High Throughput Prediction Approach for Monoclonal Antibody Aggregation at High Concentration.

摘要: Characterization of the monoclonal antibody aggregation process and identification stability factors that could be used as indicators propensity with an emphasis on a large number samples low protein material consumption. Differential scanning calorimetry, dynamic light scattering size exclusion chromatography were main methodological approaches. Conformational stability, colloidal kinetics assessed for two different IgG (mAbs) subclasses. Aggregation was induced by exposing mAbs to 55°C 3 weeks. mAb prepared in formulations concentrations from 1 mg/mL 50 mg/mL. High temperature stress revealed antibodies followed first order kinetics, which suggests rate-limiting step monomer loss unimolecular. estimated denaturation measurements. Colloidal interaction parameter k D . The correlation between conformational evaluated parameter found promising predictor antibodies. meaning using intermolecular prediction what is essentially unimolecular also discussed. This work estimates significance predictors at high part throughput, resource screening method contribution towards determining phenomena actual systems development production biopharmaceuticals.