Claims for Patent: 11,202,778

Summary for Patent: 11,202,778

Title:	Amorphous solid dispersions of dasatinib and uses thereof
Abstract:	Amorphous solid dispersions and pharmaceutical compositions of the protein kinase inhibitor dasatinib. The pharmaceutical compositions may be used in methods of treating a proliferative disorder such as cancer, or in methods of delivering dasatinib to patients without regard to whether the patient is concurrently administered a gastric acid-reducing agent, or without regard to whether the patient has an elevated gastric pH. The compositions may be particularly suitable for patients afflicted by achlorhydria or hypochlorhydria, or infection.
Inventor(s):	Wertz Christian F., Chen Tzehaw
Assignee:	Nanocopoeia, LLC
Application Number:	US17206823
Patent Claims:	1. A method of treating a proliferative disorder in a patient in need thereof , the method comprising:(a) administering to the patient a pharmaceutical composition comprising an amorphous solid dispersion, the amorphous solid dispersion consisting essentially of dasatinib, a methacrylic acid and ethyl acrylate copolymer that exhibits pH-dependent solubility, and optionally one or more functional components selected from the group consisting of antioxidants, wetting agents, and solubilizers; and(b) co-administering to the patient a gastric acid-reducing agent;wherein the dasatinib and the copolymer are present in the amorphous solid dispersion in a w/w ratio of 30:70 to 95:5 (dasatinib:copolymer).2. The method of claim 1 , wherein the gastric acid-reducing agent is administered to the patient shortly before the pharmaceutical composition is administered.3. The method of claim 1 , wherein the gastric acid-reducing agent is administered to the patient concurrently with the administration of the pharmaceutical composition.4. The method of claim 1 , wherein the gastric acid-reducing agent is administered to the patient shortly after the pharmaceutical composition is administered.5. The method of claim 1 , wherein the amorphous solid dispersion includes one or more functional components selected from the group consisting of antioxidants claim 1 , wetting agents claim 1 , and solubilizers.6. The method of claim 1 , wherein the amorphous solid dispersion consists of dasatinib and the copolymer.7. A treatment regimen for treating a proliferative disorder in a patient in need thereof claim 1 , the regimen comprising:{'sub': '2', '(a) administering to the patient a first dose, the first dose comprising a standard dosage of a proton pump inhibitor or an Hantagonist; and'}(b) within 12 hours after the first dose, administering a second dose to the patient, the second dose comprising a therapeutically effective amount of a pharmaceutical composition comprising an amorphous solid dispersion, the amorphous solid dispersion consisting essentially of dasatinib, a methacrylic acid and ethyl acrylate copolymer that exhibits pH-dependent solubility, and optionally one or more functional components selected from the group consisting of antioxidants, wetting agents, and solubilizers;wherein the dasatinib and the copolymer are present in the amorphous solid dispersion in a w/w ratio of 30:70 to 95:5 (dasatinib:copolymer); andwherein the therapeutically effective amount comprises 20 mg to 140 mg dasatinib.8. The treatment regimen of claim 7 , wherein the first dose comprises a standard dosage of a proton pump inhibitor.9. The treatment regimen of claim 7 , wherein the first dose comprises a standard dosage of a proton pump inhibitor selected from rabeprazole claim 7 , esomeprazole claim 7 , lansoprazole claim 7 , omeprazole claim 7 , pantoprazole claim 7 , dexlansoprazole claim 7 , or a combination thereof.10. The treatment regimen of claim 7 , wherein the first dose comprises a standard dosage of an Hantagonist.11. The treatment regimen of claim 7 , wherein the first dose comprises a standard dosage of an Hantagonist selected from famotidine claim 7 , cimetidine claim 7 , nizatidine claim 7 , ranitidine claim 7 , or a combination thereof.12. The treatment regimen of claim 7 , wherein the second dose is administered within 8 hours after the first dose.13. The treatment regimen of claim 7 , wherein the second dose is administered within 6 hours after the first dose.14. The treatment regimen of claim 7 , wherein the second dose is administered within 4 hours after the first dose.15. The treatment regimen of claim 7 , wherein the amorphous solid dispersion includes one or more functional components selected from the group consisting of antioxidants claim 7 , wetting agents claim 7 , and solubilizers.16. The treatment regimen of claim 7 , wherein the amorphous solid dispersion consists of dasatinib and the copolymer.17. The treatment regimen of claim 7 , wherein the copolymer is insoluble in an aqueous medium at pH of 5 or lower claim 7 , and soluble in an aqueous medium at pH 5.5 or greater.18. The treatment regimen of claim 15 , wherein the one or more functional components is selected from one or more antioxidants that are present in an amount of 0.001% to 2% by weight of the amorphous solid dispersion.19. The treatment regimen of claim 18 , wherein the one or more antioxidants comprises propyl gallate.20. The treatment regimen of claim 7 , wherein the dasatinib and the copolymer are present in the amorphous solid dispersion in a w/w ratio of 40:60 to 70:30 (dasatinib:copolymer).21. The treatment regimen of claim 7 , wherein the pharmaceutical composition comprises the amorphous solid dispersion and one or more pharmaceutically acceptable additives.22. The treatment regimen of claim 7 , wherein the pharmaceutical composition is a solid dosage form suitable for oral administration.23. The treatment regimen of claim 7 , wherein the pharmaceutical composition is a gastric acid-insensitive composition.24. The method of claim 1 , wherein the copolymer is insoluble in an aqueous medium at pH of 5 or lower claim 1 , and soluble in an aqueous medium at pH 5.5 or greater.25. The method of claim 5 , wherein the one or more functional components is selected from one or more antioxidants that are present in an amount of 0.001% to 2% by weight of the amorphous solid dispersion.26. The method of claim 25 , wherein the one or more antioxidants comprises propyl gallate.27. The method of claim 1 , wherein the dasatinib and the copolymer are present in the amorphous solid dispersion in a w/w ratio of 40:60 to 70:30 (dasatinib:copolymer).28. The method of claim 1 , wherein the pharmaceutical composition comprises the amorphous solid dispersion and one or more pharmaceutically acceptable additives.29. The method of claim 1 , wherein the pharmaceutical composition is a solid dosage form suitable for oral administration.30. The method of claim 1 , wherein the pharmaceutical composition is a gastric acid-insensitive composition.