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Last Updated: January 29, 2022

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Claims for Patent: 9,688,752

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Summary for Patent: 9,688,752
Title:Low acidic species compositions and methods for producing and using the same using displacement chromatography
Abstract: The present invention relates to low acidic species (AR) compositions comprising a protein, e.g., an antibody, or antigen-binding portion thereof, and methods for producing such low AR compositions using displacement chromatography. Methods for using such compositions to treat a disorder, e.g., a disorder in which TNF.alpha. is detrimental, are also provided.
Inventor(s): Wang; Chen (Shrewsbury, MA), Coppola; Germano (Shrewsbury, MA), Chumsae; Chris (North Andover, MA)
Assignee: AbbVie Inc. (North Chicago, IL)
Application Number:14/635,505
Patent Claims:1. A method for producing a low acidic species composition comprising an anti-TNF.alpha. antibody, or antigen-binding portion thereof, wherein the anti-TNF.alpha. antibody, or antigen-binding portion thereof, comprises a light chain variable region (LCVR) having a CDR1 domain comprising the amino acid sequence of SEQ ID NO: 7, a CDR2 domain comprising the amino acid sequence of SEQ ID NO: 5, and a CDR3 domain comprising the amino acid sequence of SEQ ID NO: 3; and a heavy chain variable region (HCVR) having a CDR1 domain comprising the amino acid sequence of SEQ ID NO: 8, a CDR2 domain comprising the amino acid sequence of SEQ ID NO: 6, and a CDR3 domain comprising the amino acid sequence of SEQ ID NO: 4, the method comprising: (a) contacting a first composition comprising the anti-TNF.alpha. antibody, or antigen-binding portion thereof with a chromatography media, wherein the first composition comprises more than 10% acidic species of the anti-TNF.alpha. antibody, or antigen-binding portion thereof, and wherein the anti-TNF.alpha. antibody, or antigen-binding portion thereof binds to the chromatography media; (b) displacing the 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 anti-TNF.alpha. antibody, or antigen-binding portion thereof, wherein the second composition comprises less than 10% acidic species of the anti-TNF.alpha. antibody, or antigen-binding portion thereof, thereby producing a low acidic species composition.

2. The method of claim 1, wherein the pH of the displacing buffer is lower than the isoelectric point of the anti-TNF.alpha. antibody, or antigen-binding portion thereof.

3. The method of claim 1, wherein the displacing buffer carries a positive charge.

4. The method of claim 1, wherein the conductivity of the displacing buffer is about 2 mS/cm to about 20 mS/cm.

5. The method of claim 1, wherein one displacing buffer is used.

6. The method of claim 1, wherein displacing the 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.

7. The method of claim 1, wherein displacing is achieved using linear displacement, a two-step displacement, or a multiple-step displacement.

8. The method of claim 1, wherein the second composition comprises less than 9% acidic species of the anti-TNF.alpha. antibody, or antigen-binding portion thereof.

9. The method of claim 1, wherein the second composition comprises less than 8% acidic species of the anti-TNF.alpha. antibody, or antigen-binding portion thereof.

10. The method of claim 1, wherein the second composition comprises less than 7% acidic species of the anti-TNF.alpha. antibody, or antigen-binding portion thereof.

11. The method of claim 1, wherein the second composition comprises less than 6% acidic species of the anti-TNF.alpha. antibody, or antigen-binding portion thereof.

12. The method of claim 1, wherein the second composition comprises less than 5% acidic species of the anti-TNF.alpha. antibody, or antigen-binding portion thereof.

13. The method of claim 1, wherein the second composition comprises less than 4.5% acidic species of the anti-TNF.alpha. antibody, or antigen-binding portion thereof.

14. The method of claim 1, wherein the second composition comprises less than 4% acidic species of the anti-TNF.alpha. antibody, or antigen-binding portion thereof.

15. The method of claim 1, wherein the second composition comprises less than 3% acidic species of the anti-TNF.alpha. antibody, or antigen-binding portion thereof.

16. The method of claim 1, wherein the second composition comprises less than 1.4% acidic species of the anti-TNF.alpha. antibody, or antigen-binding portion thereof.

17. The method of claim 1, wherein the displacing buffer comprises protamine sulfate.

18. The method of claim 1, wherein the displacing buffer comprises a quaternary ammonium salt.

19. The method of claim 1, wherein the chromatography media is an anion exchange adsorbent material.

20. The method of claim 1, wherein the chromatography media is a cation exchange adsorbent material.

21. The method of claim 20, wherein the cation exchange adsorbent material is a CEX membrane adsorber.

22. The method of claim 20, wherein cation exchange adsorbent material is a CEX resin.

23. The method of claim 1, wherein the chromatography media is a mixed mode media comprising cation exchange and hydrophobic interaction functional groups.

24. The method of claim 1, wherein the chromatography media is a mixed mode media selected from the group consisting of a cation exchange-based mixed mode resin and a cation-exchange-based mixed mode membrane adsorber.

25. The method of claim 1, wherein the displacing buffer comprises protamine sulfate, a quaternary ammonium salt, a polyelectrolyte, a polysaccharide, a low-molecular-mass dendrimer, an amino acid, a peptide, an antibiotic, a polyaromatic polyanionic compound, or an aminoglycosidepolyamine.

26. The method of claim 25, wherein the concentration of the protamine sulfate, quaternary ammonium salt, polyelectrolyte, polysaccharide, low-molecular-mass dendrimer, amino acid, peptide, antibiotic, polyaromatic polyanionic compound, or aminoglycosidepolyamine in the displacing buffer is 0.1 mM to 10 mM.

27. The method of claim 1, wherein the anti-TNF.alpha. antibody, or antigen-binding portion thereof, comprises a light chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 1 and a heavy chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 2.

28. The method of claim 27, wherein the anti-TNF.alpha. antibody, or antigen-binding portion thereof, is adalimumab, or an antigen-binding portion thereof.

Details for Patent 9,688,752

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

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