title: Aggregation risk prediction for antibodies and its application to biotherapeutic development.
abstract: Aggregation is a common problem affecting biopharmaceutical development that can have a significant effect on the quality of the product, as well as the safety to patients, particularly because of the increased risk of immune reactions. Here, we describe a new high-throughput screening algorithm developed to classify antibody molecules based on their propensity to aggregate. The tool, constructed and validated on experimental aggregation data for over 500 antibodies, is able to discern molecules with a high aggregation propensity as defined by experimental criteria relevant to bioprocessing and manufacturing of these molecules. Furthermore, we show how this tool can be combined with other computational approaches during early drug development to select molecules with reduced risk of aggregation and optimal developability properties.
authors.affiliation: a Applied Protein Services ; Lonza Biologics ; Cambridge , UK.
authors.forename: Olga
authors.initials: O
authors.lastname: Obrezanova
authors.forename: Andreas
authors.initials: A
authors.lastname: Arnell
authors.forename: Ramón Gómez
authors.initials: RG
authors.lastname: de la Cuesta
authors.forename: Maud E
authors.initials: ME
authors.lastname: Berthelot
authors.forename: Thomas R A
authors.initials: TR
authors.lastname: Gallagher
authors.forename: Jesús
authors.initials: J
authors.lastname: Zurdo
authors.forename: Yvette
authors.initials: Y
authors.lastname: Stallwood
mesh_terms: D000465:Algorithms; D000906:Antibodies / Q000737:chemistry*; D006801:Humans; D066329:Protein Aggregates
chemical_list: D000906:Antibodies; D066329:Protein Aggregates
keywords: CDR, complementarity determining region; CH1, heavy chain constant domain; CL, light chain constant domain; ELISA, enzyme-linked immunosorbent assay; Fab, fragment antigen-binding; Fv, fragment variable; IgG, immunoglobulin G; ODA, oligomer detection assay; SE-HPLC, size exclusion high pressure liquid chromatography; VH, heavy chain variable region; VL, light chain variable region; aggregation; aggregation prediction; biotherapeutics; developability assessment; monoclonal antibody