Claims for Patent: 9,346,879

Summary for Patent: 9,346,879

Title:	Protein purification methods to reduce acidic species
Abstract:	The instant invention relates to the field of protein production and purification, and in particular to compositions and processes for controlling the amount of charge variants, aggregates, and fragments of a protein of interest, as well as host cell proteins, present in purified preparations by applying particular chromatography conditions during such protein purification.
Inventor(s):	Ramasubramanyan; Natarajan (Westborough, MA), Yang; Lihua (Westborough, MA), Herigstad; Matthew Omon (Charlestown, MA), Yang; Hong (Worcester, MA), Chumsae; Christopher (North Andover, MA)
Assignee:	AbbVie Inc. (North Chicago, IL)
Application Number:	14/584,492
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 9,346,879
Patent Claims:	1. A method for producing a composition comprising adalimumab, the method comprising: contacting a first sample comprising adalimumab comprising more than 10% total acidic species of adalimumab to a first chromatography media in the presence of a loading buffer, 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, and collecting a first chromatography sample, wherein the first chromatography 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. 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 or substantially 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 adalimumab. 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 adalimumab. 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 total acidic species of adalimumab comprise a first acidic region (AR1) and a second acidic region (AR2). 20. The method of claim 1, wherein the composition comprises less than 3.8% total acidic species of adalimumab. 21. The method of claim 1, wherein the composition comprises less than 2.4% total acidic species of adalimumab. 22. The method of claim 1, wherein the composition comprises 4.7%-8.3% total acidic species of adalimumab. 23. A method for producing a composition comprising adalimumab, the method comprising: (a) contacting a first sample comprising adalimumab comprising more than 10% total acidic species of adalimumab 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; (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 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. 24. The method of claim 23, wherein the affinity chromatography media is a Protein A resin. 25. The method of claim 23, further comprising contacting the third eluted sample to a hydrophobic interaction chromatography (HIC) media. 26. The method of claim 23, 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. 27. The method of claim 23, 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. 28. The method of claim 23, wherein the second loading buffer, the third loading buffer, or both the second and third loading buffers are a Tris/Formate buffer. 29. The method of claim 23, wherein the composition comprises 2.4% to 10% total acidic species of adalimumab. 30. The method of claim 23, wherein the composition comprises 2.4% or less total acidic species of adalimumab.

Details for Patent 9,346,879

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Abbvie Inc.	HUMIRA	adalimumab	Injection	125057	12/31/2002		2032-04-20
Abbvie Inc.	HUMIRA	adalimumab	Injection	125057	02/21/2008		2032-04-20
Abbvie Inc.	HUMIRA	adalimumab	Injection	125057	04/24/2013		2032-04-20
Abbvie Inc.	HUMIRA	adalimumab	Injection	125057	09/23/2014		2032-04-20
Abbvie Inc.	HUMIRA	adalimumab	Injection	125057	11/23/2015		2032-04-20