共 34 条
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.
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页码:271 / 278
页数:8
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