# US 10,118,959 B2 · Anti-glypican-3 antibody > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 10,118,959 B2 - Document ID: US10118959B2 - Status: Granted - Kind: B2 - Application number: 14/505,932 - Filed: 2014-10-03 - Published: 2015-04-09 - Granted: 2018-11-06 - Earliest claimed: 2005-10-14 - Assignees: Chugai Seiyaku Kabushiki Kaisha; Xencor, Inc. - Applicants: Xencor, Inc.; Chugai Seiyaku Kabushiki Kaisha - Inventors: Gregory Alan Lazar; Bassil I. Dahiyat; Hisafumi Okabe; Masamichi Sugimoto; Shigeyuki Iijima; Izumi Sugo - Web page: https://patentgrep.com/patent/US10118959B2 ## CPC - A61P 35/00: Antineoplastic agents - C07K 16/18: against material from animals or humans - C07K 16/303: {Liver or Pancreas} - A61K 2039/505: {comprising antibodies} - C07K 2317/24: containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered - C07K 2317/52: Constant or Fc region; Isotype - C07K 2317/524: CH2 domain - C07K 2317/526: CH3 domain - C07K 2317/72: Increased effector function due to an Fc-modification - C07K 2317/732: Antibody-dependent cellular cytotoxicity [ADCC] - A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS - 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) ## Abstract An anti-glypican-3 antibody comprising one or more amino acid substitutions introduced in the Fc region is disclosed. Preferably, in the anti-glypican-3 antibody, one or more of the amino acid residues at the positions 239, 298, 326, 330 and 332 in the Fc region are substituted with other amino acid residues. Since the Fc-modified anti-glypican-3 antibody of the invention exhibit enhanced ADCC activity, it is useful in treating cancers, such as hepatic cancer. Also disclosed are an anticancer agent comprising the anti-glypican-3 antibody of the invention and a pharmaceutically acceptable carrier, as well as a method of treating a patient with cancer comprising administering to the patient the anticancer agent of the invention. ## Claims ### Claim 1 An anti-glypican-3 antibody that comprises a H-chain CDR1 as set forth in SEQ ID NO: 23, a H-chain CDR2 as set forth in SEQ ID NO: 24, and a H-chain CDR3 as set forth in SEQ ID NO: 25; and an L-chain CDR1 as set forth in SEQ ID NO: 26, an L-chain CDR2 as set forth in SEQ ID NO: 27, and an L-chain CDR3 as set forth in SEQ ID NO: 28; and further comprises either (a) or (b): (a) an Fc region with aspartic acid at position 239, threonine at position 326, and glutamic acid at position 332 (all positions by EU numbering); or (b) an Fc region with aspartic acid at position 239, alanine at position 298, glutamic acid at position 326, and glutamic acid at position 332 (all positions by EU numbering). ### Claim 2 An anti-glypican-3 antibody that comprises a H-chain CDR1 as set forth in SEQ ID NO: 23, a H-chain CDR2 as set forth in SEQ ID NO: 24, and a H-chain CDR3 as set forth in SEQ ID NO: 25; and an L-chain CDR1 as set forth in SEQ ID NO: 26, an L-chain CDR2 as set forth in SEQ ID NO: 27, and an L-chain CDR3 as set forth in SEQ ID NO: 28; and further comprises either (a) or (b): (a) an Fc region in which the amino acid residues at positions 239, 326 and 332 (all positions by EU numbering) are substituted with aspartic acid, threonine, and glutamic acid, respectively; or (b) an Fc region in which the amino acid residues at positions 239, 298, 326 and 332 (all positions by EU numbering) are substituted with aspartic acid, alanine, glutamic acid, and glutamic acid, respectively. ### Claim 3 (depends on 1, 2) An anticancer agent comprising the anti-glypican-3 antibody as claimed in claim 1 or 2 and a pharmaceutically acceptable carrier. ### Claim 4 An anti-glypican-3 antibody that comprises a H-chain CDR1 as set forth in SEQ ID NO: 23, a H-chain CDR2 as set forth in SEQ ID NO: 24, and a H-chain CDR3 as set forth in SEQ ID NO: 25; and an L-chain CDR1 as set forth in SEQ ID NO: 26, an L-chain CDR2 as set forth in SEQ ID NO: 27, and an L-chain CDR3 as set forth in SEQ ID NO: 28; and further comprises (a) or (b): (a) a CH2-CH3 domain comprising the amino acid sequence set forth in SEQ ID NO: 37; or (b) a CH2-CH3 domain comprising the amino acid sequence set forth in SEQ ID NO: 38. ### Claim 5 (depends on 1) The anti-glypican-3 antibody of claim 1, wherein the antibody comprises (a). ### Claim 6 (depends on 5) An anticancer agent comprising the antibody of claim 5 and a pharmaceutically acceptable carrier. ### Claim 7 (depends on 1) The anti-glypican-3 antibody of claim 1, wherein the antibody comprises (b). ### Claim 8 (depends on 7) An anticancer agent comprising the antibody of claim 7 and a pharmaceutically acceptable carrier. ### Claim 9 (depends on 4) The anti-glypican-3 antibody of claim 4, wherein the antibody comprises (a). ### Claim 10 (depends on 4) The anti-glypican-3 antibody of claim 4, wherein the antibody comprises (b).