Characterization of the Anti-Alzheimer Drug Lecanemab by Mass Spectrometry

Background: Lecanemab is a humanized mouse monoclonal antibody that is clinically approved for treating Alzheimer’s disease by binding to amyloid oligomers, protofibrils, and insoluble fibrils to clear Aβ aggregates in the brain. Although therapeutically effective, Lecanemab is also associated with side effects and its quality might vary among different batches due to impurities and modifications. Here we provide proteomics, intact protein, and N-glycoproteomics analyses of Lecanemab by liquid chromatography coupled to mass spectrometry. Results: We found the Lecanemab drug is highly pure but displays two main peaks in the chromatography and contains many species with close molecular weights around 150kD under mass spectrometric scanning. There were 40 N-glycans found on the N304 site of Lecanemab at the heavy chain. Further analysis by MSfragger identified other modifications and additional glycosites. Significance: These results provide data for identification of critical quality attributes of Lecanemab to study its therapeutic effectiveness and side effects of Lecanemab and monitor batch-to-batch qualities for efficient treatment of Alzheimer’s disease.