Characterization of native reversible self-association of a monoclonal antibody mediated by Fab-Fab interaction

Research output: Contribution to journalJournal article – Annual report year: 2019Researchpeer-review

  • Author: Gentiluomo, Lorenzo

    Wyatt Technology Europe GmbH, Germany

  • Author: Roessner, Dierk

    Wyatt Technology Europe GmbH, Germany

  • Author: Streicher, Werner W.

    Novozymes A/S, Germany

  • Author: Mahapatra, Sujata

    Novozymes A/S, Germany

  • Author: Harris, Pernille

    Department of Chemistry, Technical University of Denmark, Denmark

  • Author: Frieß, Wolfgang

    Ludwig-Maximilians-Universität München, Germany

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The native reversible self-association of monoclonal antibodies has been associated with high viscosity, liquid-liquid and liquid-solid phase separation. We investigated the native reversible self-association of an IgG1, which exerts this association even at low protein concentrations, in detail to gain further understanding of this phenomenon by extensive characterization of the association as a function of multiple factors, namely pH, temperature, salt concentration and protein concentration. The nature of the self-association of the full-length IgG1 as well as the corresponding Fab and Fc fragment was studied by viz. SEC-MALS, DLS, SLS, AUC, SAXS, AF4-MALS and intrinsic fluorescence. We rationalized the self-association as a combination of hydrophobic and electrostatic interactions driven by the Fab fragments. Finally, we investigated the long-term stability of the IgG1 molecule.
Original languageEnglish
JournalJournal of Pharmaceutical Sciences
ISSN0022-3549
DOIs
Publication statusAccepted/In press - 2019
CitationsWeb of Science® Times Cited: No match on DOI

    Research areas

  • Protein aggregation, Protein formulation(s), Self-association, Biopharmaceutical characterization, Monoclonal antibody(s), Physical stability

ID: 194240088