David Albert Driver
Eli Lilly and Company
Network
Latest external collaboration on country level. Dive into details by clicking on the dots.
Publication
Featured researches published by David Albert Driver.
Drug Metabolism and Disposition | 2012
Amita Datta-Mannan; Chi-Kin Chow; Craig Duane Dickinson; David Albert Driver; Jirong Lu; Derrick R. Witcher; Victor J. Wroblewski
The pH-dependent binding of IgGs to the neonatal Fc receptor (FcRn) plays a critical role in regulating IgG homeostasis in vivo. Enhancing interactions between Fc and FcRn via protein engineering has been successfully used as an approach for improving the pharmacokinetics of monoclonal antibodies (mAbs). Although the quantitative translatability of the in vitro FcRn affinity enhancement to an in vivo pharmacokinetic benefit has been supported by several studies, there are also published reports indicating a disconnect in this relation. The body of literature suggests there are likely additional biochemical and biophysical properties of the mAbs along with their FcRn affinity that influence the in vivo pharmacokinetics. Herein, we more broadly evaluate the in vitro Fc-FcRn interactions and biochemical properties of five humanized IgG4 antibodies each with two Fc variant sequences (T250Q/M428L and V308P) and their corresponding pharmacokinetics in cynomolgus monkeys. Our findings indicate that the FcRn affinity-pharmacokinetic relationship does not show a direct correlation either across different IgGs or between the two variant sequences within a platform. Other parameters that have been suggested to contribute to mAb pharmacokinetic properties, such as the pH-dependent dissociation of the FcRn-IgG complexes, mAb biophysical properties, and nonspecific/charge binding characteristics of the mAbs, also did not independently explain the differing pharmacokinetic behaviors. Our results suggest that there is likely not a single in vitro parameter that readily predicts in vivo pharmacokinetics, but that the relative contribution and interplay of several factors along with the FcRn binding affinity are important determinants of mAb pharmacokinetic properties.
Archive | 2009
David Bruce Baldwin; Craig Duane Dickinson; David Albert Driver; Radmila Micanovic
Archive | 2013
Ryan James Darling; Craig Duane Dickinson; David Albert Driver; Malgorzata Donata Gonciarz
Archive | 2013
Craig Duane Dickinson; David Albert Driver; Ryan James Darling; Malgorzata Donata Gonciarz; Radmila Micanovic
Archive | 2012
Craig Duane Dickinson; David Albert Driver; Ryan James Darling; Maigorzata Donata Gonciarz; Radmila Micanovic
Archive | 2016
Mansuo Lu Hayashi; Jirong Lu; David Albert Driver; Alberto Alvarado
Alzheimers & Dementia | 2017
Riazul Alam; David Albert Driver; Su Wu; Emmanuel Lozano; Stephanie L. Key; Justin T. Hole; Mansuo L. Hayashi; Jirong Lu
Archive | 2017
Alberto Alvarado; David Albert Driver; Mansuo L. Hayashi; Jirong Lu
Archive | 2017
Craig Duane Dickinson; David Albert Driver; Malgorzata Donata Gonciarz; Radmila Micanovic; Ryan James Darling
Alzheimers & Dementia | 2017
Mansuo L. Hayashi; Jirong Lu; Su Wu; Suchira Bose; Zeshan Ahmed; Jane Cooper; Tracey K. Murray; Samuel Jackson; Annalisa Cavallini; Mark A Ward; David Albert Driver; Michel Goedert; Ronald B. DeMattos; Michael J. O'Neill; Mike Hutton