Claims for Patent: 11,534,444

Summary for Patent: 11,534,444

Title:	Treatment of SMA
Abstract:	The present invention relates to 7-(4,7-diazaspiro[2.5]octan-7-yl)-2-(2,8-dimethylimidazo[1,2-b]pyridazin-6-yl)pyrido[1,2-a]pyrimidin-4-one for use in the treatment of spinal muscular atrophy (SMA), its pharmaceutical composition to be used in the treatment of SMA, its methods of treatment thereof.
Inventor(s):	Jean-Paul Pfefen, Heidemarie Kletzl, Lutz Mueller
Assignee:	Hoffmann La Roche Inc
Application Number:	US16/838,942
Patent Claims:	1. A method of treating spinal muscular atrophy (SMA) in a subject in need thereof comprising administering to said subject 7-(4,7-diazaspiro[2.5]octan-7-yl)-2-(2,8-dimethylimidazo[1,2-b]pyridazin-6-yl)pyrido[1,2-a]pyrimidin-4-one or a pharmaceutically acceptable salt thereof, wherein the administered dose of 7-(4,7-diazaspiro[2.5]octan-7-yl)-2-(2,8-dimethylimidazo[1,2-b]pyridazin-6-yl)pyrido[1,2-a]pyrimidin-4-one or a pharmaceutically acceptable salt thereof is a. 0.25 mg/kg for a subject with a body weight of less than 20 kg, and b. 5 mg for a subject with a body weight of more than or equal to 20 kg. 2. The method of claim 1, wherein the SMA is type II SMA. 3. The method of claim 1, wherein the SMA is type III SMA. 4. The method of claim 1, wherein the SMA is type II SMA and type III SMA. 5. The method of claim 1, wherein the subject is more than or equal to 2 years of age. 6. The method of claim 1, wherein 7-(4,7-diazaspiro[2.5]octan-7-yl)-2-(2,8-dimethylimidazo[1,2-b]pyridazin-6-yl)pyrido[1,2-a]pyrimidin-4-one or a pharmaceutically acceptable salt thereof is administered orally. 7. The method of claim 6, wherein the dose of 7-(4,7-diazaspiro[2.5]octan-7-yl)-2-(2,8-dimethylimidazo[1,2-b]pyridazin-6-yl)pyrido[1,2-a]pyrimidin-4-one or a pharmaceutically acceptable salt thereof is administered in an oral aqueous solution. 8. The method of claim 1, wherein 7-(4,7-diazaspiro[2.5]octan-7-yl)-2-(2,8-dimethylimidazo[1,2-b]pyridazin-6-yl)pyrido[1,2-a]pyrimidin-4-one or a pharmaceutically acceptable salt thereof is administered orally at a dose of 0.25 mg/kg for a subject with a body weight of less than 20 kg. 9. The method of claim 1, wherein 7-(4,7-diazaspiro[2.5]octan-7-yl)-2-(2,8-dimethylimidazo[1,2-b]pyridazin-6-yl)pyrido[1,2-a]pyrimidin-4-one or a pharmaceutically acceptable salt thereof is administered orally at a dose of 5 mg for a subject with a body weight of more than or equal to 20 kg. 10. The method of claim 1, wherein 7-(4,7-diazaspiro[2.5]octan-7-yl)-2-(2,8-dimethylimidazo[1,2-b]pyridazin-6-yl)pyrido[1,2-a]pyrimidin-4-one or a pharmaceutically acceptable salt thereof is administered once a day. 11. The method of claim 10, wherein 7-(4,7-diazaspiro[2.5]octan-7-yl)-2-(2,8-dimethylimidazo[1,2-b]pyridazin-6-yl)pyrido[1,2-a]pyrimidin-4-one or a pharmaceutically acceptable salt thereof is administered orally at a dose of 0.25 mg/kg per day for a subject with a body weight of less than 20 kg. 12. The method of claim 10, wherein 7-(4,7-diazaspiro[2.5]octan-7-yl)-2-(2,8-dimethylimidazo[1,2-b]pyridazin-6-yl)pyrido[1,2-a]pyrimidin-4-one or a pharmaceutically acceptable salt thereof is administered orally at a dose of 5 mg per day for a subject with a body weight of more than or equal to 20 kg. 13. A method of treating spinal muscular atrophy (SMA) in a subject in need thereof comprising administering to said subject a pharmaceutical composition comprising 7-(4,7-diazaspiro[2.5]octan-7-yl)-2-(2,8-dimethylimidazo[1,2-b]pyridazin-6-yl)pyrido[1,2-a]pyrimidin-4-one or a pharmaceutically acceptable salt thereof, wherein the administered dose of 7-(4,7-diazaspiro[2.5]octan-7-yl)-2-(2,8-dimethylimidazo[1,2-b]pyridazin-6-yl)pyrido[1,2-a]pyrimidin-4-one or a pharmaceutically acceptable salt thereof is a. 0.25 mg/kg for a subject with a body weight of less than 20 kg, and b. 5 mg for a subject with a body weight of more than or equal to 20 kg. 14. The method of claim 13, wherein the SMA is type II SMA. 15. The method of claim 13, wherein the SMA is type III SMA. 16. The method of claim 13, wherein the SMA is type II SMA and type III SMA. 17. The method of claim 13, wherein the subject is more than or equal to 2 years of age. 18. The method of claim 13, wherein the dose of 7-(4,7-diazaspiro[2.5]octan-7-yl)-2-(2,8-dimethylimidazo[1,2-b]pyridazin-6-yl)pyrido[1,2-a]pyrimidin-4-one or a pharmaceutically acceptable salt thereof is administered in a single pharmaceutical composition. 19. The method of claim 13, wherein the dose of 7-(4,7-diazaspiro[2.5]octan-7-yl)-2-(2,8-dimethylimidazo[1,2-b]pyridazin-6-yl)pyrido[1,2-a]pyrimidin-4-one or a pharmaceutically acceptable salt thereof is administered in more than one pharmaceutical composition. 20. The method of claim 13, wherein the pharmaceutical composition is administered orally. 21. The method of claim 20, wherein the pharmaceutical composition is an oral aqueous solution. 22. The method of claim 13, wherein the pharmaceutical composition to administer 7-(4,7-diazaspiro[2.5]octan-7-yl)-2-(2,8-dimethylimidazo[1,2-b]pyridazin-6-yl)pyrido[1,2-a]pyrimidin-4-one or a pharmaceutically acceptable salt thereof at a dose of 0.25 mg/kg for a subject with a body weight of less than 20 kg is a pharmaceutical composition for oral administration. 23. The method of claim 13, wherein the pharmaceutical composition to administer 7-(4,7-diazaspiro[2.5]octan-7-yl)-2-(2,8-dimethylimidazo[1,2-b]pyridazin-6-yl)pyrido[1,2-a]pyrimidin-4-one or a pharmaceutically acceptable salt thereof at a dose of 5 mg for a subject with a body weight of more than or equal to 20 kg is a pharmaceutical composition for oral administration. 24. The method of claim 13, wherein the pharmaceutical composition to administer 7-(4,7-diazaspiro[2.5]octan-7-yl)-2-(2,8-dimethylimidazo[1,2-b]pyridazin-6-yl)pyrido[1,2-a]pyrimidin-4-one or a pharmaceutically acceptable salt thereof is administered once a day. 25. The method of claim 13, wherein the pharmaceutical composition to administer 7-(4,7-diazaspiro[2.5]octan-7-yl)-2-(2,8-dimethylimidazo[1,2-b]pyridazin-6-yl)pyrido[1,2-a]pyrimidin-4-one or a pharmaceutically acceptable salt thereof at a dose of 0.25 mg/kg for a subject with a body weight of less than 20 kg is a pharmaceutical composition for administration once a day. 26. The method of claim 25, wherein the pharmaceutical composition to administer 7-(4,7-diazaspiro[2.5]octan-7-yl)-2-(2,8-dimethylimidazo[1,2-b]pyridazin-6-yl)pyrido[1,2-a]pyrimidin-4-one or a pharmaceutically acceptable salt thereof at a dose of 0.25 mg/kg for a subject with a body weight of less than 20 kg is a pharmaceutical composition for oral administration. 27. The method of claim 13, wherein the pharmaceutical composition to administer 7-(4,7-diazaspiro[2.5]octan-7-yl)-2-(2,8-dimethylimidazo[1,2-b]pyridazin-6-yl)pyrido[1,2-a]pyrimidin-4-one or a pharmaceutically acceptable salt thereof at a dose of 5 mg for a subject with a body weight of more than or equal to 20 kg is a pharmaceutical composition for administration once a day. 28. The method of claim 27, wherein the pharmaceutical composition to administer 7-(4,7-diazaspiro[2.5]octan-7-yl)-2-(2,8-dimethylimidazo[1,2-b]pyridazin-6-yl)pyrido[1,2-a]pyrimidin-4-one or a pharmaceutically acceptable salt thereof at a dose of 5 mg for a subject with a body weight of more than or equal to 20 kg is a pharmaceutical composition for oral administration. 29. The method of claim 20, wherein the pharmaceutical composition is in powder form suitable for constitution of an oral solution. 30. A method of treating spinal muscular atrophy (SMA) in a subject in need thereof comprising administering to said subject 7-(4,7-diazaspiro[2.5]octan-7-yl)-2-(2,8-dimethylimidazo[1,2-b]pyridazin-6-yl)pyrido[1,2-a]pyrimidin-4-one, or a pharmaceutically acceptable salt thereof, wherein the administered daily dose of 7-(4,7-diazaspiro[2.5]octan-7-yl)-2-(2,8-dimethylimidazo[1,2-b]pyridazin-6-yl)pyrido[1,2-a]pyrimidin-4-one, or a pharmaceutically acceptable salt thereof, is 0.25 mg/kg for a subject 2 years of age and older with a body weight of less than 20 kg, and wherein the 7-(4,7-diazaspiro[2.5]octan-7-yl)-2-(2,8-dimethylimidazo[1,2-b]pyridazin-6-yl)pyrido[1,2-a]pyrimidin-4-one, or a pharmaceutically acceptable salt thereof, is administered in an oral solution constituted from a powder form of the 7-(4,7-diazaspiro[2.5]octan-7-yl)-2-(2,8-dimethylimidazo[1,2-b]pyridazin-6-yl)pyrido[1,2-a]pyrimidin-4-one or a pharmaceutically acceptable salt thereof. 31. A method of treating spinal muscular atrophy (SMA) in a subject in need thereof comprising administering to said subject 7-(4,7-diazaspiro[2.5]octan-7-yl)-2-(2,8-dimethylimidazo[1,2-b]pyridazin-6-yl)pyrido[1,2-a]pyrimidin-4-one, or a pharmaceutically acceptable salt thereof, wherein the administered daily dose of 7-(4,7-diazaspiro[2.5]octan-7-yl)-2-(2,8-dimethylimidazo[1,2-b]pyridazin-6-yl)pyrido[1,2-a]pyrimidin-4-one, or a pharmaceutically acceptable salt thereof, is 5 mg for a subject 2 years of age and older with a body weight of more than or equal to 20 kg, and wherein the 7-(4,7-diazaspiro[2.5]octan-7-yl)-2-(2,8-dimethylimidazo[1,2-b]pyridazin-6-yl)pyrido[1,2-a]pyrimidin-4-one, or a pharmaceutically acceptable salt thereof, is administered in an oral solution constituted from a powder form of the 7-(4,7-diazaspiro[2.5]octan-7-yl)-2-(2,8-dimethylimidazo[1,2-b]pyridazin-6-yl)pyrido[1,2-a]pyrimidin-4-one or a pharmaceutically acceptable salt thereof. 32. A method of treating spinal muscular atrophy (SMA) in a subject in need thereof comprising administering to said subject 7-(4,7-diazaspiro[2.5]octan-7-yl)-2-(2,8-dimethylimidazo[1,2-b]pyridazin-6-yl)pyrido[1,2-a]pyrimidin-4-one or a pharmaceutically acceptable salt thereof, wherein the administered dose of 7-(4,7-diazaspiro[2.5]octan-7-yl)-2-(2,8-dimethylimidazo[1,2-b]pyridazin-6-yl)pyrido[1,2-a]pyrimidin-4-one or a pharmaceutically acceptable salt thereof is a. 0.15 mg/kg to 0.25 mg/kg for a subject with a body weight of less than 20 kg, and b. 5 mg for a subject with a body weight of more than or equal to 20 kg. 33. The method of claim 32, wherein the 7-(4,7-diazaspiro[2.5]octan-7-yl)-2-(2,8-dimethylimidazo[1,2-b]pyridazin-6-yl)pyrido[1,2-a]pyrimidin-4-one, or a pharmaceutically acceptable salt thereof, is administered orally. 34. The method of claim 33, wherein the 7-(4,7-diazaspiro[2.5]octan-7-yl)-2-(2,8-dimethylimidazo[1,2-b]pyridazin-6-yl)pyrido[1,2-a]pyrimidin-4-one, or a pharmaceutically acceptable salt thereof, is administered as an oral solution. 35. The method of claim 32, wherein the 7-(4,7-diazaspiro[2.5]octan-7-yl)-2-(2,8-dimethylimidazo[1,2-b]pyridazin-6-yl)pyrido[1,2-a]pyrimidin-4-one, or a pharmaceutically acceptable salt thereof, is administered daily.