A Competitive Ligand-Binding Assay to Detect Neutralizing Antibodies to a Bispecific Drug Using a Multiplex Meso Scale Discovery Platform

Abstract

Background: Monitoring appearance of neutralizing antibodies (NAbs) to multidomain large molecule drugs is a challenging task. Materials & methods: Here, we report development of a competitive ligand-binding assay for detection of NAbs to a bispecific candidate drug using a multiplex Meso Scale Discovery platform, which allows for detection of NAbs to both drug arms in the same sample. Results: The assay has sensitivity better than 250ng/ml and is tolerant to the presence of drug at concentration >600μg/ml and to the level of soluble target(s) >400ng/ml. Conclusion: Our data suggest that multiplex approach can be successfully used for development of NAb assays in competitive ligand-binding assay format.

Keywords::

• bispecific drug
• competitive ligand-binding assay
• neutralizing antibodies
• U-plex MSD

Acknowledgments

The authors appreciate the contribution of L Dyleski for introduction into the U-plex MSD technology, and of our colleagues at the Critical Reagents Group G Miller, R Ramsey and L Walus for their flawless technical expertise.

Financial & competing interests disclosure

All authors were employees of Pfizer, Inc. at the time of this work. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations. In addition, for investigations involving human subjects, informed consent has been obtained from the participants involved.