# US 10,946,073 B2 · GHRH or analogues thereof for use in treatment of hepatic disease > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 10,946,073 B2 - Document ID: US10946073B2 - Status: Granted - Kind: B2 - Application number: 17/018,878 - Filed: 2020-09-11 - Published: 2020-12-31 - Granted: 2021-03-16 - Earliest claimed: 2016-03-29 - Assignees: The General Hospital Corporation - Applicants: The General Hospital Corporation - Inventors: Steven K. Grinspoon - Web page: https://patentgrep.com/patent/US10946073B2 ## CPC - A61K 38/25: Growth hormone-releasing factor [GH-RF], i.e. somatoliberin - A61P 1/16: for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics - A61K 9/0019: {Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner (non-active ingredients are additionally classified in A61K47/00)} - 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 application relates to novel methods for preventing, slowing the progression of, or treating nonalcoholic fatty liver (NAFL), nonalcoholic steatohepatitis (NASH), and/or liver fibrosis, and/or reducing the risks of liver cancer in subjects, such as HIV-infected subjects, using a GHRH molecule, e.g., trans-3-hexenoyl-GHRH(1-44)-NH2, or a pharmaceutically acceptable salt thereof. The subjects may have particular pathological features such as liver fibrosis, a hepatic fat fraction (HFF) of at least about 10%, serum alanine aminotransferase (ALT) levels of at least about 30 U/L, and/or a NAFLD Activity Score (NAS) of at least 4 or 5. ## Claims ### Claim 1 A method for (i) preventing or delaying the onset of liver fibrosis or (ii) reducing liver fibrosis or the progression thereof, in a subject suffering from nonalcoholic fatty liver (NAFL) or nonalcoholic steatohepatitis (NASH), wherein said subject has a hepatic fat fraction (HFF) of at least about 10%, comprising administering an effective amount of trans-3-hexenoyl-GHRH(1-44)-NH2 or a pharmaceutically acceptable salt thereof to said subject. ### Claim 2 (depends on 1) The method of claim 1, wherein said subject has a hepatic fat fraction (HFF) of at least about 15%. ### Claim 3 (depends on 1) The method of claim 1, wherein said subject has a hepatic fat fraction (HFF) of at least about 20%. ### Claim 4 (depends on 1) The method of claim 1, wherein said subject has serum ALT levels of at least about 30 U/L. ### Claim 5 (depends on 1) The method of claim 1, wherein said subject has serum ALT levels of at least about 35 U/L. ### Claim 6 (depends on 1) The method of claim 1, wherein said subject has a NAFLD Activity Score (NAS) of at least 1 as measured by the NAS Clinical Research Network (NAS CRN) scoring system. ### Claim 7 (depends on 1) The method of claim 1, wherein said subject has a NAFLD Activity Score (NAS) of at least 2 as measured by the NAS Clinical Research Network (NAS CRN) scoring system. ### Claim 8 (depends on 1) The method of claim 1, wherein said subject has a NAFLD Activity Score (NAS) of at least 3 as measured by the NAS Clinical Research Network (NAS CRN) scoring system. ### Claim 9 (depends on 1) The method of claim 1, wherein said subject has a NAFLD Activity Score (NAS) of at least 4 as measured by the NAS Clinical Research Network (NAS CRN) scoring system. ### Claim 10 (depends on 1) The method of claim 1, wherein said subject has a reduction of hepatic fat fraction (HFF) by at least 4% (absolute reduction) following the treatment. ### Claim 11 (depends on 1) The method of claim 1, wherein said subject has liver fibrosis. ### Claim 12 (depends on 11) The method of claim 11, wherein said subject has a fibrosis score of at least 1C prior to the treatment. ### Claim 13 (depends on 11) The method of claim 11, wherein said subject has a fibrosis score of at least 2 prior to the treatment. ### Claim 14 (depends on 1) The method of claim 1, wherein said subject suffers from human immunodeficiency virus (HIV) infection. ### Claim 15 (depends on 1) The method claim 1, wherein said subject has a body mass index (BMI) of at least about 25. ### Claim 16 (depends on 1) The method of claim 1, wherein said pharmaceutically acceptable salt of trans-3-hexenoyl-GHRH(1-44)-NH2 is an acetate salt. ### Claim 17 (depends on 1) The method of claim 1, wherein said trans-3-hexenoyl-GHRH(1-44)-NH2 or pharmaceutically acceptable salt thereof is administered by subcutaneous injection. ### Claim 18 (depends on 1) The method of claim 1, wherein said trans-3-hexenoyl-GHRH(1-44)-NH2 or pharmaceutically acceptable salt thereof is present in a pharmaceutical composition comprising at least one pharmaceutically acceptable excipient. ### Claim 19 (depends on 18) The method of claim 18, wherein said trans-3-hexenoyl-GHRH(1-44)-NH2 or pharmaceutically acceptable salt thereof is present in said pharmaceutical composition at a dose of about 1 mg/ml to about 10 mg/ml. ### Claim 20 (depends on 18) The method of claim 18, wherein said trans-3-hexenoyl-GHRH(1-44)-NH2 or pharmaceutically acceptable salt thereof is present in said pharmaceutical composition at a dose of about 1 mg/ml to about 8 mg/ml. ### Claim 21 (depends on 18) The method of claim 18, wherein said trans-3-hexenoyl-GHRH(1-44)-NH2 or pharmaceutically acceptable salt thereof is present in said pharmaceutical composition at a dose of about 4 mg/ml to about 8 mg/ml. ### Claim 22 (depends on 1) The method of claim 1, wherein said trans-3-hexenoyl-GHRH(1-44)-NH2 or pharmaceutically acceptable salt thereof is administered at a daily dose of about 1 mg to about 2 mg.