Claims for Patent: 9,683,033

Summary for Patent: 9,683,033

Title:	Cell culture methods to reduce acidic species
Abstract:	The instant invention relates to the field of protein production and purification, and in particular to compositions and processes for controlling the amount of acidic species expressed by host cells, as well as to compositions and processes for controlling the amount of acidic species present in purified preparations.
Inventor(s):	Subramanian; Kartik (Northborough, MA), Zeng; Xiaobei (Carolina, PR), Dong; Diane D. (Shrewsbury, MA), Lim; Wen Chung (Worcester, MA), Gifford; Kathreen A. (Marlborough, MA), Chumsae; Christopher (North Andover, MA)
Assignee:	ABBVIE, INC. (North Chicago, IL)
Application Number:	15/008,895
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 9,683,033
Patent Claims:	1. A composition comprising adalimumab, wherein the composition comprises less than 10% total acidic species of adalimumab, wherein the acidic species of adalimumab are product-related impurities and do not include process-related impurities comprising host cells and lysed host cells, and wherein the acidic species of adalimumab correspond to the peaks that elute earlier than the main peak in a WCX-10 HPLC chromatogram of adalimumab as shown in FIG. 141. 2. The composition of claim 1, wherein the WCX-10 HPLC chromatogram is generated using a first mobile phase of 10 mM Sodium Phosphate dibasic (pH 7.5) and a second mobile phase of 10 mM Sodium Phosphate dibasic, 500 mM Sodium Chloride (pH 5.5), and wherein the WCX-10 HPLC chromatogram is generated using detection at 280 nm. 3. The composition of claim 1, wherein the acidic species of adalimumab comprise a first acidic region (AR1) and a second acidic region (AR2). 4. The composition of claim 1, wherein the composition comprises 9% or less acidic species of adalimumab. 5. The composition of claim 1, wherein the composition comprises 6%-8% acidic species of adalimumab. 6. The composition of claim 1, wherein the adalimumab is produced in a mammalian host cell grown in cell culture. 7. The composition of claim 6, wherein the mammalian host cell is selected from the group consisting of a CHO cell, an NSO cell, a COS cell, and an SP2 cell. 8. The composition of claim 7, wherein the mammalian host cell is a CHO cell. 9. The composition of claim 8, wherein the composition is lyophilized. 10. A pharmaceutical composition suitable for administration to a subject comprising the composition of claim 8 and a pharmaceutically acceptable carrier. 11. The pharmaceutical composition of claim 10, wherein adalimumab is present in the pharmaceutical composition at a concentration of 0.1-250 mg/ml. 12. The pharmaceutical composition of claim 10, wherein the pharmaceutical composition comprises one or more excipient. 13. The pharmaceutical composition of claim 12, wherein the one or more excipient is selected from the group consisting of a buffer, an isotonic agent, a surfactant or a combination thereof. 14. The pharmaceutical composition of claim 13, wherein the pharmaceutical composition comprises the surfactant polysorbate 80. 15. The pharmaceutical composition of claim 13, wherein the pharmaceutical composition comprises an amino acid buffer. 16. The pharmaceutical composition of claim 15, wherein the amino acid is histidine. 17. The pharmaceutical composition of claim 13, wherein the pharmaceutical composition comprises the isotonic agent mannitol. 18. A method for treating a subject in need thereof, comprising administering to the subject the pharmaceutical composition of claim 10, thereby treating the subject. 19. A composition comprising adalimumab, wherein the composition comprises less than 10% total acidic species of adalimumab, wherein the acidic species of adalimumab are product-related impurities and do not include process-related impurities comprising host cells and lysed host cells, wherein the acidic species of adalimumab correspond to the peaks that elute earlier than the main peak in a WCX-10 HPLC chromatogram of adalimumab, and wherein the WCX-10 HPLC chromatogram is generated using a first mobile phase of 10 mM Sodium Phosphate dibasic (pH 7.5) and a second mobile phase of 10 mM Sodium Phosphate dibasic, 500 mM Sodium Chloride (pH 5.5), and wherein the WCX-10 HPLC chromatogram is generated using detection at 280 nm. 20. The composition of claim 19, wherein the acidic species of adalimumab comprise a first acidic region (AR1) and a second acidic region (AR2). 21. The composition of claim 19, wherein the composition comprises 9% or less acidic species of adalimumab. 22. The composition of claim 19, wherein the composition comprises 6%-8% acidic species of adalimumab. 23. The composition of claim 19, wherein the adalimumab is produced in a mammalian host cell grown in cell culture. 24. The composition of claim 23, wherein the mammalian host cell is selected from the group consisting of a CHO cell, an NSO cell, a COS cell, and an SP2 cell. 25. The composition of claim 24, wherein the mammalian host cell is a CHO cell. 26. A pharmaceutical composition suitable for administration to a subject comprising the composition of claim 25 and a pharmaceutically acceptable carrier. 27. The pharmaceutical composition of claim 26, wherein adalimumab is present in the pharmaceutical composition at a concentration of 0.1-250 mg/ml. 28. The pharmaceutical composition of claim 26, wherein the pharmaceutical composition comprises one or more excipient. 29. The pharmaceutical composition of claim 28, wherein the one or more excipient is selected from the group consisting of a buffer, an isotonic agent, a surfactant or a combination thereof. 30. A method for treating a subject in need thereof, comprising administering to the subject the pharmaceutical composition of claim 26, thereby treating the subject.

Details for Patent 9,683,033

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Abbvie Inc.	HUMIRA	adalimumab	Injection	125057	December 31, 2002	9,683,033	2036-01-28
Abbvie Inc.	HUMIRA	adalimumab	Injection	125057	February 21, 2008	9,683,033	2036-01-28
Abbvie Inc.	HUMIRA	adalimumab	Injection	125057	April 24, 2013	9,683,033	2036-01-28
Abbvie Inc.	HUMIRA	adalimumab	Injection	125057	September 23, 2014	9,683,033	2036-01-28
Abbvie Inc.	HUMIRA	adalimumab	Injection	125057	November 23, 2015	9,683,033	2036-01-28
Abbvie Inc.	HUMIRA	adalimumab	Injection	125057	March 09, 2016	9,683,033	2036-01-28

International Patent Family for US Patent 9,683,033

Country	Patent Number	Estimated Expiration
World Intellectual Property Organization (WIPO)	2014159554
World Intellectual Property Organization (WIPO)	2014143205
World Intellectual Property Organization (WIPO)	2014143184
World Intellectual Property Organization (WIPO)	2014142882
World Intellectual Property Organization (WIPO)	2013158279
World Intellectual Property Organization (WIPO)	2013158275