# US 11,896,719 B2 · Pharmaceutical compositions > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 11,896,719 B2 - Document ID: US11896719B2 - Status: Granted - Kind: B2 - Application number: 18/100,396 - Filed: 2023-01-23 - Published: 2023-09-21 - Granted: 2024-02-13 - Earliest claimed: 2022-01-24 - Assignees: Calliditas Therapeutics AB - Applicants: Calliditas Therapeutics AB - Inventors: Eva Kristina Riesel; Lena Margareta Pereswetoff-Morath; Kari Sandvold; Christian Olle Andreas Pedersen - Web page: https://patentgrep.com/patent/US11896719B2 ## CPC - A61K 9/4891: {Coated capsules; Multilayered drug free capsule shells (with drug coating for immediate release A61K9/4808; osmotic devices A61K9/0004)} - A61K 9/5078: {with drug-free core} - A61K 9/2846: {Poly(meth)acrylates} - A61K 9/5047: {Cellulose ethers containing no ester groups, e.g. hydroxypropyl methylcellulose} - A61K 31/58: containing heterocyclic rings, e.g. danazol, stanozolol, pancuronium or digitogenin (digitoxin {A61K31/7048}) - A61P 13/12: of the kidneys - 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 invention provides for a method of treatment of IgA nephropathy, which method comprises: (i) identifying a pharmaceutically acceptable composition intended to treat IgA nephropathy comprising budesonide and one or more pharmaceutically-acceptable excipients that provide for a modified release of said budesonide after administration to the gastrointestinal tract, which composition fulfils the following requirements in a standard in vitro USP<711>/Ph.Eur. 2.9.3 dissolution test using a dissolution apparatus according to Apparatus 2 (Paddle Apparatus) of said test; (a) the composition fulfils the requirement that no more than about 10% of the budesonide is released into the dissolution medium within about 120 minutes, when the dissolution medium is aqueous and has a pH of about 1.2; (b) the composition fulfils the requirement that no more than about 10% of the budesonide is released into a pharmaceutically-relevant dissolution medium within about 30 minutes; and (c) the composition fulfils the requirement that at least about 70% of the budesonide is released into the pharmaceutically-relevant dissolution medium within about 120 minutes; (ii) wherein the method comprises the step of administering said composition to a patient with IgA nephropathy in need of said treatment. ## Claims ### Claim 1 A method of treating IgA nephropathy in a subject in need thereof, comprising administering to the subject a pharmaceutical composition comprising one or more cores comprising budesonide; wherein the one or more cores are coated with an extended release pharmaceutically-acceptable polymeric blend comprising ethylcellulose in an amount of about 51.8 wt. % of the extended release pharmaceutically-acceptable polymeric blend and hydroxypropylmethyl cellulose in an amount of about 27.3 wt. % of the extended release pharmaceutically-acceptable polymeric blend; wherein the extended release pharmaceutically-acceptable polymeric blend is present in an amount of from about 5 wt. % to about 18 wt. % of the total coated core weight; wherein the pharmaceutical composition is orally administered as a capsule that comprises an enteric coating in an amount of from about 34 mg to about 46 mg per capsule; wherein the pharmaceutical composition meets the following release profile in a standard in vitro USP<711> dissolution test using a dissolution apparatus according to Apparatus 2 (Paddle Apparatus) at a paddle rotation speed of 100 rpm: a) no more than about 10% of the budesonide is released into an aqueous dissolution medium with a pH of about 1.2 within about 120 minutes; b) no more than about 10% of the budesonide is released into a pharmaceutically-relevant dissolution medium within about 30 minutes, wherein the pharmaceutically-relevant dissolution medium is a Level 1 Fasted State Simulated Intestinal Fluid at a pH of about 6.5, or a phosphate buffer medium at a pH of about 6.8; and c) at least about 70% of the budesonide is released into the pharmaceutically-relevant dissolution medium within about 120 minutes; and wherein the subject is administered a daily dose of about 16 mg of budesonide. ### Claim 2 (depends on 1) The method of claim 1, wherein the budesonide is substantially released to the ileum region of the small intestine in the subject. ### Claim 3 (depends on 2) The method of claim 2, wherein at least about 60% of the initial content of budesonide is released to the ileum region of the small intestine in the subject. ### Claim 4 (depends on 2) The method of claim 2, wherein at least about 90% of the initial content of budesonide is released to the ileum region of the small intestine in the subject. ### Claim 5 (depends on 1) The method of claim 1, wherein the pharmaceutically-relevant dissolution medium is a Level 1 Fasted State Simulated Intestinal Fluid at a pH of about 6.5. ### Claim 6 (depends on 1) The method of claim 1, wherein the pharmaceutically-relevant dissolution medium is a phosphate buffer medium at a pH of about 6.8. ### Claim 7 A method of treating IgA nephropathy in a subject in need thereof, comprising administering to the subject a pharmaceutical composition comprising one or more cores comprising budesonide; wherein the one or more cores are coated with an extended release pharmaceutically-acceptable polymeric blend comprising ethylcellulose in an amount of from about 47 wt. % to about 56 wt. % of the extended release pharmaceutically-acceptable polymeric blend and hydroxypropylmethyl cellulose in an amount of from about 32 wt. % to about 22 wt. % of the extended release pharmaceutically-acceptable polymeric blend; wherein the extended release pharmaceutically-acceptable polymeric blend is present in an amount of from about 5 wt. % to about 18 wt. % of the total coated core weight; wherein the pharmaceutical composition is orally administered as a capsule that comprises an enteric coating in an amount of from about 34 mg to about 46 mg per capsule; wherein the pharmaceutical composition meets the following release profile in a standard in vitro USP<711> dissolution test using a dissolution apparatus according to Apparatus 2 (Paddle Apparatus) at a paddle rotation speed of 100 rpm: a) no more than about 10% of the budesonide is released into an aqueous dissolution medium with a pH of about 1.2 within about 120 minutes; b) no more than about 10% of the budesonide is released into a pharmaceutically-relevant dissolution medium within about 30 minutes, wherein the pharmaceutically-relevant dissolution medium is a Level 1 Fasted State Simulated Intestinal Fluid at a pH of about 6.5, or a phosphate buffer medium at a pH of about 6.8; and c) at least about 70% of the budesonide is released into the pharmaceutically-relevant dissolution medium within about 120 minutes; and wherein the subject is administered a daily dose of about 16 mg of budesonide. ### Claim 8 (depends on 7) The method of claim 7, wherein the extended release pharmaceutically-acceptable polymeric blend is present in an amount of from about 6 wt. % to about 13 wt. % of the total coated core weight. ### Claim 9 (depends on 7) The method of claim 7, wherein the extended release pharmaceutically-acceptable polymeric blend is present in an amount of 9.1 wt. % (±2%) of the total coated core weight. ### Claim 10 (depends on 9) The method of claim 9, wherein the budesonide is substantially released to the ileum region of the small intestine in the subject. ### Claim 11 (depends on 10) The method of claim 10, wherein at least about 60% of the initial content of budesonide is released to the ileum region of the small intestine in the subject. ### Claim 12 (depends on 10) The method of claim 10, wherein at least about 90% of the initial content of budesonide is released to the ileum region of the small intestine in the subject. ### Claim 13 (depends on 7) The method of claim 7, wherein the pharmaceutically-relevant dissolution medium is a Level 1 Fasted State Simulated Intestinal Fluid at a pH of about 6.5. ### Claim 14 (depends on 7) The method of claim 7, wherein the pharmaceutically-relevant dissolution medium is a phosphate buffer medium at a pH of about 6.8. ### Claim 15 (depends on 5) The method of claim 5, wherein the Level 1 Fasted State Simulated Intestinal Fluid comprises an added surfactant. ### Claim 16 (depends on 15) The method of claim 15, wherein the added surfactant is present in an amount of about 0.5 mg/mL. ### Claim 17 (depends on 6) The method of claim 6, wherein the phosphate buffer medium comprises an added surfactant. ### Claim 18 (depends on 17) The method of claim 17, wherein the surfactant is present in an amount of about 0.5 mg/mL. ### Claim 19 (depends on 13) The method of claim 13, wherein the Level 1 Fasted State Simulated Intestinal Fluid comprises an added surfactant. ### Claim 20 (depends on 19) The method of claim 19, wherein the added surfactant is present in an amount of about 0.5 mg/mL. ### Claim 21 (depends on 14) The method of claim 14, wherein the phosphate buffer medium comprises an added surfactant. ### Claim 22 (depends on 21) The method of claim 21, wherein the surfactant is present in an amount of about 0.5 mg/mL. ### Claim 23 (depends on 1) The method of claim 1, wherein the capsule is a size 1 capsule. ### Claim 24 (depends on 7) The method of claim 7, wherein the capsule is a size 1 capsule. ### Claim 25 (depends on 1) The method of claim 1, wherein the extended release pharmaceutically-acceptable polymeric blend is present in an amount of from about 6 wt. % to about 13 wt. % of the total coated core weight. ### Claim 26 (depends on 1) The method of claim 1, wherein the ethylcellulose is present in an amount of 51.8 wt. % (±2%) of the extended release pharmaceutically-acceptable polymeric blend, the hydroxypropylmethyl cellulose is present in an amount of 27.3 wt. % (±2%) of the extended release pharmaceutically-acceptable polymeric blend, the extended release pharmaceutically-acceptable polymeric blend is present in an amount of 9.1 wt. % (±2%) of the total coated core weight, and the capsule is a size 1 capsule.