Methods for inactivating viruses during a protein purification process

Patent metadata

Field	Value
Publication number	US-9809799-B2
Application number	US-201314390924-A
Country	US
Kind code	B2
Filing date	Jun 13, 2013
Priority date	Jun 29, 2012
Publication date	Nov 7, 2017
Grant date	Nov 7, 2017

Abstract

The present application relates to novel and improved methods of achieving virus inactivation during a protein purification process.

First claim

What is claimed is:

1. A method of inactivating one or more viruses in a Protein A eluate as the Protein A eluate flows from a Protein A affinity chromatography step to a flow-through purification step, the method comprising mixing the Protein A eluate with one or more virus inactivating agents using one or more in-line static mixers, wherein the flow of the Protein A eluate through the static mixer is in the laminar flow range comprising a Reynolds number below 100, wherein complete virus inactivation is achieved in less than 10 minutes or less than 5 minutes or less than 2 minutes or less than 1 minute.

2. A method for inactivating one or more viruses, the method comprising:
a. subjecting a sample comprising a target protein to a Protein A affinity chromatography process, thereby to obtain an eluate; and
b. continuously transferring the eluate to an in-line static mixer to mix one or more virus inactivating agents with the eluate for a duration of time which is equal to or less than 10 minutes, wherein the flow of the eluate through the static mixer is in the laminar flow range comprising a Reynolds number below 100, thereby to inactivate one or more viruses.

3. The method of claim 2 , wherein the Protein A affinity chromatography process is performed in batch mode.

4. The method of claim 2 , wherein the Protein A affinity chromatography process is performed in a continuous mode.

5. The method of claim 4 , wherein the process comprises continuous multi-column chromatography.

6. The method of claim 2 , wherein the one or more virus inactivating agents is an acid.

7. The method of claim 2 , wherein the target protein is an antibody.

8. The method of claim 2 , further comprising the step of continuously transferring output from step (b) into a flow-through purification process step.

9. The method of claim 8 , wherein the flow-through purification step comprises two or more matrices selected from activated carbon, anion exchange media, cation exchange media and virus filter.

10. The method of claim 1 , wherein the flow-through purification step comprises two or more matrices selected from activated carbon, anion exchange media, cation exchange media and virus filter.

Assignees

• Emd Millipore Corp

Inventors

• Xenopoulos Alex

Classifications

• C12N7/00 Primary

  Viruses; Bacteriophages; Compositions thereof; Preparation or purification thereof (preparing medicinal viral antigen or antibody compositions, e.g. virus vaccines, A61K39/00) · CPC title

• C12N2740/10061

  Methods of inactivation or attenuation · CPC title

• C07K1/16 Primary

  by chromatography · CPC title

• C07K1/36

  by a combination of two or more processes of different types · CPC title

• B01D15/3809

  of the antigen-antibody type, e.g. protein A, G or L chromatography · CPC title