# US 11,306,143 B2 · Combination of TIM-4 antagonist and PD-1 antagonist and methods of use > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 11,306,143 B2 - Document ID: US11306143B2 - Status: Granted - Kind: B2 - Application number: 16/314,732 - Filed: 2017-07-05 - Published: 2019-12-26 - Granted: 2022-04-19 - Earliest claimed: 2016-07-06 - Assignees: Bristol-Myers Squibb Company - Applicants: Bristol-Myers Squibb Company - Inventors: Sean E. Doyle; Mark J. Selby; Eric Chadwick - Web page: https://patentgrep.com/patent/US11306143B2 ## CPC - C07K 16/2818: {against CD28 or CD152} - A61K 9/0019: {Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner (non-active ingredients are additionally classified in A61K47/00)} - A61P 1/04: for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants - A61P 11/00: Drugs for disorders of the respiratory system - A61P 25/00: Drugs for disorders of the nervous system - A61P 35/00: Antineoplastic agents - A61P 35/02: specific for leukemia - A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 - C07K 16/2803: {against the immunoglobulin superfamily} - A61K 2039/507: {Comprising a combination of two or more separate antibodies} - C07K 2317/76: Antagonist effect on antigen, e.g. neutralization or inhibition of binding - C07K: PEPTIDES (peptides in foodstuffs A23; obtaining protein compositions for foodstuffs, working-up proteins for foodstuffs A23J; preparations for medicinal purposes A61K; peptides containing beta-lactam rings C07D; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, C07D; ergot alkaloids of the cyclic peptide type C07D519/02; macromolecular compounds having statistically distributed amino acid units in their molecules, i.e. when the preparation does not provide for a specific; but for a random sequence of the amino acid units, homopolyamides and block copolyamides derived from amino acids C08G69/00; macromolecular products derived from proteins C08H1/00; preparation of glue or gelatine C09H; single cell proteins, enzymes C12N; genetic engineering processes for obtaining peptides C12N15/00; compositions for measuring or testing processes involving enzymes C12Q; investigation or analysis of biological material G01N33/00) - A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D) - A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS ## Abstract Provided are methods and compositions for treating cancer using an effective amount of a PD-1 antagonist (e.g., an antibody) in combination with a TIM-4 antagonist (e.g., an antibody). ## Claims ### Claim 1 A method of treating cancer in a subject, the method comprising administering to the subject an effective amount of an anti-PD-1 antibody and an anti-TIM-4 antibody, wherein the anti-TIM-4 antibody inhibits efferocytosis of tumor cells. ### Claim 2 (depends on 1) The method of claim 1, wherein the anti-PD-1 antibody comprises the CDR1, CDR2 and CDR3 domains in a heavy chain variable region having the sequence set forth in SEQ ID NO: 13, and the CDR1, CDR2 and CDR3 domains in a light chain variable region having the sequence set forth in SEQ ID NO: 15. ### Claim 3 (depends on 1) The method of claim 1, wherein the anti-PD-1 antibody comprises: (a) a heavy chain variable region CDR1 having the sequence set forth in SEQ ID NO: 17; (b) a heavy chain variable region CDR2 having the sequence set forth in SEQ ID NO: 18; (c) a heavy chain variable region CDR3 having the sequence set forth in SEQ ID NO: 19; (d) a light chain variable region CDR1 having the sequence set forth in SEQ ID NO: 20; (e) a light chain variable region CDR2 having the sequence set forth in SEQ ID NO: 21; and (f) a light chain variable region CDR3 having the sequence set forth in SEQ ID NO: 22. ### Claim 4 (depends on 1) The method of claim 1, wherein the anti-PD-1 antibody comprises heavy and light chain variable regions having the sequences set forth in SEQ ID NOs: 13 and 15, respectively. ### Claim 5 (depends on 1) The method of claim 1, wherein the anti-PD-1 antibody comprises heavy and light chains having the sequences as set forth in SEQ ID NOs: 11 and 12, respectively. ### Claim 6 (depends on 1) The method of claim 1, wherein the anti-PD-1 antibody and TIM-4 antibody are formulated for intravenous administration. ### Claim 7 (depends on 1) The method of claim 1, wherein the anti-PD-1 antibody is administered prior to administration of the TIM-4 antibody. ### Claim 8 (depends on 1) The method of claim 1, wherein the TIM-4 antibody is administered prior to administration of the anti-PD-1 antibody. ### Claim 9 (depends on 1) The method of claim 1, wherein the TIM-4 antibody and the anti-PD-1 antibody are administered simultaneously. ### Claim 10 (depends on 1) The method of claim 1, wherein the cancer is selected from the group consisting of leukemia, lymphoma, blastoma, carcinoma, sarcoma, small-cell lung cancer, non-small cell lung cancer, gastrointestinal cancer, colorectal cancer, glioblastoma and colon carcinoma. ### Claim 11 (depends on 1) The method of claim 1, which comprises administration of an additional therapeutic agent. ### Claim 12 A composition comprising a PD-1 antibody and a TIM-4 antibody. ### Claim 13 (depends on 1) A kit for treating a cancer in a subject, the kit comprising: (a) a dose of a PD-1 antibody; (b) a dose of a TIM-4 antibody; and (c) instructions for using the PD-1 antibody and TIM-4 antibody in the method of claim 1.