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  • Title: Application of Affinity-Capture Self-Interaction Nanoparticle Spectroscopy in Predicting Protein Stability, Especially for Co-Formulated Antibodies.
    Author: Zhou M, Yan Z, Li H, Liu X, Sun P.
    Journal: Pharm Res; 2021 Apr; 38(4):721-732. PubMed ID: 33754257.
    Abstract:
    PURPOSE: From traditional monoclonal antibodies to more and more complex mAb-based formulations, biopharmaceutical faces one challenge after another. To avoid these issues, identification of therapeutic proteins in the initial discovery process that has high stability and low self-interaction would simplify the development of safe and effective antibody therapeutics. METHOD: Affinity-capture self-interaction nanoparticle spectroscopy (AC-SINS) is a new prediction method capable of identifying mAbs with different self-association propensity. In this study, 10 formulated monoclonal antibody (mAb) therapeutics include different mAb isotypes and co-formulated antibodies were measured by AC-SINS and some biophysical methods to predict protein stability. The prediction results of all 10 mAbs were compared to their stability data (Δ%monomer and Δ%HMWs) at accelerated (25°C and 40°C) and long-term storage conditions (4°C) as measured by size exclusion chromatography. RESULT: AC-SINS method has a good predictive correlation with each mAbs and co-formulated antibodies. There were no physicochemical, intermolecular, or biological interactions that occurred between the two components of co-formulated antibodies which confirmed by Analytical ultracentrifugation (AUC). CONCLUSION: Here we discuss the correlation between each method and protein stability, and also use AC-SINS assay to predict the stability of co-formulated antibodies for the first time. This may be an effective way to predict the stability of these complex mAb-based formulations such as co-formulated mAbs.
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