Claims for Patent: 12,275,688

Summary for Patent: 12,275,688

Title:	Crystalline solids of MEK inhibitor N-((R)-2,3-dihydroxypropoxy)-3,4-difluoro-2-(2-fluoro-4-iodo-phenylamino)-benzamide and uses thereof
Abstract:	The present disclosure relates to: a) crystalline forms of N—((R)-2,3-dihydroxypropoxy)-3,4-difluoro-2-(2-fluoro-4-iodo-phenylamino)-benzamide; b) pharmaceutical compositions comprising one or more crystalline forms of N—((R)-2,3-dihydroxypropoxy)-3,4-difluoro-2-(2-fluoro-4-iodo-phenylamino)-benzamide, and, optionally, one or more pharmaceutically acceptable carriers; c) methods of treating a tumor a cancer, or a Rasopathy disorder by administering one or more crystalline forms of N—((R)-2,3-dihydroxypropoxy)-3,4-difluoro-2-(2-fluoro-4-iodo-phenylamino)-benzamide to a subject in need thereof; and methods of producing essentially pure Form IV of N—((R)-2,3-dihydroxypropoxy)-3,4-difluoro-2-(2-fluoro-4-iodo-phenylamino)-benzamide.
Inventor(s):	Kristin Patterson, Jiping Liu, Ricky Wayne Couch, Peter Gregory Varlashkin, Mai Li, Yonghong Gan
Assignee:	SpringWorks Therapeutics Inc , Patheon API Manufacturing Inc
Application Number:	US18/413,575
Patent Claims:	1. A capsule comprising: a. about 1 mg of N—((R)-2,3-dihydroxypropoxy)-3,4-difluoro-2-(2-fluoro-4-iodo-phenylamino)-benzamide of Formula (I) wherein the N—((R)-2,3-dihydroxypropoxy)-3,4-difluoro-2-(2-fluoro-4-iodo-phenylamino)-benzamide constitutes about 0.1 wt/wt % to about 7 wt/wt % of the capsule; b. about 50 wt/wt % to about 98 wt/wt % of one or more diluents; c. about 1 wt/wt % to about 10 wt/wt % of one or more disintegrants; and d. about 0 wt/wt % to about 5 wt/wt % of one or more lubricants. 2. The capsule of claim 1, wherein the capsule comprises a gelatin capsule which encapsulates components (a) to (d). 3. The capsule of claim 1, wherein the N—((R)-2,3-dihydroxypropoxy)-3,4-difluoro-2-(2-fluoro-4-iodo-phenylamino)-benzamide is crystalline. 4. The capsule of claim 3, wherein the crystalline N—((R)-2,3-dihydroxypropoxy)-3,4-difluoro-2-(2-fluoro-4-iodo-phenylamino)-benzamide is Form IV. 5. The capsule of claim 3, wherein the crystalline N—((R)-2,3-dihydroxypropoxy)-3,4-difluoro-2-(2-fluoro-4-iodo-phenylamino)-benzamide exhibits an onset of melting at 110° C. according to differential scanning calorimetry. 6. The capsule of claim 1, wherein the capsule comprises: a. about 1 mg of N—((R)-2,3-dihydroxypropoxy)-3,4-difluoro-2-(2-fluoro-4-iodo-phenylamino)-benzamide of Formula (I) wherein the N—((R)-2,3-dihydroxypropoxy)-3,4-difluoro-2-(2-fluoro-4-iodo-phenylamino)-benzamide constitutes about 0.25 wt/wt % to about 1.5 wt/wt % of the capsule; (b) about 85 wt/wt % to about 95 wt/wt % of one or more diluents; (c) about 3.5 wt/wt % to about 6 wt/wt % of one or more disintegrants; and (d) about 0.5 wt/wt % to about 2 wt/wt % of one or more lubricants. 7. The capsule of claim 1, wherein the capsule comprises: a. about 1 mg of N—((R)-2,3-dihydroxypropoxy)-3,4-difluoro-2-(2-fluoro-4-iodo-phenylamino)-benzamide; b. about 121.2 mg of microcrystalline cellulose; c. about 6.5 mg of croscarmellose sodium; and d. about 1.3 mg magnesium stearate. 8. A method of administering N—((R)-2,3-dihydroxypropoxy)-3,4-difluoro-2-(2-fluoro-4-iodo-phenylamino)-benzamide to a subject in need thereof comprising orally administering to the subject the capsule of claim 1. 9. A method of treating a human subject who has neurofibromatosis type 1 comprising orally administering to the subject the capsule of claim 1. 10. The method of claim 9, wherein the subject has a neurofibroma associated with neurofibromatosis type 1. 11. A capsule comprising: a. about 2 mg of N—((R)-2,3-dihydroxypropoxy)-3,4-difluoro-2-(2-fluoro-4-iodo-phenylamino)-benzamide of Formula (I) wherein the N—((R)-2,3-dihydroxypropoxy)-3,4-difluoro-2-(2-fluoro-4-iodo-phenylamino)-benzamide constitutes about 0.1 wt/wt % to about 7 wt/wt % of the capsule; b. about 50 wt/wt % to about 98 wt/wt % of one or more diluents; c. about 1 wt/wt % to about 10 wt/wt % of one or more disintegrants; and d. about 0 wt/wt % to about 5 wt/wt % of one or more lubricants. 12. The capsule of claim 11, wherein the capsule comprises a gelatin capsule which encapsulates components (a) to (d). 13. The capsule of claim 11, wherein the N—((R)-2,3-dihydroxypropoxy)-3,4-difluoro-2-(2-fluoro-4-iodo-phenylamino)-benzamide is crystalline. 14. The capsule of claim 13, wherein the crystalline N—((R)-2,3-dihydroxypropoxy)-3,4-difluoro-2-(2-fluoro-4-iodo-phenylamino)-benzamide is Form IV. 15. The capsule of claim 13, wherein the crystalline N—((R)-2,3-dihydroxypropoxy)-3,4-difluoro-2-(2-fluoro-4-iodo-phenylamino)-benzamide exhibits an onset of melting at 110° C. according to differential scanning calorimetry. 16. The capsule of claim 11, wherein the capsule comprises: a. about 2 mg of N—((R)-2,3-dihydroxypropoxy)-3,4-difluoro-2-(2-fluoro-4-iodo-phenylamino)-benzamide of Formula (I) wherein the N—((R)-2,3-dihydroxypropoxy)-3,4-difluoro-2-(2-fluoro-4-iodo-phenylamino)-benzamide constitutes about 0.25 wt/wt % to about 1.5 wt/wt % of the capsule; (b) about 85 wt/wt % to about 95 wt/wt % of one or more diluents; (c) about 3.5 wt/wt % to about 6 wt/wt % of one or more disintegrants; and (d) about 0.5 wt/wt % to about 2 wt/wt % of one or more lubricants. 17. The capsule of claim 11, wherein the capsule comprises: a. about 2 mg of N—((R)-2,3-dihydroxypropoxy)-3,4-difluoro-2-(2-fluoro-4-iodo-phenylamino)-benzamide; b. about 242.4 mg of microcrystalline cellulose; c. about 13 mg of croscarmellose sodium; and d. about 2.6 mg magnesium stearate. 18. A method of administering N—((R)-2,3-dihydroxypropoxy)-3,4-difluoro-2-(2-fluoro-4-iodo-phenylamino)-benzamide to a subject in need thereof comprising orally administering to the subject the capsule of claim 11. 19. A method of treating a human subject who has neurofibromatosis type 1 comprising orally administering to the subject the capsule of claim 11. 20. The method of claim 19, wherein the subject has a neurofibroma associated with neurofibromatosis type 1.