Claims for Patent: 9,359,434

Summary for Patent: 9,359,434

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:	14/842,933
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 9,359,434
Patent Claims:	1. A method for producing a composition comprising adalimumab, the method comprising culturing a mammalian cell producing adalimumab in cell culture media comprising 2 g/L to 11 g/L of each of one or more basic amino acids, to produce a composition comprising adalimumab, wherein the composition comprises less than 20% total acidic species of adalimumab, 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. 2. The method of claim 1, wherein the one or more basic amino acid is selected from the group consisting of arginine, lysine, ornithine, and histidine, and combinations thereof. 3. The method of claim 1, wherein the one or more basic amino acids comprises arginine. 4. The method of claim 1, wherein the one or more basic amino acids comprises lysine. 5. The method of claim 1, wherein the one or more basic amino acids comprises histidine. 6. The method of claim 1, wherein the one or more basic amino acids comprises ornithine. 7. The method of claim 1, wherein the cell culture media comprises 3 g/L to 11 g/L of each of the one or more basic amino acids. 8. The method of claim 1, wherein the cell culture media comprises 3 g/L to 8 g/L of each of the one or more basic amino acids. 9. The method of claim 1, wherein the cell culture media further comprises one or more of calcium and niacinamide. 10. The method of claim 1, wherein the composition comprises 9% to 15% total acidic species of adalimumab. 11. The method of claim 1, wherein the composition comprises less than 12% total acidic species of adalimumab. 12. The method of claim 1, wherein the composition comprises less than 10% total acidic species of adalimumab. 13. The method of claim 1, wherein the pH of the cell culture media is 6.7 or lower. 14. The method of claim 1, 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. 15. The method of claim 1, further comprising isolating the adalimumab. 16. The method of claim 1, wherein said culture media is production media, growth media, or both production media and growth media. 17. A method for producing a composition comprising adalimumab, the method comprising culturing a mammalian cell producing adalimumab in cell culture media comprising 2 g/L to 11 g/L_of each of one or more basic amino acids, wherein the one or more basic amino acids is present in the cell culture media at a concentration sufficient to produce a composition that has at least 10% fewer acidic species of adalimumab than a composition comprising adalimumab produced by culturing the cell in a cell culture media comprising less than 2 g/L of each of the one or more basic amino acids, 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. 18. The method of claim 17, wherein the one or more basic amino acid is selected from the group consisting of arginine, lysine, ornithine, and histidine, and combinations thereof. 19. The method of claim 17, wherein the one or more basic amino acids comprises arginine. 20. The method of claim 17, wherein the one or more basic amino acids comprises lysine. 21. The method of claim 17, wherein the one or more basic amino acids comprises histidine. 22. The method of claim 17, wherein the one or more basic amino acids comprises ornithine. 23. The method of claim 17, wherein the cell culture media comprises 3 g/L to 11 g/L of each of the one or more basic amino acids. 24. The method of claim 17, wherein the cell culture media comprises 3 g/L to 8 g/L of each of the one or more basic amino acids. 25. The method of claim 17, wherein the cell culture media further comprises one or more of calcium and niacinamide. 26. The method of claim 17, wherein the composition comprises 9% to 15% total acidic species of adalimumab. 27. The method of claim 17, wherein the composition comprises less than 10% total acidic species of adalimumab. 28. The method of claim 17, wherein the pH of the cell culture media is 6.7 or lower. 29. The method of claim 17, 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. 30. The method of claim 17, further comprising isolating the adalimumab.

Details for Patent 9,359,434

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Abbvie Inc.	HUMIRA	adalimumab	Injection	125057	12/31/2002		2032-04-20
Abbvie Inc.	HUMIRA	adalimumab	Injection	125057	02/21/2008		2032-04-20
Abbvie Inc.	HUMIRA	adalimumab	Injection	125057	04/24/2013		2032-04-20
Abbvie Inc.	HUMIRA	adalimumab	Injection	125057	09/23/2014		2032-04-20
Abbvie Inc.	HUMIRA	adalimumab	Injection	125057	11/23/2015		2032-04-20
Abbvie Inc.	HUMIRA	adalimumab	Injection	125057	03/09/2016		2032-04-20
Abbvie Inc.	HUMIRA	adalimumab	Injection	125057	10/17/2016		2032-04-20