High concentration formulation studies of an IgG2 antibody using small angle X-ray scattering.

Purpose: Concentrated protein formulations are strongly influenced by protein-protein interactions. These can be probed at low protein concentration by e.g.

Extensive small-angle X-ray scattering studies of blood coagulation factor VIIa reveal interdomain flexibility.

Blood coagulation factor VIIa (FVIIa) is used in the treatment of replacement therapy resistant hemophilia patients, and FVIIa is normally activated upon complex formation with tissue factor (TF), potentially in context with structural rearrangements. The solution behavior of uncomplexed FVIIa is important for understanding the mechanism of activation and for the stability and activity of the pharmaceutical product. However, crystal structures of FVIIa in complex with TF and of truncated free FVIIa reveal different overall conformations while previous small-angle scattering studies suggest FVIIa always to be fully extended in solution.