# US 10,864,194 B2 · Methods for treating heterotopic ossification > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 10,864,194 B2 - Document ID: US10864194B2 - Status: Granted - Kind: B2 - Application number: 16/308,012 - Filed: 2017-06-08 - Published: 2019-07-18 - Granted: 2020-12-15 - Earliest claimed: 2016-06-08 - Assignees: Clementia Pharmaceuticals Inc. - Applicants: Clementia Pharmaceuticals Inc. - Inventors: Clarissa Desjardins; Donna Roy Grogan; Jeffrey Neal Packman; Mark Harnett - Web page: https://patentgrep.com/patent/US10864194B2 ## CPC - A61K 31/415: 1,2-Diazoles - A61K 9/0053: {Mouth and digestive tract, i.e. intraoral and peroral administration} - A61K 31/00: Medicinal preparations containing organic active ingredients - A61P 19/04: for non-specific disorders of the connective tissue - A61P 19/08: for bone diseases, e.g. rachitism, Paget's disease - A61P 31/00: Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics - 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)} - A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca - 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 features dosing regimens and pharmaceutical formulations for oral administration of palovarotene. The dosing regimens can reduce heterotopic ossification, reduce the number of flare-ups, and/or reduce the severity of flare-ups in subjects suffering from fibrodysplasia ossificans progressiva. ## Claims ### Claim 1 A method of reducing heterotopic ossification in a subject with fibrodysplasia ossificans progressiva, said method comprising: (i) during a period when the subject is not experiencing any flare-up symptom orally administering daily to the subject an amount of 5±0.5 mg of palovarotene, or a pharmaceutically acceptable salt thereof, and (ii) during a period when the subject is experiencing at least one flare-up symptom orally administering to the subject an amount of 20±1.0 mg of palovarotene, or a pharmaceutically acceptable salt thereof, daily for a period of 20 to 40 days, and after the period of 20 to 40 days, and amount of 10±1.0 mg of palovarotene, or a pharmaceutically acceptable salt hereof, daily for a period of 14 to 112 days. ### Claim 2 (depends on 1) The method of claim 1, wherein the 10±1.0 mg amount is administered daily for a period of 14 to 84 days. ### Claim 3 A method of reducing heterotopic ossification in a subject with fibrodysplasia ossificans progressiva, said method comprising: (i) during a period when the subject is not experiencing any flare-up symptom orally administering daily to the subject an amount of 5 mg of palovarotene, or a pharmaceutically acceptable salt thereof, and (ii) during a period when the subject is experiencing at least one flare-up symptom orally administering daily to the subject an amount of 20 mg of palovarotene, or a pharmaceutically acceptable salt thereof, for 28 days, and after the 28 days, orally administering daily to the subject an amount of 10 mg of palovarotene, or a pharmaceutically acceptable salt thereof, for at least 56 days. ### Claim 4 (depends on 1) The method of claim 1, wherein the 10±1.0 mg amount is administered daily for a period of 84 days. ### Claim 5 (depends on 1) The method of claim 1, wherein the 10±1.0 mg amount is administered daily for a period of 14 to 56 days. ### Claim 6 (depends on 1) The method of claim 1, wherein the 10±1.0 mg amount is administered daily for a period of 56 days. ### Claim 7 (depends on 1) The method of claim 1, wherein the 10±1.0 mg amount is administered daily for a period of 56 days, and for an additional 28 days if the subject continues to experience at least one flare-up symptom. ### Claim 8 (depends on 1) The method of claim 1, wherein the 10±1.0 mg amount is administered daily for a period of 112 days. ### Claim 9 (depends on 1) The method of claim 1, wherein the 20±1.0 mg amount is administered daily for a period of 28 ±4 days. ### Claim 10 (depends on 1) The method of claim 1, wherein the 20±1.0 mg amount is administered daily for a period of 28 days. ### Claim 11 (depends on 1) The method of claim 1, wherein the subject weighs greater than 60 kg. ### Claim 12 (depends on 1) The method of claim 1, wherein the subject has a skeletal maturity of 90% or greater. ### Claim 13 (depends on 1) The method of claim 1, further comprising administering to the subject an antihistamine. ### Claim 14 (depends on 13) The method of claim 13, wherein the antihistamine is administered topically. ### Claim 15 (depends on 13) The method of claim 13, wherein the antihistamine is administered systemically. ### Claim 16 (depends on 1) The method of claim 1, further comprising administering to the skin of the subject an emollient. ### Claim 17 (depends on 1) The method of claim 1, wherein the at least one flare-up symptom is chosen from swelling, pain, erythema, warmth, stiffness, and decreased range of motion. ### Claim 18 (depends on 1) The method of claim 1, wherein the daily amount is of palovarotene. ### Claim 19 (depends on 1) The method of claim 1, wherein the daily amount is of a pharmaceutically acceptable salt of palovarotene. ### Claim 20 (depends on 3) The method of claim 3, wherein the 10 mg daily amount is administered for 56 days. ### Claim 21 (depends on 3) The method of claim 3, wherein the 10 mg daily amount is administered for 56 days and for an additional 28 days if the subject continues to experience at least one flare-up symptom. ### Claim 22 (depends on 3) The method of claim 3, wherein the subject weighs greater than 60 kg. ### Claim 23 (depends on 3) The method of claim 3, wherein the subject has a skeletal maturity of 90% or greater. ### Claim 24 (depends on 3) The method of claim 3 further comprising administering to the subject an antihistamine. ### Claim 25 (depends on 24) The method of claim 24, wherein the antihistamine is administered topically. ### Claim 26 (depends on 24) The method of claim 24, wherein the antihistamine is administered systemically. ### Claim 27 (depends on 3) The method of claim 3, further comprising administering to the skin of the subject an emollient. ### Claim 28 (depends on 3) The method of claim 3, wherein the at least one flare-up symptom is chosen from swelling, pain, erythema, warmth, stiffness, and decreased range of motion. ### Claim 29 (depends on 3) The method of claim 3, wherein the daily amount is of palovarotene. ### Claim 30 (depends on 3) The method of claim 3, wherein the daily amount is of a pharmaceutically acceptable salt of palovarotene.