Journal article
Characterization of native reversible self-association of a monoclonal antibody mediated by Fab-Fab interaction
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.
| Language: | English |
|---|---|
| Year: | 2020 |
| Pages: | 443-451 |
| ISSN: | 15206017 and 00223549 |
| Types: | Journal article |
| DOI: | 10.1016/j.xphs.2019.09.021 |
| ORCIDs: | Harris, Pernille |
Biopharmaceutical characterization Monoclonal antibody(s) Physical stability Protein aggregation Protein formulation(s) Self-association
Antibodies, Monoclonal Chemistry, Pharmaceutical Chromatography, Gel Chromatography, High Pressure Liquid Drug Stability Dynamic Light Scattering Hydrogen-Ion Concentration Hydrophobic and Hydrophilic Interactions Immunoglobulin Fab Fragments Immunoglobulin Fc Fragments Immunoglobulin G Protein Aggregates Protein Stability Temperature Ultracentrifugation Viscosity biopharmaceutical characterization monoclonal antibody(s) physical stability protein aggregation protein formulation(s) self-association
