title: Fab-dsFv: A bispecific antibody format with extended serum half-life through albumin binding.
abstract: 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.
authors.affiliation: a UCB Celltech , Slough , UK.
authors.forename: Emma
authors.initials: E
authors.lastname: Davé
authors.affiliation: a UCB Celltech , Slough , UK.
authors.forename: Ralph
authors.initials: R
authors.lastname: Adams
authors.affiliation: a UCB Celltech , Slough , UK.
authors.forename: Oliver
authors.initials: O
authors.lastname: Zaccheo
authors.affiliation: a UCB Celltech , Slough , UK.
authors.forename: Bruce
authors.initials: B
authors.lastname: Carrington
authors.affiliation: a UCB Celltech , Slough , UK.
authors.forename: Joanne E
authors.initials: JE
authors.lastname: Compson
authors.affiliation: a UCB Celltech , Slough , UK.
authors.forename: Sarah
authors.initials: S
authors.lastname: Dugdale
authors.forename: Michael
authors.initials: M
authors.lastname: Airey
authors.affiliation: a UCB Celltech , Slough , UK.
authors.forename: Sarah
authors.initials: S
authors.lastname: Malcolm
authors.affiliation: a UCB Celltech , Slough , UK.
authors.forename: Hanna
authors.initials: H
authors.lastname: Hailu
authors.affiliation: a UCB Celltech , Slough , UK.
authors.forename: Gavin
authors.initials: G
authors.lastname: Wild
authors.affiliation: a UCB Celltech , Slough , UK.
authors.forename: Alison
authors.initials: A
authors.lastname: Turner
authors.affiliation: a UCB Celltech , Slough , UK.
authors.forename: James
authors.initials: J
authors.lastname: Heads
authors.affiliation: a UCB Celltech , Slough , UK.
authors.forename: Kaushik
authors.initials: K
authors.lastname: Sarkar
authors.affiliation: a UCB Celltech , Slough , UK.
authors.forename: Andrew
authors.initials: A
authors.lastname: Ventom
authors.affiliation: a UCB Celltech , Slough , UK.
authors.forename: Diane
authors.initials: D
authors.lastname: Marshall
authors.affiliation: a UCB Celltech , Slough , UK.
authors.forename: Mark
authors.initials: M
authors.lastname: Jairaj
authors.affiliation: a UCB Celltech , Slough , UK.
authors.forename: Tim
authors.initials: T
authors.lastname: Kopotsha
authors.affiliation: a UCB Celltech , Slough , UK.
authors.forename: Louis
authors.initials: L
authors.lastname: Christodoulou
authors.affiliation: a UCB Celltech , Slough , UK.
authors.forename: Miren
authors.initials: M
authors.lastname: Zamacona
authors.affiliation: a UCB Celltech , Slough , UK.
authors.forename: Alastair D
authors.initials: AD
authors.lastname: Lawson
authors.affiliation: a UCB Celltech , Slough , UK.
authors.forename: Sam
authors.initials: S
authors.lastname: Heywood
authors.affiliation: a UCB Celltech , Slough , UK.
authors.forename: David P
authors.initials: DP
authors.lastname: Humphreys
mesh_terms: D000818:Animals; D018033:Antibodies, Bispecific / Q000097:blood* / Q000737:chemistry / Q000276:immunology; D006207:Half-Life; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000097:blood / Q000737:chemistry; D007135:Immunoglobulin Variable Region / Q000097:blood / Q000737:chemistry; D051379:Mice; D012709:Serum Albumin / Q000276:immunology / Q000378:metabolism*
chemical_list: D018033:Antibodies, Bispecific; D007140:Immunoglobulin Fab Fragments; D007135:Immunoglobulin Variable Region; D012709:Serum Albumin
keywords: Anti-albumin; Fab; FcRn; anti-albumin Fv; human serum albumin; serum half-life