Claims for Patent: 9,181,337

Summary for Patent: 9,181,337

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), Perez Thiele; Mayda (Vega Alta, PR), Zeng; Xiaobei (Carolina, PR), Wong; Chee Furng (Singapore, SG), Kaymakcalan; Zehra (Westborough, MA), Jing; Ying (Wellesley, MA), Chumsae; Christopher (North Andover, MA)
Assignee:	AbbVie, Inc. (North Chicago, IL)
Application Number:	14/077,988
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 9,181,337
Patent Claims:	1. A composition comprising a human anti-TNF.alpha. antibody, wherein less than 65% of the lysine variant species in said composition 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. 2. The composition of claim 1, wherein said human anti-TNF.alpha.antibody is adalimumab. 3. The composition of claim 2, wherein less than 60% of the lysine variant species in said composition have zero C-terminal lysines (Lys 0). 4. The composition of claim 2, wherein 50-60% of the lysine variant species in said composition have zero C-terminal lysines (Lys 0). 5. The composition of claim 2, wherein less than 55% of the lysine variant species in said composition have zero C-terminal lysines (Lys 0). 6. The composition of claim 1, wherein said composition is lyophilized. 7. A composition comprising a human anti-TNF.alpha. antibody, wherein the sum of the lysine variant species having one C-terminal lysine (Lys 1) and the lysine variant species having two C-terminal lysines (Lys 2) in said composition is greater than 35%, 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. 8. The composition of claim 7, wherein said human anti-TNF.alpha. antibody is adalimumab. 9. The composition of claim 8, wherein the sum of the lysine variant species having one C-terminal lysine (Lys 1) and the lysine variant species having two C-terminal lysines (Lys 2) in said composition is greater than 40%. 10. The composition of claim 8, wherein the sum of the lysine variant species having one C-terminal lysine (Lys 1) and the lysine variant species having two C-terminal lysines (Lys 2) in said composition is 40-50%. 11. The composition of claim 8, wherein the sum of the lysine variant species having one C-terminal lysine (Lys 1) and the lysine variant species having two C-terminal lysines (Lys 2) in said composition is greater than 50%. 12. The composition of claim 8, wherein greater than 25% of the lysine variant species in said composition have one C-terminal lysine (Lys 1). 13. The composition of claim 8, wherein greater than 30% of the lysine variant species in said composition have one C-terminal lysine (Lys 1). 14. The composition of claim 7, wherein said composition is lyophilized. 15. A pharmaceutical formulation comprising the composition of claim 1 and a pharmaceutically acceptable carrier. 16. A pharmaceutical formulation comprising the composition of claim 7 and a pharmaceutically acceptable carrier. 17. A pharmaceutical formulation comprising a composition comprising a human anti-TNF.alpha. antibody, wherein less than 65% of the lysine variant species in said composition 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; and a pharmaceutically acceptable carrier. 18. A pharmaceutical formulation comprising a composition comprising a human anti-TNF.alpha. antibody, wherein the sum of the lysine variant species having one C-terminal lysine (Lys 1) and the lysine variant species having two C-terminal lysines (Lys 2) in said composition is greater than 35%, 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; and a pharmaceutically acceptable carrier. 19. The composition of claim 2, wherein said adalimumab is produced in a mammalian host cell grown in cell culture. 20. The composition of claim 19, 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. 21. The composition of claim 8, wherein said adalimumab is produced in a mammalian host cell grown in cell culture. 22. The composition of claim 21, 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. 23. The pharmaceutical composition of claim 17, wherein said human anti-TNF.alpha. antibody is adalimumab. 24. The pharmaceutical composition of claim 23, wherein less than 60% of the lysine variant species in said composition have zero C-terminal lysines (Lys 0). 25. The pharmaceutical composition of claim 23, wherein adalimumab is present in said pharmaceutical composition at a concentration of 25-100 mg/ml. 26. The pharmaceutical composition of claim 23, wherein said pharmaceutical composition comprises one or more excipient selected from the group consisting of a buffering agent, a surfactant and a polyol, or a combination thereof. 27. The pharmaceutical composition of claim 18, wherein said human anti-TNF.alpha. antibody is adalimumab. 28. The pharmaceutical composition of claim 27, wherein the sum of the lysine variant species having one C-terminal lysine (Lys 1) and the lysine variant species having two C-terminal lysines (Lys 2) in said composition is greater than 40%. 29. The pharmaceutical composition of claim 27, wherein the sum of the lysine variant species having one C-terminal lysine (Lys 1) and the lysine variant species having two C-terminal lysines (Lys 2) in said composition is 40-50%. 30. The pharmaceutical composition of claim 27, wherein the sum of the lysine variant species having one C-terminal lysine (Lys 1) and the lysine variant species having two C-terminal lysines (Lys 2) in said composition is greater than 50%.

Details for Patent 9,181,337

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