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The Relative Rate of Immunoglobulin Gamma 1 Fragmentation

Authors :
Tim J. Kamerzell
Y. John Wang
Megan Li
Junyan A. Ji
Shaily Arora
Source :
Journal of Pharmaceutical Sciences. 100:1341-1349
Publication Year :
2011
Publisher :
Elsevier BV, 2011.

Abstract

The physicochemical stability of protein therapeutics is of significant pharmaceutical interest. Immunoglobulin gamma (IgG) hinge region fragmentation has recently garnered attention as an important degradation route of therapeutic monoclonal antibodies. In this work, the rates and relative amount of fragment species are compared for five different IgGs (IgG1–5) with widely varying solution properties. Native size-exclusion chromatography (SEC), sodium dodecyl sulfate (SDS)-based SEC, and capillary electrophoresis-SDS were used to characterize IgG1 fragmentation after storage at 30°C, 40°C, and 50°C. Two-dimensional correlation analysis of the chromatograms as a function of time was used to illustrate the relative rates of cleavage. Interestingly, the relative rate of Fab cleavage was greater than that of other species. An average apparent energy of activation for IgG1 fragmentation was also measured for all five molecules. This work suggests that IgG1 fragmentation is primarily hinge sequence dependent and other IgG1 molecules should behave similarly within the limits of the solution conditions used.

Details

ISSN :
00223549
Volume :
100
Database :
OpenAIRE
Journal :
Journal of Pharmaceutical Sciences
Accession number :
edsair.doi.dedup.....bb7e9ba38a20d0e09cf73a7b564400ed
Full Text :
https://doi.org/10.1002/jps.22389