Bispecific antibodies are a class of engineered antibodies with the ability to bind to two distinct antigens. Compared to monoclonal antibodies, single chain variable fragment-IgG bispecific antibodies are prone to high levels of aggregate (10-30%), which can impact product yields and must be removed during downstream polishing steps. Mixed mode chromatography (MMC) provides a potential method of aggregate control due to its multiple modes of protein-ligand interactions, resulting in enhanced selectivity compared to traditional ion exchange and hydrophobic interaction chromatography resins. Ceramic hydroxyapatite (CHT) is an MMC resin often used as a polishing step for many high aggregate forming species; however, its scalability issues raise the need for an alternative aggregate removal step. Initial studies showed that weak mixed-mode cation exchange (CEX) resins clear aggregates with high selectivity and minimal breakthrough while operating in flow-through mode. To further investigate potential alternatives to CHT, we evaluated prototype POROS™ mixed-mode CEX resins from Thermo Fisher Scientific to study the impact of ligand density, operating pH and arginine concentration on aggregate removal ability.

Investigations of weak mixed-mode cation exchange chromatography for control of aggregates in bispecific antibodies

Macromolecular Chemistry: The Second Century

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ACS Spring 2020 National Meeting & Expo

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.