SAXS study on protein-protein interactions in freeze concentrates on understanding the impact of formulation and temperature during freezing

SAXS has been used to gain deeper insight into protein-protein (PP) distances and interactions by the structure factor S(q). But there is a lack of knowledge about highly concentrated states of 200 g/L protein and above, in particular, those formed upon freezing of bulk solution for frozen storage, as ice crystallizes out and solutes, protein, and excipients like cryoprotectant or buffer, concentrate. Furthermore, more insights into the relationship between S(q) and viscosity are to be obtained. The focus of the study is to investigate 1. the impact of freeze concentration on PP distance and interactions, 2. the effect of formulation on PPI and PP distance in the freeze-concentrate, 3. the relationship between viscosity and S(q) and comparison to theoretical SAXS data obtained by molecular dynamics simulations. Pharmaceutically relevant monoclonal antibodies will be used.