Drug Discovery & Development

Application Notes

Presentations

Selecting the Best Construct During Protein Engineering

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 stability of these potential therapeutics is of paramount importance for their manufacturing and formulation as drug products.

DSC can quickly and easily identify the most stable engineered protein construct based on thermal shifts. Increases in thermal stability correlate well with increased expression levels as well as increases in the amount of functional protein in isolate fractions (Data and image courtesy of Stephen Demarest, Biogen-Idec).

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.

Why use DSC for construct selection during biotherapeutic engineering?

• Quickly and easily guide the selection of stable protein constructs
• Rapidly reduce the number of candidates processed downstream