Claims for Patent: 12,252,479

Summary for Patent: 12,252,479

Title:	Crystalline forms OF N-[4-(chlorodifluoromethoxy)phenyl]-6-[(3R)-3-hydroxypyrrolidin-1-yl]-5-(1H-pyrazol-5-yl)pyridine-3-carboxamide
Abstract:	The present invention describes specific crystalline forms of N-[4-(Chlorodifluoromethoxy)phenyl]-6-[(3R)-3-hydroxypyrrolidin-1-yl]-5-(1H-pyrazol-5-yl)pyridine-3-carboxamide. The present invention further relates to methods for preparing said crystalline forms, pharmaceutical compositions comprising said crystalline forms, and methods of using said crystalline forms and pharmaceutical compositions to treat disease.
Inventor(s):	Stephanie Kay Dodd, Arnaud Grandeury, Emmanuel SUFFERT, Evgenia ROUSAKI
Assignee:	Novartis AG , Novartis Pharma AG
Application Number:	US17/858,713
Patent Claims:	1. A method for treating an ABL1/BCR-ABL1-mediated disorder, comprising administering to a patient in need of such treatment a therapeutically effective amount of a crystalline form A of asciminib hydrochloride, wherein the crystalline form A of asciminib hydrochloride is characterized by having an x-ray powder diffraction pattern comprising reflections at 2-Theta angles of 12.6±0.2°, 18.9±0.2° and 20.9±0.2°, when measured at a temperature in the range of from 20 to 25° C. with Cu-Kalpha1,2 radiation having a wavelength of 0.1541 Å. 2. The method of claim 1, wherein the crystalline form A of asciminib hydrochloride is characterized by having an x-ray powder diffraction pattern comprising reflections at 2-Theta angles of 12.6±0.2°, 17.0±0.2°, 18.9±0.2°, 20.9±0.2° and 32.5±0.2°, when measured at a temperature in the range of from 20 to 25° C. with Cu-Kalpha1,2 radiation having a wavelength of 0.1541 Å. 3. The method of claim 1, wherein the crystalline form A of asciminib hydrochloride is characterized by having an x-ray powder diffraction pattern comprising at least three 2 theta values selected from the group consisting of 8.5°±0.2° 9.5°±0.2°, 11.8°±0.2°, 12.3°±0.2°, 12.6°±0.2°, 13.9°±0.2°, 14.8°±0.2°, 15.9°±0.2°, 16.5°±0.2°, 17.0°±0.2°, 17.6°±0.2°, 18.9°±0.2°, 19.1°±0.2°, 19.8°±0.2°, 20.4°±0.2° 20.9°±0.2°, 21.2°±0.2°, 22.4°±0.2°, 22.7°±0.2°, 23.9°±0.2°, 24.3°±0.2°, 24.8°±0.2° 25.0°±0.2°, 25.9°±0.2°, 26.8°±0.2°, 27.0°±0.2°, 28.3°±0.2°, 28.6°±0.2°, 28.9°±0.2°, 29.8°±0.2°, 30.5°±0.2°, 31.3°±0.2°, 31.5°±0.2°, 31.8°±0.2°, 32.1°±0.2°, 32.5°±0.2° 32.9°±0.2°, 33.6°±0.2°, 34.0°±0.2°, 34.6°±0.2°, 35.0°±0.2°, 35.6°±0.2°, 36.3°±0.2° and 38.8°±0.2°, when measured at a temperature in the range of from 20 to 25° C. with Cu-Kalpha1,2 radiation having a wavelength of 0.1541 Å. 4. The method of claim 1, wherein the crystalline form A of asciminib hydrochloride is characterized by having an x-ray powder diffraction pattern comprising at least four 2 theta values selected from the group consisting of 8.5°±0.2° 9.5°±0.2°, 11.8°±0.2°, 12.3°±0.2°, 12.6°±0.2°, 13.9°±0.2°, 14.8°±0.2°, 15.9°±0.2°, 16.5°±0.2°, 17.0°±0.2°, 17.6°±0.2°, 18.9°±0.2°, 19.1°±0.2°, 19.8°±0.2°, 20.4°±0.2°, 20.9°±0.2°, 21.2°±0.2°, 22.4°±0.2°, 22.7°±0.2°, 23.9°±0.2°, 24.3°±0.2°, 24.8°±0.2°, 25.0°±0.2°, 25.9°±0.2°, 26.8°±0.2°, 27.0°±0.2°, 28.3°±0.2°, 28.6°±0.2°, 28.9°±0.2°, 29.8°±0.2°, 30.5°±0.2°, 31.3°±0.2°, 31.5°±0.2°, 31.8°±0.2°, 32.1°±0.2°, 32.5°±0.2°, 32.9°±0.2°, 33.6°±0.2°, 34.0°±0.2°, 34.6°±0.2°, 35.0°±0.2°, 35.6°±0.2°, 36.3°±0.2° and 38.8°±0.2°, when measured at a temperature in the range of from 20 to 25° C. with Cu-Kalpha1,2 radiation having a wavelength of 0.1541 Å. 5. The method of claim 1, wherein the crystalline form A of asciminib hydrochloride is characterized by having an x-ray powder diffraction pattern comprising at least five 2 theta values selected from the group consisting of 8.5°±0.2°, 9.5°±0.2°, 11.8°±0.2°, 12.3°±0.2°, 12.6°±0.2°, 13.9°±0.2°, 14.8°±0.2°, 15.9°±0.2°, 16.5°±0.2°, 17.0°±0.2°, 17.6°±0.2°, 18.9°±0.2°, 19.1°±0.2°, 19.8°±0.2°, 20.4°±0.2°, 20.9°±0.2°, 21.2°±0.2°, 22.4°±0.2°, 22.7°±0.2°, 23.9°±0.2°, 24.3°±0.2°, 24.8°±0.2°, 25.0°±0.2°, 25.9°±0.2°, 26.8°±0.2°, 27.0°±0.2°, 28.3°±0.2°, 28.6°±0.2°, 28.9°±0.2°, 29.8°±0.2°, 30.5°±0.2°, 31.3°±0.2°, 31.5°±0.2°, 31.8°±0.2°, 32.1°±0.2°, 32.5°±0.2°, 32.9°±0.2°, 33.6°±0.2°, 34.0°±0.2°, 34.6°±0.2°, 35.0°±0.2°, 35.6°±0.2°, 36.3°±0.2° and 38.8°±0.2°, when measured at a temperature in the range of from 20 to 25° C. with Cu-Kalpha1,2 radiation having a wavelength of 0.1541 Å. 6. The method of claim 1, wherein the crystalline form A of asciminib hydrochloride is characterized by having a differential scanning calorimetry curve comprising an endothermic peak having an onset temperature of 90° C., when measured at a heating rate of 2° C./min. 7. The method of claim 1, wherein the crystalline form A of asciminib hydrochloride is characterized by having a thermogravimetric analysis curve showing a mass loss of not more than 3.3 weight % based on the weight of the crystalline form, when heated from 30 to 300° C. at a rate of 20° C./min. 8. The method of claim 1, wherein the crystalline form A of asciminib hydrochloride is characterized by having an x-ray powder diffraction pattern similar to FIG. 8 . 9. The method of claim 1, wherein the crystalline form A of asciminib hydrochloride is characterized by the following unit cell parameters from x-ray diffraction data measured at 100K: Space symmetry Triclinic Space group P1 Cell Volume (Å3) 1053.6(6) Crystal Density (g/cm3) 1.533 a (Å) 8.203(3) b (Å) 11.116(3) c (Å) 12.627(4) beta (°) 97.711(12) Z 2. 10. The method of claim 1, wherein the crystalline form A of asciminib hydrochloride is characterized by the following unit cell parameters from x-ray diffraction data measured at 298K: Space symmetry Triclinic Space group P1 Cell Volume (Å3) 1082.9(6) Crystal Density (g/cm3) 1.491 a (Å) 8.245(3) b (Å) 11.352(4) c (Å) 12.697(4) beta (°) 97.289(18) Z 2. 11. The method of claim 1, wherein the ABL1/BCR-ABL1-mediated disorder is a cancer selected from chronic myeloid leukemia and acute lymphoblastic leukemia. 12. The method of claim 11, wherein the ABL1/BCR-ABL1-mediated disorder is chronic myeloid leukemia.