Claims for Patent: 9,315,574

Summary for Patent: 9,315,574

Title:	Low acidic species compositions and methods for producing and using the same
Abstract:	The instant invention relates to low acidic species (AR) compositions comprising a protein, e.g., an antibody, or antigen-binding portion thereof, and methods, e.g., cell culture and/or protein purification methods, for producing such low AR compositions. Methods for using such compositions to treat a disorder, e.g., a disorder in which TNF.alpha. is detrimental, are also provided.
Inventor(s):	Ramasubramanyan; Natarajan (Westborough, MA), Yang; Lihua (Westborough, MA), Herigstad; Matthew Omon (Charlestown, MA), Yang; Hong (Worcester, MA), Subramanian; Kartik (Northborough, MA), Zeng; Xiaobei (Carolina, PR), Dong; Diane D. (Shrewsbury, MA), Lim; Wen Chung (Worcester, MA), Gifford; Kathreen A. (Marlborough, MA), Kaymakcalan; Zehra (Westborough, MA), Chumsae; Christopher (North Andover, MA)
Assignee:	AbbVie, Inc. (North Chicago, IL)
Application Number:	14/584,619
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 9,315,574
Patent Claims:	1. A method for producing a composition comprising an immunoglobulin comprising the 6 CDR domains of adalimumab, the method comprising: contacting a first sample comprising the immunoglobulin, wherein the sample comprises more than 10% total acidic species of the immunoglobulin, to a first chromatography media in the presence of a loading buffer to produce a first chromatography sample, wherein the first chromatography media is selected from the group consisting of an ion exchange chromatography media, an affinity chromatography media and a hydrophobic interaction chromatography (HIC) media, wherein the first chromatography sample comprises a composition of the immunoglobulin comprising less than 10% total acidic species of the immunoglobulin, wherein the acidic species of the immunoglobulin correspond to the peaks that elute earlier than the main peak in a WCX-10 HPLC chromatogram of the immunoglobulin, wherein the WCX-10 HPLC chromatogram is generated using a first mobile phase of 10 mM Sodium Phosphate dibasic (pH 7.5) and a second mobile phase of 10 mM Sodium Phosphate dibasic, 500 mM Sodium Chloride (pH 5.5), and wherein the WCX-10 HPLC chromatogram is generated using detection at 280 nm. 2. The method of claim 1, wherein producing the first chromatography sample comprises washing the first chromatography media with a wash buffer. 3. The method of claim 2, wherein the wash buffer is the same as the loading buffer. 4. The method of claim 1, wherein the first chromatography sample is a flow through chromatography sample which comprises less than 10% total acidic species of the immunoglobulin. 5. The method of claim 1, wherein producing the first chromatography sample comprises eluting the first chromatography sample, thereby producing a first eluted sample which comprises less than 10% total acidic species of the immunoglobulin. 6. The method of claim 5, further comprising contacting the first eluted sample to a second chromatography media and eluting the sample, thereby producing a second eluted sample, wherein the second chromatography media is selected from the group consisting of an ion exchange chromatography media, an affinity chromatography media and a hydrophobic interaction chromatography (HIC) media. 7. The method of claim 6, further comprising contacting the second eluted sample to a third chromatography media and eluting the sample, thereby producing a third eluted sample, wherein the third chromatography media is selected from the group consisting of an ion exchange chromatography media, an affinity chromatography media and a hydrophobic interaction chromatography (HIC) media. 8. The method of claim 7, wherein the first chromatography media is an affinity chromatography media, the second chromatography media is an ion exchange chromatography media and the third chromatography media is a hydrophobic interaction chromatography (HIC) media. 9. The method of claim 7, wherein the first chromatography media is an affinity chromatography media, the second chromatography media is an ion exchange chromatography media and the third chromatography media is an ion exchange chromatography media. 10. The method of claim 9, wherein the affinity chromatography media is a protein A chromatography media, the ion exchange chromatography media used as the second chromatography media is an anion exchange (AEX) chromatography media and the ion exchange chromatography media used as the third chromatography media is a cation exchange (CEX) chromatography media. 11. The method of claim 1, wherein the first chromatography media is an ion exchange chromatography media selected from the group consisting of an anion exchange (AEX) chromatography adsorbent material, a cation exchange (CEX) chromatography adsorbent material, a cation exchange mixed mode media, and an anion exchange mixed mode media. 12. The method of claim 11, wherein the cation exchange (CEX) adsorbent material is selected from the group consisting of a CEX resin and a CEX membrane adsorber. 13. The method of claim 11, wherein the anion exchange (AEX) adsorbent material is selected from the group consisting of an AEX resin and an AEX membrane adsorber. 14. The method of claim 1, wherein the first chromatography media is an affinity chromatography media. 15. The method of claim 14, wherein the affinity chromatography media is a Protein A chromatography media. 16. The method of claim 1, wherein the first chromatography media is a hydrophobic interaction chromatography (HIC) media. 17. The method of claim 1, wherein the first chromatography media is a mixed mode media comprising ion exchange and hydrophobic interaction functional groups. 18. The method of claim 1, wherein the first chromatography media is a CEX adsorbent material or a mixed mode media, and the pH of the loading buffer is lower than the isoelectric point of adalimumab. 19. The method of claim 1, wherein the immunoglobulin is adalimumab and wherein the total acidic species of adalimumab comprise a first acidic region (AR1) and a second acidic region (AR2). 20. The composition of claim 19, wherein the first acidic region (AR1) and the second acidic region (AR2) comprise charge variants, structure variants and fragmentation variants. 21. The composition of claim 20, wherein the charge variants comprise one or more of deamidation variants, glycation variants, afucosylation variants, MGO variants or citric acid variants, the structure variants comprise one or more of glycosylation variants or acetonation variants, and the fragmentation variants comprise one or more of Fab fragment variants, C-terminal truncation variants or variants missing a heavy chain variable domain. 22. The method of claim 1, wherein the composition comprises 9% or less, 8% or less, 7% or less, 6% or less, 5% or less, 4.5% or less, 4% or less, 3.5% or less, 3% or less, 2.5% or less, or 2% or less total acidic species of the immunoglobulin comprising the 6 CDR domains of adalimumab. 23. The method of claim 1, wherein the immunoglobulin is adalimumab. 24. The method of claim 1, wherein the composition comprises 1.4% to 10% total acidic species of the immunoglobulin comprising the 6 CDR domains of adalimumab. 25. The method of claim 1, wherein the composition comprises 1.4% or less total acidic species of the immunoglobulin comprising the 6 CDR domains of adalimumab. 26. A method for producing a composition comprising an immunoglobulin comprising the 6 CDR domains of adalimumab, the method comprising: (a) contacting a first sample comprising the immunoglobulin, wherein the sample comprises more than 10% total acidic species of the immunoglobulin, to an affinity chromatography media in a first loading buffer, and eluting a first eluted sample from the affinity chromatography media; (b) contacting the first eluted sample to a second chromatography media in a second loading buffer and eluting a second eluted sample from the second chromatography media; and (c) contacting the second eluted sample to a third chromatography media in a third loading buffer and eluting a third eluted sample from the third chromatography media; wherein the third eluted sample comprises a composition of the immunoglobulin comprising less than 10% total acidic species of the immunoglobulin, wherein the acidic species of the immunoglobulin correspond to the peaks that elute earlier than the main peak in a WCX-10 HPLC chromatogram of the immunoglobulin, wherein the WCX-10 HPLC chromatogram is generated using a first mobile phase of 10 mM Sodium Phosphate dibasic (pH 7.5) and a second mobile phase of 10 mM Sodium Phosphate dibasic, 500 mM Sodium Chloride (pH 5.5), and wherein the WCX-10 HPLC chromatogram is generated using detection at 280 nm. 27. The method of claim 26, wherein the second chromatography media is selected from the group consisting of an anion exchange (AEX) chromatography adsorbent material, a cation exchange (CEX) chromatography adsorbent material, a mixed mode media, a cation exchange mixed mode media, and an anion exchange mixed mode media. 28. The method of claim 26, wherein the third chromatography media is selected from the group consisting of an anion exchange (AEX) chromatography adsorbent material a cation exchange (CEX) chromatography adsorbent material, a mixed mode media, a cation exchange mixed mode media, and an anion exchange mixed mode media. 29. The method of claim 26, wherein the second loading buffer, the third loading buffer, or both the second and third loading buffers are a Tris/Formate buffer. 30. The method of claim 26, wherein the composition comprises 1.4% to 10% total acidic species of the immunoglobulin comprising the 6 CDR domains of adalimumab. 31. The method of claim 26, wherein the composition comprises 1.4% or less total acidic species of the immunoglobulin comprising the 6 CDR domains of adalimumab. 32. The method of claim 26, wherein the composition comprises 9% or less, 8% or less, 7% or less, 6% or less, 5% or less, 4.5% or less, 4% or less, 3.5% or less, 3% or less, 2.5% or less, or 2% or less total acidic species of the immunoglobulin comprising the 6 CDR domains of adalimumab. 33. The method of claim 26, wherein the immunoglobulin is adalimumab. 34. A method for producing a composition comprising an immunoglobulin comprising the 6 CDR domains of adalimumab, the method comprising: (a) contacting a first sample comprising the immunoglobulin, wherein the sample comprises more than 10% total acidic species of the immunoglobulin, to a protein A chromatography media in a first loading buffer, and eluting a first eluted sample from the protein A chromatography media; (b) contacting the first eluted sample to an anion exchange (AEX) chromatography media in a second loading buffer and eluting a second eluted sample from the AEX chromatography media; and (c) contacting the second eluted sample to a cation exchange (CEX) chromatography media in a third loading buffer and eluting a third eluted sample from the CEX chromatography media; wherein the third eluted sample comprises a composition of the immunoglobulin comprising less than 10% total acidic species of the immunoglobulin, wherein the acidic species of the immunoglobulin correspond to the peaks that elute earlier than the main peak in a WCX-10 HPLC chromatogram of the immunoglobulin, wherein the WCX-10 HPLC chromatogram is generated using a first mobile phase of 10 mM Sodium Phosphate dibasic (pH 7.5) and a second mobile phase of 10 mM Sodium Phosphate dibasic, 500 mM Sodium Chloride (pH 5.5), and wherein the WCX-10 HPLC chromatogram is generated using detection at 280 nm. 35. The method of claim 34, wherein the immunoglobulin is adalimumab. 36. The method of claim 34, wherein the composition comprises 1.4% to 10% total acidic species of the immunoglobulin comprising the 6 CDR domains of adalimumab. 37. The method of claim 34, wherein the composition comprises 1.4% or less total acidic species of the immunoglobulin comprising the 6 CDR domains of adalimumab. 38. The method of claim 34, wherein the composition comprises 9% or less, 8% or less, 7% or less, 6% or less, 5% or less, 4.5% or less, 4% or less, 3.5% or less, 3% or less, 2.5% or less, or 2% or less total acidic species of the immunoglobulin comprising the 6 CDR domains of adalimumab. 39. A method for producing a composition comprising adalimumab, the method comprising: (a) contacting a first sample comprising adalimumab, wherein the sample comprises more than 10% total acidic species of adalimumab, to a protein A chromatography media in a first loading buffer, and eluting a first eluted sample from the protein A chromatography media; (b) contacting the first eluted sample to an anion exchange (AEX) chromatography media in a second loading buffer and eluting a second eluted sample from the AEX chromatography media; and (c) contacting the second eluted sample to a cation exchange (CEX) chromatography media in a third loading buffer and eluting a third eluted sample from the CEX chromatography media; wherein the third eluted sample comprises a composition of adalimumab comprising less than 10% total acidic species of adalimumab, wherein the acidic species of adalimumab correspond to the peaks that elute earlier than the main peak in a WCX-10 HPLC chromatogram of adalimumab, wherein the WCX-10 HPLC chromatogram is generated using a first mobile phase of 10 mM Sodium Phosphate dibasic (pH 7.5) and a second mobile phase of 10 mM Sodium Phosphate dibasic, 500 mM Sodium Chloride (pH 5.5), and wherein the WCX-10 HPLC chromatogram is generated using detection at 280 nm. 40. The method of claim 39, wherein the composition comprises 1.4% to 10% total acidic species of adalimumab. 41. The method of claim 39, wherein the composition comprises 1.4% or less total acidic species of adalimumab. 42. The method of claim 39, wherein the composition comprises 9% or less, 8% or less, 7% or less, 6% or less, 5% or less, 4.5% or less, 4% or less, 3.5% or less, 3% or less, 2.5% or less, or 2% or less total acidic species of adalimumab.

Details for Patent 9,315,574

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Abbvie Inc.	HUMIRA	adalimumab	Injection	125057	12/31/2002		2033-10-18
Abbvie Inc.	HUMIRA	adalimumab	Injection	125057	02/21/2008		2033-10-18
Abbvie Inc.	HUMIRA	adalimumab	Injection	125057	04/24/2013		2033-10-18
Abbvie Inc.	HUMIRA	adalimumab	Injection	125057	09/23/2014		2033-10-18
Abbvie Inc.	HUMIRA	adalimumab	Injection	125057	11/23/2015		2033-10-18
Abbvie Inc.	HUMIRA	adalimumab	Injection	125057	03/09/2016		2033-10-18
Abbvie Inc.	HUMIRA	adalimumab	Injection	125057	10/17/2016		2033-10-18