My watch list
my.bionity.com  
Login  

Getting the Full Picture: Predicting the Aggregation Propensity of mAbs

Fully Automated Chemical and Thermal Denaturation Study Predicts Long-Term Stability in Formulations

Dennis Breitsprecher, Pawel Linke, Anna Schulze, Franziska Söltl, Patrick Garidel, Michaela Blech

Chemical denaturation curve of a mAb, analyzed by detecting changes in the fluorescence emission ratio using the Prometheus NT.Plex

Chemical denaturation of lysozyme at different pH values

Comparison of aggregation prediction by chemical denaturation and long-term stability measurements in formulations 1-5. (A) Chemical denaturation data (B) Determination of monomer contents (C) Turbidity measurements

Analysis of mAb stability by nanoDSF. Thermal unfolding curves of mAb1 in formulations F01-F05

Analysis of mAb stability by nanoDSF with backreflection aggregation detection

One of the most important parameters in the development of therapeutic biologics is their long-term stability. While after purification being seemingly stable in a variety of formulations, many antibodies display very slow aggregation kinetics over time. This gradual aggregation could thus far only be evaluated by monitoring monomer contents and aggregates over months or even years. Predictive methods are therefore urgently needed to speed up the development of biologics. Here we demonstrate that the Prometheus NT.Plex by NanoTemper Technologies can be used for predicting long-term stability in only a few hours. The approach uses a combination of thermal and chemical unfolding analysis in a high-throughput setting. We show that chemical denaturation is a tool which can determine folding enthalpies of monoclonal antibodies (mAbs) to predict their long-term stability in formulation screenings. Using the Prometheus NT.Plex nanoDSF instrument with aggregation detection optics, we screened 5 formulations at different mAb concentrations for their thermal and chemical stability. The obtained unfolding data correlates with long-term turbidity and monomer content over time, showing that the Prometheus NT.Plex can be used to rapidly predict the long-term stability of biologics within 1 day.

Facts, background information, dossiers
  • thermal denaturation
  • chemical denaturation
  • long-term stability
  • unfolding analysis
  • turbidity
More about NanoTemper Technologies
  • White papers

    Assess Enzyme Stability without Buffer Limitations

    Would you like to assess enzyme stability without any buffer restrictions? Read more about thermal unfolding analysis of an esterase in detergents more

    nanoDSF Goes GPCR Characterization

    Learn how nanoDSF evaluates compounds for lead discovery and improves receptor stability for biophysical assays by screening buffer conditions more

    Predicting the Long-Term Stability of Biologics

    Learn how to predict long-term mAb stability in a formulation screen by quantification of conformational and colloidal stability more

  • Videos

    A Revolution in Protein Stability Analysis

    The assessment of thermal stability parameters of biologics is an integral part of biopharmaceutical research. The ever growing number of biologics in the development pipelines worldwide demands rapid and precise methods to quickly screen large sets of conditions in an easy and straightforw ... more

  • News

    Growth Champions 2017

    We have some great news! FOCUS and Statista have ranked the 500 fastest-growing companies in Germany and we made the list! They identified companies with exceptional growth rates between the years 2012 and 2015 as “Growth Champions 2017”. We’re proud to announce that NanoTemper Technologies ... more

  • Companies

    NanoTemper Technologies GmbH

    NanoTemper Technologies – We care about your research At NanoTemper Technologies, we develop highly innovative instrument and software solutions for biomolecular analysis. Our global application centers ensure unparalleled customer care and support. We are passionate about achieving excel ... more

Your browser is not current. Microsoft Internet Explorer 6.0 does not support some functions on Chemie.DE