Claims for Patent: 11,254,649

Summary for Patent: 11,254,649

Title:	Crystalline fumarate salt of (S)-[3,4-difluoro-2-(2-fluoro-4-iodophenylamino)phenyl] [3-hydroxy-3-(piperidin-2-yl) azetidin-1-yl]-methanone
Abstract:	This disclosure relates to the crystalline fumarate salt of (S)[3,4-difluoro-2-(2-fluoro-4-iodophenylamino)phenyl] [3-hydroxy-3-(piperidin-2-yl) azetidin-1-yl]-methanone. The disclosure also relates to pharmaceutical compositions comprising the crystalline fumarate salt of (S)[3,4-difluoro-2-(2-fluoro-4-iodophenylamino)phenyl] [3-hydroxy-3-(piperidin-2-yl) azetidin-1-yl]-methanone. The disclosure also relates to methods of treating cancers comprising administering to a patient in need thereof the crystalline fumarate salt of (S)-[3,4-difluoro-2-(2-fluoro-4-iodophenylamino)phenyl] [3-hydroxy-3-(piperidin-2-yl) azetidin-1-yl]-methanone.
Inventor(s):	Brown; Adrian St. Clair (Ely, GB)
Assignee:	Exelixis, Inc. (Alameda, CA)
Application Number:	16/746,161
Patent Claims:	1. A hemifumarate salt of (S)[3,4-difluoro-2-(2-fluoro-4-iodophenylamino)phenyl] [3-hydroxy-3-(piperidin-2-yl) azetidin-l-yl]-methanone having the formula: ##STR00013## 2. The hemifumarate salt of claim 1, wherein the salt is amorphous. 3. The hemifumarate salt of claim 1, wherein the salt is crystalline. 4. A pharmaceutical composition comprising a hemifumarate salt of (S)-[3,4-difluoro-2-(2-fluoro-4-iodophenylamino)phenyl] [3-hydroxy-3-(piperidin-2-yl)azetidin-l-yl]-methanone having the formula: ##STR00014## and a pharmaceutically acceptable excipient. 5. The pharmaceutical composition of claim 4, wherein the hemifumarate salt is amorphous. 6. The pharmaceutical composition of claim 4, wherein the hemifumarate salt is crystalline. 7. A method of treating cancer in a subject, the cancer chosen from melanoma, breast cancer, colorectal cancer, non-small cell lung cancer, acute myeloid leukemia, and pancreatic cancer, said method comprising administering to a subject in need of the treatment a therapeutically effective amount of a hemifumarate salt of (S)-[3,4-difluoro-2-(2-fluoro-4-iodophenylamino)phenyl] [3-hydroxy-3-(piperidin-2-yl) azetidin-1-yl]-methanone having the formula: ##STR00015## 8. The method of claim 7, wherein the cancer is selected from the group consisting of BRAF V600 mutant melanoma, triple negative breast cancer, and KRAS mutant colorectal cancer. 9. The method of claim 7, wherein the cancer is BRAF V600 mutant melanoma. 10. The method of claim 7, wherein the hemifumarate salt is amorphous. 11. The method of claim 7, wherein the hemifumarate salt is crystalline. 12. A method of treating BRAF V600 mutant melanoma in a subject, the method comprising: administering to the subject in need of the treatment a therapeutically effective amount of a hemifumarate salt of (S)- 8 3,4-difluoro-2-(2-fluoro-4-iodophenylamino)phenyl] [3-hydroxy-3-(piperidin-2-yl) azetidin-l-yl]-methanone having the formula ##STR00016## in combination with vemurafenib. 13. The method of claim 12, wherein the administering of the hemifumarate salt of (S)-[3,4-difluoro-2-(2-fluoro-4-iodophenylamino)phenyl] [3-hydroxy-3-(piperidin-2-yl) azetidin-1-yl]-methanone takes place prior or subsequent to, or concurrent with vemurafenib. 14. The method of claim 12, wherein the hemifumarate salt is amorphous. 15. The method of claim 12, wherein the hemifumarate salt is crystalline.