Claims for Patent: 9,663,810

Summary for Patent: 9,663,810

Title:	Methods of cell culture
Abstract:	Polypeptide preparations having target levels of glycans, and methods of producing such polypeptide preparations using putrescine, are described.
Inventor(s):	Prentice; Holly (Carlisle, MA)
Assignee:	Momenta Pharmaceuticals, Inc. (Cambridge, MA)
Application Number:	14/941,984
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 9,663,810
Patent Claims:	1. A method of producing a recombinant protein preparation having a target value of fucosylated glycans, the method comprising: (a) providing a cell genetically engineered to express a recombinant protein; (b) culturing the cell in a culture medium comprising 0.1 mg/L to 10 mg/L putrescine under conditions in which the cell expresses the recombinant protein; and (c) harvesting a preparation of the recombinant protein produced by the cell that meets the target value of the fucosylated glycans wherein the target value of fucosylated glycans is a level at least 10% higher than a level of fucosylated glycans in a preparation produced by culturing the cell in the medium not comprising 0.1 mg/L to 10 mg/L putrescine. 2. The method of claim 1, wherein the recombinant protein is a recombinant therapeutic protein. 3. The method of claim 1, wherein the recombinant protein is a recombinant therapeutic antibody. 4. The method of claim 1, wherein the target value is a level of fucosylated glycans in a reference therapeutic protein. 5. The method of claim 1, wherein the target value is a level of fucosylated glycans in a reference therapeutic antibody. 6. The method of claim 1, further comprising evaluating a level of fucosylated glycans in the recombinant protein preparation. 7. The method of claim 1, wherein the target value is: (a) 70% to 100% fucosylated glycans. 8. The method of claim 1, wherein the culture medium further comprises one or more of lysine, ammonium, DMSO, copper, glucose, a growth factor, a vitamin, a lipid, and a peptone. 9. The method of claim 4, wherein the reference therapeutic protein is selected from the group consisting of: abatacept, abciximab, adalimumab, aflibercept, alefacept, alemtuzumab, basiliximab, bevacizumab, belatacept, certolizumab, cetuximab, daclizumab, eculizumab, efalizumab, entanercept, gemtuzumab, ibritumomab, infliximab, muromonab-CD3, natalizumab, omalizumab, palivizumab, panitumumab, ranibizumab, rilonacept, rituximab, tositumomab, and trastuzumab. 10. A method of producing a recombinant protein preparation, the method comprising: (a) providing a target value of fucosylated glycans; (b) providing a cell genetically engineered to express a recombinant protein; (c) culturing the cell in a culture medium comprising 0.1 mg/L to 10 mg/L putrescine under conditions in which the cell expresses the recombinant protein; (d) harvesting a preparation of the recombinant protein produced by the cell; and (e) formulating the preparation into a drug product if the preparation meets the target value of fucosylated glycans wherein the target value of fucosylated glycans is a level at least 10% higher than a level of fucosylated glycans in a preparation produced by culturing the cell in the medium not comprising 0.1 mg/L to 10 mg/L putrescine. 11. The method of claim 10, further comprising evaluating a level of fucosylated glycans in the recombinant protein preparation. 12. The method of claim 10, wherein the culture medium further comprises one or more of lysine, ammonium, DMSO, copper, glucose, a growth factor, a vitamin, a lipid, and a peptone. 13. The method of claim 6 or 11, further comprising recording the evaluated level of fucosylated glycans in a batch record for the preparation. 14. A method of increasing a level of fucosylated glycans in a recombinant protein preparation, the method comprising: (a) providing a cell genetically engineered to express a recombinant protein; (b) culturing the cell in a culture medium comprising 0.1 mg/L to 10 mg/L putrescine under conditions in which the cell expresses the recombinant protein; and (c) harvesting a preparation of the recombinant protein produced by the cell, wherein the preparation has a level of fucosylated glycans, that is at least 10% higher than a level of fucosylated glycans in a preparation of the recombinant protein produced by culturing the cell in the medium not comprising 0.1 mg/L to 10 mg/L putrescine. 15. The method of claim 14, further comprising measuring a level of fucosylated glycans. 16. The method of claim 14, wherein the culture medium further comprises one or more of lysine, ammonium, DMSO, copper, glucose, a growth factor, a vitamin, a lipid, and a peptone. 17. The method of claim 15, further comprising recording the evaluated level of fucosylated glycans in a batch record for the preparation. 18. The method of any one of claims 1, 10, or 14, wherein the culturing step comprises a first stage and a second stage, wherein the first stage comprises culturing the cell in the culture medium comprising a first level of putrescine, and the second stage comprises culturing the cell in the culture medium comprising a second level of putrescine which is increased relative to the first level. 19. The method of claim 18, wherein the second level is 0.1 mg/L to 10 mg/L putrescine. 20. The method of claim 18, wherein the first stage comprises culturing the cell in the first level of putrescine for 1 to 8 days. 21. The method of claim 20, wherein the second stage comprises culturing the cell in the second level of putrescine for 1 to 12 days. 22. The method of any one of claims 1, 10, or 14, wherein the cell is a Chinese Hamster Ovary (CHO) cell. 23. The method of any one of claims 1, 10 or 14, wherein the recombinant protein is selected from the group consisting of: abatacept, abciximab, adalimumab, aflibercept, alefacept, alemtuzumab, basiliximab, bevacizumab, belatacept, certolizumab, cetuximab, daclizumab, eculizumab, efalizumab, entanercept, gemtuzumab, ibritumomab, infliximab, muromonab-CD3, natalizumab, omalizumab, palivizumab, panitumumab, ranibizumab, rilonacept, rituximab, tositumomab, and trastuzumab. 24. The method of any one of claims 1, 10, or 14, wherein the culturing step comprises adding putrescine to the culture medium.

Details for Patent 9,663,810

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Centocor Ortho Biotech Products, L.p.	ORTHOCLONE OKT3	muromanab-cd3	Injection	103463	09/14/1992		2039-02-26
Janssen Biotech, Inc.	REOPRO	abciximab	Injection	103575	12/22/1994		2039-02-26
Genentech, Inc.	RITUXAN	rituximab	Injection	103705	11/26/1997		2039-02-26
Idec Pharmaceuticals Corp.	RITUXAN	rituximab	Injection	103737	02/19/2002		2039-02-26