Protein A Alternatives: Mixed Mode Resins For High Throughput mAb Feedstocks

By Al Jackewitz, Tosoh Bioscience, LLC.

Abstract:

Mixed mode resins are in demand where there is a requirement for higher chromatographic capacity and throughput. Cation exchange resins significantly improve elution kinetics and serve as replacements for Protein A capture columns.

This white paper contrasts performance between existing and new resins. TOYOPEARL GigaCap® S-650M and TOYOPEARL® MX-Trp-650M are two of the four resins reviewed.

The data provided will inform you of:

• conductivity and dilution ranges during loading.
• dynamic binding capacities performances between resins.
• resolution and peak shape comparisons in numerous agarose materials.

Introduction:

Recent advances in upstream expression of monoclonal antibodies have resulted in downstream target feedstock concentrations of 10 g/L and higher.  While many of the workhorse Protein A resins used for capture have dynamic binding capacities (DBC) in the 30-45 g/L range, industry interest has grown in alternative chromatographic methods having higher capacity and throughput. 

Newer, improved cation exchange resins such as TOYOPEARL GigaCap® S-650M with typical mAb DBC of 145 g/L, and significantly improved elution kinetics, have been reported as replacements for Protein A capture columns. The use of a GigaCap-type resin results in higher titer mAb pool fractions in significantly less water volume after elution.  However, high conductivity feedstocks in many cases need to be diluted in order to achieve the high mAb DBC reported by the manufacturer for the resin. The additional water, tankage and process time adds additional cost to the loading step. 

Tosoh Bioscience is pleased to announce the new TOYOPEARL® MX-Trp-650M resin which shows both high DBC and tolerance to feedstocks with conductivities up to 17 mS/cm. The new mixed mode (MM) resin has also been engineered to have excellent elution kinetics.