研究期間：10308~10407;Understanding and Overcoming Analytic, Formulation, Manufacturing, and Regulatory Challenges of protein drug or biosimilars covers the latest trends and challenges of both academic and R&D of pharmaphutical companies. The focus are on: understanding and controlling biologics aggregation, improving detection and quantitation of aggregates, analyzing subvisible and visible particles with various techniques, understanding aggregates as an inducing factor in immungenicity, and improving structural analysis and modeling to predict protein aggregation. In a word to describe all the above attention focus is “second virial coefficient B22” of biologics and its conjugates in solution. The investigation is first to cope the theoretical developments of the current methods for B22 measurements, especially focus is on Self Interaction Chromatography (SIC). Secondly, based on our extensive experience on Isothermal Titration Calorimetry (ITC), we will derive a statistic thermodynamics model to obtain B22 from biologics solution dilution enthalpy measurements. Finally, the B22 value will be featured with the experiments results of biologics aggregation behavior in protein purifcation, protein conformational disease (PCD) and protein crystallization. The study will discuss in-depth the effects of solutes (co-solvent, including PEG, Arigine, salts) on B22 of protein in solution and the measurements of the protein aggregation and crystallization will be investigated by Static Light Scattering and Crystallization measurements.
