Monoclonal antibodies (mAbs) are often formulated at high concentrations in order to achieve
therapeutic dosage. At high protein concentrations, the spatial distances between individual
protein molecules decrease significantly, as a result, a variety of non-specific protein-protein
interactions (PPI) can take place, causing protein aggregation and/or elevated solution viscosity.
In order to address this problem, excipients are frequently used to improve the physical stability
and viscosity of mAb formulations. In this study, we examined the physical stability and viscosity
of concentrated mAb formulations using a series of excipients. In particular, small angle X-ray
scattering (SAXS) experiments were performed to obtain the experimental effective structure factor
S(q) eff , which contains information on the nature of PPI at high protein concentrations. To take the
configurational flexibility of an antibody protein into account, ensembles of atomistic structures were
obtained using SASSIE, variations in S(q) eff were then calculated from experimental total scattering
I(q) and collections of P(q).