# US 10,479,833 B2 · Anti-CTLA-4 antibodies and methods of use thereof > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 10,479,833 B2 - Document ID: US10479833B2 - Status: Granted - Kind: B2 - Application number: 16/165,833 - Filed: 2018-10-19 - Published: 2019-05-09 - Granted: 2019-11-19 - Earliest claimed: 2015-05-29 - Assignees: Agenus Inc.; Ludwig Institute for Cancer Research; Memorial Sloan Kettering Cancer Center - Applicants: Agenus Inc.; Ludwig Institute for Cancer Research Ltd; Memorial Sloan Kettering Cancer Center - Inventors: Marc van Dijk; Cornelia Anne Mundt; Gerd Ritter; David Schaer; Jedd David Wolchok; Taha Merghoub; David Adam Savitsky; Nicholas Stuart Wilson - Web page: https://patentgrep.com/patent/US10479833B2 ## CPC - C07K 16/2818: {against CD28 or CD152} - A61K 47/6849: {the antibody targeting a receptor, a cell surface antigen or a cell surface determinant} - A61K 51/1027: {against receptors, cell-surface antigens or cell-surface determinants} - A61P 31/00: Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics - A61P 35/00: Antineoplastic agents - A61P 37/04: Immunostimulants - C07K 16/283: {against Fc-receptors, e.g. CD16, CD32, CD64 (CD23 C07K16/2851)} - A61K 2039/505: {comprising antibodies} - C07K 2317/21: from primates, e.g. man - C07K 2317/33: Crossreactivity, e.g. for species or epitope, or lack of said crossreactivity - C07K 2317/34: Identification of a linear epitope shorter than 20 amino acid residues or of a conformational epitope defined by amino acid residues - C07K 2317/41: Glycosylation, sialylation, or fucosylation - C07K 2317/52: Constant or Fc region; Isotype - C07K 2317/56: variable (Fv) region, i.e. VH and/or VL - C07K 2317/565: Complementarity determining region [CDR] - C07K 2317/567: Framework region [FR] - C07K 2317/73: Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation - C07K 2317/76: Antagonist effect on antigen, e.g. neutralization or inhibition of binding - C07K 2317/92: Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value - 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 The instant disclosure provides antibodies that specifically bind to human CTLA-4 and antagonize CTLA-4 function. Also provided are pharmaceutical compositions comprising these antibodies, nucleic acids encoding these antibodies, expression vectors and host cells for making these antibodies, and methods of treating a subject using these antibodies. ## Claims ### Claim 1 An isolated antibody that specifically binds to human CTLA-4 protein, comprising: a heavy chain variable region comprising the CDRH1, CDRH2 and CDRH3 amino acid sequences of SEQ ID NOs: 1, 2, and 3, respectively; and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 8. ### Claim 2 (depends on 1) The isolated antibody of claim 1, wherein the amino acid sequence of the light chain variable region consists of the amino acid sequence of SEQ ID NO: 8. ### Claim 3 (depends on 1) The isolated antibody of claim 1, wherein the antibody comprises a light chain comprising the amino acid sequence of SEQ ID NO: 13. ### Claim 4 (depends on 3) The isolated antibody of claim 3, wherein the amino acid sequence of the light chain consists of the amino acid sequence of SEQ ID NO: 13. ### Claim 5 An isolated antibody that specifically binds to human CTLA-4 protein, comprising: a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 7; and a light chain variable region comprising the CDRL1, CDRL2 and CDRL3 amino acid sequences of SEQ ID NOs: 4, 5, and 6, respectively. ### Claim 6 (depends on 5) The isolated antibody of claim 5, wherein the amino acid sequence of the heavy chain variable region consists of the amino acid sequence of SEQ ID NO: 7. ### Claim 7 (depends on 5) The isolated antibody of claim 5, wherein the antibody comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 93. ### Claim 8 (depends on 7) The isolated antibody of claim 7, wherein the amino acid sequence of the heavy chain consists of the amino acid sequence of SEQ ID NO: 93. ### Claim 9 (depends on 5) The isolated antibody of claim 5, wherein the antibody comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 12. ### Claim 10 (depends on 9) The isolated antibody of claim 9, wherein the amino acid sequence of the heavy chain consists of the amino acid sequence of SEQ ID NO: 12. ### Claim 11 An isolated antibody that specifically binds to human CTLA-4 protein, comprising: a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 7; and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 8. ### Claim 12 (depends on 11) The isolated antibody of claim 11, wherein the amino acid sequence of the heavy chain variable region consists of the amino acid sequence of SEQ ID NO: 7, and the amino acid sequence of the light chain variable region consists of the amino acid sequence of SEQ ID NO: 8. ### Claim 13 An isolated antibody that specifically binds to human CTLA-4 protein, comprising: a heavy chain and a light chain, wherein the heavy chain comprises the amino acid sequence of SEQ ID NO: 93; and the light chain comprises the amino acid sequence of SEQ ID NO: 13. ### Claim 14 (depends on 13) The isolated antibody of claim 13, wherein the amino acid sequence of the heavy chain consists of the amino acid sequence of SEQ ID NO: 93. ### Claim 15 (depends on 13) The isolated antibody of claim 13, wherein the heavy chain comprises the amino acid sequence of SEQ ID NO: 12. ### Claim 16 (depends on 13) The isolated antibody of claim 13, wherein the amino acid sequence of the heavy chain consists of the amino acid sequence of SEQ ID NO: 12. ### Claim 17 (depends on 13) The isolated antibody of claim 13, wherein the amino acid sequence of the light chain consists of the amino acid sequence of SEQ ID NO: 13. ### Claim 18 (depends on 13) The isolated antibody of claim 13, wherein the amino acid sequence of the heavy chain consists of the amino acid sequence of SEQ ID NO: 93, and the amino acid sequence of the light chain consists of the amino acid sequence of SEQ ID NO: 13. ### Claim 19 (depends on 13) The isolated antibody of claim 13, wherein the heavy chain comprises the amino acid sequence of SEQ ID NO: 12, and the amino acid sequence of the light chain consists of the amino acid sequence of SEQ ID NO: 13. ### Claim 20 (depends on 13) The isolated antibody of claim 13, wherein the amino acid sequence of the heavy chain consists of the amino acid sequence of SEQ ID NO: 12, and the amino acid sequence of the light chain consists of the amino acid sequence of SEQ ID NO: 13. ### Claim 21 (depends on 1) A pharmaceutical composition comprising the antibody of claim 1 and a pharmaceutically acceptable carrier or excipient. ### Claim 22 (depends on 5) A pharmaceutical composition comprising the antibody of claim 5 and a pharmaceutically acceptable carrier or excipient. ### Claim 23 (depends on 11) A pharmaceutical composition comprising the antibody of claim 11 and a pharmaceutically acceptable carrier or excipient. ### Claim 24 (depends on 12) A pharmaceutical composition comprising the antibody of claim 12 and a pharmaceutically acceptable carrier or excipient. ### Claim 25 (depends on 13) A pharmaceutical composition comprising the antibody of claim 13 and a pharmaceutically acceptable carrier or excipient. ### Claim 26 (depends on 18) A pharmaceutical composition comprising the antibody of claim 18 and a pharmaceutically acceptable carrier or excipient. ### Claim 27 (depends on 20) A pharmaceutical composition comprising the antibody of claim 20 and a pharmaceutically acceptable carrier or excipient. ### Claim 28 (depends on 11) The isolated antibody of claim 11, wherein the antibody comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 93. ### Claim 29 (depends on 28) The isolated antibody of claim 28, wherein the amino acid sequence of the heavy chain consists of the amino acid sequence of SEQ ID NO: 93. ### Claim 30 (depends on 11) The isolated antibody of claim 11, wherein the antibody comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 12. ### Claim 31 (depends on 30) The isolated antibody of claim 30, wherein the amino acid sequence of the heavy chain consists of the amino acid sequence of SEQ ID NO: 12. ### Claim 32 (depends on 11) The isolated antibody of claim 11, wherein the antibody comprises a light chain amino acid sequence of SEQ ID NO: 13. ### Claim 33 (depends on 32) The isolated antibody of claim 32, wherein the amino acid sequence of the light chain consists of the amino acid sequence of SEQ ID NO: 13. ### Claim 34 (depends on 11) The isolated antibody of claim 11, wherein the antibody comprises a heavy chain and a light chain, wherein the heavy chain comprises the amino acid sequence of SEQ ID NO: 97; and the light chain comprises the amino acid sequence of SEQ ID NO: 13.