Anti-serum albumin domain antibodies in the development of highly potent, efficacious and long-acting interferon.
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)-alpha2b, 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-alpha2b fused to an Albudab shows higher potency, increased serum half-life and greater efficacy than human serum albumin fused to IFN-alpha2b. AlbudAbs are therefore an ideal platform technology for creation of therapeutics with agonist activity and long serum half-lives.
Walker
Adam
A
Biopharm R&D, Domantis Ltd, Cambridge, UK. Adam.Walker@Domantis.com
Dunlevy
Gráinne
G
Rycroft
Daniel
D
Topley
Peter
P
Holt
Lucy J
LJ
Herbert
Tom
T
Davies
Marie
M
Cook
Fiona
F
Holmes
Steve
S
Jespers
Laurent
L
Herring
Chris
C
D000906:Antibodies / Q000737:chemistry / Q000235:genetics* / Q000276:immunology; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000737:chemistry / Q000493:pharmacokinetics* / Q000494:pharmacology; D015202:Protein Engineering / Q000379:methods; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000493:pharmacokinetics; D011994:Recombinant Proteins; D012709:Serum Albumin / Q000737:chemistry / Q000276:immunology*; D020349:Surface Plasmon Resonance; D014407:Tumor Cells, Cultured
D000906:Antibodies; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011993:Recombinant Fusion Proteins; D011994:Recombinant Proteins; D012709:Serum Albumin