Drug Discovery & Development

Protein Engineering

Monoclonal antibodies, antibody-like proteins, and other biotherapeutics represent a large and growing number of molecular entities entering human clinical trials in virtually all disease indications. The long-term stability of these potential therapeutics is of paramount importance for their manufacturing and formulation as drug products. 

Differential Scanning Calorimetry (DSC) provides rapid, accurate, and easy to perform measurement of the thermal transition midpoint (Tm), which has proven to be exceptionally good indicator of the relative stability of engineered proteins.  DSC can identify stable engineered construct candidates early, before any bioprocessing, and eliminate those that are more likely to fail.  DSC enables users to save time and money by culling constructs that are likely to fail early in the process and focus on those that are more viable for downstream development.

 

In addition to monitoring stability during protein engineering, biological activity must also be monitored. Various analytical methods are commonly employed to monitor the biological activity of engineered biotherapeutics to confirm that proteins remain functionally active before development ensues.  Isothermal Titration Calorimetry (ITC) provides a rapid, accurate and easy to perform method to monitor the biological activity of a biotherapeutic.  Activity is assayed by monitoring both the binding of proteins to their therapeutic targets and the binding stoichiometry to ensure that a biotherapeutic retains functional activity.  Using ITC, biological activity is monitored in solution, label-free, requiring no immobilization and minimal assay development, thus providing unique benefits over traditional methods.

Why use microcalorimetry during biotherapeutic engineering?

  • Quickly and easily guide the selection of stable protein constructs.
  • Rapidly reduce the number of candidates processed downstream.
  • All measures are done in solution, label-free, requiring no immobilization and minimal assay development.
  • Monitor both binding affinity and stoichiometry in a single experiment.
  • Quickly and easily assess whether engineered protein is active.

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