Claims for Patent: 10,864,194

Summary for Patent: 10,864,194

Title:	Methods for treating heterotopic ossification
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.
Inventor(s):	Clarissa Desjardins, Donna Roy GROGAN, Jeffrey Neal PACKMAN, Mark Harnett
Assignee:	Clementia Pharmaceuticals Inc
Application Number:	US16/308,012
Patent Claims:	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. 2. The method of claim 1, wherein the 10±1.0 mg amount is administered daily for a period of 14 to 84 days. 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. 4. The method of claim 1, wherein the 10±1.0 mg amount is administered daily for a period of 84 days. 5. The method of claim 1, wherein the 10±1.0 mg amount is administered daily for a period of 14 to 56 days. 6. The method of claim 1, wherein the 10±1.0 mg amount is administered daily for a period of 56 days. 7. 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. 8. The method of claim 1, wherein the 10±1.0 mg amount is administered daily for a period of 112 days. 9. The method of claim 1, wherein the 20±1.0 mg amount is administered daily for a period of 28 ±4 days. 10. The method of claim 1, wherein the 20±1.0 mg amount is administered daily for a period of 28 days. 11. The method of claim 1, wherein the subject weighs greater than 60 kg. 12. The method of claim 1, wherein the subject has a skeletal maturity of 90% or greater. 13. The method of claim 1, further comprising administering to the subject an antihistamine. 14. The method of claim 13, wherein the antihistamine is administered topically. 15. The method of claim 13, wherein the antihistamine is administered systemically. 16. The method of claim 1, further comprising administering to the skin of the subject an emollient. 17. 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. 18. The method of claim 1, wherein the daily amount is of palovarotene. 19. The method of claim 1, wherein the daily amount is of a pharmaceutically acceptable salt of palovarotene. 20. The method of claim 3, wherein the 10 mg daily amount is administered for 56 days. 21. 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. 22. The method of claim 3, wherein the subject weighs greater than 60 kg. 23. The method of claim 3, wherein the subject has a skeletal maturity of 90% or greater. 24. The method of claim 3 further comprising administering to the subject an antihistamine. 25. The method of claim 24, wherein the antihistamine is administered topically. 26. The method of claim 24, wherein the antihistamine is administered systemically. 27. The method of claim 3, further comprising administering to the skin of the subject an emollient. 28. 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. 29. The method of claim 3, wherein the daily amount is of palovarotene. 30. The method of claim 3, wherein the daily amount is of a pharmaceutically acceptable salt of palovarotene.