# US 9,518,113 B2 · Monoclonal antibodies to interleukin 35 and methods of use thereof to inhibit regulatory T cell function > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 9,518,113 B2 - Document ID: US9518113B2 - Status: Granted - Kind: B2 - Application number: 14/796,494 - Filed: 2015-07-10 - Published: 2016-04-14 - Granted: 2016-12-13 - Earliest claimed: 2006-09-22 - Assignees: St. Jude Children's Research Hospital - Applicants: St. Jude Children's Research Hospital - Inventors: Dario Vignali; Creg Workman; Lauren Collison; Kate Vignali - Web page: https://patentgrep.com/patent/US9518113B2 ## CPC - C07K 16/244: {Interleukins [IL]} - A61K 39/39533: {against materials from animals} - A61K 39/3955: {against proteinaceous materials, e.g. enzymes, hormones, lymphokines} - A61K 40/11: T-cells, e.g. tumour infiltrating lymphocytes [TIL] or regulatory T [Treg] cells; Lymphokine-activated killer [LAK] cells - A61K 40/22: Immunosuppressive or immunotolerising - A61K 40/416: {Antigens related to auto-immune diseases; Preparations to induce self-tolerance} - A61P 35/00: Antineoplastic agents - C12N 5/0636: {T lymphocytes} - A61K 2039/505: {comprising antibodies} - C07K 2317/21: from primates, e.g. man - C07K 2317/24: containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered - C07K 2317/35: Valency - C07K 2317/622: Single chain antibody (scFv) - 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 - C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00) ## Abstract Methods for regulating T cell function in a subject, particularly regulatory T cell activity are provided. Methods of the invention include administering to a subject a therapeutically effective amount of an Interleukin 35-specific binding agent, such as an antibody or small molecule inhibitor. The invention further provides methods for enhancing the immunogenicity of a vaccine or overcoming a suppressed immune response to a vaccine in a subject, including administering to the subject a therapeutically effective amount of an IL35-specific binding agent and administering to the subject a vaccine. In one embodiment the vaccine is a cancer vaccine. ## Claims ### Claim 1 A pharmaceutical composition comprising an excipient and an isolated human or humanized monoclonal antibody or antigen-binding fragment thereof capable of binding human Interleukin 35 (IL35) heterodimer, wherein the antibody is present in the composition in an amount effective to inhibit a regulatory T- cell function in a human subject to whom the composition is administered. ### Claim 2 (depends on 1) The pharmaceutical composition of claim 1, wherein the monoclonal antibody specifically binds to the Epstein-Barr-virus-induced gene 3 (EBI3) subunit of IL35. ### Claim 3 (depends on 1) The pharmaceutical composition of claim 1, wherein the monoclonal antibody specifically binds to the p35 subunit of IL35. ### Claim 4 (depends on 1) The pharmaceutical composition of claim 1, wherein the monoclonal antibody does not specifically bind to Interleukin 12 (IL12). ### Claim 5 (depends on 1) The pharmaceutical composition of claim 1, wherein the monoclonal antibody specifically binds to the EBI3 subunit of IL35 and specifically blocks IL35 regulatory T-cell activity. ### Claim 6 (depends on 1) The pharmaceutical composition of claim 1, wherein the monoclonal antibody specifically binds to the p35 subunit of IL35 and specifically blocks IL35 regulatory T-cell activity. ### Claim 7 (depends on 1) The pharmaceutical composition of claim 1, wherein the monoclonal antibody specifically interferes with IL35 formation or activity. ### Claim 8 (depends on 1) The pharmaceutical composition of claim 1, wherein the monoclonal antibody is present in the composition in an amount effective to inhibit IL35 immunoregulatory activity. ### Claim 9 (depends on 1) The pharmaceutical composition of claim 1, wherein the monoclonal antibody is present in the composition in an amount effective to reduce and/or block of one or more of the suppressive effects mediated by regulatory T-cells. ### Claim 10 (depends on 1) The pharmaceutical composition of claim 1, wherein the monoclonal antibody is present in the composition in an amount effective to inhibit the activation and/or proliferation of regulatory T-cells relative to the activation and/or proliferation of effector T-cells. ### Claim 11 (depends on 1) The pharmaceutical composition of claim 1, wherein the monoclonal antibody is present in the composition in an amount effective to prevent or overcome induction of tumor antigen tolerance by regulatory T-cells in a subject. ### Claim 12 (depends on 1) The pharmaceutical composition of claim 1, wherein the monoclonal antibody is monovalent, bivalent, or a single-chain antibody. ### Claim 13 (depends on 1) The pharmaceutical composition of claim 1, wherein the monoclonal antibody is present in the composition in an amount from about 0.1 to about 200 mg/kg body weight in single or divided doses. ### Claim 14 A monoclonal antibody that specifically binds to human IL35. ### Claim 15 (depends on 1) The pharmaceutical composition of claim 1, wherein the monoclonal antibody does not specifically bind to Interleukin 27 (IL27). ### Claim 16 (depends on 14) The monoclonal antibody of claim 14, wherein the antibody is humanized or is a fully human antibody. ### Claim 17 (depends on 14) The monoclonal antibody of claim 14, wherein the antibody is an antigen-binding fragment of the full-size monoclonal antibody . ### Claim 18 (depends on 17) The monoclonal antibody of claim 17, wherein the fragment comprises a Fab. ### Claim 19 (depends on 1) The pharmaceutical composition of claim 1, wherein the monoclonal antibody specifically interferes with IL35 formation. ### Claim 20 (depends on 1) The pharmaceutical composition of claim 1, wherein the monoclonal antibody specifically interferes with IL35 activity. ### Claim 21 (depends on 1) The pharmaceutical composition of claim 1, wherein the monoclonal antibody specifically competes with binding of an IL35 subunit. ### Claim 22 (depends on 1) A method of inhibiting a regulatory T-cell function in a subject, comprising administering to a subject in need of inhibiting a regulatory T-cell function a therapeutically effective amount of the pharmaceutical composition of claim 1, wherein the therapeutically effective amount of said antibody inhibits a regulatory T-cell function in said subject. ### Claim 23 (depends on 15) A method of inhibiting a regulatory T cell function in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of the antibody of claim 15.