Preclinical Development – Biomolecular
2019 PharmSci 360
In vivo non-clinical pharmacokinetic (PK) assessment is routinely conducted during lead candidate selection process in order to de-risk any PK related liabilities due to non-specific clearance mechanisms. While non-specific monoclonal antibody (mAb) clearance in humans can be reasonably predicted from cynomolgous monkeys (cynos), these assessments are typically conducted first in rodents to select candidate(s) for further evaluation. In the present work, we generated huIgG1 mAbs against a novel membrane bound receptor that were cross-reactive in multiple species including mouse, cyno and human. As expected, these mAbs exhibited target-mediated drug disposition (TMDD) in mice. The overall objective of this work was to estimate non-specific clearance of these cross-reactive mAbs in mice using a TMDD model. More specifically, this approach focused on achieving a mAb screening process which was efficient yet less resource intensive - Without this approach, additional 100 mice would have been required for mAb screening and additional resources.