(446g) Gauging Colloidal and Thermal Stability in Human IgG1 – Sugar Solutions Through Diffusivity Measurements

Monoclonal antibodies are the fastest growing class of biotherapeutics. Ensuring their colloidal stability in liquid dispersions is crucial for maintaining therapeutic efficacy and economic viability. Sugars are often added to increase the colloidal and thermal stability of protein; yet, determining which sugar is the most stabilizing requires time and sample-consuming stability tests. Here we show that the extent of stabilization by different sugars can be gauged by analyzing the proteins' diffusive virial coefficient k_D. This protein interaction parameter is measured conveniently in a non-invasive, high-throughput manner using dynamic light scattering. It is found to correlate closely with experimental dimerization rate constants and melting temperatures for antibodies in different sugar solutions. The proposed analysis thus provides a rapid test of the subtle differences between inherently similar sugar-protein interactions; it should greatly facilitate the formulation of protein therapeutics. Among the tested sugars we observe a trend of disaccharides providing more efficient stabilization than monosaccharides. Circular dichroism spectroscopy further suggests that the sugar induced thermal stabilization involves a reversibly formed intermediate protein conformation between the native and fully denatured state.