Selective detection of complementarity-determining regions of monoclonal antibody by limiting protease access to the substrate: nano-surface and molecular-orientation limited proteolysis

Patent expiration of blockbuster drugs is expected to trigger the rapid growth in the demand for developing new therapeutic antibody drugs in the near future. In generic and biosimilar drug development, rapid and versatile identification of specific sequences of monoclonal antibodies will become the key factor in their quality control. 1,2 Unlike low-molecular weight drugs, little emphasis has been placed on the accurate quantitation of the drug concentration in the blood following administration. However, clinical trial results of Trastuzumab in HER2-positive advanced gastric cancer patients demonstrated a significant correlation between the blood concentration of Trastuzumab and patient survival rates, emphasizing the importance of blood concentration measurements for future antibody drugs. 3 Versatile and robust analytical methods for the direct detection of future generation antibody drugs will be desired in preclinical and clinical trials for drug characterization and pharmacokinetic/pharmacodynamic assessments.