Claims for Patent: 12,016,861

Summary for Patent: 12,016,861

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:	US18/089,338
Patent Claims:	1. A method of delivering nilotinib to a patient suffering from a proliferative disorder, the method comprising administering to the patient a therapeutically effective amount of a pharmaceutical composition comprising an amorphous solid dispersion, the amorphous solid dispersion comprising nilotinib 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); and wherein the administered amount of nilotinib is 50% to 80% less than a dose required for delivering a therapeutically effective amount of nilotinib in the fasted state using a conventional immediate-release crystalline nilotinib formulation. 2. The method of claim 1, wherein the proliferative disorder is Philadelphia chromosome positive chronic myeloid leukemia. 3. The method 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%. 4. The method of claim 1, wherein the one or more polymers consists essentially of a hydroxypropyl methylcellulose acetate succinate. 5. The method of claim 1, wherein the amorphous solid dispersion consists essentially of nilotinib and the one or more polymers. 6. The method of claim 1, wherein the amorphous solid dispersion consists essentially of nilotinib and hydroxypropyl methylcellulose acetate succinate. 7. The method 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). 8. The method 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). 9. The method of claim 1, wherein the administered amount of nilotinib is 60% to 80% less than the dose required for delivering a therapeutically effective amount of nilotinib in the fasted state using the conventional immediate-release crystalline nilotinib formulation. 10. The method of claim 1, wherein the pharmaceutical composition is presented as a solid dosage form suitable for oral administration, wherein the solid dosage form comprises 25 mg to 100 mg nilotinib per dosage unit. 11. The method of claim 1, wherein the conventional immediate-release crystalline nilotinib formulation comprises crystalline nilotinib monohydrochloride monohydrate presented in capsule form. 12. A method of delivering nilotinib to a patient suffering from a proliferative disorder, the method comprising administering to the patient a therapeutically effective amount of 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); and wherein the administered amount of nilotinib is 50% to 80% less than a dose required for delivering a therapeutically effective amount of nilotinib in the fasted state using a conventional immediate-release crystalline nilotinib formulation. 13. The method of claim 12, wherein the proliferative disorder is Philadelphia chromosome positive chronic myeloid leukemia. 14. The method of claim 12, 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 method of claim 12, wherein the one or more polymers consists essentially of a hydroxypropyl methylcellulose acetate succinate. 16. The method of claim 12, wherein the amorphous solid dispersion consists essentially of nilotinib free base and the one or more polymers. 17. The method of claim 12, wherein the amorphous solid dispersion consists essentially of nilotinib free base and hydroxypropyl methylcellulose acetate succinate. 18. The method of claim 12, 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). 19. The method of claim 12, 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). 20. The method of claim 12, wherein the administered amount of nilotinib is 60% to 80% less than the dose required for delivering a therapeutically effective amount of nilotinib in the fasted state using the conventional immediate-release crystalline nilotinib formulation. 21. The method of claim 12, wherein the pharmaceutical composition is presented as a solid dosage form suitable for oral administration, wherein the solid dosage form comprises 25 mg to 100 mg nilotinib per dosage unit. 22. The method of claim 12, wherein the conventional immediate-release crystalline nilotinib formulation comprises crystalline nilotinib monohydrochloride monohydrate presented in capsule form.