Claims for Patent: 12,029,740

Summary for Patent: 12,029,740

Title:	Amorphous nilotinib microparticles and uses thereof
Abstract:	Amorphous solid dispersions and pharmaceutical compositions of the protein kinase inhibitor nilotinib. The pharmaceutical compositions may be used in methods of treating a proliferative disorder such as cancer. In some embodiments, the pharmaceutical compositions can be administered without regard to food consumption. In other embodiments, the pharmaceutical compositions can be administered at a significantly lower dose as compared to a commercially available immediate-release nilotinib formulation, while providing a comparable therapeutic effect.
Inventor(s):	Christian F. Wertz, Tzehaw Chen, Joseph McTarsney
Assignee:	Flex Pharma LLC
Application Number:	US17/866,939
Patent Claims:	1. A pharmaceutical composition comprising an amorphous solid dispersion, the amorphous solid dispersion comprising nilotinib free base and one or more polymers; wherein the one or more polymers comprises a hydroxypropyl methylcellulose acetate succinate that exhibits pH-dependent solubility; wherein the nilotinib and the one or more polymers are present in the amorphous solid dispersion in a w/w ratio of 35:65 to 80:20 (nilotinib:polymer); wherein the pharmaceutical composition meets one or more bioequivalence criteria when administered to healthy human subjects under fasted conditions as compared to a reference composition administered to the subjects under fasted conditions; wherein the reference composition is a conventional immediate-release nilotinib formulation comprising crystalline nilotinib monohydrochloride monohydrate; wherein the amount of nilotinib in the pharmaceutical composition is 50% to 80% less than the amount of nilotinib in the reference composition; and wherein the one or more bioequivalence criteria is selected from: (a) a 90% confidence interval for AUC, which is between 80% and 125%; and (b) a 90% confidence interval for Cmax, which is between 80% and 125%. 2. The pharmaceutical composition of claim 1, wherein the one or more polymers comprise a hydroxypropyl methylcellulose acetate succinate characterized by an acetyl substitution of 7% to 11% and a succinyl substitution of 10% to 14%. 3. The pharmaceutical composition of claim 1, wherein the one or more polymers consists essentially of a hydroxypropyl methylcellulose acetate succinate. 4. The pharmaceutical composition of claim 1, wherein the amorphous solid dispersion consists essentially of nilotinib and the one or more polymers. 5. The pharmaceutical composition of claim 1, wherein the nilotinib and the one or more polymers are present in the amorphous solid dispersion in a w/w ratio of 40:60 to 70:30 (nilotinib:polymer). 6. The pharmaceutical composition of claim 1, wherein the nilotinib and the one or more polymers are present in the amorphous solid dispersion in a w/w ratio of 50:50 (nilotinib:polymer). 7. The pharmaceutical composition of claim 1, wherein the amount of nilotinib in the pharmaceutical composition is 60% to 80% less than the amount of nilotinib in the reference composition. 8. The pharmaceutical composition of claim 1, wherein the pharmaceutical composition is presented as a solid dosage form suitable for oral administration, and comprising 25 mg to 100 mg nilotinib. 9. The pharmaceutical composition of claim 1, wherein the reference composition comprises 200 mg crystalline nilotinib monohydrochloride monohydrate presented in capsule form. 10. The pharmaceutical composition of claim 1, wherein the AUC is AUC0-24h. 11. The pharmaceutical composition of claim 1, wherein the AUC is AUClast. 12. The pharmaceutical composition of claim 1, wherein the AUC is AUCinf. 13. A pharmaceutical composition comprising an amorphous solid dispersion, the amorphous solid dispersion comprising nilotinib free base and one or more polymers; wherein the one or more polymers comprises a hydroxypropyl methylcellulose acetate succinate that exhibits pH-dependent solubility; wherein the nilotinib and the one or more polymers are present in the amorphous solid dispersion in a w/w ratio of 35:65 to 80:20 (nilotinib:polymer); wherein the pharmaceutical composition meets one or more bioequivalence criteria when administered to healthy human subjects under fed conditions as compared to a reference composition administered to the subjects under fasted conditions; wherein the reference composition is a conventional immediate-release nilotinib formulation comprising crystalline nilotinib monohydrochloride monohydrate; wherein the amount of nilotinib in the pharmaceutical composition is 50% to 80% less than the amount of nilotinib in the reference composition; and wherein the one or more bioequivalence criteria is selected from: (a) a 90% confidence interval for AUC, which is between 80% and 125%; and (b) a 90% confidence interval for Cmax, which is between 80% and 125%. 14. The pharmaceutical composition of claim 13, wherein the one or more polymers comprise a hydroxypropyl methylcellulose acetate succinate characterized by an acetyl substitution of 7% to 11% and a succinyl substitution of 10% to 14%. 15. The pharmaceutical composition of claim 13, wherein the one or more polymers consists essentially of a hydroxypropyl methylcellulose acetate succinate. 16. The pharmaceutical composition of claim 13, wherein the amorphous solid dispersion consists essentially of nilotinib and the one or more polymers. 17. The pharmaceutical composition of claim 13, wherein the nilotinib and the one or more polymers are present in the amorphous solid dispersion in a w/w ratio of 40:60 to 70:30 (nilotinib:polymer). 18. The pharmaceutical composition of claim 13, wherein the nilotinib and the one or more polymers are present in the amorphous solid dispersion in a w/w ratio of 50:50 (nilotinib:polymer). 19. The pharmaceutical composition of claim 13, wherein the amount of nilotinib in the pharmaceutical composition is 60% to 80% less than the amount of nilotinib in the reference composition. 20. The pharmaceutical composition of claim 13, wherein the pharmaceutical composition is presented as a solid dosage form suitable for oral administration, and comprising 25 mg to 100 mg nilotinib. 21. The pharmaceutical composition of claim 13, wherein the reference composition comprises 200 mg crystalline nilotinib monohydrochloride monohydrate presented in capsule form. 22. The pharmaceutical composition of claim 13, wherein the AUC is AUC0-24h. 23. The pharmaceutical composition of claim 13, wherein the AUC is AUClast. 24. The pharmaceutical composition of claim 13, wherein the AUC is AUCinf.