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PEDS Advance Access originally published online on April 2, 2008
Protein Engineering Design and Selection 2008 21(5):283-288; doi:10.1093/protein/gzm067
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© The Author 2008. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oxfordjournals.org

Anti-serum albumin domain antibodies for extending the half-lives of short lived drugs

Lucy J. Holt1, Amrik Basran, Kate Jones, Jennifer Chorlton, Laurent S. Jespers, Neil D. Brewis and Ian M. Tomlinson

Domantis Limited, 315 Cambridge Science Park, Cambridge, CB4 0WG, UK

1 To whom correspondence should be addressed. lucy.holt{at}domantis.com

We have used phage display to isolate a range of human domain antibodies (dAbs) that bind to mouse, rat and/or human serum albumin (SA) and can be expressed at very high levels in bacterial, yeast or mammalian cell culture. In contrast to non-SA-binding dAbs, which have terminal half-lives of less than 45 min, the half-lives of these 12 kDa ‘AlbudAbs’ can match the half-life of SA itself. To demonstrate the use of AlbudAbs for extending the half-lives of therapeutic drugs, we created a fusion of the interleukin-1 receptor antagonist (IL-1ra) with an AlbudAb. Soluble IL-1ra is potent inhibitor of IL-1 signalling that is approved for the treatment of rheumatoid arthritis but has a relatively short in vivo half-life. Here we show that although the AlbudAb/IL-1ra fusion has a similar in vitro potency, its in vivo efficacy can be dramatically improved due to its extended serum half-life. AlbudAbs could potentially be used to generate a range of long half-life versions of many different drugs in order to improve their dosing regimen and/or clinical effect.

Keywords: AlbudAb/albumin/domain antibody/half-life/dAb

Received October 22, 2007; revised October 22, 2007; accepted October 24, 2007.


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