Characterization of the Anti-Alzheimer Drug Lecanemab by Mass Spectrometry

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. Herein, we provide proteomics, intact protein, and N-glycoproteomics analyses of lecanemab by liquid chromatography coupled with mass spectrometry. We found that the lecanemab drug is highly pure but displays two major peaks in the chromatography and contains many species with close molecular weights around 150 kDa under mass spectrometric scanning. There were 40 N-glycans found at the N304 site of lecanemab of the heavy chain. Further analysis by MSFragger identified other modifications and additional glycosites. These results provide data as resource for the identification of critical quality attributes of lecanemab in studying its therapeutic effectiveness, side effects, and possible batch-to-batch qualities.