The effectiveness of flow-through anion-exchange polishing steps requires retention of a variety of impurities that differ in their strength of adsorption, and the relatively weak adsorption of some host-cell protein (HCP) impurities may lead to inadequate clearance. Such effects may be amplified by intrinsic retention differences among different resins. Models that can capture this sensitivity would be useful in directing experimental design efforts. To that end, the present study seeks approximate models to predict HCP adsorption equilibria from protein sequences and to integrate them into column models for flow-through chromatography. In the absence of HCP structural information, coarse-grained calculations of molecular-level interactions are performed using a colloidal representation of the protein and the resin, making use of HCP sequence and other structural information. Adsorption energetics are estimated from numerical solutions to continuum electrostatics equations. The resulting retention predictions are compared to those from colloidal models, and their accuracy is assessed by comparison to column experimental data.

Modeling host-cell protein retention to expedite ion-exchange resin screening for flow-through polishing

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.