Claims for Patent: 9,475,858

Summary for Patent: 9,475,858

Title:	Cell culture process
Abstract:	A method for producing recombinant polypeptides, including antibodies, having targeted levels of carboxyl terminal (C-terminal) lysine or arginine residues is presented. The method involves culturing cells expressing said polypeptides in cell culture medium having sufficient levels of lysine, arginine, and/or agents that change intracellular pH. Culturing the cells under such conditions does not affect cell growth, cell viability, or titer.
Inventor(s):	Prentice; Holly (Carlisle, MA)
Assignee:	Momenta Pharmaceuticals, Inc. (Cambridge, MA)
Application Number:	14/131,005
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 9,475,858
Patent Claims:	1. A method of manufacturing a preparation of a recombinant antibody, comprising: culturing a cell in a medium comprising 2 g/L lysine to 8 g/L lysine under conditions in which the cell expresses a recombinant antibody; isolating the recombinant antibody, thereby producing a preparation of the recombinant antibody; and formulating the preparation into a drug product if the preparation meets a target value of C-terminal variants of the recombinant antibody, wherein the C-terminal variants differ in amino acid sequence only by the presence or absence of a lysine at their carboxyl termini. 2. The method of claim 1, further comprising providing the target value of C-terminal variants of the recombinant antibody. 3. The method of claim 1, wherein the medium comprises 3 g/L lysine to 7 g/L lysine. 4. The method of claim 1, wherein the medium comprises 4 g/L lysine to 6 g/L lysine. 5. The method of claim 1, wherein the medium comprises 5 g/L lysine. 6. The method of claim 1, wherein the method further comprises measuring a level of one or more C-terminal variants of the recombinant antibody in the preparation. 7. The method of claim 1, wherein the C-terminal variants of the recombinant antibody comprise one or more of a K1 lysine variant of the recombinant antibody and a K2 lysine variant of the recombinant antibody. 8. The method of claim 7, wherein the level of one or more of K1 lysine variant and K2 lysine variant in the preparation is increased relative to a preparation of the recombinant antibody produced using a medium not comprising 2 g/L lysine to 8 g/L lysine. 9. The method of claim 7, wherein the method further comprises providing a target value of one or more of K1 lysine variants of the recombinant antibody and K2 lysine variants of the recombinant antibody. 10. The method of claim 9, wherein the target value of K1 lysine variants of the recombinant antibody is 12% to 25% of the recombinant antibody in the preparation. 11. The method of claim 9, wherein the target value of K1 lysine variants of the recombinant antibody is 15% to 20% of the recombinant antibody in the preparation. 12. The method of claim 9, wherein the target value of K2 lysine variants of the recombinant antibody is 2% to 6% of the recombinant antibody in the preparation. 13. The method of claim 9, wherein the target value of K2 lysine variants of the recombinant antibody is 3% to 5% of the recombinant antibody in the preparation. 14. The method of claim 1, wherein the cell is a CHO cell. 15. The method of claim 1, wherein the antibody is adalimumab. 16. The method of claim 1, wherein the medium has a pH of 6.8 to 7.0. 17. The method of claim 1, wherein the medium has a pH of 6.9. 18. The method of claim 1, wherein the cell is cultured at a temperature of 34.degree. C. to 37.degree. C. 19. The method of claim 1, wherein the cell is cultured at a temperature of 36.degree. C. 20. A method of manufacturing a preparation of a recombinant antibody, comprising: culturing a cell in a medium comprising 2 g/L arginine to 8 g/L arginine under conditions in which the cell expresses a recombinant antibody; isolating the recombinant antibody, thereby producing a preparation of the recombinant antibody; and formulating the preparation into a drug product if the preparation meets a target value of C-terminal variants of the recombinant antibody, wherein the C-terminal variants differ in amino acid sequence only by the presence or absence of a lysine at their carboxyl termini. 21. The method of claim 20, further comprising providing the target value of C-terminal variants of the recombinant antibody. 22. The method of claim 20, wherein the medium comprises 3 g/L arginine to 7 g/L arginine. 23. The method of claim 20, wherein the medium comprises 4 g/L arginine to 6 g/L arginine. 24. The method of claim 20, wherein the medium comprises 5 g/L arginine. 25. The method of claim 20, wherein the method further comprises measuring a level of one or more C-terminal variants of the recombinant antibody in the preparation. 26. The method of claim 20, wherein the C-terminal variants of the recombinant antibody comprise one or more of a K1 lysine variant of the recombinant antibody and a K2 lysine variant of the recombinant antibody. 27. The method of claim 26, wherein the level of one or more of K1 lysine variant and K2 lysine variant in the preparation is increased relative to a preparation of the recombinant antibody produced using a medium not comprising 2 g/L arginine to 8 g/L arginine. 28. The method of claim 26, wherein the method further comprises providing a target value of one or more of K1 lysine variants of the recombinant antibody and K2 lysine variants of the recombinant antibody. 29. The method of claim 28, wherein the target value of K1 lysine variants of the recombinant antibody is 12% to 25% of the recombinant antibody in the preparation. 30. The method of claim 28, wherein the target value of K1 lysine variants of the recombinant antibody is 15% to 20% of the recombinant antibody in the preparation. 31. The method of claim 28, wherein the target value of K2 lysine variants of the recombinant antibody is 2% to 6% of the recombinant antibody in the preparation. 32. The method of claim 28, wherein the target value of K2 lysine variants of the recombinant antibody is 3% to 5% of the recombinant antibody in the preparation. 33. The method of claim 20, wherein the cell is a CHO cell. 34. The method of claim 20, wherein the antibody is adalimumab. 35. The method of claim 20, wherein the medium has a pH of 6.8 to 7.0. 36. The method of claim 20, wherein the medium has a pH of 6.9. 37. The method of claim 20, wherein the cell is cultured at a temperature of 34.degree. C. to 37.degree. C. 38. The method of claim 20, wherein the cell is cultured at a temperature of 36.degree. C.

Details for Patent 9,475,858

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Abbvie Inc.	HUMIRA	adalimumab	Injection	125057	12/31/2002		2031-07-08
Abbvie Inc.	HUMIRA	adalimumab	Injection	125057	02/21/2008		2031-07-08
Abbvie Inc.	HUMIRA	adalimumab	Injection	125057	04/24/2013		2031-07-08
Abbvie Inc.	HUMIRA	adalimumab	Injection	125057	09/23/2014		2031-07-08
Abbvie Inc.	HUMIRA	adalimumab	Injection	125057	11/23/2015		2031-07-08
Abbvie Inc.	HUMIRA	adalimumab	Injection	125057	03/09/2016		2031-07-08