FRs):
an FR-L1 comprising the amino acid sequence of DIVMTQSPDSLAVSLGERATINC (SEQ ID NO: 7);
an FR-L2 comprising the amino acid sequence of WYQQKPGQPPNLLIY (SEQ ID NO: 8);
an FR-L3 comprising the amino acid sequence of GVPDRFSGSGSGTDFTLTISSLQAEDVAVYYC (SEQ ID NO: 9); and
an FR-L4 comprising the amino acid sequence of FGPGTKVEIK (SEQ ID NO: 10).

3. The antibody of claim 1 , wherein the antibody further comprises the following heavy chain variable region FRs:
an FR-H1 comprising the amino acid sequence of X 1 VQLQQSGPGLVKPSQTLSLTCAISGDSVS (SEQ ID NO: 11), wherein X 1 is Q or E;
an FR-H2 comprising the amino acid sequence of WIRQSPSRGLEWLG (SEQ ID NO: 12);
an FR-H3 comprising the amino acid sequence of RITINPDTSKNQFSLQLNSVTPEDTAVFYCTR (SEQ ID NO: 13); and
an FR-H4 comprising the amino acid sequence of WGQGTLVTVSS (SEQ ID NO: 14).

4. The antibody of claim 3 , wherein X 1 is Q.

5. The antibody of claim 3 , wherein X 1 is E.

6. The antibody of claim 1 , wherein the antibody comprises a VH domain comprising an amino acid sequence having at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 34 or 35 and a VL domain comprising an amino acid sequence having at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 36.

7. The antibody of claim 1 , wherein the antibody comprises a VH domain comprising an amino acid sequence having at least 96% sequence identity to the amino acid sequence of SEQ ID NO: 34 or 35 and a VL domain comprising an amino acid sequence having at least 96% sequence identity to the amino acid sequence of SEQ ID NO: 36.

8. The antibody of claim 1 , wherein the antibody comprises a VH domain comprising an amino acid sequence having at least 97% sequence identity to the amino acid sequence of SEQ ID NO: 34 or 35 and a VL domain comprising an amino acid sequence having at least 97% sequence identity to the amino acid sequence of SEQ ID NO: 36.

9. The antibody of claim 1 , wherein the antibody comprises a VH domain comprising an amino acid sequence having at least 98% sequence identity to the amino acid sequence of SEQ ID NO: 34 or 35 and a VL domain comprising an amino acid sequence having at least 98% sequence identity to the amino acid sequence of SEQ ID NO: 36.

10. The antibody of claim 1 , wherein the antibody comprises a VH domain comprising an amino acid sequence having at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 34 or 35 and a VL domain comprising an amino acid sequence having at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 36.

11. The antibody of claim 1 , wherein the antibody is a monoclonal antibody.

12. The antibody of claim 11 , wherein the antibody is a human antibody.

13. The antibody of claim 1 , wherein the antibody is a full-length antibody.

14. The antibody of claim 1 , wherein the antibody is an antibody fragment that binds TIGIT selected from the group consisting of Fab, Fab′, Fab′-SH, Fv, single chain variable fragment (scFv), and (Fab′) 2 fragments.

15. The antibody of claim 1 , wherein the antibody is an IgG class antibody.

16. The antibody of claim 15 , wherein the IgG class antibody is an IgG1 subclass antibody.

17. An antibody that specifically binds to human TIGIT, wherein the antibody comprises a VH domain comprising the amino acid sequence of SEQ ID NO: 34 and a VL domain comprising the amino acid sequence of SEQ ID NO: 36.

18. The antibody of claim 17 , wherein the antibody is a monoclonal antibody.

19. The antibody of claim 18 , wherein the antibody is a human antibody.

20. The antibody of claim 17 , wherein the antibody is a full-length antibody.

21. The antibody of claim 17 , wherein the antibody is an antibody fragment that binds TIGIT selected from the group consisting of Fab, Fab′, Fab′-SH, Fv, single chain variable fragment (scFv), and (Fab′) 2 fragments.

22. The antibody of claim 17 , wherein the antibody is an IgG class antibody.

23. The antibody of claim 22 , wherein the IgG class antibody is an IgG1 subclass antibody.

24. An antibody that specifically binds to human TIGIT, wherein the antibody comprises a VH domain comprising the amino acid sequence of SEQ ID NO: 35 and a VL domain comprising the amino acid sequence of SEQ ID NO: 36.

25. The antibody of claim 12 , wherein the antibody is a monoclonal antibody.

26. The antibody of claim 25 , wherein the antibody is a human antibody.

27. The antibody of claim 12 , wherein the antibody is a full-length antibody.

28. The antibody of claim 12 , wherein the antibody is an antibody fragment that binds TIGIT selected from the group consisting of Fab, Fab′, Fab′-SH, Fv, single chain variable fragment (scFv), and (Fab′) 2 fragments.

29. The antibody of claim 12 , wherein the antibody is an IgG class antibody.

30. The antibody of claim 29 , wherein the IgG class antibody is an IgG1 subclass antibody.

Assignees

• Genentech Inc

Inventors

• Grogan Jane L
• Johnston Robert J
• Wu Yan
• Liang Wei-Ching
• Lupardus Patrick
• Yadav Mahesh
• Seshasayee Dhaya
• Hazen Meredith

Classifications

• A61P43/00

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

• A61P37/04

  Immunostimulants · CPC title

• A61P37/02

  Immunomodulators · CPC title

• A61P37/00

  Drugs for immunological or allergic disorders · CPC title

• A61P35/02

  specific for leukemia · CPC title