# US 10,501,497 B2 · Cyclic polypeptides, method for obtaining them and the therapeutic use thereof > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 10,501,497 B2 - Document ID: US10501497B2 - Status: Granted - Kind: B2 - Application number: 15/762,921 - Filed: 2016-09-23 - Published: 2018-09-20 - Granted: 2019-12-10 - Earliest claimed: 2015-09-25 - Assignees: Axoltis Pharma - Applicants: Axoltis Pharma - Inventors: Dominique Bridon; Stéphane Gobron - Web page: https://patentgrep.com/patent/US10501497B2 ## CPC - C07K 7/64: Cyclic peptides containing only normal peptide links - 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 25/00: Drugs for disorders of the nervous system - A61P 25/02: for peripheral neuropathies - A61P 25/16: Anti-Parkinson drugs - A61P 25/28: for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia - C07K 14/78: Connective tissue peptides, e.g. collagen, elastin, laminin, fibronectin, vitronectin or cold insoluble globulin [CIG] - 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 invention relates to a polypeptide #including the following amino acid sequence: W-S-X1-W-X2-X3-C-S-X4-C-G (SEQ ID NO: 59), wherein X1, X2 and X3 are, independently of one another, S or G, X4 is R-S or V-S or V-T or R-T, and both cysteines form a disulfide bridge. ## Claims ### Claim 1 Polypeptide comprising the amino acid sequence SEQ ID NO: 59, wherein the two cysteines form a disulfide bridge; and wherein the polypeptide is substantially free of the reduced or dimeric or oligomeric forms of the polypeptide as well as derivatives of the polypeptide in which the thiol groups are in the sulfoxide or sulfone form. ### Claim 2 (depends on 1) Polypeptide according to claim 1 wherein the amino acid sequence comprises SEQ ID NO: 1. ### Claim 3 (depends on 1) Polypeptide according to claim 1 wherein the amino acid sequence comprises SEQ ID NO: 2. ### Claim 4 (depends on 3) A pharmaceutical composition of comprising as active ingredient a polypeptide according to claim 3 and one or more pharmaceutically-acceptable excipients. ### Claim 5 (depends on 4) The pharmaceutical composition of claim 4 further comprising a second polypeptide comprising the amino acid sequence SEQ ID NO: 59 wherein the two cysteines form a disulfide bridge; and wherein the second polypeptide is substantially free of the reduced or dimeric or oligomeric forms of the second polypeptide as well as derivatives of the second polypeptide in which the thiol groups are in the sulfoxide or sulfone form. ### Claim 6 (depends on 1) Polypeptide according to claim 1 wherein the polypeptide consists of the amino acid sequence SEQ ID NO: 69. ### Claim 7 (depends on 1) Polypeptide according to claim 1 wherein the polypeptide consists of the amino acid sequence SEQ ID NO: 2. ### Claim 8 (depends on 7) Polypeptide according to claim 7, wherein the polypeptide has a purity greater than 80%. ### Claim 9 (depends on 1) Polypeptide according to claim 1 wherein the polypeptide consists of the amino acid sequence SEQ ID NO: 59 and wherein the polypeptide has a purity greater than 80%. ### Claim 10 (depends on 1) Pharmaceutical composition comprising as active ingredient a polypeptide according to claim 1 and one or more pharmaceutically-acceptable excipients. ### Claim 11 Method for obtaining the polypeptide of amino acid sequence SEQ ID NO: 59 having the two cysteines form a disulfide bridge, from a starting polypeptide of sequence SEQ ID NO: 70, wherein the starting polypeptide of sequence SEQ ID NO: 70 is in solution; comprising forming a disulfide bridge in the presence of albumin in the starting polypeptide of sequence SEQ ID NO: 70. ### Claim 12 (depends on 11) Method according to claim 11 wherein albumin and the starting polypeptide are present in a molar:molar ratio of 1:1 to 1:100. ### Claim 13 (depends on 12) The method of claim 12, wherein said molar:molar ratio is 1:1 to 1:10. ### Claim 14 (depends on 12) The method of claim 12, wherein said molar:molar ratio is 1:1. ### Claim 15 (depends on 11) Method according to claim 11 wherein the forming a disulfide bridge in the presence of albumin in the starting polypeptide is carried out in ambient air. ### Claim 16 (depends on 11) The method according to claim 11, wherein the forming a disulfide bridge in the presence of albumin in the starting polypeptide is carried out without detaching the starting polypeptide from the resin used for the peptide synthesis of these polypeptides, and wherein the polypeptide of sequence SEQ ID NO: 59 is then obtained by separating the polypeptide from the resin after the disulfide bond formation. ### Claim 17 Method for obtaining the polypeptide of amino acid sequence SEQ ID NO: 2 from a starting polypeptide of sequence SEQ ID NO: 58: comprising forming a disulfide bridge in the presence of albumin in the starting polypeptide of sequence SEQ ID NO: 58. ### Claim 18 (depends on 17) Method according to claim 17, wherein albumin and the starting polypeptide are present in a molar:molar ratio of 1:1 to 1:100. ### Claim 19 (depends on 18) The method of claim 18, wherein said molar:molar ratio is 1:1 to 1:10. ### Claim 20 (depends on 18) The method of claim 18, wherein said molar:molar ratio is 1:1. ### Claim 21 (depends on 17) The method according to claim 17, wherein the forming a disulfide bridge in the presence of albumin in the starting polypeptide is carried out in ambient air. ### Claim 22 (depends on 17) The method according to claim 17, wherein the forming a disulfide bridge in the presence of albumin in the starting polypeptide is carried out without detaching the starting polypeptide from the resin used for the peptide synthesis of the polypeptide, and wherein the polypeptide of sequence SEQ ID NO: 2 is then obtained by separating the polypeptide from the resin after the disulfide bond formation.