Abstract:
:As part of a series of articles in this special issue evaluating model IgG1-Fc glycoforms for biosimilarity analysis, 3 well-defined IgG1-Fc glycoforms (high mannose-Fc, Man5-Fc, and N-acetylglucosamine-Fc) and a nonglycosylated Fc protein (N297Q-Fc) were examined in this work to elucidate chemical degradation pathways. The 4 proteins underwent a combination of accelerated thermal stability studies and 4 independent forced degradation studies (UV light, metal-catalyzed oxidation, peroxyl radicals, and hydrogen peroxide) at pH 6.0. Our results highlight chemical degradations at Asn315, Met428, Trp277, and Trp313. A cross-comparison of the different Fc glycoforms, stress conditions, and the observed chemical reactions revealed that both the deamidation of Asn315 and the transformation of Trp277 into glycine hydroperoxide were glycan dependent during incubation for 3 months at 40 °C. Our data will show that different glycans not only affect chemical degradation differently but also do lead to different impurity profiles, which can affect chemical degradation.
journal_name
J Pharm Scijournal_title
Journal of pharmaceutical sciencesauthors
Mozziconacci O,Okbazghi S,More AS,Volkin DB,Tolbert T,Schöneich Cdoi
10.1016/j.xphs.2015.10.024subject
Has Abstractpub_date
2016-02-01 00:00:00pages
575-587issue
2eissn
0022-3549issn
1520-6017pii
S0022-3549(15)00025-8journal_volume
105pub_type
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