Claims for Patent: 8,663,945

Summary for Patent: 8,663,945

Title:	Methods of producing anti-TNF-alpha antibodies in mammalian cell culture
Abstract:	The invention describes improved methods and compositions for producing a recombinant protein, e.g., an antibody, in mammalian cell culture. In addition, the invention provides improved cell culture media, including improved production media, feed solutions, and combination feeds, which may be used to improve protein productivity in mammalian cell culture.
Inventor(s):	Pla; Itzcoatl A. (Worcester, MA), Matuck; Joseph C. (Worcester, MA), Fann; John C. (Shrewsbury, MA), Schulz; Christof (Ayer, MA), Roy; Nicole A. (Worcester, MA), Bruton; David F. (Enfield, CT), McIntire; James (Castro Valley, CA), Yu-Hsiang; David Chang (Solana Beach, CA), Seewoester; Thomas (Simi Valley, CA)
Assignee:	AbbVie Inc (North Chicago, IL)
Application Number:	13/308,075
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 8,663,945
Patent Claims:	1. A method of producing an anti-TNF.alpha. antibody in a mammalian cell culture, said method comprising: a) culturing Chinese Hamster Ovary (CHO) cells comprising a nucleic acid encoding the antibody, or a fragment thereof, in a cell culture growth medium to form the mammalian cell culture; and b) culturing the CHO cells in a cell culture production medium, wherein glucose is added to the mammalian cell culture to maintain a glucose concentration of at least 2 g/L, such that the anti-TNF.alpha. antibody is produced, wherein the anti-TNF.alpha. antibody comprises a light chain variable region (LCVR) having a CDR3 domain comprising the amino acid sequence of SEQ ID NO:3, a CDR2 domain comprising the amino acid sequence of SEQ ID NO:5, and a CDR1 domain comprising the amino acid sequence of SEQ ID NO: 7, and comprises a heavy chain variable region (HCVR) having a CDR3 domain comprising the amino acid sequence of SEQ ID NO:4, a CDR2 domain comprising the amino acid sequence of SEQ ID NO: 6, and a CDR1 domain comprising the amino acid sequence of SEQ ID NO:8. 2. The method of claim 1, wherein the CHO cells are cultured in a cell culture growth medium at a temperature ranging from 32.degree. to 38.degree. C. 3. The method of claim 1, wherein the CHO cells are cultured in a cell production medium at a temperature ranging from 32.degree. to 38.degree. C. 4. The method of claim 1, wherein the CHO cells are cultured in a cell growth phase at a temperature of about 35.degree. C. 5. The method of claim 1, wherein the cell culture growth media comprises methotrexate. 6. The method of claim 1, wherein the cell culture production media comprises methotrexate. 7. The method of claim 1, wherein the cell culture growth media comprises at least one hydrolysate. 8. The method of claim 1, wherein the cell culture production media comprises at least one hydrolysate. 9. The method of claim 1, wherein the culturing of the CHO cells is performed in a large-scale cell culture. 10. The method of claim 1, wherein the mammalian cell culture further comprises a cell protectant. 11. The method of claim 1, wherein the glucose concentration is maintained from 2 g/L to 5 g/L. 12. A method of producing an anti-TNF.alpha. antibody in a mammalian cell culture, said method comprising: a) culturing Chinese Hamster Ovary (CHO) cells comprising a nucleic acid encoding the antibody, or a fragment thereof, in a cell culture growth medium to form the mammalian cell culture; and b) culturing the CHO cells in a cell culture production medium, wherein glucose is added to the mammalian cell culture to maintain a glucose concentration of at least 2 g/L, such that the anti-TNF.alpha. antibody is produced, wherein the anti-TNF.alpha. antibody comprises a light chain variable region (LCVR) comprising the amino acid sequence of SEQ ID NO:1, and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:2. 13. The method of claim 12, wherein the CHO cells are cultured in a cell culture growth medium at a temperature ranging from 32.degree. C. to 38.degree. C. 14. The method of claim 12, wherein the CHO cells are cultured in a cell production medium at a temperature ranging from 32.degree. to 38.degree. C. 15. The method of claim 12, wherein the CHO cells are cultured in a cell growth phase at a temperature of about 35.degree. C. 16. The method of claim 12, wherein the cell culture growth media comprises methotrexate. 17. The method of claim 12, wherein the cell culture production media comprises methotrexate. 18. The method of claim 12, wherein the cell culture growth media comprises at least one hydrolysate. 19. The method of claim 12, wherein the cell culture production media comprises at least one hydrolysate. 20. The method of claim 12, wherein the culturing of the CHO cells is performed in a large-scale cell culture. 21. The method of claim 12, wherein the mammalian cell culture further comprises a cell protectant. 22. The method of claim 12, wherein the glucose concentration is maintained from 2 g/L to 5 g/L. 23. A method of producing adalimumab in a mammalian cell culture, said method comprising: a) culturing Chinese Hamster Ovary (CHO) cells comprising a nucleic acid encoding adalimumab, or a fragment thereof, in a cell culture growth medium to form the mammalian cell culture; and b) culturing the CHO cells in a cell culture production medium, wherein glucose is added to the mammalian cell culture to maintain a glucose concentration of at least 2 g/L, such that adalimumab is produced. 24. The method of claim 23, wherein the CHO cells are cultured in a cell culture growth medium at a temperature ranging from 32.degree. C. to 38.degree. C. 25. The method of claim 23, wherein the CHO cells are cultured in a cell production medium at a temperature ranging from 32.degree. to 38.degree. C. 26. The method of claim 23, wherein the cell growth phase is at a temperature of about 35.degree. C. 27. The method of claim 23, wherein the cell culture growth media comprises methotrexate. 28. The method of claim 23, wherein the cell culture production media comprises methotrexate. 29. The method of claim 23, wherein the cell culture growth media comprises at least one hydrolysate. 30. The method of claim 23, wherein the cell culture production media comprises at least one hydrolysate. 31. The method of claim 23, wherein the culturing of the CHO cells is performed in a large-scale cell culture. 32. The method of claim 23, wherein the mammalian cell culture further comprises a cell protectant. 33. The method of claim 23, wherein the glucose concentration is maintained from 2 g/L to 5 g/L. 34. A method of producing an anti-TNF.alpha. antibody, or an antigen-binding fragment thereof, in a mammalian cell culture, said method comprising culturing Chinese Hamster Ovary (CHO) cells expressing the anti-TNF.alpha. antibody, or the antigen-binding fragment thereof, in a cell culture production medium, wherein glucose is added to the cell culture production medium to maintain a glucose concentration of at least 2 g/L, such that the anti-TNF.alpha. antibody, or the antigen-binding fragment thereof, is produced, wherein the anti-TNF.alpha. antibody, or the antigen-binding fragment thereof, comprises a light chain variable region (LCVR) having a CDR3 domain comprising the amino acid sequence of SEQ ID NO: 3, a CDR2 domain comprising the amino acid sequence of SEQ ID NO: 5, and a CDR1 domain comprising the amino acid sequence of SEQ ID NO: 7, and comprises a heavy chain variable region (HCVR) having a CDR3 domain comprising the amino acid sequence of SEQ ID NO: 4, a CDR2 domain comprising the amino acid sequence of SEQ ID NO: 6, and a CDR1 domain comprising the amino acid sequence of SEQ ID NO: 8. 35. The method of claim 34, wherein the glucose concentration is maintained from 2 g/L to 5 g/L. 36. The method of claim 34, wherein the anti-TNF.alpha. antibody, or antigen-binding fragment thereof, comprises a light chain variable region (LCVR) comprising the amino acid sequence of SEQ ID NO:1, and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:2. 37. The method of claim 36, wherein the glucose concentration is maintained from 2 g/L to 5 g/L. 38. The method of claim 34, wherein the anti-TNF.alpha. antibody is adalimumab, or an antigen-binding fragment thereof. 39. The method of claim 38, wherein the glucose concentration is maintained from 2 g/L to 5 g/L.

Details for Patent 8,663,945

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Abbvie Inc.	HUMIRA	adalimumab	Injection	125057	December 31, 2002		2026-09-13
Abbvie Inc.	HUMIRA	adalimumab	Injection	125057	February 21, 2008		2026-09-13
Abbvie Inc.	HUMIRA	adalimumab	Injection	125057	April 24, 2013		2026-09-13
Abbvie Inc.	HUMIRA	adalimumab	Injection	125057	September 23, 2014		2026-09-13
Abbvie Inc.	HUMIRA	adalimumab	Injection	125057	November 23, 2015		2026-09-13
Abbvie Inc.	HUMIRA	adalimumab	Injection	125057	March 09, 2016		2026-09-13
Abbvie Inc.	HUMIRA	adalimumab	Injection	125057	October 17, 2016		2026-09-13