title: Developability assessment during the selection of novel therapeutic antibodies.
abstract: Therapeutic antibodies and antibody derivatives comprise the majority of today's biotherapeutics. Routine methods to generate novel antibodies, such as immunization and phage-display, often give rise to several candidates with desired functional properties. On the contrary, resource-intense steps such as the development of a cell line, a manufacturing process, or a formulation, are typically carried out for only one candidate. Therefore, "developability," that is, the likelihood for the successful development of a lead candidate into a stable, manufacturable, safe, and efficacious drug, may be used as an additional selection criterion. Employing a set of small-scale, fast, and predictive tests addressing biochemical and biophysical features, as well as in vivo fate can help to identify a clinical candidate molecule with promising properties at an early stage of drug development. This article gives an overview of existing methods for developability testing and shows how these assays can be interlaced in the lead selection process.
authors.affiliation: Roche Pharma Research and Early Development, Roche Innovation Center Penzberg, Nonnenwald 2, 82377 Penzberg, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Jarasch
authors.affiliation: Roche Pharma Research and Early Development, Roche Innovation Center Penzberg, Nonnenwald 2, 82377 Penzberg, Germany.
authors.forename: Hans
authors.initials: H
authors.lastname: Koll
authors.affiliation: Roche Pharma Research and Early Development, Roche Innovation Center Penzberg, Nonnenwald 2, 82377 Penzberg, Germany.
authors.forename: Joerg T
authors.initials: JT
authors.lastname: Regula
authors.affiliation: Roche Pharma Research and Early Development, Roche Innovation Center Penzberg, Nonnenwald 2, 82377 Penzberg, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Bader
authors.affiliation: Roche Pharma Research and Early Development, Roche Innovation Center Penzberg, Nonnenwald 2, 82377 Penzberg, Germany.
authors.forename: Apollon
authors.initials: A
authors.lastname: Papadimitriou
authors.affiliation: Roche Pharma Research and Early Development, Roche Innovation Center Penzberg, Nonnenwald 2, 82377 Penzberg, Germany. Electronic address: hubert.kettenberger@roche.com.
authors.forename: Hubert
authors.initials: H
authors.lastname: Kettenberger
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry / Q000276:immunology / Q000494:pharmacology*; D055808:Drug Discovery / Q000379:methods*; D006031:Glycosylation; D006801:Humans; D008958:Models, Molecular; D011487:Protein Conformation; D055550:Protein Stability
chemical_list: D000911:Antibodies, Monoclonal
keywords: analytical biochemistry; bioinformatics; biotechnology; deamidation; degradation products; immune response; in silico modeling; monoclonal antibody; oxidation; pharmacokinetics