# US 9,434,778 B2 · Modified FGF-21 polypeptides comprising an internal deletion and uses thereof > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 9,434,778 B2 - Document ID: US9434778B2 - Status: Granted - Kind: B2 - Application number: 14/921,796 - Filed: 2015-10-23 - Published: 2016-04-28 - Granted: 2016-09-06 - Earliest claimed: 2014-10-24 - Assignees: Bristol-Myers Squibb Company - Applicants: Bristol-Myers Squibb Company - Inventors: Paul E. Morin; Daniel Cohen; Ranjan Mukherjee; Timothy P. Reilly; Rose C. Christian; Dasa Lipovsek; Ray Camphausen; John Krupinski - Web page: https://patentgrep.com/patent/US9434778B2 ## CPC - C07K 14/50: Fibroblast growth factor [FGF] - A61K 38/1825: {Fibroblast growth factor [FGF]} - A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca - A61K 47/60: the organic macromolecular compound being a polyoxyalkylene oligomer, polymer or dendrimer, e.g. PEG, PPG, PEO or polyglycerol - A61K 47/64: Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent (peptidic linkers A61K47/65) - A61P 1/00: Drugs for disorders of the alimentary tract or the digestive system - A61P 1/04: for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants - A61P 1/16: for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics - A61P 1/18: for pancreatic disorders, e.g. pancreatic enzymes - A61P 3/00: Drugs for disorders of the metabolism (of the blood or the extracellular fluid A61P7/00) - A61P 3/04: Anorexiants; Antiobesity agents - A61P 3/06: Antihyperlipidemics - A61P 3/10: for hyperglycaemia, e.g. antidiabetics - A61P 5/28: Antiandrogens - A61P 9/00: Drugs for disorders of the cardiovascular system - A61P 9/04: Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure - A61P 9/10: for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis - A61P 11/00: Drugs for disorders of the respiratory system - A61P 13/12: of the kidneys - A61P 17/00: Drugs for dermatological disorders - A61P 17/02: for treating wounds, ulcers, burns, scars, keloids, or the like - A61P 27/02: Ophthalmic agents - A61P 27/12: for cataracts - 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) - C07K 2319/00: Fusion polypeptide - C07K 2319/30: Non-immunoglobulin-derived peptide or protein having an immunoglobulin constant or Fc region, or a fragment thereof, attached thereto - 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 Modified FGF-21 polypeptides and uses thereof are provided, for example, for the treatment of diseases associated with fibrosis. Modified FGF-21 polypeptides are disclosed that contain an internal deletion and optionally replacement peptide, optionally modified with at least one non-naturally-encoded amino acid, and/or optionally fused to a fusion partner. ## Claims ### Claim 1 A modified FGF-21 polypeptide comprising a polypeptide having an amino acid sequence having at least 98% amino acid sequence identity to SEQ ID NO: 102. ### Claim 2 (depends on 1) The modified FGF-21 polypeptide of claim 1, wherein said amino acid sequence comprises at least one non-naturally encoded amino acid. ### Claim 3 (depends on 2) The modified FGF-21 polypeptide of claim 2, wherein said at least one non-naturally encoded amino acid comprises a phenylalanine derivative. ### Claim 4 (depends on 3) The modified FGF-21 polypeptide of claim 3, wherein said at least one non-naturally encoded amino acid comprises para-acetyl-L-phenylalanine. ### Claim 5 (depends on 4) The modified FGF-21 polypeptide of claim 4, wherein said amino acid sequence comprises para-acetyl-L-phenylalanine at a position corresponding to amino acid 109 in SEQ ID NO: 102 which corresponds to amino acid 108 in SEQ ID NO: 1. ### Claim 6 (depends on 2) The modified FGF-21 polypeptide of claim 2, wherein said at least one non-naturally encoded amino acid is linked to a half-life extending moiety. ### Claim 7 (depends on 6) The modified FGF-21 polypeptide of claim 6, wherein said half-life extending moiety comprises a poly(ethylene glycol). ### Claim 8 (depends on 7) The modified FGF-21 polypeptide of claim 7, wherein said poly(ethylene glycol) has an average molecular weight of about 30 kDa. ### Claim 9 (depends on 1) The modified FGF-21 polypeptide of claim 1, wherein said amino acid sequence comprises at least one non-naturally encoded amino acid at a position corresponding to amino acid 109 in SEQ ID NO: 102 which corresponds to amino acid 108 in SEQ ID NO: 1. ### Claim 10 (depends on 1) The modified FGF-21 polypeptide of claim 1, wherein said amino acid sequence has at least 99% amino acid sequence identity to SEQ ID NO: 102. ### Claim 11 (depends on 1) The modified FGF-21 polypeptide of claim 1, wherein said modified FGF-21 polypeptide sequence is fused to a fusion partner. ### Claim 12 (depends on 11) The modified FGF-21 polypeptide of claim 11, wherein the fusion partner comprises an Fc domain or fragment thereof. ### Claim 13 (depends on 1) A composition comprising the modified FGF-21 polypeptide of claim 1 and a pharmaceutically acceptable carrier or excipient. ### Claim 14 A modified FGF-21 polypeptide comprising a polypeptide having the amino acid sequence of SEQ ID NO: 202. ### Claim 15 (depends on 14) The modified FGF-21 polypeptide of claim 14, wherein said modified FGF-21 polypeptide is linked to a half-life extending moiety. ### Claim 16 (depends on 15) The modified FGF-21 polypeptide of claim 15, wherein said half-life extending moiety comprises a poly(ethylene glycol). ### Claim 17 (depends on 16) The modified FGF-21 polypeptide of claim 16, wherein said poly(ethylene glycol) has an average molecular weight of about 30 kDa. ### Claim 18 (depends on 14) A composition comprising the modified FGF-21 polypeptide of claim 14 and a pharmaceutically acceptable carrier or excipient. ### Claim 19 A modified FGF-21 polypeptide comprising a polypeptide having the amino acid sequence of SEQ ID NO: 202, wherein the para-acetyl-L-phenylalanine in SEQ ID NO: 202 is linked to a poly(ethylene glycol) having an average molecular weight of about 30 kDa. ### Claim 20 (depends on 19) A composition comprising the modified FGF-21 polypeptide of claim 19 and a pharmaceutically acceptable carrier or excipient.