title: Pharmacokinetic properties of IgG and various Fc fusion proteins in mice.
abstract: Fusion to an IgG Fc region is an established strategy to extend the half-life of therapeutic proteins. Most Fc fusion proteins, however, do not achieve the long half-life of IgGs. Based on findings that scFv-Fc fusion proteins exhibit a shorter half-life than the corresponding IgG molecules, we performed a comparative study of different antibody-derived Fc fusion proteins. We could confirm that fusion of single-chain Fv (scFv) and single-chain diabody (scDb) molecules to an Fc region yields in fusion proteins with substantially extended half-lives compared with the single-chain versions. However, even fusion proteins with a size similar to that of IgG, e.g., scDb-Fc, did not have a half-life as long as an IgG molecule. Binding to the neonatal Fc receptor (FcRn) under acidic and neutral conditions was similar for IgG and all Fc fusion proteins. However, we observed differences between IgG and the Fc fusion proteins for dissociation of FcRn-bound proteins induced by shifting from acidic to neutral pH, reflecting the physiological release mechanism, further supporting a contribution of the kinetics of pH-dependent release from FcRn to the pharmacokinetic properties of IgG and Fc fusion proteins.
authors.affiliation: a Institute of Cell Biology and Immunology; University of Stuttgart ; Allmandring 31; 70569 ; Stuttgart ; Germany.
authors.forename: Felix
authors.initials: F
authors.lastname: Unverdorben
authors.affiliation: a Institute of Cell Biology and Immunology; University of Stuttgart ; Allmandring 31; 70569 ; Stuttgart ; Germany.
authors.forename: Fabian
authors.initials: F
authors.lastname: Richter
authors.affiliation: a Institute of Cell Biology and Immunology; University of Stuttgart ; Allmandring 31; 70569 ; Stuttgart ; Germany.
authors.forename: Meike
authors.initials: M
authors.lastname: Hutt
authors.affiliation: a Institute of Cell Biology and Immunology; University of Stuttgart ; Allmandring 31; 70569 ; Stuttgart ; Germany.
authors.forename: Oliver
authors.initials: O
authors.lastname: Seifert
authors.affiliation: b Novimmune; 14 chemin des Aulx; 1228 Plan-les-Ouates ; Geneva ; Switzerland.
authors.forename: Pauline
authors.initials: P
authors.lastname: Malinge
authors.affiliation: b Novimmune; 14 chemin des Aulx; 1228 Plan-les-Ouates ; Geneva ; Switzerland.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Fischer
authors.affiliation: a Institute of Cell Biology and Immunology; University of Stuttgart ; Allmandring 31; 70569 ; Stuttgart ; Germany.
authors.forename: Roland E
authors.initials: RE
authors.lastname: Kontermann
mesh_terms: D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D005260:Female; D057809:HEK293 Cells; D006801:Humans; D007141:Immunoglobulin Fc Fragments / Q000494:pharmacology*; D007074:Immunoglobulin G / Q000494:pharmacology*; D051379:Mice; D011993:Recombinant Fusion Proteins / Q000493:pharmacokinetics / Q000494:pharmacology
chemical_list: D007141:Immunoglobulin Fc Fragments; D007074:Immunoglobulin G; D011993:Recombinant Fusion Proteins
keywords: Fc fusion protein; half-life; immunoglobulin G (IgG); neonatal Fc receptor (FcRn); pharmacokinetics