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Dive into the research topics where David Albert Driver is active.

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Featured researches published by David Albert Driver.


Drug Metabolism and Disposition | 2012

FcRn Affinity-Pharmacokinetic Relationship Of Five Human IgG4 Antibodies Engineered For Improved In Vitro FcRn Binding Properties In Cynomolgus Monkeys

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

Variants of fibroblast growth factor 21

David Bruce Baldwin; Craig Duane Dickinson; David Albert Driver; Radmila Micanovic


Archive | 2013

Fibroblast growth factor 21 proteins

Ryan James Darling; Craig Duane Dickinson; David Albert Driver; Malgorzata Donata Gonciarz


Archive | 2013

Fibroblast growth factor 21 variants

Craig Duane Dickinson; David Albert Driver; Ryan James Darling; Malgorzata Donata Gonciarz; Radmila Micanovic


Archive | 2012

Fibroblast growth factor 21 variants having improved pharmacological potency and/or improved pharmaceutical stability

Craig Duane Dickinson; David Albert Driver; Ryan James Darling; Maigorzata Donata Gonciarz; Radmila Micanovic


Archive | 2016

Antibodies to tau and uses thereof

Mansuo Lu Hayashi; Jirong Lu; David Albert Driver; Alberto Alvarado


Alzheimers & Dementia | 2017

PRECLINICAL CHARACTERIZATION OF AN ANTIBODY [LY3303560] TARGETING AGGREGATED TAU

Riazul Alam; David Albert Driver; Su Wu; Emmanuel Lozano; Stephanie L. Key; Justin T. Hole; Mansuo L. Hayashi; Jirong Lu


Archive | 2017

ANTICUERPOS CONTRA TAU Y SUS USOS

Alberto Alvarado; David Albert Driver; Mansuo L. Hayashi; Jirong Lu


Archive | 2017

variantes do fator de crescimento de fibroblastos 21

Craig Duane Dickinson; David Albert Driver; Malgorzata Donata Gonciarz; Radmila Micanovic; Ryan James Darling


Alzheimers & Dementia | 2017

AGGREGATE-SELECTIVE ANTI-TAU ANTIBODY MC-1 DEMONSTRATED ROBUST IN VITRO AND IN VIVO ACTIVITY TO NEUTRALIZE TRANSMISSIBLE TAU AND REDUCE TAU PATHOLOGY

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

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Jirong Lu

Eli Lilly and Company

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Su Wu

Eli Lilly and Company

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