Biomarkers are defined as being able to be “objectively measured and evaluated as indicators of normal biological processes, pathogenic processes or pharmacologic responses to therapeutic interventions” [1]. The use of biomarkers represents a competitive advantage in drug discovery and development to improve drug discovery effectiveness, facilitate dose selection, evaluate pharmacodynamic (PD) effect and target engagement, assess safety and select patients for treatment. There are many analytical platforms for biomarker measurements including ligand-binding assays (LBAs), MS, flow cytometry and molecular profiling methodologies such as DNA sequencing and immunohistochemistry. Some of these technologies provide quantitative results while the others are considered semiquantitative or qualitative. For soluble marker measurement, LBAs are broadly applied due to their supreme specificity, sensitivity and high sample throughput. However, this methodology highly relies on the specificity and quality of the reagent (antibody), and in most cases requires a pair of antibodies which sometimes may not be available in the early phase of drug discovery and development. In addition, when measuring a drug target for large molecule therapeutics such as monoclonal antibodies, a sandwich LBA requires two different functioning binding sites on the analyte to measure the drug-free form and three binding sites to measure the drug-bound form. This is a great challenge especially for small protein biomarkers, which may not have multiple epitopes available or where the access to the nearby epitopes may be blocked after being bound to monoclonal antibody therapeutics.
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