Anti-serum albumin domain antibodies in the development of highly potent, efficacious and long-acting interferon

被引:44
作者
Walker, Adam [1 ]
Dunlevy, Grainne [1 ]
Rycroft, Daniel [1 ]
Topley, Peter [2 ]
Holt, Lucy J. [1 ]
Herbert, Tom [1 ]
Davies, Marie [1 ]
Cook, Fiona [2 ]
Holmes, Steve [1 ]
Jespers, Laurent [1 ]
Herring, Chris [1 ]
机构
[1] Domantis Ltd, Biopharm R&D, Cambridge CB4 0WG, England
[2] GlaxoSmithKline Med Res Ctr, Biopharm R&D, Stevenage SG1 2NY, Herts, England
关键词
domain antibody; interferon; albumin; AlbudAb; pharmacokinetics; CHRONIC HEPATITIS-C; DOUBLE-STRANDED-RNA; ANTIVIRAL RESPONSES; INITIAL TREATMENT; PLUS RIBAVIRIN; FUSION PROTEIN; ALPHA; RECEPTOR; PHAGE; RECOGNITION;
D O I
10.1093/protein/gzp091
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Serum albumin-binding domain antibodies (AlbudAbs) have previously been shown to greatly extend the serum half-life of the interleukin-1 receptor antagonist IL-1ra. We have subsequently extended this approach to look at the in vitro activity, in vivo efficacy and pharmacokinetics of an agonist molecule, interferon (IFN)-alpha 2b, fused to an AlbudAb. Here we describe this molecule and show that in this format AlbudAb half-life extension technology displays significant advantages in comparison with other methods of half-life extension, in particular genetic fusion to serum albumin. When compared directly IFN-alpha 2b fused to an Albudab shows higher potency, increased serum half-life and greater efficacy than human serum albumin fused to IFN-alpha 2b. AlbudAbs are therefore an ideal platform technology for creation of therapeutics with agonist activity and long serum half-lives.
引用
收藏
页码:271 / 278
页数:8
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