# US 2021/0330749 A1 · Glucagon analogues as long-acting glp-1/glucagon receptor agonists in the treatment of fatty liver disease and steatohepatitis > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 2021/0330749 A1 - Document ID: US20210330749A1 - Status: Published application - Kind: A1 - Application number: 17/237,210 - Filed: 2021-04-22 - Published: 2021-10-28 - Earliest claimed: 2020-04-24 - Assignees: Boehringer Ingelheim International GmbH - Applicants: Boehringer Ingelheim International GmbH - Inventors: Leo THOMAS - Web page: https://patentgrep.com/patent/US20210330749A1 ## CPC - C07K 14/605: Glucagons - A61K 38/26: Glucagons - A61K 47/542: {Carboxylic acids, e.g. a fatty acid or an amino acid} - A61P 1/16: for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics - 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: 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 present invention relates to the medical use of specific long-acting glucagon analogues having dual GLP-1/glucagon receptor agonist activity in the prevention and/or treatment of metabolic liver disease, particularly non-alcoholic fatty liver disease (NAFLD), non-alcoholic fatty liver (NAFL), non-alcoholic steatohepatitis (NASH), NAFLD-associated liver fibrosis and/or cirrhosis. ## Claims ### Claim 1 A method for preventing or treating a metabolic liver disease, comprising administering to a patient in need thereof a therapeutically effective amount of a compound of formula I R—H—X2-QGTFTSDYSKYL-X15-X16-X17-X18-AKDFI-X24-WLE-X28-A-NH2 (I) wherein R is selected from H, C1-4 alkyl and acetyl; X2 is selected from Aib and Ac4c; X15 is selected from Asp and Glu; X16 is selected from Glu and ψ; X17 is selected from Arg and ψ; X18 is selected from Ala and Arg; X24 is selected from Glu and ψ; X28 is selected from Ser and ψ; wherein the compound contains one and only one ψ and wherein said ψ is a residue of Lys, in which the amino group of the side chain is conjugated to a substituent selected from the group consisting of HOOC—(CH2)16—(CO)-isoGlu-Peg3-Peg3-, and HOOC—(CH2)16—(CO)-isoGlu-GSGSGG-. ### Claim 2 (depends on 1) The method according to claim 1, wherein X24 is ψ; ### Claim 3 (depends on 1) The method according to claim 1, wherein ψ is Lys(-GGSGSG-isoGlu-(CO)—(CH2)16—COOH). ### Claim 4 (depends on 1) The method according to claim 1, wherein the compound is selected from the group consisting of H—H-Aib-QGTFTSDYSKYLD-K([17-carboxy-heptadecanoyl]-isoGlu-Peg3-Peg3)-RAAKDFIEWLESA-NH2 (Compound 1), H—H-Aib-QGTFTSDYSKYLDERAAKDFI-K([17-carboxy-heptadecanoyl]-isoGlu-GSGSGG)-WLESA-NH2 (Compound 2), H—H-Ac4c-QGTFTSDYSKYLDE-K([17-carboxy-heptadecanoyl]-isoGlu-Peg3-Peg3)-RAKDFIEWLESA-NH2 (Compound 3) H—H-Aib-QGTFTSDYSKYLE-K([17-carboxy-heptadecanoyl]-isoGlu-GSGSGG)-RAAKDFIEWLESA-NH2 (Compound 4), H—H-Ac4c-QGTFTSDYSKYLDERAAKDFI-K([17-carboxy-heptadecanoyl]-isoGlu-GSGSGG)-WLESA-NH2 (Compound 5), and H—H-Ac4c-QGTFTSDYSKYLDERAAKDFIEWLE-K([17-carboxy-heptadecanoyl]-isoGlu-GSGSGG)-A-NH2 (Compound 6). ### Claim 5 (depends on 1) The method according to claim 1, wherein the metabolic liver disease is non-alcoholic fatty liver disease (NAFLD). ### Claim 6 (depends on 1) The method according to claim 1, wherein the metabolic liver disease is non-alcoholic fatty liver (NAFL), non-alcoholic steatohepatitis (NASH), NAFLD-associated liver fibrosis or NAFLD-associated liver cirrhosis. ### Claim 7 (depends on 1) The method according to claim 1, wherein the metabolic liver disease is non-alcoholic steatohepatitis (NASH) associated with liver fibrosis. ### Claim 8 (depends on 7) The method according to claim 7, wherein the patient is diagnosed as having a NAFLD activity score (NAS) of at least 4 and, optionally, as having liver fibrosis. ### Claim 9 (depends on 8) The method according to claim 8, wherein at least 1 point of the NAS arises each from the ballooning and the inflammation subscore. ### Claim 10 A method of preventing or treating a metabolic liver disease, the method comprising administering to a patient in need thereof a pharmaceutical composition comprising a compound of formula I R—H—X2-QGTFTSDYSKYL-X15-X16-X17-X18-AKDFI-X24-WLE-X28-A-NH22 (I) wherein R is selected from H, C1-4 alkyl and acetyl; X2 is selected from Aib and Ac4c; X15 is selected from Asp and Glu; X16 is selected from Glu and ψ; X17 is selected from Arg and ψ; X18 is selected from Ala and Arg; X24 is selected from Glu and ψ; X28 is selected from Ser and ψ; wherein the compound contains one and only one ψ and wherein said ψ is a residue of Lys, in which the amino group of the side chain is conjugated to a substituent selected from the group consisting of HOOC—(CH2)16—(CO)-isoGlu-Peg3-Peg3-, and HOOC—(CH2)16—(CO)-isoGlu-GSGSGG-. ### Claim 11 (depends on 10) The method according to claim 10, wherein the metabolic liver disease is non-alcoholic fatty liver disease (NAFLD). ### Claim 12 (depends on 10) The method according to claim 10, wherein the metabolic liver disease is non-alcoholic steatohepatitis (NASH) associated with liver fibrosis. ### Claim 13 (depends on 12) The method according to claim 12, wherein the patient is diagnosed as having a NAS of at least 4 and, optionally, as having liver fibrosis.