# US 12,565,517 B2 · Cyclic peptide having CTLA-4 inhibitory activity and use thereof > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 12,565,517 B2 - Document ID: US12565517B2 - Status: Granted - Kind: B2 - Application number: 17/767,550 - Filed: 2020-09-30 - Published: 2024-03-21 - Granted: 2026-03-03 - Earliest claimed: 2019-10-08 - Assignees: GeneFrontier Corporation - Applicants: GeneFrontier Corporation - Inventors: Kanehisa Kojoh; Kumiko Tsuihiji; Shizue Katoh; Mikiko Nakamura - Web page: https://patentgrep.com/patent/US12565517B2 ## CPC - A61P 35/00: Antineoplastic agents - C07K 7/64: Cyclic peptides containing only normal peptide links - A61P 37/04: Immunostimulants - A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 - C07K 7/08: having 12 to 20 amino acids (gastrins C07K14/595; somatostatins C07K14/655; melanotropins C07K14/68) - A61K 38/00: Medicinal preparations containing peptides (peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00) - 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 The present invention provides a cyclic peptide which comprises the amino acid sequence represented by formula (I) X1-His-Pro-X4-Leu-X6-X7-X8-Ser-X10-His-Phe (I) in the cycle and has an activity to specifically bind to human CTLA-4, wherein X1, X4, X6, X7, X8 and X10 are each independently any amino acid. ## Claims ### Claim 1 A cyclic peptide having a cyclic structure formed by an intrapeptide bond between two amino acids in the peptide, which comprises the amino acid sequence represented by formula (I): X1-His-Pro-X4-Leu-X6-X7-X8-Ser-X10-His-Phe (I) (SEQ ID NO: 212) in the cyclic structure and has an activity to specifically bind to human CTLA-4, wherein X1, X4, X6, X7, X8 and X10 are each independently any amino acid. ### Claim 2 (depends on 1) The cyclic peptide according to claim 1, wherein the cyclic peptide comprises the amino acid sequence represented by formula (II): X0-X1-His-Pro-X4-Leu-X6-X7-X8-Ser-X10-His-Phe-X00 (II) (SEQ ID NO: 213) wherein X0 and X00 are each independently any amino acid, and wherein the peptide is cyclized by an intramolecular bond between X0 and X00. ### Claim 3 (depends on 2) The cyclic peptide according to claim 2, wherein the cyclic peptide comprises the amino acid sequence represented by formula (III): (Y)m-X0-X1-His-Pro-X4-Leu-X6-X7-X8-Ser-X10-His-Phe-X00-(Z)n (III) (SEQ ID NO: 214) wherein (Y)m is an amino acid sequence having a length of m amino acid(s), (Z)n is an amino acid sequence having a length of n amino acid(s), m is any integer selected from the group consisting of 0, 1 and 2, and n is any integer selected from the group consisting of 0, 1 and 2. ### Claim 4 (depends on 2) The cyclic peptide according to claim 2, wherein X0 and X00 are each independently an amino acid having a side chain containing a thiol group. ### Claim 5 (depends on 4) The cyclic peptide according to claim 4, wherein X0 is Cys, and X00 is Cys. ### Claim 6 (depends on 4) The cyclic peptide according to claim 4, wherein the peptide is cyclized by an intramolecular disulfide bond between a thiol group in the side chain of X0 and a thiol group in the side chain of X00. ### Claim 7 (depends on 1) The cyclic peptide according to claim 1, wherein X6 is Leu, Pro, Gln, Lys or Arg, and X7 is Val, Leu, Ile or Thr. ### Claim 8 (depends on 7) The cyclic peptide according to claim 7, wherein X6 is Pro, and X7 is Ile. ### Claim 9 (depends on 3) The cyclic peptide according to claim 3, wherein n is 2, (Z)n consists of an amino acid sequence represented by X+1-X+2, and X+1 and X+2 are each independently any amino acid. ### Claim 10 (depends on 3) The cyclic peptide according to claim 3, wherein m is 2, (Y)m consists of an amino acid sequence represented by X−2-X−1, and X−2 and X−1 are each independently any amino acid. ### Claim 11 (depends on 10) The cyclic peptide according to claim 10, wherein X−2 is Gly, and X−1 is Gly, Ser or Asp. ### Claim 12 (depends on 1) The cyclic peptide according to claim 1, wherein the amino acid sequence represented by formula (I) consists of (1a) an amino acid sequence from the position 4 to position 15 in the amino acid sequence represented by any of SEQ ID NOs: 30-211, or (2a) an amino acid sequence having a substitution at least at one amino acid corresponding to one selected from X1, X4, X6, X7, X8 and X10 in an amino acid sequence from the position 4 to position 15 in the amino acid sequence represented by any of SEQ ID NOs: 30-211. ### Claim 13 (depends on 2) The cyclic peptide according to claim 2, wherein the amino acid sequence represented by formula (II) consists of (1b) an amino acid sequence from position 3 to position 16 in the amino acid sequence represented by any of SEQ ID NOs: 30-211, or (2b) an amino acid sequence having a substitution at least at one amino acid corresponding to one selected from X1, X4, X6, X7, X8 and X10 in an amino acid sequence from position 3 to position 16 in the amino acid sequence represented by any of SEQ ID NOs: 30-211. ### Claim 14 (depends on 3) The cyclic peptide according to claim 3, wherein the amino acid sequence represented by formula (III) consists of (1c) the amino acid sequence represented by any of SEQ ID NOs: 30-211, or (2c) an amino acid sequence having a substitution at least at one amino acid corresponding to one selected from X-2, X-1, X1, X4, X6, X7, X8, X10, X+1 and X+2 in the amino acid sequence represented by any of SEQ ID NOs: 30-211. ### Claim 15 (depends on 1) A pharmaceutical composition which comprises the cyclic peptide according to claim 1 and a pharmaceutically acceptable carrier or excipient. ### Claim 16 (depends on 1) A method for treating a tumor in a subject, which comprises administering an effective amount of the cyclic peptide according to claim 1 to the subject, wherein the tumor is selected from the group consisting of malignant lymphoma, colorectal cancer, non-small cell lung cancer, ovarian cancer, renal cancer, prostate cancer, and malignant melanoma.