Behavior of Monoclonal Antibodies: Relation Between the Second Virial Coefficient (B2) at Low Concentrations and Aggregation Propensity and Viscosity at High Concentrations

ABSTRACTPurposeTo investigate relationship between second virial coefficient B2 and viscosity and aggregation propensity of highly concentrated monoclonal antibody (MAbs) solutions.MethodsIntermolecular interactions of 3 MAbs solutions with varying pH were characterized according to B2 estimated by analytical ultracentrifugation sedimentation equilibrium with initial loading concentrations <10 mg/mL. Viscosity measurements and stability assessments of MAb solutions at concentrations higher than 100 mg/mL were conducted.ResultsB2 of all MAb solutions depended on solution pH and have qualitative correlation with viscosity and aggregation propensity. The more negative the B2 values, the more viscous the solution, acquiring increased propensity to aggregate. Solutions with B2 values of ~2 × 10−5 mL·mol/g2 acquire similar viscosity and aggregation propensity regardless of amino acid sequences; for solutions with negative B2 values, viscosity and aggregation propensity differed depending on sequences. Results suggest attractive intermolecular interactions represented by negative B2 values are influenced by surface properties of individual MAbs.ConclusionsB2 can be used, within certain limitations, as an effective indicator of viscosity and aggregation propensity of highly concentrated MAb solutions.

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