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Drug Removal Strategies in Competitive Ligand Binding Neutralizing Antibody (NAb) Assays: Highly Drug-Tolerant Methods and Interpreting Immunogenicity Data

Authors
  • Partridge, Michael A.1
  • Karayusuf, Elif Kabuloglu1
  • Shyu, Gary1
  • Georgaros, Camille1
  • Torri, Albert1
  • Sumner, Giane1
  • 1 Regeneron Pharmaceuticals, Inc., 777 Old Saw Mill River Road, Tarrytown, New York, 10591, USA , Tarrytown (United States)
Type
Published Article
Journal
The AAPS Journal
Publisher
American Association of Pharmaceutical Scientists
Publication Date
Aug 17, 2020
Volume
22
Issue
5
Identifiers
DOI: 10.1208/s12248-020-00497-2
Source
Springer Nature
Keywords
License
Yellow

Abstract

Neutralizing anti-drug antibody (NAb) assays often have lower drug tolerance (DT) than trough drug concentrations, potentially under-estimating NAb incidence. To improve DT, drug-specific proteins were coupled to magnetic beads to deplete drug in the sample. To avoid interference from carryover, drug-specific proteins that did not interfere in the NAb assay, such as target or non-blocking anti-drug antibodies, were selected. With the drug depletion step, DT improved by > 10-fold in two competitive ligand binding NAb assays. Analysis of anti-drug antibody positive clinical samples with elevated drug levels demonstrated that NAb incidence was under-estimated without the drug depletion step. However, these NAb-positive samples had low titer and no impact on drug concentrations.

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