An Affinity Capture Elution (ACE) assay for detection of anti-drug antibody to monoclonal antibody therapeutics in the presence of high levels of drug.

Monoclonal antibody therapeutics typically have relatively long half-lives and can be dosed at high levels. Although formation of anti-drug antibodies (ADA) is relatively rare, detection of these antibodies can be very difficult in the presence of high circulating levels of drug. Typically these ADA are detected by bridging ELISAs which can be very sensitive to even low levels of drug. We describe an ELISA method based on affinity capture of ADA on solid-phase drug followed by removal of excess free drug, release and transfer of bound ADA and subsequent detection using biotinylated drug. The assay is both sensitive and highly tolerant to free drug with detection of 500 ng/ml of ADA readily achieved in the presence of 500 mug/ml of drug.