# US 10,864,213 B2 · Treatment > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 10,864,213 B2 - Document ID: US10864213B2 - Status: Granted - Kind: B2 - Application number: 15/310,693 - Filed: 2015-05-11 - Published: 2017-04-27 - Granted: 2020-12-15 - Earliest claimed: 2014-05-12 - Assignees: Verona Pharma PLC - Applicants: Verona Pharma PLC - Inventors: Katharine Abbott-Banner; John Hanrahan; David Thomas - Web page: https://patentgrep.com/patent/US10864213B2 ## CPC - A61K 31/519: ortho- or peri-condensed with heterocyclic rings - A61K 31/404: Indoles, e.g. pindolol - A61K 31/443: containing a five-membered ring with oxygen as a ring hetero atom - A61K 31/47: Quinolines; Isoquinolines - A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca - A61P 1/00: Drugs for disorders of the alimentary tract or the digestive system - A61P 11/00: Drugs for disorders of the respiratory system - A61P 11/06: Antiasthmatics - A61P 11/12: Mucolytics - A61P 15/00: Drugs for genital or sexual disorders (for disorders of sex hormones A61P5/24); Contraceptives - A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 - 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 provides a compound for use in treating or preventing a disease or condition selected from cystic fibrosis, chronic obstructive pulmonary disease (COPD), asthma, mild pulmonary disease, bronchitis, bronchiectasis, idiopathic bronchiectasis, allergic bronchopulmonary aspergillosis, sinusitis, rhinosinusitis, CFTR-related metabolic syndrome (CRMS), pancreatitis, idiopathic chronic pancreatitis and Sjörgren's syndrome, or for use in preventing male infertility caused by congenital absence of the vas deferens, in a patient by modulating CFTR activity, which compound is 9,10-dimethoxy-2-(2,4,6-trimethylphenylimino)-3-(N-carbamoyl-2-aminoethyl)-3,4,6,7-tetrahydro-2H-pyrimido[6,1-a]isoquinolin-4-one or a pharmaceutically acceptable acid addition salt thereof. The invention also provides a composition comprising (i) 9,10-dimethoxy-2-(2,4,6-trimethylphenylimino)-3-(N-carbamoyl-2-aminoethyl)-3,4,6,7-tetrahydro-2H-pyrimido[6,1-a]isoquinolin-4-one or a pharmaceutically acceptable acid addition salt thereof and (ii) a leukotriene receptor antagonist. The invention also provides a composition comprising (i) 9,10-dimethoxy-2-(2,4,6-trimethylphenylimino)-3-(N-carbamoyl-2-aminoethyl)-3,4,6,7-tetrahydro-2H-pyrimido[6,1-a]isoquinolin-4-one or a pharmaceutically acceptable acid addition salt thereof and (ii) a CFTR potentiator or a CFTR corrector. ## Claims ### Claim 1 A method for treating or preventing cystic fibrosis in a patient by modulating CFTR activity, which method comprises administering a compound to the patient, which compound is 9,10-dimethoxy-2-(2,4,6-trimethylphenylimino)-3-(N-carbamoyl-2-aminoethyl)-3,4,6,7-tetrahydro-2H-pyrimido[6,1-a]isoquinolin-4-one or a pharmaceutically acceptable acid addition salt thereof, wherein the patient has a CFTR mutation selected from the group consisting of class II CFTR mutations and class IV CFTR mutations. ### Claim 2 (depends on 1) A method according to claim 1, wherein the CFTR mutation is a class IV CFTR mutation. ### Claim 3 (depends on 1) A method according to claim 1, wherein the CFTR mutation is selected from the group consisting of ΔF508, R117H, R117C, R347P and R334W. ### Claim 4 (depends on 1) A method according to claim 1, wherein the patient is heterozygous with (i) one allele displaying a class IV CFTR mutation and (ii) the other allele displaying a class II CFTR mutation. ### Claim 5 (depends on 1) A method according to claim 1, wherein the patient is susceptible to, or suffering from, diarrhoea. ### Claim 6 (depends on 5) A method according to claim 5, wherein the patient is suffering from a disease selected from the group consisting of ulcerative colitis, Crohn's disease, microscopic colitis, celiac disease, irritable bowel syndrome, bile acid malabsorption, and diverticulitis. ### Claim 7 (depends on 1) A method according to claim 1, which comprises administering the compound to the patient by inhalation. ### Claim 8 A method for increasing mucous mobility and/or reducing mucous viscosity, or for use in facilitating mucous membrane clearance from the airways, in a patient suffering from cystic fibrosis, which method comprises administering a compound to the patient, which compound is 9,10-dimethoxy-2-(2,4,6-trimethylphenylimino)-3-(N-carbamoyl-2-aminoethyl)-3,4,6,7-tetrahydro-2H-pyrimido[6,1-a]isoquinolin-4-one or a pharmaceutically acceptable acid addition salt thereof, wherein the patient has a CFTR mutation selected from the group consisting of class II CFTR mutations and class IV CFTR mutations. ### Claim 9 A method of treating or preventing cystic fibrosis in a patient by modulating CFTR activity, which method comprises administering to the patient (a) 9,10-dimethoxy-2-(2,4,6-trimethylphenylimino)-3-(N-carbamoyl-2-aminoethyl)-3,4,6,7-tetrahydro-2H-pyrimido[6,1-a]isoquinolin-4-one or a pharmaceutically acceptable acid addition salt thereof and (b) a leukotriene receptor antagonist, wherein the patient has a CFTR mutation selected from the group consisting of class II CFTR mutations and class IV CFTR mutations. ### Claim 10 A method of treating or preventing cystic fibrosis in a patient by modulating CFTR activity, which method comprises administering to the patient (a) 9,10-dimethoxy-2-(2,4,6-trimethylphenylimino)-3-(N-carbamoyl-2-aminoethyl)-3,4,6,7tetrahydro-2H-pyrimido[6,1-a]isoquinolin-4-one or a pharmaceutically acceptable acid addition salt thereof and (b) a CFTR potentiator or a CFTR corrector, wherein the patient has a CFTR mutation selected from the group consisting of class II CFTR mutations and class IV CFTR mutations.