TY - JOUR
T1 - Measuring aggregates, self-association, and weak interactions in concentrated therapeutic antibody solutions
AU - Chaturvedi, Sumit K
AU - Parupudi, Arun
AU - Juul-Madsen, Kristian
AU - Nguyen, Ai
AU - Vorup-Jensen, Thomas
AU - Dragulin-Otto, Sonia
AU - Zhao, Huaying
AU - Esfandiary, Reza
AU - Schuck, Peter
PY - 2020
Y1 - 2020
N2 - 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.
AB - 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.
KW - Trace aggregation
KW - hydrodynamics
KW - nonideality
KW - protein interactions
KW - sedimentation velocity
KW - self-association
KW - virial coefficient
UR - http://www.scopus.com/inward/record.url?scp=85090354618&partnerID=8YFLogxK
U2 - 10.1080/19420862.2020.1810488
DO - 10.1080/19420862.2020.1810488
M3 - Journal article
C2 - 32887536
SN - 1942-0862
VL - 12
JO - mAbs
JF - mAbs
IS - 1
M1 - 1810488
ER -