Identification of Sites of Degradation in a Therapeutic Monoclonal Antibody by Peptide Mapping
- 1 January 1992
- journal article
- Published by Springer Science and Business Media LLC in Pharmaceutical Research
- Vol. 9 (11), 1386-1393
- https://doi.org/10.1023/a:1015894409623
Abstract
A peptide mapping procedure was developed to locate regions of a monoclonal antibody, OKT3, that undergo chemical modification as the molecule degrades upon storage. The structures of these peptide degradation products were investigated. Deamidation at specific asparagine residues and oxidation of a cysteine and several methionines were found to be major routes of OKT3 degradation. A unique chain cross-linked degradation product was also observed and characterized. Changing the storage conditions of the antibody affected the relative distribution of degradation products. These results were useful in the development of more stable formulations for OKT3, and the methods can be used in the characterization of other monoclonal antibodies intended for therapeutic use.Keywords
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