# US 11,306,106 B2 · Pharmaceutical compositions containing substituted polycyclic pyridone derivatives and prodrug thereof > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 11,306,106 B2 - Document ID: US11306106B2 - Status: Granted - Kind: B2 - Application number: 16/937,877 - Filed: 2020-07-24 - Published: 2020-11-19 - Granted: 2022-04-19 - Earliest claimed: 2016-08-10 - Assignees: Shionogi & Co., Ltd. - Applicants: Shionogi & Co., Ltd. - Inventors: Makoto Kawai - Web page: https://patentgrep.com/patent/US11306106B2 ## CPC - A61K 9/0014: {Skin, i.e. galenical aspects of topical compositions (non-active ingredients are additionally classified in A61K47/00; A61K9/0009, A61K9/0021, A61K9/7015, A61K9/7023 take precedence; cosmetic preparations A61K8/00, A61Q; preparations for wound dressings or bandages A61L26/00)} - C07D 498/14: Ortho-condensed systems - 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 9/0056: {Mouth soluble or dispersible forms; Suckable, eatable, chewable coherent forms; Forms rapidly disintegrating in the mouth; Lozenges; Lollipops; Bite capsules; Baked products; Baits or other oral forms for animals} - A61K 9/0075: {for inhalation via a dry powder inhaler [DPI], e.g. comprising micronized drug mixed with lactose carrier particles} - A61K 9/0095: {Drinks; Beverages; Syrups; Compositions for reconstitution thereof, e.g. powders or tablets to be dispersed in a glass of water; Veterinary drenches (A61K9/0007 takes precedence; eatable gels or foams A61K9/0056; oral mucosa adhesive forms A61K9/006)} - A61K 9/06: Ointments; Bases therefor; {Other semi-solid forms, e.g. creams, sticks, gels (composition of ointments, creams or gels A61K47/00)} - A61K 9/1623: {Sugars or sugar alcohols, e.g. lactose; Derivatives thereof; Homeopathic globules} - A61K 9/2018: {Sugars, or sugar alcohols, e.g. lactose, mannitol; Derivatives thereof, e.g. polysorbates} - A61K 9/4858: {Organic compounds} - A61K 9/7038: {Transdermal patches of the drug-in-adhesive type, i.e. comprising drug in the skin-adhesive layer} - A61K 31/5383: ortho- or peri-condensed with heterocyclic ring systems - A61P 31/12: Antivirals - A61P 31/16: for influenza or rhinoviruses - A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 - C07B 2200/13: Crystalline forms, e.g. polymorphs - 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) - C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08) - A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS - C07B: GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR (preparation of carboxylic acid esters by telomerisation C07C67/47; telomerisation C08F) ## Abstract The present invention provides a pharmaceutical composition containing the following compound having antiviral action: wherein each of the symbols is defined in the specification. ## Claims ### Claim 1 A method for treating a disease caused by a virus having cap-dependent endonuclease comprising administering to a patient in need thereof a crystal of the compound of the following formula: wherein the crystal is selected from the group consisting of: (i) crystal Form I having two or more peaks in diffraction angles (2θ) selected from 8.6±0.2°, 14.1±0.2°, 17.4±0.2°, 20.0±0.2°, 24.0±0.2°, 26.3±0.2°, 29.6±0.2° and 35.4±0.2° in an X-ray powder diffraction spectrum, (ii) crystal Form II having two or more peaks in diffraction angles (2θ) selected from 4.4±0.2°, 8.9±0.2°, 11.7±0.2°, 14.9±0.2°, 22.3±0.2°, 24.4±0.2°, 28.0±0.2° and 31.5±0.2° in an X-ray powder diffraction spectrum, and (iii) crystal Form III having two or more peaks in diffraction angles (2θ) selected from 4.4±0.2°, 8.7±0.2°, 10.6±0.2°, 17.3±0.2°, 17.5±0.2°, 22.0±0.2°, 24.0±0.2°, 24.1±0.2° and 31.0±0.2° in an X-ray powder diffraction spectrum. ### Claim 2 (depends on 1) The method according to claim 1, wherein the crystal is (i) crystal Form I having peaks in diffraction angles (2θ) of 8.6±0.2°, 14.1±0.2°, 17.4±0.2°, 20.0±0.2°, 24.0±0.2°, 26.3±0.2°, 29.6±0.2° and 35.4±0.2° in an X-ray powder diffraction spectrum. ### Claim 3 (depends on 1) The method according to claim 1, wherein the (i) crystal Form I is administered orally in a single dose. ### Claim 4 (depends on 1) The method according to claim 1, wherein 40 mg or 80 mg of the (i) crystal Form I is administered in a single dose. ### Claim 5 (depends on 1) The method according to claim 1, wherein 5 to 40 mg of the (i) crystal Form I is administered in a single dose depending on the body weight of the patient. ### Claim 6 (depends on 1) The method according to claim 1, wherein 40 mg of the (i) crystal Form I is administered in two tablets of 20 mg per tablet. ### Claim 7 (depends on 1) The method according to claim 1, wherein the (i) crystal Form I is administered and the patient is a human 12 years old or older. ### Claim 8 (depends on 1) The method according to claim 1, wherein the crystal is (ii) crystal Form II having peaks in diffraction angles (2θ) of 4.4±0.2°, 8.9±0.2°, 11.7±0.2°, 14.9±0.2°, 22.3±0.2°, 24.4±0.2°, 28.0±0.2° and 31.5±0.2° in an X-ray powder diffraction spectrum. ### Claim 9 (depends on 1) The method according to claim 1, wherein the (ii) crystal Form II is administered orally in a single dose. ### Claim 10 (depends on 1) The method according to claim 1, wherein 40 mg or 80 mg of the (ii) crystal Form II is administered in a single dose. ### Claim 11 (depends on 1) The method according to claim 1, wherein 5 to 40 mg of the (ii) crystal Form II is administered in a single dose depending on the body weight of the patient. ### Claim 12 (depends on 1) The method according to claim 1, wherein 40 mg of the (ii) crystal Form II is administered in two tablets of 20 mg per tablet. ### Claim 13 (depends on 1) The method according to claim 1, wherein the (ii) crystal Form II is administered and the patient is a human 12 years old or older. ### Claim 14 (depends on 1) The method according to claim 1, wherein the crystal is (iii) crystal Form III having peaks in diffraction angles (2θ) of 4.4±0.2°, 8.7±0.2°, 10.6±0.2°, 17.3±0.2°, 17.5±0.2°, 22.0±0.2°, 24.0±0.2°, 24.1±0.2° and 31.0±0.2° in an X-ray powder diffraction spectrum. ### Claim 15 (depends on 1) The method according to claim 1, wherein the (iii) crystal Form III is administered orally in a single dose. ### Claim 16 (depends on 1) The method according to claim 1, wherein 40 mg or 80 mg of the (iii) crystal Form III is administered in a single dose. ### Claim 17 (depends on 1) The method according to claim 1, wherein 5 to 40 mg of the (iii) crystal Form III is administered in a single dose depending on the body weight of the patient. ### Claim 18 (depends on 1) The method according to claim 1, wherein 40 mg of the (iii) crystal Form III is administered in two tablets of 20 mg per tablet. ### Claim 19 (depends on 1) The method according to claim 1, wherein the (iii) crystal Form III is administered and the patient is a human 12 years old or older. ### Claim 20 A method for treating influenza comprising administering to a patient in need thereof a crystal of the compound of the following formula: wherein the crystal is selected from the group consisting of: (i) crystal Form I having two or more peaks in diffraction angles (2θ) selected from 8.6±0.2°, 14.1±0.2°, 17.4±0.2°, 20.0±0.2°, 24.0±0.2°, 26.3±0.2°, 29.6±0.2° and 35.4±0.2° in an X-ray powder diffraction spectrum, (ii) crystal Form II having two or more peaks in diffraction angles (2θ) selected from 4.4±0.2°, 8.9±0.2°, 11.7±0.2°, 14.9±0.2°, 22.3±0.2°, 24.4±0.2°, 28.0±0.2° and 31.5±0.2° in an X-ray powder diffraction spectrum, and (iii) crystal Form III having two or more peaks in diffraction angles (2θ) selected from 4.4±0.2°, 8.7±0.2°, 10.6±0.2°, 17.3±0.2°, 17.5±0.2°, 22.0±0.2°, 24.0±0.2°, 24.1±0.2° and 31.0±0.2° in an X-ray powder diffraction spectrum. ### Claim 21 (depends on 20) The method according to claim 20, wherein the crystal is (i) crystal Form I having peaks in diffraction angles (2θ) of 8.6±0.2°, 14.1±0.2°, 17.4±0.2°, 20.0±0.2°, 24.0±0.2°, 26.3±0.2°, 29.6±0.2° and 35.4±0.2° in an X-ray powder diffraction spectrum. ### Claim 22 (depends on 20) The method according to claim 20, wherein the (i) crystal Form I is administered orally in a single dose. ### Claim 23 (depends on 20) The method according to claim 20, wherein 40 mg or 80 mg of the (i) crystal Form I is administered in a single dose. ### Claim 24 (depends on 20) The method according to claim 20, wherein 5 to 40 mg of the (i) crystal Form I is administered in a single dose depending on the body weight of the patient. ### Claim 25 (depends on 20) The method according to claim 20, wherein 40 mg of the (i) crystal Form I is administered in two tablets of 20 mg per tablet. ### Claim 26 (depends on 20) The method according to claim 20, wherein the (i) crystal Form I is administered and the patient is a human 12 years old or older. ### Claim 27 (depends on 20) The method according to claim 20, wherein the crystal is (ii) crystal Form II having peaks in diffraction angles (2θ) of 4.4±0.2°, 8.9±0.2°, 11.7±0.2°, 14.9±0.2°, 22.3±0.2°, 24.4±0.2°, 28.0±0.2° and 31.5±0.2° in an X-ray powder diffraction spectrum. ### Claim 28 (depends on 20) The method according to claim 20, wherein the (ii) crystal Form II is administered orally in a single dose. ### Claim 29 (depends on 20) The method according to claim 20, wherein 40 mg or 80 mg of the (ii) crystal Form II is administered in a single dose. ### Claim 30 (depends on 20) The method according to claim 20, wherein 5 to 40 mg of the (ii) crystal Form II is administered in a single dose depending on the body weight of the patient. ### Claim 31 (depends on 20) The method according to claim 20, wherein 40 mg of the (ii) crystal Form II is administered in two tablets of 20 mg per tablet. ### Claim 32 (depends on 20) The method according to claim 20, wherein the (ii) crystal Form II is administered and the patient is a human 12 years old or older. ### Claim 33 (depends on 20) The method according to claim 20, wherein the crystal is (iii) crystal Form III having peaks in diffraction angles (2θ) of 4.4±0.2°, 8.7±0.2°, 10.6±0.2°, 17.3±0.2°, 17.5±0.2°, 22.0±0.2°, 24.0±0.2°, 24.1±0.2° and 31.0±0.2° in an X-ray powder diffraction spectrum. ### Claim 34 (depends on 20) The method according to claim 20, wherein the (iii) crystal Form III is administered orally in a single dose. ### Claim 35 (depends on 20) The method according to claim 20, wherein 40 mg or 80 mg of the (iii) crystal Form III is administered in a single dose. ### Claim 36 (depends on 20) The method according to claim 20, wherein 5 to 40 mg of the (iii) crystal Form III is administered in a single dose depending on the body weight of the patient. ### Claim 37 (depends on 20) The method according to claim 20, wherein 40 mg of the (iii) crystal Form III is administered in two tablets of 20 mg per tablet. ### Claim 38 (depends on 20) The method according to claim 20, wherein the (iii) crystal Form III is administered and the patient is a human 12 years old or older. ### Claim 39 A method for preventing influenza comprising administering to a patient in need thereof a crystal of the compound of the following formula: wherein the crystal is selected from the group consisting of: (i) crystal Form I having two or more peaks in diffraction angles (2θ) selected from 8.6±0.2°, 14.1±0.2°, 17.4±0.2°, 20.0±0.2°, 24.0±0.2°, 26.3±0.2°, 29.6±0.2° and 35.4±0.2° in an X-ray powder diffraction spectrum, (ii) crystal Form II having two or more peaks in diffraction angles (2θ) selected from 4.4±0.2°, 8.9±0.2°, 11.7±0.2°, 14.9±0.2°, 22.3±0.2°, 24.4±0.2°, 28.0±0.2° and 31.5±0.2° in an X-ray powder diffraction spectrum, and (iii) crystal Form III having two or more peaks in diffraction angles (2θ) selected from 4.4±0.2°, 8.7±0.2°, 10.6±0.2°, 17.3±0.2°, 17.5±0.2°, 22.0±0.2°, 24.0±0.2°, 24.1±0.2° and 31.0±0.2° in an X-ray powder diffraction spectrum. ### Claim 40 (depends on 39) The method according to claim 39, wherein the crystal is (i) crystal Form I having peaks in diffraction angles (2θ) of 8.6±0.2°, 14.1±0.2°, 17.4±0.2°, 20.0±0.2°, 24.0±0.2°, 26.3±0.2°, 29.6±0.2° and 35.4±0.2° in an X-ray powder diffraction spectrum. ### Claim 41 (depends on 39) The method according to claim 39, wherein the (i) crystal Form I is administered orally in a single dose. ### Claim 42 (depends on 39) The method according to claim 39, wherein 40 mg or 80 mg of the (i) crystal Form I is administered in a single dose. ### Claim 43 (depends on 39) The method according to claim 39, wherein 5 to 40 mg of the (i) crystal Form I is administered in a single dose depending on the body weight of the patient. ### Claim 44 (depends on 39) The method according to claim 39, wherein 40 mg of the (i) crystal Form I is administered in two tablets of 20 mg per tablet. ### Claim 45 (depends on 39) The method according to claim 39, wherein the (i) crystal Form I is administered and the patient is a human 12 years old or older. ### Claim 46 (depends on 39) The method according to claim 39, wherein the crystal is (ii) crystal Form II having peaks in diffraction angles (2θ) of 4.4±0.2°, 8.9±0.2°, 11.7±0.2°, 14.9±0.2°, 22.3±0.2°, 24.4±0.2°, 28.0±0.2° and 31.5±0.2° in an X-ray powder diffraction spectrum. ### Claim 47 (depends on 39) The method according to claim 39, wherein the (ii) crystal Form II is administered orally in a single dose. ### Claim 48 (depends on 39) The method according to claim 39, wherein 40 mg or 80 mg of the (ii) crystal Form II is administered in a single dose. ### Claim 49 (depends on 39) The method according to claim 39, wherein 5 to 40 mg of the (ii) crystal Form II is administered in a single dose depending on the body weight of the patient. ### Claim 50 (depends on 39) The method according to claim 39, wherein 40 mg of the (ii) crystal Form II is administered in two tablets of 20 mg per tablet. ### Claim 51 (depends on 39) The method according to claim 39, wherein the (ii) crystal Form II is administered and the patient is a human 12 years old or older. ### Claim 52 (depends on 39) The method according to claim 39, wherein the crystal is (iii) crystal Form III having peaks in diffraction angles (2θ) of 4.4±0.2°, 8.7±0.2°, 10.6±0.2°, 17.3±0.2°, 17.5±0.2°, 22.0±0.2°, 24.0±0.2°, 24.1±0.2° and 31.0±0.2° in an X-ray powder diffraction spectrum. ### Claim 53 (depends on 39) The method according to claim 39, wherein the (iii) crystal Form III is administered orally in a single dose. ### Claim 54 (depends on 39) The method according to claim 39, wherein 40 mg or 80 mg of the (iii) crystal Form III is administered in a single dose. ### Claim 55 (depends on 39) The method according to claim 39, wherein 5 to 40 mg of the (iii) crystal Form III is administered in a single dose depending on the body weight of the patient. ### Claim 56 (depends on 39) The method according to claim 39, wherein 40 mg of the (iii) crystal Form III is administered in two tablets of 20 mg per tablet. ### Claim 57 (depends on 39) The method according to claim 39, wherein the (iii) crystal Form III is administered and the patient is a human 12 years old or older.