Measuring aggregates, self-association, and weak interactions in concentrated therapeutic antibody solutions

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 -