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

Lorenzo Gentiluomo*, Dierk Roessner, Werner Streicher, Sujata Mahapatra, Pernille Harris, Wolfgang Frieß

*Corresponding author for this work

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Abstract

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
Volume109
Issue number1
Pages (from-to)443-451
ISSN0022-3549
DOIs
Publication statusPublished - 2020

Keywords

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

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