Biopharma is facing increased purification challenges due to increased molecular diversity, e.g. new ”multispecific” antibodies. Together with stronger requirements to remove product related impurities, this will make polishing more important in the future.<br/>Mixed-mode chromatography with multimodal ligands can provide unique selectivities and thus play a key role in the purification of complex feed streams. The goal of the present study is to develop an iterative framework for development and selection of new multimodal resins for future purification challenges. We have developed a chemically diverse virtual library of multimodal cation exchange ligands, to create a library based around the Capto<sup>TM</sup> MMC resin, designed towards varied properties such as hydrophobicity, H-bonding, etc. A selected subset of the ligands was coupled to the Capto MMC ImpRes base matrix and evaluated chromatographically in a high throughput plate study of protein binding at low loading to assess chromatographic diversity. Additionally, the adsorption mechanisms of a monoclonal antibody (mAb) were studied and the preferential interaction adsorption model used to provide estimates of: (a) the total number of water molecules and counter salt ions released during mAb adsorption, and (b) hydrophobic contact area for various isocratic conditions. The separation resolution between the mAb and Fab fragments, as well as high molecular weight aggregates were studied using gradient elution. Promising new resins were identified and the modelling points to the importance of tuning the ligand hydrophobicity, but also highlights the role of other ligand-specific modes of interaction (e.g. π-π interactions). The improved performance of several new resins in separation applications will be discussed. The iterative approach proves to be a promising method for identifying new ligands for biopharmaceutical purification challenges.

Iterative mapping approach for identifying next generation multimodal chromatography resins: Chemical diversity, high throughput screening, and chromatographic modelling

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.