Claims for Patent: 10,286,072

Summary for Patent: 10,286,072

Title:	Methods of manufacturing stable aqueous formulations of adalimumab
Abstract:	The invention provides aqueous pharmaceutical adalimumab compositions suitable for long-term storage of adalimumab, methods of manufacture of these compositions, methods of administration, and kits containing same.
Inventor(s):	Manning; Mark (Johnstown, CO), Payne; Robert W. (Fort Collins, CO)
Assignee:	Coherus Biosciences, Inc. (Redwood City, CA)
Application Number:	15/729,295
Patent Claims:	1. A method of manufacturing an aqueous adalimumab formulation, wherein: the aqueous adalimumab formulation comprises: (i) adalimumab; (ii) buffer; and (iii) stabilizer; and wherein the formulation is free of polyol, has a pH of about 5 to about 6, and is stable for one week at 40.degree. C. or two weeks at 25.degree. C., and the method comprises (a) creating a formulation buffer comprising the buffer of the aqueous adalimumab formulation; and (b) contacting a solution comprising adalimumab with the formulation buffer. 2. The method of claim 1, wherein the stabilizer is selected from the group consisting of an amino acid, a salt, EDTA, and a metal ion. 3. The method of claim 2, wherein the amino acid is selected from the group consisting of glycine, arginine and a combination thereof. 4. The method of claim 2, wherein the salt is selected from the group consisting of sodium chloride and sodium sulfate. 5. The method of claim 4, wherein the salt is, or includes, sodium sulfate. 6. The method of claim 5, wherein the buffer contains no citrate and consists of histidine, succinate, or a combination thereof; and wherein the composition may further optionally include (i) phosphate acting as a stabilizer and not as a buffer, so that the composition has a pH of about 5 to about 6 without phosphate or (ii) PS80 surfactant; or both. 7. The method of claim 6, wherein histidine is the sole buffer in the composition; the composition has osmolality of about 180 to 420 mOsM; the composition is suitable for administration to a subject as a single dosage; the composition has a concentration of adalimumab in the range of 30 to about 50 mg/mL; and the dosage contains about 10 to 80 mg of adalimumab. 8. The method of claim 7, wherein the dosage is about 40 mg and results in less pain upon administration to a subject in comparison to an adalimumab composition having a buffer that comprises citrate. 9. A method of manufacturing an aqueous adalimumab formulation, wherein: the aqueous adalimumab formulation has a pH of about 5 to about 6 and comprises: (i) adalimumab; (ii) buffer, free of citrate, and consisting essentially of histidine, succinate, or both; and (iii) stabilizer consisting essentially of: (a) glycine, arginine, or both; or (a) and (b); where (b) is sodium chloride, sodium sulfate, or both, wherein the composition is free of polyol, and is stable for one week at 40.degree. C. or two weeks at 25.degree. C., and the method comprises (a) creating a formulation buffer comprising the buffer of the aqueous adalimumab formulation; and (b) contacting a solution comprising adalimumab with the formulation buffer. 10. The method of claim 9 comprising histidine as the sole buffer, and glycine. 11. The method of claim 9 comprising histidine as the sole buffer, and arginine. 12. The method of claim 9, wherein (b) is, or includes, sodium sulfate. 13. The method of claim 9 further comprising phosphate acting as a stabilizer and not as a buffer so that the composition has a pH of about 5 to about 6 without phosphate; and, optionally, a surfactant. 14. The method of claim 9 having osmolality of about 180 to 420 mOsM; wherein the composition is suitable for administration to a subject as a single dosage; the composition has a concentration of adalimumab in the range of 30 to about 50 mg/mL; and the dosage contains about 10 to 80 mg of adalimumab. 15. The method of claim 14, wherein the dosage is about 40 mg and results in less pain upon administration to a subject in comparison to an adalimumab composition having a buffer comprising citrate. 16. A method of manufacturing an aqueous adalimumab formulation, wherein: the aqueous adalimumab composition comprises adalimumab and a citrate-free buffer, is free of a polyol, has a pH of about 5 to about 6, and is stable for one week at 40.degree. C. or two weeks at 25.degree. C., and the method comprises (a) creating a formulation buffer comprising the buffer of the aqueous adalimumab formulation; and (b) contacting a solution comprising adalimumab with the formulation buffer. 17. The method of claim 16 comprising: (i) adalimumab; (ii) buffer consisting solely of histidine, succinate, or a combination thereof; and (iii) glycine, arginine, or both. 18. The method of claim 17 further comprising phosphate acting as a stabilizer and not as a buffer. 19. The method of claim 17 further comprising a salt selected from sodium chloride and sodium sulfate. 20. The method of claim 17 having osmolality of about 180 to 420 mOsM; wherein the composition is suitable for administration to a subject as a single dosage; the composition having a concentration of adalimumab in the range of 30 to about 50 mg/mL; the dosage containing about 40 mg of adalimumab and resulting in less pain upon administration to a subject in comparison to an adalimumab composition having a buffer that comprises citrate.

Details for Patent 10,286,072

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Abbvie Inc.	HUMIRA	adalimumab	Injection	125057	12/31/2002		2039-05-18
Abbvie Inc.	HUMIRA	adalimumab	Injection	125057	02/21/2008		2039-05-18
Abbvie Inc.	HUMIRA	adalimumab	Injection	125057	04/24/2013		2039-05-18