The pharmacokinetics of an albumin-binding Fab (AB.Fab) can be modulated as a function of affinity for albumin

Protein Engineering, Design & Selection : PEDS
Allen NguyenMark S Dennis

Abstract

An AB.Fab (albumin-binding Fab) consists of a Fab and a phage-derived albumin-binding peptide. This molecule is capable of binding both antigen and albumin simultaneously. Using a Fab derived from Herceptin we generated a panel of AB.Fab variants with wide-ranging affinities for albumin. An assay that measured AB.Fab binding to albumin in solution was developed to most accurately reflect the binding affinity for albumin in vivo. Affinity varied depending upon the species of albumin tested. For rat and rabbit albumin, affinities ranged from 0.04 to 2.5 microM. Reduced affinity for albumin correlated with a reduced half-life and higher clearance rates in both species; the beta half-life ranged 6-fold while clearance ranged over 50-fold in rats and 20-fold in rabbits. To estimate the pharmacokinetic properties of an AB.Fab in humans, AB.Fab variants with similar affinities for rat and rabbit albumin were selected. Using their pharmacokinetic parameters and the principles of allometric scaling for albumin, we estimate an approximate beta half-life for an AB.Fab with 0.5 microM affinity for albumin of up to 4 days in humans with a clearance of 76 ml/h. These variants demonstrate the ability to modulate the clearance of a Fab fragmen...Continue Reading

Citations

Feb 5, 2010·Biotechnology Letters·A ConstantinouM P Deonarain
Jun 21, 2011·Molecular Imaging and Biology : MIB : the Official Publication of the Academy of Molecular Imaging·Cynthia A Davies-VennEva M Sevick-Muraca
Oct 24, 2012·Journal of Medicinal Chemistry·Alessandro AngeliniChristian Heinis
Aug 10, 2010·Acta Pharmacologica Sinica·Jing Li, Zhenping Zhu
May 24, 2008·Protein Engineering, Design & Selection : PEDS·Andreas JonssonPer-Ake Nygren
Sep 8, 2010·Protein Engineering, Design & Selection : PEDS·Jonas HoppRoland E Kontermann
Nov 10, 2013·International Journal of Nanomedicine·Christina G Siontorou
Oct 24, 2013·BioDrugs : Clinical Immunotherapeutics, Biopharmaceuticals and Gene Therapy·Gabriele ProetzelDerry C Roopenian
Sep 9, 2011·Biometals : an International Journal on the Role of Metal Ions in Biology, Biochemistry, and Medicine·Theodore J ZwangMatthew H Sazinsky
Dec 19, 2014·Expert Opinion on Drug Delivery·Darrell Sleep
Aug 5, 2014·Expert Opinion on Biological Therapy·Marina KovalevaCaroline Barelle
Jun 8, 2012·Journal of Pharmaceutical Sciences·Michael J HackettMoo J Cho
Apr 21, 2009·Biotechnology Advances·Nina E Weisser, J Christopher Hall
Jun 26, 2008·Current Opinion in Immunology·Aran F LabrijnJanine Schuurman
Jul 29, 2008·Current Opinion in Immunology·Leonard G Presta
Jun 11, 2008·Advanced Drug Delivery Reviews·Greg M ThurberK Dane Wittrup
May 23, 2009·British Journal of Pharmacology·Patrick ChamesDaniel Baty
Oct 20, 2006·Current Opinion in Biotechnology·Aaron K SatoClive R Wood
Mar 27, 2016·Pharmacology & Therapeutics·João Pedro MartinsBruno Sarmento
Sep 27, 2014·Therapeutic Apheresis and Dialysis : Official Peer-reviewed Journal of the International Society for Apheresis, the Japanese Society for Apheresis, the Japanese Society for Dialysis Therapy·Jingwei NiRuiyan Zhang
Jun 10, 2015·Journal of Controlled Release : Official Journal of the Controlled Release Society·Malin BernJan Terje Andersen
Nov 4, 2011·MAbs·Timothy T Kuo, Victoria G Aveson
May 4, 2013·Biochimica Et Biophysica Acta·Darrell SleepLeslie R Evans
Jun 15, 2011·Free Radical Biology & Medicine·Chika NishizakiYoshinobu Takakura
Jan 1, 2013·Computational and Structural Biotechnology Journal·Johan Nilvebrant, Sophia Hober
Jun 6, 2013·Journal of Controlled Release : Official Journal of the Controlled Release Society·Sung In LimInchan Kwon
Feb 13, 2015·Frontiers in Immunology·Kine Marita Knudsen SandJan Terje Andersen
Feb 19, 2015·Breast Cancer : the Journal of the Japanese Breast Cancer Society·Qiongchao JiangHui Zhi
Dec 26, 2016·Protein Expression and Purification·Jun GuoJiang-Wei Li
Mar 9, 2017·Protein & Cell·Rudo Simeon, Zhilei Chen
Feb 24, 2009·Current Protocols in Protein Science·Christoph Rader
Nov 1, 2017·Protein Engineering, Design & Selection : PEDS·Daniel SteinerH Kaspar Binz
Mar 28, 2008·Angewandte Chemie·Christoph E DumelinDario Neri

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