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We have developed a mAb physiologically\u2010based pharmacokinetic model that describes intracellular trafficking, neonatal Fc receptor (FcRn) recycling, and nonspecific clearance of mAbs. We extended this model to capture target binding as a function of target affinity, expression, and turnover. For mAbs engineered to have an extended half\u2010life, the model was able to accurately predict the terminal half\u2010life (82% within 2\u2010fold error of the observed value) in the human FcRn transgenic (Tg32) homozygous mouse and human. The model also accurately captures the trend in pharmacokinetic and target coverage data for a set of mAbs with differing catch and release properties in the Tg32 mouse. The mechanistic nature of this model allows us to explore different engineering techniques early in drug discovery, potentially expanding the number of \u201cdruggable\u201d targets.<\/jats:p>","DOI":"10.1002\/psp4.12547","type":"journal-article","created":{"date-parts":[[2020,7,22]],"date-time":"2020-07-22T13:07:32Z","timestamp":1595423252000},"page":"534-541","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["A Physiologically\u2010Based Pharmacokinetic Model for the Prediction of \u201cHalf\u2010Life Extension\u201d and \u201cCatch and Release\u201d Monoclonal Antibody Pharmacokinetics"],"prefix":"10.1002","volume":"9","author":[{"given":"Hannah M.","family":"Jones","sequence":"first","affiliation":[{"name":"BioMedicine Design Pfizer Worldwide R&amp;D Cambridge Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Tolsma","sequence":"additional","affiliation":[{"name":"RES Group Inc. 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