Related Experiment Video
Updated: Dec 8, 2025
12:28
Bacterial Inner-membrane Display for Screening a Library of Antibody Fragments
Published on: October 15, 2016
11.9K
An accelerated surface-mediated stress assay of antibody instability for developability studies
Marie R G Kopp1, Adriana-Michelle Wolf Pérez2,3, Marta Virginia Zucca1
1Department of Chemistry and Applied Biosciences, Institute for Chemical and Bioengineering, Swiss Federal Institute of Technology , Zurich, Switzerland.
Mabs
|September 21, 2020
Summary
A new hydrophobic nanoparticle surface-stress assay effectively predicts monoclonal antibody (mAb) instability and aggregation, complementing existing developability screening methods for therapeutic product development.
Area of Science:
- Biopharmaceutical Development
- Protein Engineering
- Analytical Chemistry
Background:
- High physical stability is crucial for therapeutic monoclonal antibody (mAb) development.
- Existing developability assays struggle to predict protein aggregation induced by interfaces.
- Novel methods are needed to assess mAb stability against air-water and solid-liquid interfaces.
Purpose of the Study:
- To investigate a hydrophobic nanoparticle surface-mediated stress assay (HNSSA) for early-stage mAb developability assessment.
- To evaluate the HNSSA's ability to predict protein aggregation and instability.
- To correlate HNSSA results with other established developability properties.
Main Methods:
- Developed and applied a hydrophobic nanoparticle surface-stress assay (HNSSA).
- Tested the assay on a library of 14 humanized IgG4 variants with diverse developability profiles.
- Correlated HNSSA-induced aggregation with storage stability, self-association (AC-SINS), and nonspecific interactions (CIC, SMAC).
Main Results:
- The HNSSA successfully identified variants prone to aggregation under agitation and air-water interfaces.
- Significant correlations were observed between HNSSA results and other developability metrics.
- The assay demonstrated potential in predicting aggregation propensity based on surface interactions.
Conclusions:
- The hydrophobic nanoparticle surface-stress assay (HNSSA) is a promising tool for assessing mAb stability against interfaces.
- This assay can complement existing techniques to improve early-stage prediction of protein aggregation.
- HNSSA enhances the evaluation of mAb developability potential during drug development.
