Thirty-five years on from the FDA's approval of a first monoclonal antibody (mAb), these biologics account for nearly a fifth of the agency's new drug approvals each year. mAbs offer exquisite specificity and affinity for both secreted and cell-surface targets. Different formats of antibody can be used to mop up circulating proteins, to block signalling pathways outright, to drive the internalization and degradation of cell-surface receptors, to deliver small-molecule payloads to specific cell types, to recruit immune cells to cancer cells, and more. Whereas medicinal chemists can toil for years to find small molecules with activity against a given target, antibody discovery can take a matter of months.
Developability and comparability assessment of current and next generation of biologics such as engineered mAbs, Fc-fusion proteins, BsAbs and 3G-ADCs requires state-of-the-art analytical and structural methods. Antibody-based products Critical Quality Attributes will be discussed, and case studies will be presented based on native and ion mobility MS, Collision Induced Unfolding (CIU), multiplexed Top and Middle-Down MS, multiple fragmentation techniques, comprising high energy collisional-, electron-transfer and UV photo-dissociation (HCD, ETD and UVPD), CE-MS and quantification of trace-level HCPs by MS.