Claims for Patent: 11,384,086

Summary for Patent: 11,384,086

Title:	Crystalline forms of 3-(imidazo[1,2-b]pyridazin-3-ylethynyl)-4-methyl-n-{4-[(4-methylpiperazin- -1- yl)methyl]-3-(trifluoromethyl)phenyl}benzamide and its mono hydrochloride salt
Abstract:	Novel crystalline forms of 3-(imidazo[1,2-b]pyridazin-3-ylethynyl)-4-methyl-N-{4-[(4-methylpiperazin- -1-yl)methyl]-3-(trifluoromethyl)phenyl}benzamide free base and 3-(imidazo[1,2-b]pyridazin-3-ylethynyl)-4-methyl-N-{4-[(4-methylpiperazin- -1-yl)methyl]-3-(trifluoromethyl)phenyl}benzamide mono hydrochloride, pharmaceutical compositions thereof and methods of their preparation and use are disclosed herein.
Inventor(s):	Murray; Christopher K. (Lexington, MA), Rozamus; Leonard W. (Andover, MA), Chaber; John J. (Westford, MA), Sharma; Pradeep K. (Westford, MA)
Assignee:	ARIAD PHARMACEUTICALS, INC. (Cambridge, MA)
Application Number:	17/318,876
Patent Claims:	1. Crystalline anhydrous ponatinib hydrochloride, characterized by an X-ray diffraction pattern comprising 2.theta. values (.+-.0.3) at 5.9, 7.1, 12.5, 19.3, 23.8, and 26.1. 2. The crystalline anhydrous ponatinib hydrochloride of claim 1, having a thermogravimetric analysis thermogram comprising a weight loss of no more than 1.0% w/w from about 30.degree. C. to about 225.degree. C. 3. The crystalline anhydrous ponatinib hydrochloride of claim 1, having a differential scanning calorimetry thermogram comprising an endotherm with a maximum at 264.1.degree. C. 4. A pharmaceutical composition comprising crystalline anhydrous ponatinib hydrochloride characterized by an X-ray diffraction pattern comprising 2.theta. values (.+-.0.3) at 5.9, 7.1, 12.5, 19.3, 23.8, and 26.1 and a pharmaceutically acceptable carrier. 5. The pharmaceutical composition according to claim 4, wherein the crystalline anhydrous ponatinib hydrochloride has a thermogravimetric analysis thermogram comprising a weight loss of no more than 1.0% w/w from about 30.degree. C. to about 225.degree. C. 6. The pharmaceutical composition according to claim 4, wherein the crystalline anhydrous ponatinib hydrochloride has a differential scanning calorimetry thermogram comprising an endotherm with a maximum at 264.1.degree. C. 7. A method for treating chronic myeloid leukemia in a subject in need thereof comprising administering to the subject a therapeutically effective amount of crystalline anhydrous ponatinib hydrochloride characterized by an X-ray diffraction pattern comprising 2.theta. values (.+-.0.3) at 5.9, 7.1, 12.5, 19.3, 23.8, and 26.1 or a pharmaceutical composition comprising the crystalline anhydrous ponatinib hydrochloride and a pharmaceutically acceptable carrier. 8. The method according to claim 7, wherein the subject has chronic phase chronic myeloid leukemia. 9. The method according to claim 8, wherein the subject has acute phase chronic myeloid leukemia. 10. The method according to claim 8, wherein the subject has blast phase chronic myeloid leukemia. 11. The method according to claim 7, wherein the subject has chronic phase, acute phase, or blast phase chronic myeloid leukemia with resistance or intolerance to at least one prior tyrosine-kinase inhibitor. 12. The method according to claim 7, wherein the subject has chronic phase, acute phase, or blast phase chronic myeloid leukemia with resistance or intolerance to at least two prior tyrosine-kinase inhibitors. 13. The method according to claim 7, wherein the leukemia results from a mutation in the Bcr-Abl kinase domain. 14. The method according to claim 7, wherein the crystalline anhydrous ponatinib hydrochloride has a thermogravimetric analysis thermogram comprising a weight loss of no more than 1.0% w/w from about 30.degree. C. to about 225.degree. C. 15. The method according to claim 7, wherein the crystalline anhydrous ponatinib hydrochloride has a differential scanning calorimetry thermogram comprising an endotherm with a maximum at 264.1.degree. C. 16. A method for treating Philadelphia chromosome positive acute lymphoblastic leukemia in a subject in need thereof comprising administering to the subject a therapeutically effective amount of crystalline form of ponatinib hydrochloride characterized by an X-ray diffraction pattern comprising 2.theta. values (.+-.0.3) at 5.9, 7.1, 12.5, 19.3, 23.8, and 26.1 or a pharmaceutical composition comprising the crystalline anhydrous ponatinib hydrochloride and a pharmaceutically acceptable carrier. 17. The method of claim 16, wherein the leukemia results from a mutation in the Bcr-Abl kinase domain. 18. The method according to claim 16, wherein the crystalline anhydrous ponatinib hydrochloride has a thermogravimetric analysis thermogram comprising a weight loss of no more than 1.0% w/w from about 30.degree. C. to about 225.degree. C. 19. The method according to claim 16, wherein the crystalline anhydrous ponatinib hydrochloride has a differential scanning calorimetry thermogram comprising an endotherm with a maximum at 264.1.degree. C.