title: Development of a fast workflow to screen the charge variants of therapeutic antibodies.
abstract: 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).
authors.affiliation: Centre d'Immunologie Pierre Fabre, 5 Avenue Napoléon III, 74160, Saint-Julien-en-Genevois, France. Electronic address: elsa.wagner@pierre-fabre.com.
authors.forename: Elsa
authors.initials: E
authors.lastname: Wagner-Rousset
authors.affiliation: School of Pharmaceutical Sciences, University of Geneva, University of Lausanne, Boulevard d'Yvoy 20, 1211 Geneva 4, Switzerland.
authors.forename: Szabolcs
authors.initials: S
authors.lastname: Fekete
authors.affiliation: Centre d'Immunologie Pierre Fabre, 5 Avenue Napoléon III, 74160, Saint-Julien-en-Genevois, France.
authors.forename: Laura
authors.initials: L
authors.lastname: Morel-Chevillet
authors.affiliation: Centre d'Immunologie Pierre Fabre, 5 Avenue Napoléon III, 74160, Saint-Julien-en-Genevois, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Colas
authors.affiliation: Centre d'Immunologie Pierre Fabre, 5 Avenue Napoléon III, 74160, Saint-Julien-en-Genevois, France.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Corvaïa
authors.affiliation: LSMBO, IPHC, Université de Strasbourg, 25 rue Becquerel, 67087 Strasbourg, France.
authors.forename: Sarah
authors.initials: S
authors.lastname: Cianférani
authors.affiliation: School of Pharmaceutical Sciences, University of Geneva, University of Lausanne, Boulevard d'Yvoy 20, 1211 Geneva 4, Switzerland.
authors.forename: Davy
authors.initials: D
authors.lastname: Guillarme
authors.affiliation: Centre d'Immunologie Pierre Fabre, 5 Avenue Napoléon III, 74160, Saint-Julien-en-Genevois, France. Electronic address: alain.beck@pierre-fabre.com.
authors.forename: Alain
authors.initials: A
authors.lastname: Beck
mesh_terms: D000068879:Adalimumab / Q000378:metabolism; D000595:Amino Acid Sequence; D000911:Antibodies, Monoclonal / Q000378:metabolism*; D001426:Bacterial Proteins / Q000378:metabolism; D000068258:Bevacizumab / Q000378:metabolism; D002852:Chromatography, Ion Exchange; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000378:metabolism; D007141:Immunoglobulin Fc Fragments / Q000737:chemistry / Q000378:metabolism; D010449:Peptide Mapping; D010455:Peptides / Q000032:analysis* / Q000302:isolation & purification; D000069283:Rituximab / Q000378:metabolism; D016415:Sequence Alignment
chemical_list: D000911:Antibodies, Monoclonal; D001426:Bacterial Proteins; D007140:Immunoglobulin Fab Fragments; D007141:Immunoglobulin Fc Fragments; C442815:Mac-1-like protein, Streptococcus; D010455:Peptides; D000068258:Bevacizumab; D000069283:Rituximab; D000068879:Adalimumab
keywords: Cation exchange chromatography; Charge variants; Developability; IdeS; Trastuzumab