Claims for Patent: 10,519,164

Summary for Patent: 10,519,164

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-carboxamide 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):	Ayman ALLIAN, Jayanthy Jayanth, Ben Klünder, Mohamed-Eslam F. Mohamed, Ahmed A. Othman, Patrick J. Marroum, Peter T. Mayer
Assignee:	AbbVie Inc
Application Number:	US16/453,684
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 10,519,164
Patent Claims:	1. An oral extended release once-daily pharmaceutical composition comprising (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 administration of a single dose of the oral extended release once-daily pharmaceutical composition to healthy adult subjects results in a mean AUCinf from about 220 ng·hours/mL to about 450 ng·hours/mL 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, and wherein administration of a single dose of the oral extended release once-daily pharmaceutical composition to healthy adult subjects under fasting conditions results in a mean Cmax from about 25 ng/mL to about 40 ng/mL 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-carboxide. 2. The composition of claim 1, wherein the administration under fasting conditions results in a mean AUCinf from about 220 ng·hours/mL to about 320 ng·hours/mL. 3. The composition of claim 1, wherein the administration under fed conditions results in a mean AUCinf from about 240 ng·hours/mL to about 450 ng·hours/mL. 4. The composition of claim 1, wherein the difference in the mean AUCinf under fed conditions versus fasting conditions is about 30% or less. 5. The composition of claim 1, wherein the administration under fasting conditions results in a mean Cmax from about 25 ng/mL to about 30 ng/mL. 6. The composition of claim 1, wherein the difference in the mean Cmax under fed conditions versus fasting conditions is about 30% or less. 7. The composition of claim 4, wherein the administration under fasting conditions results in a mean Cmax from about 25 ng/mL to about 30 ng/mL. 8. The composition of claim 4, wherein the difference in the mean Cmax under fed conditions versus fasting conditions is about 30% or less. 9. The composition of claim 1, wherein the administration results in a mean Tmax from about 2.0 to about 4.0 hours 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. 10. The composition of claim 9, wherein the administration under fasting conditions results in a mean Tmax of about 3.0 hours. 11. An oral extended release once-daily pharmaceutical composition comprising (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 oral extended release once-daily pharmaceutical composition is bioequivalent to an oral extended release once-daily film-coated tablet consisting of: (i) in the intragranular core: 15.4 mg of Freebase Hydrate Form C, 40.0 mg of microcrystalline cellulose, and 4.8 mg of hydroxypropyl methyl cellulose; (ii) in the extragranular core: 122.5 mg of Microcrystalline cellulose, 100.6 mg of mannitol, 96.0 mg of tartaric acid, 91.2 mg of hydroxypropyl methyl cellulose, 2.4 mg of colloidal silicon dioxide/silica, and 7.2 mg of magnesium stearate; and (iii) 14.4 mg of a film coat comprising polyvinyl alcohol, titanium dioxide, polyethylene glycol 3350, talc, and iron oxide.