Development of a fast workflow to screen the charge variants of therapeutic antibodies.
Fiche publication
Date publication
mai 2017
Journal
Journal of chromatography. A
Auteurs
Membres identifiés du Cancéropôle Est :
Dr CIANFERANI Sarah
Tous les auteurs :
Wagner-Rousset E, Fekete S, Morel-Chevillet L, Colas O, Corvaïa N, Cianférani S, Guillarme D, Beck A
Lien Pubmed
Résumé
Chemical or enzymatic modifications of therapeutic monoclonal antibodies (mAbs) having high risk towards safety and efficacy are defined as critical quality attributes (CQAs). During therapeutic mAbs process development, a variety of analytical techniques have to be used for the thorough characterization and quantitative monitoring of CQAs. This paper describes the development of a rapid analytical platform to assess and rank charge variants of mAbs. The workflow is first based on a cation exchange chromatography (CEX) comparative analysis of intact IgGs versus F(ab)'2 and Fc sub-domains generated by IdeS digestion. This analytical procedure was validated with FDA and EMA approved mAbs. Then, functional assays and peptide mapping can be performed in a second instance. This approach can be used during the early stage of drug research and development to screen lead molecules and select optimized candidates (best clone, best formulation) which could be "easily" developed (OptimAbs).
Mots clés
Cation exchange chromatography, Charge variants, Developability, IdeS, Trastuzumab
Référence
J Chromatogr A. 2017 May;1498:147-154