Models for antibody behaviour in hydrophobic interaction chromatography, and in self-association

Max Hebditch, Aisling Roche, Robin A. Curtis, Jim Warwicker

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    Abstract

    Monoclonal antibodies (mAbs) form an increasingly important sector of the pharmaceutical market, and their behaviour in production, processing, and formulation is a key factor in development. With datasets of solution properties for mAbs becoming available, and with amino acid sequences, and structures for many Fabs, it is timely to examine what features correlate with measured data. Here, previously published data for hydrophobic interaction chromatography (HIC) and the formation of high molecular weight species (HMWS) are studied. Unsurprisingly, aromatic sidechain content of complementarity determining regions (CDRs), underpins much of the variability in HIC data. However, this is not reflected in non-polar solvent accessible surface enrichment at the antigen combining site, consistent with a view in which hydrophobic interaction strength is dependent on curvature as well as extent of an interface. Sequence properties are also superior to surface-based structural properties in correlations to the HMWS data. Combined length of CDRs is the most important factor, which could be an indication of flexibility that facilitates CDR-CDR interactions in mAb self-association. These observations couple to our understanding of protein physicochemical properties, laying the groundwork for improved developability models.
    Original languageEnglish
    JournalJournal of Pharmaceutical Sciences
    Early online date23 Nov 2018
    DOIs
    Publication statusPublished - 2018

    Research Beacons, Institutes and Platforms

    • Manchester Institute of Biotechnology

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