Predicting Diffusion and Viscous Dissipation in Therapeutic Antibody Solutions

Therapeutic antibodies represent the fastest growing segment of the biopharmaceutical industry. Their application to treatment of cancers and autoimmune diseases is prolific. The engineering of antibodies, processes for their production, and mechanisms for administration is of intense scientific interest. Because of their sequence specific, heterogeneous charge distribution, antibodies can interact strongly, which has a significant impact on solution rheology. The viscosity of antibody solutions is a key parameter and constraint on processes such as ultra-filtration and administration routes such as subcutaneous or intravitreal injection. No methods exist currently to predict the rheology and dynamics of concentrated antibody solutions. I will present the results of a study of two antibodies via coarse-grained simulations. The simulations incorporate hydrodynamic interactions between the suspended proteins as well as appropriate colloidal interactions among the coarse-grained domains. The simulations reproduce the static structure factor of each antibody measured via neutron scattering, and different estimates of the intermolecular friction are used bound the short-time self-diffusivity measured via neutron spin echo. The shear stress autocorrelation function and the zero shear viscosity are computed. Good agreement is found with the measured viscosity of one of the antibodies. However, the simulations significantly underestimate the viscosity of the other antibody. This too can be attributed to uncertainty in the intermolecular friction and suggests potential avenues for future investigation.