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Tosstorff, Andreas ORCID: 0000-0002-4969-3667; Svilenov, Hristo ORCID: 0000-0001-5863-9569; Peters, Günther H. J.; Harris, Pernille; Winter, Gerhard ORCID: 0000-0002-7413-6627 (12. September 2019): Structure-based Discovery of a new Protein-Aggregation Breaking Excipient. In: European Journal of Pharmaceutics and Biopharmaceutics
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Abstract

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 liquid formulation developer’s toolbox is limited to achieve these goals: pH, ionic strength and concentration of a very limited number of excipients are the only solution parameters to be varied. In this work, we present a structure-based approach to discover new molecules that successfully reduce the aggregation of proteins and apply it to the model protein Interferon-alpha-2a.