Measuring aggregates, self-association, and weak interactions in concentrated therapeutic antibody solutions. Issue 1 (1st January 2020)

• Record Type: Journal Article
• Authors: Chaturvedi, Sumit K.; Parupudi, Arun; Juul-Madsen, Kristian; Nguyen, Ai; Vorup-Jensen, Thomas; Dragulin-Otto, Sonia; Zhao, Huaying; Esfandiary, Reza; Schuck, Peter
• Is Part Of: MAbs. Volume 12:Issue 1(2020)
• Publication Date: 2020-01-01
• Subjects: Trace aggregation -- nonideality -- virial coefficient -- self-association -- hydrodynamics -- protein interactions -- sedimentation velocity; Monoclonal antibodies -- Therapeutic use -- Periodicals; Monoclonal antibodies -- Periodicals; Antibodies, Monoclonal -- Periodicals; 616.0798
• DOI: 10.1080/19420862.2020.1810488
• Languages: English
• ISSNs: 1942-0862

Abstract

ABSTRACT: Monoclonal antibodies are a class of biotherapeutics used for an increasing variety of disorders, including cancer, autoimmune, neurodegenerative, and viral diseases. Besides their antigen specificity, therapeutic use also mandates control of their solution interactions and colloidal properties in order to achieve a stable, efficacious, non-immunogenic, and low viscosity antibody solution at concentrations in the range of 50–150 mg/mL. This requires characterization of their reversible self-association, aggregation, and weak attractive and repulsive interactions governing macromolecular distance distributions in solution. Simultaneous measurement of these properties, however, has been hampered by solution nonideality. Based on a recently introduced sedimentation velocity method for measuring macromolecular size distributions in a mean-field approximation for hydrodynamic interactions, we demonstrate simultaneous measurement of polydispersity and weak and strong solution interactions in a panel of antibodies with concentrations up to 45 mg/mL. By allowing approximately an order of magnitude higher concentrations than previously possible in sedimentation velocity size distribution analysis, this approach can substantially improve efficiency and sensitivity for characterizing polydispersity and interactions of therapeutic antibodies at or close to formulation conditions.