Claims for Patent: 9,499,616

Summary for Patent: 9,499,616

Title:	Modulated lysine variant species compositions and methods for producing and using the same
Abstract:	The instant invention relates to modulated lysine variant species compositions comprising a protein, e.g., an antibody, or antigen-binding portion thereof, and methods, e.g., cell culture and/or protein purification methods, for producing such modulated lysine variant species compositions. Methods for using such compositions to treat a disorder, e.g., a disorder in which TNF.alpha. is detrimental, are also provided.
Inventor(s):	Subramanian; Kartik (Northborough, MA), Thiele; Mayda Perez (Vega Alta, PR), Zeng; Xiaobei (Carolina, PR), Wong; Chee Furng (Singapore, SG), Kaymakcalan; Zehra (Westborough, MA), Jing; Ying (Wellesley, MA), Chumsae; Christopher M. (North Andover, MA)
Assignee:	ABBVIE INC. (Chicago, IL)
Application Number:	14/923,966
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 9,499,616
Patent Claims:	1. A method for producing a composition comprising a human anti-TNF.alpha. antibody, comprising culturing a cell producing the antibody in a cell culture media comprising an amount of one or more basic amino acids sufficient to produce a composition comprising the antibody in which less than 65% of the lysine variant species of the antibody have zero C-terminal lysines (Lys 0), wherein the lysine variant species include the main peak and peaks that elute at a relative residence time later than the main peak, as detected using weak cation-exchange chromatography, and wherein the antibody comprises a light chain variable region (LCVR) having a CDR1 domain comprising the amino acid sequence of SEQ ID NO:7, a CDR2 domain comprising the amino acid sequence of SEQ ID NO:5, and a CDR3 domain comprising the amino acid sequence of SEQ ID NO:3; and a heavy chain variable region (HCVR) having a CDR1 domain comprising the amino acid sequence of SEQ ID NO:8, a CDR2 domain comprising the amino acid sequence of SEQ ID NO:6, and a CDR3 domain comprising the amino acid sequence of SEQ ID NO:4. 2. The method of claim 1, wherein the antibody is adalimumab. 3. The method of claim 2, wherein the one or more amino acids in the cell culture media is selected from the group consisting of arginine, lysine, histidine, ornithine, and combinations thereof. 4. The method of claim 3, wherein the one or more amino acids in the cell culture media is ornithine. 5. The method of claim 3, wherein the one or more amino acids in the cell culture media is arginine. 6. The method of claim 5, wherein the arginine concentration in the cell culture media is 6 to 9 g/L. 7. The method of claim 5, wherein the arginine concentration in the cell culture media is 6 g/L or more, 8 g/L or more, or 9 g/L or more. 8. The method of claim 3, wherein the one or more amino acids in the cell culture media is lysine. 9. The method of claim 8, wherein the lysine concentration in the cell culture media is 4 to 10 g/L. 10. The method of claim 8, wherein the lysine concentration in the cell culture media is 4 g/L or more, 8 g/L or more, or 10 g/L or more. 11. The method of claim 3, wherein the one or more amino acids in the cell culture media is histidine. 12. The method of claim 11, wherein the histidine concentration in the cell culture media is 8 g/L or more. 13. The method of claim 1, wherein 61% or less of the lysine variant species of said antibody have zero C-terminal lysines (Lys 0). 14. The method of claim 1, wherein 60% or less of the lysine variant species of said antibody have zero C-terminal lysines (Lys 0). 15. The method of claim 1, wherein 58% or less of the lysine variant species of said antibody have zero C-terminal lysines (Lys 0). 16. The method of claim 1, wherein 55% or less of the lysine variant species of said antibody have zero C-terminal lysines (Lys 0). 17. The method of claim 1, wherein 48% or less of the lysine variant species of said antibody have zero C-terminal lysines (Lys 0). 18. The method of claim 1, wherein the cell is a mammalian cell. 19. The method of claim 18, wherein the mammalian cell is selected from the group consisting of CHO cells, NS0 myeloma cells, COS cells, and SP2 cells. 20. A method for producing a composition comprising a human anti-TNF.alpha. antibody, comprising culturing a cell producing the antibody in a cell culture media comprising an amount of lysine sufficient to produce a composition comprising the antibody in which less than 65% of the lysine variant species of the antibody have zero C-terminal lysines (Lys 0), wherein the lysine variant species include the main peak and peaks that elute at a relative residence time later than the main peak, as detected using weak cation-exchange chromatography, and wherein the human anti-TNF.alpha. antibody comprises a light chain variable region (LCVR) having a CDR1 domain comprising the amino acid sequence of SEQ ID NO:7, a CDR2 domain comprising the amino acid sequence of SEQ ID NO:5, and a CDR3 domain comprising the amino acid sequence of SEQ ID NO:3; and a heavy chain variable region (HCVR) having a CDR1 domain comprising the amino acid sequence of SEQ ID NO:8, a CDR2 domain comprising the amino acid sequence of SEQ ID NO:6, and a CDR3 domain comprising the amino acid sequence of SEQ ID NO:4. 21. The method of claim 20, wherein the antibody is adalimumab. 22. The method of claim 21, wherein the lysine concentration in the cell culture media is 4 to 10 g/L. 23. The method of claim 21, wherein the lysine concentration in the cell culture media is 4 g/L or more. 24. The method of claim 21, wherein the lysine concentration in the cell culture media is 8 g/L or more. 25. The method of claim 21, wherein the lysine concentration in the cell culture media is 10 g/L or more. 26. The method of claim 21, wherein 61% or less of the lysine variant species of said antibody have zero C-terminal lysines (Lys 0). 27. The method of claim 21, wherein 55% or less of the lysine variant species of said antibody have zero C-terminal lysines (Lys 0). 28. The method of claim 21, wherein 48% or less of the lysine variant species of said antibody have zero C-terminal lysines (Lys 0). 29. The method of claim 21, wherein the cell is a mammalian cell. 30. The method of claim 29, wherein the mammalian cell is selected from the group consisting of CHO cells, NS0 myeloma cells, COS cells, and SP2 cells.

Details for Patent 9,499,616

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Abbvie Inc.	HUMIRA	adalimumab	Injection	125057	12/31/2002		2033-10-18
Abbvie Inc.	HUMIRA	adalimumab	Injection	125057	02/21/2008		2033-10-18
Abbvie Inc.	HUMIRA	adalimumab	Injection	125057	04/24/2013		2033-10-18
Abbvie Inc.	HUMIRA	adalimumab	Injection	125057	09/23/2014		2033-10-18
Abbvie Inc.	HUMIRA	adalimumab	Injection	125057	11/23/2015		2033-10-18
Abbvie Inc.	HUMIRA	adalimumab	Injection	125057	03/09/2016		2033-10-18