Claims for Patent: 9,708,399

Summary for Patent: 9,708,399

Title:	Protein purification using displacement chromatography
Abstract:	Disclosed herein are compositions and methods for the isolation and purification of proteins from a sample. In particular, the present invention relates to compositions and methods for isolating and purifying proteins incorporating a displacement chromatographic step. The present invention is also directed toward pharmaceutical compositions comprising one or more antibodies purified by a method described herein.
Inventor(s):	Wang; Chen (Shrewsbury, MA), Coppola; Germano (Shrewsbury, MA), Chumsae; Chris (North Andover, MA)
Assignee:	ABBVIE, INC. (North Chicago, IL)
Application Number:	14/733,085
Patent Claims:	1. A method for producing a low acidic species human anti-TNF.alpha. antibody composition comprising a human anti-TNF.alpha. antibody, or antigen-binding portion thereof, wherein the human anti-TNF.alpha. antibody, or antigen-binding portion thereof, comprises a light chain variable region (LCVR) having a CDR1 domain, a CDR2 domain, and a CDR3 domain of adalimumab; and a heavy chain variable region (HCVR) having a CDR1 domain, a CDR2 domain, and a CDR3 domain of adalimumab, the method comprising: (a) contacting a first composition comprising the human anti-TNF.alpha. antibody, or antigen-binding portion thereof, with a chromatography media, wherein the first composition comprises more than 10% total acidic species of the human anti-TNF.alpha. antibody, or antigen-binding portion thereof; wherein the acidic species of the human anti-TNF.alpha. antibody, or antigen-binding portion thereof, comprise species selected from the group consisting of charge variants, structure variants, fragmentation variants, and any combinations thereof, wherein the acidic species of the human anti-TNF.alpha. antibody, or antigen-binding portion thereof, do not include process-related impurities selected from the group consisting of host cell proteins, host cell DNA, and media components, and wherein the human anti-TNF.alpha. antibody, or antigen-binding portion thereof, binds to the chromatography media; (b) displacing the human anti-TNF.alpha. antibody, or antigen-binding portion thereof, bound to the chromatography media with a displacing buffer; and (c) collecting a second composition comprising the displaced human anti-TNF.alpha. antibody, or antigen-binding portion thereof, wherein the second composition comprises less than 10% total acidic species of human anti-TNF.alpha. antibody, or antigen-binding portion thereof, thereby producing a low acidic species human anti-TNF.alpha. antibody composition. 2. The method of claim 1, wherein the chromatography media is an ion exchange adsorbent material. 3. The method of claim 2, wherein the ion exchange adsorbent material is an anion exchange adsorbent material. 4. The method of claim 2, wherein the ion exchange adsorbent material is an cation exchange adsorbent material. 5. The method of claim 4, wherein the cation exchange (CEX) adsorbent material is selected from the group consisting of a CEX resin and a CEX membrane adsorber. 6. The method of claim 1, wherein the chromatography media is a multimodal adsorbent material comprising cation exchange and hydrophobic interaction functional groups. 7. The method of claim 1, wherein the pH of the displacing buffer is lower than the isoelectric point of the human anti-TNF.alpha. antibody, or antigen-binding portion thereof. 8. The method of claim 7, wherein the pH of the displacing buffer is about 6.0 to about 8.0. 9. The method of claim 1, wherein the displacing buffer carries positive charge. 10. The method of claim 1, wherein the conductivity of the displacing buffer is about 2 to about 20 mS/cm. 11. The method of claim 1, wherein the chromatography media is present in a column having a length of about 10 cm to about 30 cm and wherein flow residence time is about 5 min to about 25 min. 12. The method of claim 1, wherein displacing the human anti-TNF.alpha. antibody, or antigen-binding portion thereof, bound to the chromatography media comprises using a first displacing buffer followed by using a second displacing buffer. 13. The method of claim 1, wherein displacing is achieved using a multiple-step displacement, a two-step displacement, or a linear displacement. 14. The method of claim 1, wherein the displacing buffer comprises protamine sulfate. 15. The method of claim 14, wherein the displacing buffer comprises 0.1 to 5 mM protamine sulfate. 16. The method of claim 15, wherein the displacing buffer comprises 0.25 mM protamine sulfate. 17. The method of claim 1, wherein the displacing buffer comprises a quaternary ammonium salt. 18. The method of claim 17, wherein the displacing comprises 0.1 to 10 mM quaternary ammonium salt. 19. The method of claim 18, wherein the displacing buffer comprises 0.5 mM quaternary ammonium salt. 20. The method of claim 1, wherein one displacing buffer is used. 21. The method of claim 1, wherein the chromatography media is a mixed mode media. 22. The method of claim 1, wherein the second composition comprises less than 9% total acidic species of the human anti-TNF.alpha. antibody, or antigen-binding portion thereof. 23. The method of claim 1, wherein the second composition comprises less than 8% total acidic species of the human anti-TNF.alpha. antibody, or antigen-binding portion thereof. 24. The method of claim 1, wherein the second composition comprises less than 7% total acidic species of the human anti-TNF.alpha. antibody, or antigen-binding portion thereof. 25. The method of claim 1, wherein the second composition comprises less than 6% total acidic species of the human anti-TNF.alpha. antibody, or antigen-binding portion thereof. 26. The method of claim 1, wherein the second composition comprises less than 5% total acidic species of the human anti-TNF.alpha. antibody, or antigen-binding portion thereof. 27. The method of claim 1, wherein the second composition comprises less than 4.5% total acidic species of the human anti-TNF.alpha. antibody, or antigen-binding portion thereof. 28. The method of claim 1, wherein the second composition comprises less than 4% total acidic species of the human anti-TNF.alpha. antibody, or antigen-binding portion thereof. 29. The method of claim 1, wherein the second composition comprises less than 3% total acidic species of the human anti-TNF.alpha. antibody, or antigen-binding portion thereof. 30. The method of claim 1, wherein the second composition comprises less than 1.4% total acidic species of the human anti-TNF.alpha. antibody, or antigen-binding portion thereof. 31. The method of claim 1, wherein the human anti-TNF.alpha. antibody, or antigen-binding portion thereof, is adalimumab, or an antigen-binding portion thereof.

Details for Patent 9,708,399

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