Claims for Patent: 10,676,435

Summary for Patent: 10,676,435

Title:	Crystalline L-arginine salt of (R)-2-(7-(4-cyclopentyl-3-(trifluoromethyl)benzyloxy)-1,2,3,4-tetrahydrocyclo-penta [b]indol-3-yl)acetic acid(Compound 1) for use in SIPI receptor-associated disorders
Abstract:	The present invention relates to, inter alia, a novel crystalline free-plate habit or morphology, processes for preparing the crystalline free-plate habit, and uses of the crystalline free-plate habit of the L-arginine salt of (R)-2-(7-(4-cyclopentyl-3-(trifluoromethyl)benzyloxy)-1,2,3,4-tetrahydrocyclo-penta[b]indol-3-yl)acetic acid (Compound 1) in the treatment of S1Preceptor-associated disorders, for example, diseases and disorders mediated by lymphocytes, transplant rejection, autoimmune diseases and disorders, inflammatory diseases and disorders (e.g., acute and chronic inflammatory conditions), cancer, and conditions characterized by an underlying defect in the vascular integrity or that are associated with angiogenesis such as may be pathologic (e.g., as may occur in inflammation, tumor development, and atherosclerosis).
Inventor(s):	Blackburn Anthony C., Castro Ryan O., Hadd Mark Allen, Ma You-An, Montalban Antonio Garrido, Rueter Jaimie Karyn, Selvey Lee Alani, Shakya Sagar Raj, Carlos Marlon
Assignee:	Arena Pharmaceuticals, Inc.
Application Number:	US16379265
Patent Claims:	1. A method for treating an S1Preceptor-associated disorder in an individual comprising administering to said individual in need thereof a therapeutically effective amount of a crystalline free-plate habit of L-arginine salt of (R)-2-(7-(4-cyclopentyl-3-(trifluoromethyl)benzyloxy)-1 ,2 ,3 ,4-tetrahydrocyclopenta[b]indol-3-yl)acetic acid; wherein said crystalline free-plate habit has a BET specific surface area of about 0.1 m/g to about 5.0 m/g , wherein said disorder is selected from the group consisting of: biliary cirrhosis , psoriatic arthritis , rheumatoid arthritis , type I diabetes , multiple sclerosis , inflammatory skin disease , psoriasis , atopic dermatitis , acne , inflammatory bowel disease , Crohn's disease , ulcerative colitis , systemic lupus erythematosus , and transplant rejection.2. The method according to claim 1 , wherein the crystalline free-plate habit has a BET specific surface area of about 0.6 m/g to about 4.0 m/g.3. A method according to claim 1 , wherein the crystalline free-plate habit has a powder X-ray diffraction pattern comprising peaks claim 1 , in terms of 2θ claim 1 , at 8.2°±0.2° claim 1 , 16.4°±0.2° claim 1 , and 20.5°±0.2°.4. The method according to claim 1 , wherein the crystalline free-plate habit has a powder X-ray diffraction pattern comprising peaks claim 1 , in terms of 2θ claim 1 , at 8.2°±0.2° claim 1 , 16.4°±0.2° claim 1 , 20.5°±0.2° claim 1 , and 24.6°±0.2°.5. The method according to claim 1 , wherein the crystalline free-plate habit has a powder X-ray diffraction pattern comprising peaks claim 1 , in terms of 2θ claim 1 , at 8.2°±0.2° claim 1 , 16.4°±0.2° claim 1 , 20.5°±0.2° claim 1 , 24.6°±0.2° claim 1 , 28.8°±0.2° claim 1 , and 37.3°±0.2°.6. The method according to claim 1 , wherein the crystalline free-plate habit has a differential scanning calorimetry trace comprising an endotherm with an extrapolated onset temperature of 205.0° C. to 208.5° C. at a scan rate of 10° C./minute.7. The method according to claim 1 , wherein the crystalline free-plate habit has a differential scanning calorimetry trace comprising an endotherm with an extrapolated onset temperature of 205.5° C. to 208.1° C. at a scan rate of 10° C./minute.8. The method according to claim 1 , wherein the crystalline free-plate habit has a differential scanning calorimetry trace conducted at a scan rate of 10° C./minute comprising an endotherm substantially as depicted in any one of and .9. The method according to claim 1 , wherein the crystalline free-plate habit has a dynamic moisture sorption (DMS) profile with an adsorption phase from 30% RH to 90% RH wherein said crystalline free-plate habit gains about 0.3% weight or less at 90% RH.10. The method according to claim 1 , wherein the crystalline free-plate habit has:1) a powder X-ray diffraction pattern comprising peaks, in terms of 2θ, at 8.2°±0.2°, 16.4°±0.2°, 20.5°±0.2°, and 24.6°±0.2°;2) a differential scanning calorimetry trace comprising an endotherm with an extrapolated onset temperature of 205.5° C. tot 208.5° C. at a scan rate of 10° C./minute;3) a dynamic moisture sorption (DMS) profile with an adsorption phase from 30% RH to 90% RH wherein said crystalline free-plate habit gains about 0.3% weight or less at 90% RH; and/or{'sup': 2', '2, '4) a BET specific surface area of about 0.6 m/g to about 4.0 m/g.'}11. The method according to claim 1 , wherein the crystalline free-plate habit has:1) a powder X-ray diffraction pattern comprising peaks, in terms of 2θ, at 8.2°±0.2°, 16.4°±0.2°, 20.5°±0.2°, 24.6°±0.2°, 28.8°±0.2°, and 37.3°±0.2°;2) a differential scanning calorimetry trace comprising an endotherm with an extrapolated onset temperature of 205.5° C. to 208.1° C. at a scan rate of 10° C./minute;3) a dynamic moisture sorption (DMS) profile with an adsorption phase from 30% RH to 90% RH wherein said crystalline free-plate habit gains about 0.2% weight or less at 90% RH; and/or{'sup': 2', '2, '4) a BET specific surface area of about 0.6 m/g to about 4.0 m/g.'}12. The method accordingly to claim 1 , wherein said disorder is psoriasis.13. The method accordingly to claim 1 , wherein said disorder is atopic dermatitis.14. The method accordingly to claim 1 , wherein said disorder is psoriatic arthritis.15. The method accordingly to claim 1 , wherein said disorder is rheumatoid arthritis.16. The method accordingly to claim 1 , wherein said disorder is inflammatory bowel disease.17. The method accordingly to claim 1 , wherein said disorder is Crohn's disease.18. The method accordingly to claim 1 , wherein said disorder is ulcerative colitis.19. The method accordingly to claim 1 , wherein said disorder is multiple sclerosis.20. The method accordingly to claim 1 , wherein said disorder is systemic lupus erythematosus.21. The method accordingly to claim 1 , wherein said disorder is biliary cirrhosis.22. The method accordingly to claim 1 , wherein said disorder is type I diabetes.23. The method accordingly to claim 1 , wherein said disorder is inflammatory skin disease.24. The method accordingly to claim 1 , wherein said disorder is acne.25. The method accordingly to claim 1 , wherein said disorder is transplant rejection.