A universal assay for determining the quantity of therapeutic monoclonal antibodies and their corresponding anti-drug-antibodies in samples

A method for determining the presence and quantity of therapeutic monoclonal antibody and/or an antibody against a therapeutical monoclonal antibody and/or a neutralizing antibody against a therapeutical monoclonal antibody in a biological sample, the method comprising the steps of:

• a. providing a first conjugate comprising the target of the therapeutic monoclonal antibody and a first conjugated moiety,
• b. providing a second conjugate comprising the target of the therapeutic monoclonal antibody and a second conjugated moiety, wherein the first and the second moieties are solid particles, or wherein the first moiety is an enzyme and the second moiety a substrate for the first moiety, or wherein the first moiety is an fluorophore and the second moiety a modulator of the fluorescence provided by the first moiety,
• c. providing a reaction liquid comprising the first and the second conjugates and adding a known spike amount of the therapeutic monoclonal antibody to the reaction liquid, and contacting the sample with the reaction liquid, whereby a detection liquid comprising the sample, the spike amount of the therapeutic monoclonal antibody and the first and the second conjugates, is formed,
• d. detecting the change in spectrophotometric signal of the detection liquid following contacting the sample with the reaction liquid in step c, and
• e. determining the quantity of the therapeutic monoclonal antibody by comparing the obtained results with an internal standard,
• f. determining the presence or absence of an antibody against the therapeutical monoclonal antibody and/or a neutralizing antibody against the therapeutical monoclonal antibody by comparing the obtained measurement with the measurement expected from the added known amount of the therapeutic monoclonal antibody.