Process for the purification of antibodies

• US 7,750,129 B2
• Filed: 02/25/2005
• Issued: 07/06/2010
• Est. Priority Date: 02/27/2004
• Status: Active Grant

• Current Assignee: Cytiva Bioprocess R&D AB (Danaher Corporation)
• Original Assignee: GE Healthcare Bio-Sciences AB (GE Healthcare Technologies, Inc.)
• Inventors: Gronberg, Anna, Thevenin, Nicolas, Johansson, Bo-Lennart, Maloisel, Jean-Luc, Johansson, Hans J.
• Primary Examiner(s): Saunders; David A
• Application Number:
  US10/589,717
• Publication Number:
  US 20070167613A1
• Time in Patent Office: 1,957 Days
• Field of Search: None
• US Class Current: 530/413
• CPC Class Codes: B01D 15/3847 Multimodal interactions
• CPC Class Codes: B01J 20/3242 Layers with a functional group, e.g. an affinity material, a ligand, a reactant or a complexing group
• CPC Class Codes: B01J 20/3246 having a well defined chemical structure
• CPC Class Codes: B01J 20/3253 comprising a cyclic structure not containing any of the heteroatoms nitrogen, oxygen or sulfur, e.g. aromatic structures
• CPC Class Codes: B01J 20/3255 comprising a cyclic structure containing at least one of the heteroatoms nitrogen, oxygen or sulfur, e.g. heterocyclic or heteroaromatic structures
• CPC Class Codes: B01J 20/3285 Coating or impregnation layers comprising different type of functional groups or interactions, e.g. different ligands in various parts of the sorbent, mixed mode, dual zone, bimodal, multimodal, ionic or hydrophobic, cationic or anionic, hydrophilic or hydrophobic

Abstract

The present invention relates to a process for the purification of antibodies from one or more impurities in a liquid, which process comprises contacting said liquid with a first chromatography resin comprised of a support to which multi-modal ligands have been immobilised to adsorb the antibodies to the resin, wherein each multi-modal ligand comprises at least one cation-exchanging group and at least one aromatic or heteroaromatic ring system; adding an eluent to release the antibodies from the resin; and contacting the eluate so obtained with a second chromatography resin. In one embodiment, the ring-forming atoms of the aromatic or heteroaromatic entity are selected from the group consisting of C, S and O, and the cation exchanging group is a weak cation exchanger.

Claims

1. A process for the purification of one or more antibodies from a liquid, comprising:

contacting said liquid in a first step, which is a capture step, with a first chromatography resin including a support to which multi-modal ligands have been immobilised to adsorb the antibodies to the resin, wherein each multi-modal ligand includes at least one cation-exchanging group and at least one aromatic or heteroaromatic ring system;

adding an eluent to release the antibodies from the resin; and

contacting the eluate so obtained with a second chromatography resin;

wherein the liquid contacted with the first chromatography resin is a cell culture liquid or a fermentation broth and host cell residues are removed in the first step.

2. The process of claim 1, wherein the cation-exchanging group of the multi-modal ligands is a weak cation exchanger.

3. The process of claim 1, wherein the second chromatography resin is selected from the group consisting of ion exchange chromatography;

hydrophobic interaction chromatography (HIC);

immobilised metal affinity chromatography (IMAC); and

affinity chromatography.

4. The process of claim 3, wherein the second chromatography resin is ion exchange chromatography.

5. The process of claim 1, wherein the second chromatography resin is anion exchange chromatography.

6. The process of claim 1, wherein the second chromatography resin is multimodal anion exchange chromatography.

7. The process of claim 1, wherein antibodies are recovered from the flow-through of the second chromatography resin.

8. The process of claim 1, wherein antibodies and/or impurities are eluted from the second chromatography resin.

9. The process of claim 1, wherein the antibodies are monoclonal antibodies.

10. The process of claim 1, wherein the antibodies are polyclonal antibodies.

11. A process for the purification of one or more antibodies from a liquid, comprising:

contacting said liquid in a first step, which is a capture step, with a first chromatography resin to adsorb the antibodies to ligands, which resin is multimodal and comprises a support to which the ligands have been immobilised, wherein the resin includes cation-exchanging groups and aromatic or heteroaromatic ring systems present on different ligands;

adding an eluent to release the antibodies from the resin; and

contacting the eluate so obtained with a second chromatography resin;

wherein the liquid contacted with the first chromatography resin is a cell culture liquid or a fermentation broth and host cell residues are removed in the first step.