The criticality of high-resolution N-linked carbohydrate assays and detailed characterization of antibody effector function in the context of biosimilar development.

Abstract:

:Accurate measurement and functional characterization of antibody Fc domain N-linked glycans is critical to successful biosimilar development. Here, we describe the application of methods to accurately quantify and characterize the N-linked glycans of 2 IgG1 biosimilars with effector function activity, and show the potential pitfalls of using assays with insufficient resolution. Accurate glycan assessment was combined with glycan enrichment using lectin chromatography or production with glycosylation inhibitors to produce enriched pools of key glycan species for subsequent assessment in cell-based antibody-dependent cell-mediated cytotoxicity and complement-dependent cytotoxicity effector function assays. This work highlights the challenges of developing high-quality biosimilar candidates and the need for modern biotechnology capabilities. These results show that high-quality analytics, combined with sensitive cell-based assays to study in vivo mechanisms of action, is an essential part of biosimilar development.

journal_name

MAbs

journal_title

mAbs

authors

Brady LJ,Velayudhan J,Visone DB,Daugherty KC,Bartron JL,Coon M,Cornwall C,Hinckley PJ,Connell-Crowley L

doi

10.1080/19420862.2015.1016692

subject

Has Abstract

pub_date

2015-01-01 00:00:00

pages

562-70

issue

3

eissn

1942-0862

issn

1942-0870

journal_volume

7

pub_type

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