Antibodies against TIM3 and uses thereof

Patent metadata

Field	Value
Publication number	US-12312403-B2
Application number	US-202318175420-A
Country	US
Kind code	B2
Filing date	Feb 27, 2023
Priority date	Jul 14, 2016
Publication date	May 27, 2025
Grant date	May 27, 2025

Abstract

Provided herein are antibodies, or antigen-binding portions thereof, that bind to T-cell immunoglobulin and mucin-domain containing-3 (TIM3) protein. Also provided are uses of these antibodies, or antigen-binding portions thereof, in therapeutic applications, such as treatment of cancer. Further provided are cells that produce the antibodies, or antigen-binding portions thereof, polynucleotides encoding the heavy and/or light chain regions of the antibodies, or antigen-binding portions thereof, and vectors comprising the polynucleotides encoding the heavy and/or light chain regions of the antibodies, or antigen-binding portions thereof.

First claim

What is claimed is:

1. A method of stimulating an immune response in a subject, comprising administering to the subject an antibody that binds to human T-cell immunoglobulin and mucin-domain containing-3 (TIM3), wherein the antibody comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises a heavy chain CDR1, CDR2, and CDR3 comprising the amino acid sequences set forth in SEQ ID NOs: 41, 122, and 126, respectively, and the VL comprises a light chain CDR1, CDR2, and CDR3 comprising the amino acid sequences set forth in SEQ ID NOs: 64, 66, and 68, respectively.

2. The method of claim 1 , wherein the immune response comprises an antigen-specific T cell response.

3. The method of claim 1 , wherein T cell activation is stimulated, T cell proliferation is stimulated, IFN-γ production by T cells is stimulated, or a combination thereof.

4. The method of claim 1 , wherein the subject has a tumor and an immune response against the tumor is stimulated.

5. The method of claim 1 , wherein the VH comprises an amino acid sequence having at least about 90% sequence identity to the amino acid sequence set forth in SEQ ID NO: 364, and wherein the VL comprises an amino acid sequence having at least about 90% sequence identity to the amino acid sequence set forth in SEQ ID NO: 60.

6. The method of claim 1 , wherein the VH comprises the amino acid sequence set forth in SEQ ID NO: 364, and wherein the VL comprises the amino acid sequence set forth in SEQ ID NO: 60.

7. The method of claim 1 , wherein
(a) the heavy chain comprises an amino acid sequence having at least about 90% sequence identity to the amino acid sequence set forth in SEQ ID NO: 349 and the light chain comprises an amino acid sequence having at least about 90% sequence identity to the amino acid sequence set forth in SEQ ID NO: 29;
(b) the heavy chain comprises an amino acid sequence having at least about 90% sequence identity to the amino acid sequence set forth in SEQ ID NO: 351 and the light chain comprises an amino acid sequence having at least about 90% sequence identity to the amino acid sequence set forth in SEQ ID NO: 29;
(c) the heavy chain comprises an amino acid sequence having at least about 90% sequence identity to the amino acid sequence set forth in SEQ ID NO: 353 and the light chain comprises an amino acid sequence having at least about 90% sequence identity to the amino acid sequence set forth in SEQ ID NO: 29;
(d) the heavy chain comprises an amino acid sequence having at least about 90% sequence identity to the amino acid sequence set forth in SEQ ID NO: 350 and the light chain comprises an amino acid sequence having at least about 90% sequence identity to the amino acid sequence set forth in SEQ ID NO: 29;
(e) the heavy chain comprises an amino acid sequence having at least about 90% sequence identity to the amino acid sequence set forth in SEQ ID NO: 352 and the light chain comprises an amino acid sequence having at least about 90% sequence identity to the amino acid sequence set forth in SEQ ID NO: 29; or
(f) the heavy chain comprises an amino acid sequence having at least about 90% sequence identity to the amino acid sequence set forth in SEQ ID NO: 354 and the light chain comprises an amino acid sequence having at least about 90% sequence identity to the amino acid sequence set forth in SEQ ID NO: 29.

8. The method of claim 1 , wherein the heavy chain comprises the amino acid sequence set forth in SEQ ID NO: 349 and the light chain comprises the amino acid sequence set forth in SEQ ID NO: 29.

9. The method of claim 1 , wherein the heavy chain comprises the amino acid sequence set forth in SEQ ID NO: 351 and the light chain comprises the amino acid sequence set forth in SEQ ID NO: 29.

10. The method of claim 1 , wherein the heavy chain comprises the amino acid sequence set forth in SEQ ID NO: 353 and the light chain comprises the amino acid sequence set forth in SEQ ID NO: 29.

11. The method of claim 1 , wherein the heavy chain comprises the amino acid sequence set forth in SEQ ID NO: 350 and the light chain comprises the amino acid sequence set forth in SEQ ID NO: 29.

12. The method of claim 1 , wherein the heavy chain comprises the amino acid sequence set forth in SEQ ID NO: 352 and the light chain comprises the amino acid sequence set forth in SEQ ID NO: 29.

13. The method of claim 1 , wherein the heavy chain comprises the amino acid sequence set forth in SEQ ID NO: 354 and the light chain comprises the amino acid sequence set forth in SEQ ID NO: 29.

14. The method of claim 1 , wherein the antibody is selected from the group consisting of an IgGI, an IgG2, an IgG3, an IgG4, and a variant thereof.

15. The method of claim 1 , wherein the antibody comprises an effectorless IgG1 Fc.

16. The method of claim 1 , further comprising administering one or more additional therapeutic.

17. The method of claim 16 , wherein the additional therapeutic comprises an anti-PD-1 antibody, an anti-LAG-3 antibody, an anti-CTLA-4 antibody, an anti-GITR antibody, or an anti-PD-L1 antibody.

Assignees

• Bristol Myers Squibb Co

Inventors

• Schebye Xiao Min
• Selby Mark J
• Han Michelle Minhua
• BEE Christine
• Deng Andy X
• Chuntharapai Anan
• Devaux Brigitte
• Li Huiming
• Sheppard Paul O
• Korman Alan J
• Ardourel Daniel F
• DEYANOVA Ekaterina
• Huang Richard
• Chen Guodong
• Kuhne Michelle
• Truong Hong-An

Classifications

• G01N33/5759

  involving compounds localised on the membrane of tumour or cancer cells · CPC title

• C07K2317/734

  Complement-dependent cytotoxicity [CDC] · CPC title

• C07K2317/732

  Antibody-dependent cellular cytotoxicity [ADCC] · CPC title

• C07K2317/24

  containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered · CPC title

• C07K16/2878

  against the NGF-receptor/TNF-receptor superfamily, e.g. CD27, CD30, CD40, CD95 · CPC title