# US 10,870,700 B2 · Neutralization of inhibitory pathways in lymphocytes > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 10,870,700 B2 - Document ID: US10870700B2 - Status: Granted - Kind: B2 - Application number: 16/071,499 - Filed: 2017-01-20 - Published: 2019-01-31 - Granted: 2020-12-22 - Earliest claimed: 2016-01-21 - Assignees: Innate Pharma - Applicants: Innate Pharma - Inventors: Pascale Andre; Mathieu Blery; Caroline Denis; Carine Paturel; Nicolai Wagtmann - Web page: https://patentgrep.com/patent/US10870700B2 ## CPC - C07K 16/2803: {against the immunoglobulin superfamily} - A61P 35/00: Antineoplastic agents - C07K 16/2818: {against CD28 or CD152} - A61K 2039/505: {comprising antibodies} - 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) - A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS - 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) ## Abstract This invention relates to the use of NKG2A-neutralizing agents to treat cancers that are poorly responsive to PD-1 neutralizing agents, as well as to the combined use of NKG2A-neutralizing agents and PD-1 neutralizing agents for the treatment of cancer. ## Claims ### Claim 1 A method for treating cancer in an individual who is being treated with an agent that neutralizes the inhibitory activity of PD-1, the treatment comprising: a) determining levels of NKG2A expression on NK and/or CD8 T cells in the individual; and b) upon a determination that the individual has increased levels of NKG2A expression on NK and/or CD8 T cells, administering to the individual an antibody that neutralizes the inhibitory activity of a human NKG2A polypeptide; wherein the antibody that neutralizes the inhibitory activity of NKG2A comprises the CDR1, CDR2 and CDR3 domains of a heavy chain having the sequence set forth in any one of SEQ ID NOS: 4-8, and the CDR1, CDR2 and CDR3 domains of a light chain having the sequence set forth in SEQ ID NO: 9. ### Claim 2 (depends on 1) The method of claim 1, wherein the individual has a cancer that has relapsed or progressed upon or following treatment with an antibody that neutralizes the inhibitory activity of human PD-1. ### Claim 3 (depends on 1) The method of claim 1, wherein the individual has a cancer that is predicted based on one or more predictive factors to progress or relapse upon or following treatment with an antibody that neutralizes the inhibitory activity of human PD-1. ### Claim 4 (depends on 1) The method of claim 1, wherein the individual has not experienced a complete response upon or following treatment with an antibody that neutralizes the inhibitory activity of human PD-1. ### Claim 5 (depends on 1) The method of claim 1, wherein the individual has an elevated number of NKG2A-expressing NK and/or CD8 T cells. ### Claim 6 (depends on 1) The method of claim 1, wherein the antibody that neutralizes the inhibitory activity of human NKG2A is administered in combination with an antibody that neutralizes the inhibitory activity of PD-1. ### Claim 7 (depends on 1) The method of claim 1, wherein the antibody that neutralizes the inhibitory activity of human NKG2A and the antibody that neutralizes the inhibitory activity of PD-1 are formulated for separate administration and are administered concurrently or sequentially. ### Claim 8 (depends on 1) The method of claim 1, wherein the cancer is a solid tumor. ### Claim 9 (depends on 1) The method of claim 1, wherein the cancer is selected from the group consisting of lung cancer, renal cell carcinoma (RCC), melanoma, colorectal cancer, and ovarian cancer. ### Claim 10 (depends on 1) The method of claim 1, wherein the cancer is head and neck squamous cell carcinoma. ### Claim 11 (depends on 1) The method of claim 1, wherein said antibody that neutralizes the inhibitory activity of NKG2A is a non-depleting antibody. ### Claim 12 (depends on 1) The method of claim 1, wherein said antibody is IgG4 antibody. ### Claim 13 (depends on 11) The method of claim 11, wherein said antibody lacks an Fe domain or comprises an Fc domain that is modified to reduce binding between the Fc domain and an Fey receptor. ### Claim 14 (depends on 11) The method of claim 11, wherein said antibody is an antibody fragment. ### Claim 15 (depends on 11) The method of claim 11, wherein said antibody fragment is selected from Fab, Fab′, Fab′-SH, F(ab′) 2, Fv, a diabody, a single-chain antibody fragment, or a multispecific antibody comprising multiple different antibody fragments. ### Claim 16 (depends on 1) The method of claim 1, wherein the antibody that neutralizes the inhibitory activity of NKG2A is administered to the individual in an amount effective to neutralize the inhibitory activity of NKG2A on NK and/or CD8 T cells.