Issue link: https://resources.nanotempertech.com/i/1527198
mAb22 mAb2 55 60 65 70 75 80 85 90 55 60 65 70 75 80 85 90 Turbidity (IP, °C) Ratio (IP Fab , °C) Thermal & colloïdal stabilities of 25 mAbs © 2024 NanoTemper Technologies, GmbH, Munich, Germany. All Rights Reserved. The Panta allows us to quickly perform a comprehensive ranking of our mAbs and the combination of multiple parameters improves our confidence in the selection of the best candidates for clinical development. Figure 2: Ranking of 25 mAbs using both thermal and colloidal stability properties. The temperature at which the formation of large aggregates start is plotted against the ratio of the second inflection point, IP Fab , characterizing the melting temperature (T m ) of the Fab domain. A linear correlation is observed between thermal and colloidal stability. Interestingly, 4 outliers show lower colloidal stability and can be triaged out, in profit of mAbs showing higher values both for T m and T turb . C A S E S T U D Y Results and Benefits Elsa's team has investigated a panel of 25 hits which are binders of the same biological target. All mAbs are hIgG1-K formulated in an His-buffer at a concentration of 2 mg /mL, making comparison of data within the mAb series possible. Among the panel, data of 2 mAbs are displayed in Figure 1. The thermal stability curves display 3 transitions each. IP Fab – which correspond to the unfolding transition of variable domains – occurs at 87°C for mAb2 whereas it is measured at 61°C for mAb22. Similarly, turbidity (T turb ) and particle sizes increase earlier during the temperature ramp for mAb22, showing less stable variable domains for mAb22 than mAb2. Dr. Elsa Wagner Senior Scientist, Pierre Fabre Figure 1: Simultaneous stability measurements of mAb2 and mAb22 across a thermal ramp from 25°C to 95°C at a ramp of 1°C/min. Stability High Low Prometheus Panta increases the set of physicochemical parameters in Dr. Wagner's developability assessment without needing multiple instruments. This streamlines her developability platform, reducing complexity, cost, and sample consumption, while generating more valuable data. By measuring multiple stability parameters in parallel, she gains a comprehensive view of her mAb's developability, enabling confident decision-making about candidates. The Solution Prometheus Panta offers simultaneous DLS, nanoDSF, SLS, and backreflection measurements, providing comprehensive data on thermal unfolding, particle sizing, and aggregation from a single measurement. Its high-resolution analysis enables Dr. Wagner to identify multiple unfolding transitions corresponding to the different mAb domains, correlate stability parameters, and confidently advance the best candidates for further development. Outliers 3.162 10 31.623 100 316.228 1000 3162.278 10000 31622.777 Cumulant Radius [nm] 80 90 100 110 120 130 140 150 160 170 Turbidity [mAU] 0.6 0.65 0.7 0.75 0.8 0.85 Ratio 350 nm / 330 nm 30 40 50 60 70 80 90 Temperature [°C] mAb22 mAb2 Cumulant Radius [nm] Turbidity [mAU] Ratio 350nm / 330nm Temperature [°C] IP Fab 22 IP Fab 2 T turb 22 T turb 2