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Antibodies 2015, 4(3), 141-156; doi:10.3390/antib4030141

Pre-Clinical Intravenous Serum Pharmacokinetics of Albumin Binding and Non-Half-Life Extended Nanobodies®

Ablynx N.V., Technologiepark 21, 9052 Zwijnaarde, Belgium
Nanobody is a registered trademark of Ablynx NV.
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Academic Editor: Friedrich Koch-Nolte
Received: 29 May 2015 / Revised: 24 June 2015 / Accepted: 6 July 2015 / Published: 10 July 2015
(This article belongs to the Special Issue Nanobodies)
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Abstract

Nanobodies are antigen-binding, single variable domain proteins derived from naturally-occurring, heavy chain only antibodies. They are highly soluble, stable, and can be linked to build multi-specific formats. Several Nanobodies are currently in clinical development in different therapeutic areas, for both chronic and acute applications. For the former, prolonged exposure is achieved by half-life extending moieties that target endogenous albumin, while for the latter, non-half-life extended constructs are preferable. To demonstrate the general pharmacokinetic behavior of both formats, serum levels of seven intravenously administered Nanobodies were analyzed in cynomolgus monkeys, mice or rabbits. In monkeys, the total clearance of a monomeric irrelevant Nanobody was rapid (2.0 mL/(min*kg)) and approximated the species glomerular filtration rate, indirectly suggesting that the Nanobody was mainly eliminated via the kidneys. When linked to an anti-albumin Nanobody, a 376-fold decrease in clearance was observed, resulting in a terminal half-life of 4.9 days, corresponding to the expected species albumin half-life. Similar conclusions were drawn for (non-) half-life extended mono-, bi- and trimeric Nanobodies in mice or rabbits, suggesting that these kinetic principles apply across species. Applying this knowledge to species translation and study design is crucial for successful pre-clinical development of novel therapeutic Nanobody candidates. View Full-Text
Keywords: nanobodies; pharmacokinetics; albumin; half-life extension; pre-clinical nanobodies; pharmacokinetics; albumin; half-life extension; pre-clinical
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Hoefman, S.; Ottevaere, I.; Baumeister, J.; Sargentini-Maier, M.L. Pre-Clinical Intravenous Serum Pharmacokinetics of Albumin Binding and Non-Half-Life Extended Nanobodies®. Antibodies 2015, 4, 141-156.

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