CHROMATOGRAPHY PROCESS FOR RESOLVING HETEROGENEOUS ANTIBODY AGGREGATES

摘要

Disclosed are methods and processes utilizing multi-modal chromatography as a polishing step to separate heterogeneously charged (basic and acidic) aggregates and other impurities from partially a partially purified bulk product monoclonal antibody product. The resulting chromatographic process provides a scaleable production process that is cost effective and increases the productivity of the purification process over a platform utilizing a combination of anion and cation exchange chromatography to resolve heterogeneous aggregates.

主权项

1. A method of purifying monomeric monoclonal antibody (mAb) from a conditioned mixture comprising one or more impurities and heterogenous aggregates comprising the steps of:
a) providing a sample comprising a mAb produced in a CHO cell expression system; b) binding the mAb present in the sample to a Protein A affinity chromatography resin; c) eluting the mAb from the Protein A resin, wherein the eluted product provides a second sample, optionally referred to as a Protein A pool (PAP); d) binding the impurities present in the PAP to an anion exchange (AEX) chromatography resin; e) collecting the flow through from step (d) wherein the flow-through provides a feedstock; f) binding the impurities present in the feed solution to a polishing resin; and g) collecting the flow through product from step (f) wherein the product provides a purified monomeric mAb composition.