Claims for Patent: 10,597,400

Summary for Patent: 10,597,400

Title:	Processes for the preparation of (3S,4R)-3-ethyl-4-(3H-imidazo[1,2-a]pyrrolo[2,3-e]-pyrazin-8-yl)-n-(2,2,2-trifluoroethyl)pyrrolidine-1-carb oxamide and solid state forms thereof
Abstract:	The present disclosure relates to processes for preparing (3S,4R)-3-ethyl-4-(3H-imidazo[1,2-a]pyrrolo[2,3-e]pyrazin-8-yl)-N-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide, solid state forms thereof, and corresponding pharmaceutical compositions, methods of treatment (including treatment of rheumatoid arthritis), kits, methods of synthesis, and products-by-process.
Inventor(s):	Ahmed A. Othman, Mohamed-Eslam F. Mohamed, Ben Klünder, Aileen L. Pangan
Assignee:	AbbVie Inc
Application Number:	US16/458,622
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 10,597,400
Patent Claims:	1. A method of treating moderately to severely active rheumatoid arthritis in a subject in need thereof, comprising orally administering once daily to the subject (3S,4R)-3-ethyl-4-(3H-imidazo[1,2-a]pyrrolo[2,3-e]pyrazin-8-yl)-N-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide in an amount sufficient to deliver 15 mg, per unit dosage form, of (3S,4R)-3-ethyl-4-(3H-imidazo[1,2-a]pyrrolo[2,3-e]pyrazin-8-yl)-N-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide free base equivalent, wherein the subject achieves an ACR70 score by week twelve of treatment. 2. The method of claim 1, wherein the subject is an adult subject. 3. The method of claim 1, wherein the subject has had an inadequate response or intolerance to one or more disease-modifying antirheumatic drugs. 4. The method of claim 1, wherein the subject has had an inadequate response or intolerance to methotrexate. 5. The method of claim 1, wherein the subject has had an inadequate response or intolerance to an anti-TNF biologic agent. 6. The method of claim 1, wherein (3S,4R)-3-ethyl-4-(3H-imidazo[1,2-a]pyrrolo[2,3-e]pyrazin-8-yl)-N-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide is a free base crystalline hemihydrate. 7. The method of claim 6, wherein the free base crystalline hemihydrate has an X-ray powder diffraction pattern characterized by peaks at 13.4±0.2, 15.1±0.2, and 21.7±0.2 degrees two theta when measured at about 25° C. with monochromatic Kα1 radiation. 8. The method of claim 6, wherein the free base crystalline hemihydrate is Freebase Hydrate Form C. 9. A method of treating moderately to severely active rheumatoid arthritis in a subject in need thereof, comprising orally administering once daily to the subject (3S,4R)-3-ethyl-4-(3H-imidazo[1,2-a]pyrrolo[2,3-e]pyrazin-8-yl)-N-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide in an amount sufficient to deliver 15 mg, per unit dosage form, of (3S,4R)-3-ethyl-4-(3H-imidazo[1,2-a]pyrrolo[2,3-e]pyrazin-8-yl)-N-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide free base equivalent, wherein the subject achieves a DAS28(CRP) score of <2.6 by week twelve of treatment. 10. The method of claim 9, wherein the subject is an adult subject. 11. The method of claim 9, wherein the subject has had an inadequate response or intolerance to one or more disease-modifying antirheumatic drugs. 12. The method of claim 9, wherein the subject has had an inadequate response to methotrexate. 13. The method of claim 9, wherein the subject has had an inadequate response or intolerance to an anti-TNF biologic agent. 14. The method of claim 9, wherein (3S,4R)-3-ethyl-4-(3H-imidazo[1,2-a]pyrrolo[2,3-e]pyrazin-8-yl)-N-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide is a free base crystalline hemihydrate. 15. The method of claim 14, wherein the free base crystalline hemihydrate has an X-ray powder diffraction pattern characterized by peaks at 13.4±0.2, 15.1±0.2, and 21.7±0.2 degrees two theta when measured at about 25° C. with monochromatic Kα1 radiation. 16. The method of claim 14, wherein the free base crystalline hemihydrate is Freebase Hydrate Form C. 17. A method of treating moderately to severely active rheumatoid arthritis in a subject in need thereof, comprising orally administering once daily to the subject (3S,4R)-3-ethyl-4-(3H-imidazo[1,2-a]pyrrolo[2,3-e]pyrazin-8-yl)-N-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide in an amount sufficient to deliver 15 mg, per unit dosage form, of (3S,4R)-3-ethyl-4-(3H-imidazo[1,2-a]pyrrolo[2,3-e]pyrazin-8-yl)-N-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide free base equivalent, wherein the subject achieves a Clinical Disease Activity Index (CDAI) score of 2.8 or less by week twelve of treatment. 18. The method of claim 17, wherein the subject is an adult subject. 19. The method of claim 17, wherein the subject has had an inadequate response or intolerance to one or more disease-modifying antirheumatic drugs. 20. The method of claim 17, wherein the subject has had an inadequate response to methotrexate. 21. The method of claim 17, wherein the subject has had an inadequate response or intolerance to an anti-TNF biologic agent. 22. The method of claim 17, wherein (3S,4R)-3-ethyl-4-(3H-imidazo[1,2-a]pyrrolo[2,3-e]pyrazin-8-yl)-N-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide is a free base crystalline hemihydrate. 23. The method of claim 22, wherein the free base crystalline hemihydrate has an X-ray powder diffraction pattern characterized by peaks at 13.4±0.2, 15.1±0.2, and 21.7±0.2 degrees two theta when measured at about 25° C. with monochromatic Kα1 radiation. 24. The method of claim 22, wherein the free base crystalline hemihydrate is Freebase Hydrate Form C.