Structure-based discovery of a new protein-aggregation breaking excipient

Reducing the aggregation of proteins is of utmost interest to the pharmaceutical industry. Aggregated proteins are often less active and can cause severe immune reactions in the patient upon administration. At the same time the biopharmaceutical market is pushing for high concentration formulations and products that do not require refrigerated storage conditions. For a given protein, the only solution pH, ionic strength and concentration of a very limited number of excipients are the only parameters that can be varied to obtain a stable formulation. In this work, we present a structure-based approach to discover new molecules that successfully reduce the aggregation of proteins and apply the approach to the model protein Interferon-alpha-2a