Current Pharmaceutical Biotechnology

Zeno Foldes-Papp
Visiting Professor of Medical Biochemistry
HELIOS Clinical Center of Emergency Medicine
Department for Internal Medicine
Alte-Koelner-Strasse 9
D-51688 Koeln-Wipperfuerth
Germany

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Heterogeneity of Monoclonal Antibodies Revealed by Charge-Sensitive Methods

Author(s): J. Vlasak, R. Ionescu.

Abstract:

The expanding field of monoclonal antibody-based pharmaceuticals has triggered increased interest in analytical characterization of these large proteins and in understanding of their heterogeneity and degradation pathways. As a result, a large number of enzymatic modifications as well as chemical and physical degradations have been reported in monoclonal antibodies in recent years. Most heterogeneity is related to changes in the surface charge of the antibody, either directly, as a change in the number of charged residues, or indirectly as a chemical or physical alteration that changes surface-charge distribution. This review presents an overview of the sources of charge-related heterogeneity in monoclonal antibodies and the methods used for their detection. A detailed section is dedicated to deamidation of asparagine and isomerization of aspartic acid residues, two ubiquitous degradation pathways detected in antibodies and other proteins as well. Finally, kinetic modeling of the accumulation of antibody variants is presented as a tool to determine the expected fraction of molecules that have undergone one or more degradation reactions.

Keywords: Monoclonal antibody, charge heterogeneity, degradation, chromatography, deamidation, isomerization

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Article Details

VOLUME: 9
ISSUE: 6
Year: 2008
Page: [468 - 481]
Pages: 14
DOI: 10.2174/138920108786786402
Price: $58