Fab-dsFv: A bispecific antibody format with extended serum half-life through albumin binding.

An antibody format, termed Fab-dsFv, has been designed for clinical indications that require monovalent target binding in the absence of direct Fc receptor (FcR) binding while retaining substantial serum presence. The variable fragment (Fv) domain of a humanized albumin-binding antibody was fused to the C-termini of Fab constant domains, such that the VL and VH domains were individually connected to the Cκ and CH1 domains by peptide linkers, respectively. The anti-albumin Fv was selected for properties thought to be desirable to ensure a durable serum half-life mediated via FcRn. The Fv domain was further stabilized by an inter-domain disulfide bond. The bispecific format was shown to be thermodynamically and biophysically stable, and retained good affinity and efficacy to both antigens simultaneously. In in vivo studies, the serum half-life of Fab-dsFv, 2.6 d in mice and 7.9 d in cynomolgus monkeys, was equivalent to Fab'-PEG.

Citation

Emma Davé, Ralph Adams, Oliver Zaccheo, Bruce Carrington, Joanne E Compson, Sarah Dugdale, Michael Airey, Sarah Malcolm, Hanna Hailu, Gavin Wild, Alison Turner, James Heads, Kaushik Sarkar, Andrew Ventom, Diane Marshall, Mark Jairaj, Tim Kopotsha, Louis Christodoulou, Miren Zamacona, Alastair D Lawson, Sam Heywood, David P Humphreys. Fab-dsFv: A bispecific antibody format with extended serum half-life through albumin binding. mAbs. 2016 Oct;8(7):1319-1335

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PMID: 27532598

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