title: Comparative Evaluation of the Chemical Stability of 4 Well-Defined Immunoglobulin G1-Fc Glycoforms.
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.
authors: Department of Pharmaceutical Chemistry, University of Kansas, Lawrence, Kansas 66047.
authors: Olivier
authors: O
authors: Mozziconacci
authors: Department of Pharmaceutical Chemistry, University of Kansas, Lawrence, Kansas 66047.
authors: Solomon
authors: S
authors: Okbazghi
authors: Department of Pharmaceutical Chemistry, University of Kansas, Lawrence, Kansas 66047.
authors: Apurva S
authors: AS
authors: More
authors: Department of Pharmaceutical Chemistry, University of Kansas, Lawrence, Kansas 66047.
authors: David B
authors: DB
authors: Volkin
authors: Department of Pharmaceutical Chemistry, University of Kansas, Lawrence, Kansas 66047.
authors: Thomas
authors: T
authors: Tolbert
authors: Department of Pharmaceutical Chemistry, University of Kansas, Lawrence, Kansas 66047. Electronic address: schoneic@ku.edu.
authors: Christian
authors: C
authors: Schöneich
mesh_terms: D004353:Drug Evaluation, Preclinical / Q000379:methods; D004355:Drug Stability; D006023:Glycoproteins / Q000737:chemistry* / Q000378:metabolism; D006031:Glycosylation; D007141:Immunoglobulin Fc Fragments / Q000737:chemistry* / Q000378:metabolism; D007074:Immunoglobulin G / Q000737:chemistry* / Q000378:metabolism
chemical_list: D006023:Glycoproteins; D007141:Immunoglobulin Fc Fragments; D007074:Immunoglobulin G
keywords: H(2)O(2); UV light; antibody; biosimilar; glycoform; metal; oxidation; peroxide; stability