Claims for Patent: 9,505,834

Summary for Patent: 9,505,834

Title:	Methods for controlling the galactosylation profile of recombinantly-expressed proteins
Abstract:	The present invention relates to methods for modulating the glycosylation profile of recombinantly-expressed proteins. In particular, the present invention relates to methods of controlling the galactosylation profile of recombinantly-expressed proteins by supplementing production medium, e.g., a hydrolysate-based or a chemically defined medium, with manganese and/or D-galactose
Inventor(s):	Bengea; Cornelia (Auburn, MA), Rives; Lisa M. (Natick, MA), Hossler; Patrick (Westborough, MA)
Assignee:	AbbVie Inc. (North Chicago, IL)
Application Number:	15/086,739
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 9,505,834
Patent Claims:	1. A method for increasing the galactosylation level of a recombinantly expressed antibody comprising the heavy and light chain variable domains of adalimumab, comprising supplementing a chemically defined (CD) cell culture media used in the expression of the antibody with a manganese supplement, thereby increasing the galactosylation level of the antibody, wherein the galactosylation level of the antibody is increased as compared to the galactosylation level of the antibody recombinantly expressed in the chemically defined cell culture media which is not supplemented with the manganese supplement. 2. The method of claim 1, wherein the antibody is adalimumab. 3. The method of claim 1, wherein the manganese supplement is a biologically acceptable manganese salt. 4. The method of claim 3, wherein the biologically acceptable manganese salt is manganese (II) chloride. 5. The method of claim 1, wherein the media is supplemented with a sufficient amount of the manganese supplement to achieve a manganese concentration in the media of 1-100 .mu.M. 6. The method of claim 1, wherein the media is supplemented with a sufficient amount of the manganese supplement to achieve a manganese concentration in the media of 1-40 .mu.M. 7. The method of claim 1, wherein the media is supplemented with a sufficient amount of the manganese supplement to achieve a manganese concentration in the media of 40-100 .mu.M. 8. The method of claim 1, wherein the media is supplemented with a sufficient amount of the manganese supplement to achieve a manganese concentration in the media selected from the group consisting of 1.0, 10, 20, 25, 40, 50, 60, 75, 80, and 100 .mu.M. 9. The method of claim 1, wherein the media is further supplemented with a galactose supplement. 10. The method of claim 9, wherein the galactose supplement is a biologically acceptable galactose containing compound. 11. The method of claim 10, wherein the biologically acceptable galactose containing compound is D-(+)-galactose. 12. The method of claim 9, wherein the media is supplemented with a sufficient amount of the galactose supplement to achieve a galactose concentration in the media of 1-100 mM. 13. The method of claim 1, wherein the method further comprises culturing a mammalian cell expressing the antibody in the media. 14. The method of claim 13, wherein the mammalian cell has been adapted for growth in a CD cell culture media. 15. The method of claim 14, wherein the mammalian cell is a CHO cell or an NS0 cell. 16. A process for producing an antibody comprising the heavy and light chain variable domains of adalimumab, the process comprising culturing a mammalian cell which produces the antibody in a chemically defined cell (CD) culture media that comprises a concentration of manganese of 1-100 .mu.M, wherein said concentration of manganese is sufficient to increase the galactosylation level of the antibody as compared to the galactosylation level of the antibody produced in the chemically defined cell culture media that does not comprise said concentration of manganese, thereby producing the antibody. 17. The process of claim 16, wherein the antibody is adalimumab. 18. The process of claim 17, wherein at least 10% of the total N-linked oligosaccharides present on said adalimumab are of a galactose-containing fucosylated biantennary oligosaccharide form (sum of NA1F+NA2F). 19. The process of claim 16, wherein the media comprises a sufficient amount of manganese to achieve a manganese concentration in the media of 1-40 .mu.M. 20. The process of claim 16, wherein the media comprises a sufficient amount of manganese to achieve a manganese concentration in the media of 40-100 .mu.M. 21. The process of claim 16, wherein the media further comprises galactose. 22. The process of claim 21, wherein the media comprises a sufficient amount of galactose to achieve a galactose concentration in the media of 1-100 mM. 23. The process of claim 16, wherein the culturing is done in a suspension culture. 24. The process of claim 16, wherein the culturing is done in a bioreactor. 25. The process of claim 16, wherein the mammalian cell is a CHO cell or an NS0 cell. 26. The process of claim 16, wherein the process is a fed batch process. 27. The process of claim 16, wherein the media is selected from the group consisting of production media and feed media. 28. The process of claim 16, further comprising recovering the antibody from the cell culture media. 29. The process of claim 28, further comprising purifying the antibody from the cell culture media. 30. The process of claim 29, further comprising quantifying the levels of galactose-containing fucosylated biantennary oligosaccharides (NA1F and NA2F) and/or agalactosyl fucosylated biantennary oligosaccharides (NGA2F and NGA2F-GlcNAc)present on the antibody.

Details for Patent 9,505,834

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Abbvie Inc.	HUMIRA	adalimumab	Injection	125057	12/31/2002		2031-04-27
Abbvie Inc.	HUMIRA	adalimumab	Injection	125057	02/21/2008		2031-04-27
Abbvie Inc.	HUMIRA	adalimumab	Injection	125057	04/24/2013		2031-04-27
Abbvie Inc.	HUMIRA	adalimumab	Injection	125057	09/23/2014		2031-04-27
Abbvie Inc.	HUMIRA	adalimumab	Injection	125057	11/23/2015		2031-04-27