Structure-based Discovery of a new Protein-Aggregation Breaking Excipient

Andreas Tosstorff, Hristo Svilenov, Günther H.J. Peters, Pernille Harris, Gerhard Winter

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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 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.
Original languageEnglish
JournalEuropean Journal of Pharmaceutics and Biopharmaceutics
Volume144
Pages (from-to)207-216
Number of pages10
ISSN0939-6411
DOIs
Publication statusPublished - 2019

Keywords

  • Interferon-alpha-2a
  • Virtual screen
  • Excipient
  • Protein aggregation
  • Protein formulation

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