# US 11,298,356 B1 · Amorphous solid dispersions of dasatinib and uses thereof > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 11,298,356 B1 - Document ID: US11298356B1 - Status: Granted - Kind: B1 - Application number: 17/545,324 - Filed: 2021-12-08 - Published: 2022-03-31 - Granted: 2022-04-12 - Earliest claimed: 2020-01-24 - Assignees: Nanocopoeia, LLC - Applicants: Nanocopoeia, LLC - Inventors: Christian F. Wertz; Tzehaw Chen - Web page: https://patentgrep.com/patent/US11298356B1 ## CPC - A61K 9/146: {with organic macromolecular compounds} - A61K 31/506: not condensed and containing further heterocyclic rings - A61K 9/0053: {Mouth and digestive tract, i.e. intraoral and peroral administration} - A61K 9/10: Dispersions; Emulsions - A61K 9/2077: {Tablets comprising drug-containing microparticles in a substantial amount of supporting matrix; Multiparticulate tablets} - A61K 31/341: not condensed with another ring, e.g. ranitidine, furosemide, bufetolol, muscarine - A61K 31/4164: 1,3-Diazoles - A61K 31/426: 1,3-Thiazoles - A61K 31/4439: containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole (nicotine A61K31/465) - A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca - A61K 47/14: Esters of carboxylic acids, e.g. fatty acid monoglycerides, medium-chain triglycerides, parabens or PEG fatty acid esters - A61K 47/32: Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers {, poly(meth)acrylates, or polyvinyl pyrrolidone} - A61K 47/38: Cellulose; Derivatives thereof - A61P 35/02: specific for leukemia - 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 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 Helicobacter pylori infection. ## Claims ### Claim 1 A pharmaceutical composition comprising an amorphous solid dispersion; wherein the amorphous solid dispersion consists 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 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). ### Claim 2 (depends on 1) The pharmaceutical composition of claim 1, wherein the copolymer is insoluble in an aqueous medium at pH of 5 or lower, and soluble in an aqueous medium at pH 5.5 or greater. ### Claim 3 (depends on 1) The pharmaceutical composition of claim 1, wherein the amorphous solid dispersion consists essentially of dasatinib and the copolymer. ### Claim 4 (depends on 3) The pharmaceutical composition of claim 3, wherein the copolymer is insoluble in an aqueous medium at pH of 5 or lower, and soluble in an aqueous medium at pH 5.5 or greater. ### Claim 5 (depends on 1) The pharmaceutical composition of claim 1, wherein the amorphous solid dispersion consists of dasatinib and the copolymer. ### Claim 6 (depends on 5) The pharmaceutical composition of claim 5, wherein the copolymer is insoluble in an aqueous medium at pH of 5 or lower, and soluble in an aqueous medium at pH 5.5 or greater. ### Claim 7 (depends on 1) The pharmaceutical composition 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). ### Claim 8 (depends on 1) The pharmaceutical composition of claim 1, wherein the amorphous solid dispersion includes one or more functional components selected from the group consisting of antioxidants, wetting agents, and solubilizers. ### Claim 9 (depends on 1) The pharmaceutical composition of claim 1, wherein the one or more functional components includes one or more antioxidants that are present in an amount of 0.001% to 2% by weight of the amorphous solid dispersion. ### Claim 10 (depends on 9) The pharmaceutical composition of claim 9, wherein the one or more antioxidants includes acetylcysteine, ascorbyl palmitate, butylated hydroxyanisole (“BHA”), butylated hydroxytoluene (“BHT”), monothioglycerol, potassium nitrate, sodium ascorbate, sodium formaldehyde sulfoxylate, sodium metabisulfite, sodium bisulfate, vitamin E or a derivative thereof, propyl gallate, ethylenediaminetetraacetic acid (“EDTA”) or a salt thereof, diethylenetriaminepentaacetic acid (“DTPA”), bismuth sodium triglycollamate, or a combination thereof. ### Claim 11 (depends on 10) The pharmaceutical composition of claim 10, wherein the one or more antioxidants are present in an amount of 0.05% to 0.5% by weight of the amorphous solid dispersion. ### Claim 12 (depends on 10) The pharmaceutical composition of claim 10, wherein the one or more antioxidants comprises butylated hydroxytoluene. ### Claim 13 (depends on 10) The pharmaceutical composition of claim 10, wherein the one or more antioxidants comprises propyl gallate. ### Claim 14 (depends on 1) The pharmaceutical composition of claim 1 comprising the amorphous solid dispersion and one or more pharmaceutically acceptable additives. ### Claim 15 (depends on 1) The pharmaceutical composition of claim 1, wherein the pharmaceutical composition is a solid dosage form suitable for oral administration. ### Claim 16 (depends on 1) The pharmaceutical composition of claim 1, wherein the pharmaceutical composition is a gastric acid-insensitive composition. ### Claim 17 A kit for sale to a user, the kit comprising a pharmaceutical composition and a package insert; wherein the pharmaceutical composition comprises 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 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). ### Claim 18 (depends on 17) The kit of claim 17, wherein the package insert informs the user that the pharmaceutical composition can be co-administered with a gastric acid-reducing agent. ### Claim 19 (depends on 17) The kit of claim 17, wherein the package insert informs the user that the pharmaceutical composition can be co-administered with H2 antagonists or proton pump inhibitors. ### Claim 20 (depends on 17) The kit of claim 17, wherein the package insert does not comprise a warning that the pharmaceutical composition should not be co-administered with H2 antagonists or proton pump inhibitors. ### Claim 21 (depends on 17) The kit of claim 17, wherein the package insert informs the user that the pharmaceutical composition can be suitably administered if the user has chronically elevated gastric pH. ### Claim 22 (depends on 17) The kit of claim 17, wherein the package insert informs the user that the pharmaceutical composition can be suitably administered if the user has been diagnosed with or is afflicted by achlorhydria or hypochlorhydria. ### Claim 23 (depends on 17) The kit of claim 17, wherein the package insert informs the user that the pharmaceutical composition can be suitably administered if the user has been diagnosed with or is afflicted by Helicobacter pylori infection. ### Claim 24 (depends on 17) The kit of claim 17, wherein the copolymer is insoluble in an aqueous medium at pH of 5 or lower, and soluble in an aqueous medium at pH 5.5 or greater. ### Claim 25 (depends on 17) The kit of claim 17, 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). ### Claim 26 (depends on 17) The kit of claim 17, wherein the amorphous solid dispersion includes one or more functional components selected from the group consisting of antioxidants, wetting agents, and solubilizers. ### Claim 27 (depends on 17) The kit of claim 17, wherein the one or more functional components includes one or more antioxidants that are present in an amount of 0.001% to 2% by weight of the amorphous solid dispersion. ### Claim 28 (depends on 17) The kit of claim 17, wherein the one or more antioxidants includes acetylcysteine, ascorbyl palmitate, butylated hydroxyanisole (“BHA”), butylated hydroxytoluene (“BHT”), monothioglycerol, potassium nitrate, sodium ascorbate, sodium formaldehyde sulfoxylate, sodium metabisulfite, sodium bisulfate, vitamin E or a derivative thereof, propyl gallate, ethylenediaminetetraacetic acid (“EDTA”) or a salt thereof, diethylenetriaminepentaacetic acid (“DTPA”), bismuth sodium triglycollamate, or a combination thereof. ### Claim 29 (depends on 17) The kit of claim 17, comprising the amorphous solid dispersion and one or more pharmaceutically acceptable additives. ### Claim 30 (depends on 17) The kit of claim 17, wherein the pharmaceutical composition is a solid dosage form suitable for oral administration.