Claims for Patent: 9,499,614

Summary for Patent: 9,499,614

Title:	Methods for modulating protein glycosylation profiles of recombinant protein therapeutics using monosaccharides and oligosaccharides
Abstract:	The present invention relates to the field of protein production, and in particular to methods and compositions for modulating glycosylation of proteins expressed in host cells.
Inventor(s):	Hossler; Patrick (Westborough, MA), McDermott; Sean (Warwick, RI), Racicot; Christopher (Auburn, MA), Correia; Ivan (Winchester, MA)
Assignee:	AbbVie Inc. (North Chicago, IL)
Application Number:	14/209,821
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 9,499,614
Patent Claims:	1. A method of producing a composition comprising an immunoglobulin with an increased level of mannosylated N-glycans and/or a decreased level of fucosylated N-glycans, wherein the immunoglobulin comprises a light chain variable region of SEQ ID NO:1 and a heavy chain variable region of SEQ ID NO:2, said method comprising: culturing a mammalian host cell expressing said immunoglobulin in cell culture media supplemented with 5 mM-100 mM sucrose, thereby producing said composition comprising said immunoglobulin with an increased level of mannosylated N-glycans and/or a decreased level of fucosylated N-glycans as compared to a control, wherein said control is a composition comprising the immunoglobulin produced by culturing the mammalian host cell expressing said immunoglobulin in cell culture media which is not supplemented with sucrose. 2. The method of claim 1, further comprising purifying said composition comprising said immunoglobulin with a modulated glycosylation profile. 3. The method of claim 1, wherein the immunoglobulin is an antibody or antigen-binding portion thereof. 4. The method of claim 1, wherein the immunoglobulin is adalimumab, or an antigen binding fragment thereof. 5. The method of claim 1, wherein the immunoglobulin is a dual variable domain immunoglobulin (DVD-Ig). 6. The method of claim 1, wherein the immunoglobulin is selected from the group consisting of a TVD-IG, a half-body and a RAB. 7. The method of claim 1, further comprising supplementing the cell culture media with tagatose. 8. The method of claim 7, wherein the cell culture media is supplemented with a sufficient amount of tagatose to achieve a tagatose concentration selected from the group consisting of about 1 mM, about 5 mM, about 7 mM, about 10 mM, about 20 mM, about 30 mM, about 40 mM, about 50 mM, about 60 mM, about 70 mM, about 80 mM, about 90 mM and about 100 mM. 9. The method of claim 8, wherein the tagatose concentration is 30 mM. 10. The method of claim 1 wherein the cell culture media is supplemented with a sufficient amount of sucrose to achieve a sucrose concentration selected from the group consisting of about 5 mM, about 7 mM, about 10 mM, about 20 mM, about 30 mM, about 40 mM, about 50 mM, about 60 mM, about 70 mM, about 80 mM, about 90 mM and about 100 mM. 11. The method of claim 10, wherein the sucrose concentration is 30 mM. 12. The method of claim 1, wherein the method produces a composition comprising an immunoglobulin with an overall increase in the mannosylated N-glycan level. 13. The method of claim 12, wherein the increase in the mannosylation level comprises an increase in the level of a high mannose N-glycan oligosaccharide selected from the group consisting of Man 5 glycan, Man 6 glycan, Man 7 glycan and Man 8 glycan. 14. The method of claim 1, wherein the method produces a composition comprising an immunoglobulin with an overall decrease in the fucosylated N-glycan level. 15. The method of claim 14, wherein the overall decrease in the fucosylation level comprises an increase in NGA2F-GlcNAc and NA1F-GlcNAc and a decrease in the level of NGA2F, and NA1F in said immunoglobulin. 16. The method of claim 1, wherein the decrease in the fucosylation level comprises a decrease in the level of NGA2F, and/or NA1F in said immunoglobulin. 17. The method of claim 1, wherein said host cell is a CHO cell. 18. A method of producing a composition comprising adalimumab with a modulated glycosylation profile, said method comprising: culturing a mammalian host cell expressing adalimumab in cell culture media supplemented with 5 mM-100 mM sucrose, thereby producing said composition comprising adalimumab with an increased level of mannosylated N-glycans and/or a decreased level of fucosylated N-glycans as compared to a control, wherein said control is a composition comprising adalimumab produced by culturing the mammalian host cell expressing adalimumab in cell culture media which is not supplemented with sucrose. 19. A method of producing a composition comprising an antibody, or antigen binding fragment thereof, with a modulated glycosylation profile, wherein the antibody or antigen-binding portion thereof comprises a light chain variable region of SEQ ID NO:1 and a heavy chain variable region of SEQ ID NO:2, said method comprising: culturing a mammalian host cell expressing said antibody, or antigen binding fragment thereof, in cell culture media supplemented with 5 mM-100 mM sucrose, thereby producing said composition comprising said antibody, or antigen binding fragment thereof, with an overall increase in the level of mannosylated N-glycans and an overall decrease in the level of fucosylated N-glycans as compared to a control, wherein said control is a composition comprising the antibody, or antigen binding fragment thereof, produced by culturing the mammalian host cell expressing said antibody, or antigen binding fragment thereof, in cell culture media which is not supplemented with sucrose. 20. The method of claim 19, wherein the antibody is adalimumab, or antigen binding fragment thereof. 21. A method of producing a composition comprising an antibody, or antigen binding fragment thereof, with a modulated glycosylation profile, wherein the antibody or antigen-binding portion thereof comprises a light chain variable region of SEQ ID NO:1 and a heavy chain variable region of SEQ ID NO:2, said method comprising: culturing a mammalian host cell expressing said antibody, or antigen binding fragment thereof, in cell culture media supplemented with 5 mM-100 mM sucrose, thereby producing said composition comprising said antibody, or antigen binding fragment thereof, with an increase in antibody-dependent cellular cytotoxicity (ADCC) response as compared to a control, wherein said control is a composition comprising the antibody, or antigen binding fragment thereof, produced by culturing the mammalian host cell expressing said antibody, or antigen binding fragment thereof, in cell culture media which is not supplemented with sucrose. 22. The method of claim 21, wherein the antibody is adalimumab, or antigen binding fragment thereof.

Details for Patent 9,499,614

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Abbvie Inc.	HUMIRA	adalimumab	Injection	125057	12/31/2002		2033-03-14
Abbvie Inc.	HUMIRA	adalimumab	Injection	125057	02/21/2008		2033-03-14
Abbvie Inc.	HUMIRA	adalimumab	Injection	125057	04/24/2013		2033-03-14
Abbvie Inc.	HUMIRA	adalimumab	Injection	125057	09/23/2014		2033-03-14
Abbvie Inc.	HUMIRA	adalimumab	Injection	125057	11/23/2015		2033-03-14
Abbvie Inc.	HUMIRA	adalimumab	Injection	125057	03/09/2016		2033-03-14
Abbvie Inc.	HUMIRA	adalimumab	Injection	125057	10/17/2016		2033-03-14