Claims for Patent: 9,630,988

Summary for Patent: 9,630,988

Title:	Method for preparing a composition comprising highly concentrated antibodies by ultrafiltration
Abstract:	The present invention provides a method for preparing a composition comprising highly concentrated antibodies by ultrafiltration in batch concentration mode having a first constant feed rate step and a second controlled feed rate step.
Inventor(s):	Lau; Kelby (San Francisco, CA), Bender; Jean (Gaithersburg, MD), Tanaka; Saeko (Tokyo, JP), Wakayama; Rumiko (Tokyo, JP), Yamada; Hidenari (Tokyo, JP), Isoda; Tomonori (Tokyo, JP), Oh-Eda; Masayoshi (Tokyo, JP)
Assignee:	Chugai Seiyaku Kabushiki Kaisha (Tokyo, JP) Genentech, Inc. (South San Francisco, CA)
Application Number:	14/241,567
Patent Claims:	1. A method for preparing a composition comprising highly concentrated antibodies by ultrafiltration, wherein the method comprises the steps of: concentrating an antibody preparation by ultrafiltrating the preparation, said ultrafiltrating comprising: 1) regulating a feed flow rate of the preparation to allow a value of a feed pressure applied to an ultrafiltration membrane to increase to 85-100% of a specified maximum feed pressure of the ultrafiltration membrane; and 2) decreasing the feed flow rate to maintain or decrease the value of the feed pressure applied to the ultrafiltration membrane after step (1), wherein the feed flow rate in step (1) is maintained at 250 LMH (L/m.sup.2/hour) or higher and the feed flow rate in step (2) is decreased to 80LMH (L/m.sup.2/hour) or lower and wherein the antibody preparation directly after said ultrafiltrating has an antibody concentration above 200 g/L or a viscosity above 10 mPas. 2. The method of claim 1, wherein the antibody preparation is ultrafiltrated at ambient temperature. 3. The method of claim 1, wherein the antibody preparation is ultrafiltrated at a temperature from 10 to 30 degrees C. 4. The method of claim 1, wherein the antibody preparation is ultrafiltrated at a temperature from 15 to 30 degrees C. 5. The method of claim 1, wherein the concentrated preparation has the antibody concentration above 250 g/L or the viscosity above 40 mPa.s. 6. The method of claims 1, wherein the feed flow rate in step (1) is maintained at a constant rate. 7. The method of claim 1, wherein the maximum value of the feed pressure applied to the ultrafiltration membrane in step (1) is from 2.0 bar to 4.0 bar. 8. The method of claim 1, wherein the maximum value of the feed pressure applied to the ultrafiltration membrane in step (1) is 3.5 bar. 9. The method of claim 1, wherein step (1) is transitioned to step (2) when the retentate solution is concentrated to a protein concentration greater than 200 g/L. 10. The method of claim 1, wherein step (1) is transitioned to step (2) when the retentate solution is concentrated to a protein concentration equal or greater than 220 g/L. 11. The method of claim 1, wherein step (1) is transitioned to step (2) when the retentate solution is concentrated to a protein concentration equal to 240 g/L. 12. The method of claim 1, wherein the feed flow rate after the value of the feed pressure is decreased in step (2) is maintained at a constant rate. 13. The method of claim 1, wherein the value of the feed pressure applied to an ultrafiltration membrane in step (2) is maintained at a constant value. 14. The method of claim 1, wherein the value of the feed pressure applied to an ultrafiltration membrane in step (2) is maintained within 85-100% of the specified maximum feed pressure of the ultrafiltration membrane by reducing the feed flow rate. 15. The method of claim 13 or 14, wherein the feed flow rate is automatically regulated in a manner to maintain the feed pressure within 85-100% of the specified maximum feed pressure of the ultrafiltration membrane by a feedback control between a feed pressure and a feed flow rate. 16. The method of claim 1, further comprising between step (1) and step (2), the following step of: 3) recirculating the antibody preparation through the membrane with a permeate valve closed. 17. The method of claim 16, wherein the antibody preparation is recirculated with a retentate pressure control valve fully open. 18. The method of claim 16, wherein the feed flow rate in step (3) is maintained at a constant flow rate between 5 to 120 m LMH (L/m.sup.2/hour). 19. The method of claim 16, wherein the feed flow rate in step (3) is maintained at a constant flow rate between 10 to 80 LMH (L/m.sup.2/hour). 20. The method of claim 1, wherein the buffer composition of the antibody preparation is between 10 to 30 mmol/L histidine. 21. The method of claim 1, wherein the buffer composition of the antibody preparation is 20 mmol/L histidine. 22. The method of claim 1, wherein the pH of the antibody preparation is between pH 3.0 and pH 10.0. 23. The method of claim 1, wherein the pH of the antibody preparation is between pH 5.5 and pH 6.5. 24. The method of claim 1, wherein the pH of the antibody preparation is pH 6.0. 25. The method of claim 1, wherein the ultrafiltration membrane has a molecular weight cut off of 50 kDa or less. 26. The method of claim 1, wherein the ultrafiltration membrane has a molecular weight cut off of 30 kDa or less. 27. The method of claim 1, wherein the composition comprises highly concentrated anti-human interleukin-6 receptor monoclonal antibodies. 28. The method of claim 27, wherein the composition comprises highly concentrated tocilizumab. 29. A method for preparing a composition comprising highly concentrated proteins by ultrafiltration, wherein the method comprises the steps of: concentrating a protein preparation by ultrafiltrating the preparation, said ultrafiltrating comprising: 1) regulating a feed flow rate of the preparation to allow a value of a feed pressure applied to an ultrafiltration membrane to increase to 85-100% of a specified maximum feed pressure of the ultrafiltration membrane; and 2) decreasing the feed flow rate to maintain or decrease the value of the feed pressure applied to the ultrafiltration membrane after step (1), wherein the feed flow rate in step (1) is maintained at 250 LMH (L/m.sup.2/hour) or higher and the feed flow rate in step (2) is decreased to 80 LMH (L/m.sup.2/hour) or lower and wherein the protein preparation directly after said ultrafiltrating has a protein concentration above 200 g/L or a viscosity above 10 mPas.

Details for Patent 9,630,988

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Genentech, Inc.	ACTEMRA	tocilizumab	Injection	125276	01/08/2010		2039-02-26
Genentech, Inc.	ACTEMRA	tocilizumab	Injection	125472	10/21/2013		2039-02-26
Genentech, Inc.	ACTEMRA	tocilizumab	Injection	125472	11/19/2018		2039-02-26