Early lead selection of biotherapeutics during preclinical development requires careful characterization of a variety of molecule properties to reduce the risk for encountering unexpected obstacles during technical development. The diversity and increasing complexity of new protein formats requires a change from former platform approaches often applied for antibodies, to project specific strategies. The developability assessment concept applied at Novartis combines information addressing various technical areas, such as expression, aggregation propensity, process fit, stability, physicochemical properties, etc. This integrated concept prior to lead selection provides a thorough, yet resource-efficient approach to select suitable candidates.
In biopharmaceutical research, proteins are characterized in meticulous detail. Unsuitable candidates need to be deselected early, and only the most promising candidates are moved forward in development and into clinical testing. Understanding protein stability is an important piece of this puzzle. The Prometheus system and its nanoDSF technology allow label-free analysis of thermal and chemical stability as well as aggregation of proteins. Its low sample requirements and broad concentration range make it an ideal tool for all steps of drug development.
This presentation will demonstrate:
- the benefits of nanoDSF: label-free, highly precise and reproducible, easy-to-do measurements of any kind of protein, using just 10 µl of sample.
- how Prometheus generates unfolding temperatures (Tm and Tonset), critical denaturant concentrations (Cm), free folding energy (ΔG and ΔΔG), and aggregation results (Tagg).
- a variety of application examples.