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The Relative Rate of Immunoglobulin Gamma 1 Fragmentation
- 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.
- Subjects :
- Chromatography
biology
medicine.drug_class
Temperature
Electrophoresis, Capillary
Sodium Dodecyl Sulfate
Pharmaceutical Science
Cleavage (embryo)
Monoclonal antibody
Immunoglobulin G
chemistry.chemical_compound
chemistry
Chromatography, Gel
biology.protein
medicine
Humans
Degradation (geology)
Molecule
Antibody
Sodium dodecyl sulfate
Fragmentation (cell biology)
Immunoglobulin Fragments
Subjects
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