A colloid approach to self-assembling antibodies

TL;DR

This study uses a colloid-inspired patchy model combined with experiments and simulations to understand and predict the phase behavior, interactions, and viscosity of concentrated monoclonal antibody solutions, aiding pharmaceutical formulation.

Contribution

It introduces a simple patchy model that accurately describes antibody solution behavior, accounting for anisotropic shape and charge, and predicts effects of modifications on interactions and viscosity.

Findings

Quantitative description of structural and dynamic properties across concentrations

Effective estimation of attraction between antibody binding sites

Model's potential to guide formulation improvements

Abstract

Concentrated solutions of monoclonal antibodies have attracted considerable attention due to their importance in pharmaceutical formulations, yet their tendency to aggregate and the resulting high solution viscosity has posed considerable problems. It remains a very difficult task to understand and predict the phase behavior and stability of such solutions. Here we present a systematic study of the concentration dependence of the structural and dynamic properties of monoclonal antibodies using a combination of different scattering methods and microrheological experiments. To interpret these data, we use a colloid-inspired approach based on a simple patchy model, which explicitly takes into account the anisotropic shape and the charge distribution of the molecules. Combining theory, simulations and experiments, we are able to disentangle self-assembly and intermolecular interactions and to quantitatively describe the concentration dependence of structural and dynamic quantities such as the osmotic compressibility, the collective diffusion coefficient and the zero shear viscosity over the entire range of investigated concentrations. This simple patchy model not only allows us to consistently describe the thermodynamic and dynamic behavior of mAb solutions, but also provides a robust estimate of the attraction between their binding sites. It will thus be an ideal starting point for future work on antibody formulations, as it provides a quantitative assessment of the effects of additional excipients or chemical modifications on antibody interactions, and a prediction of their effect on solution viscosity.