TRYBE®: an Fc-free antibody format with three monovalent targeting arms engineered for long in vivo half-life. Issue 1 (31st December 2023)

• Record Type: Journal Article
• Authors: Davé, Emma; Durrant, Oliver; Dhami, Neha; Compson, Joanne; Broadbridge, Janice; Archer, Sophie; Maroof, Asher; Whale, Kevin; Menochet, Karelle; Bonnaillie, Pierre; Barry, Emily; Wild, Gavin; Peerboom, Claude; Bhatta, Pallavi; Ellis, Mark; Hinchliffe, Matthew; Humphreys, David P.; Heywood, Sam P.
• Is Part Of: MAbs. Volume 15:Issue 1(2023)
• Publication Date: 2023-12-31
• Subjects: TrYbe® -- multi-specific -- monovalent -- Fc-free -- targeting -- multivalent antigen -- albumin binder; Monoclonal antibodies -- Therapeutic use -- Periodicals; Monoclonal antibodies -- Periodicals; Antibodies, Monoclonal -- Periodicals; 616.0798
• DOI: 10.1080/19420862.2022.2160229
• Languages: English
• ISSNs: 1942-0862

Abstract

ABSTRACT: TrYbe® is an Fc-free therapeutic antibody format, capable of engaging up to three targets simultaneously, with long in vivo half-life conferred by albumin binding. This format is shown by small-angle X-ray scattering to be conformationally flexible with favorable 'reach' properties. We demonstrate the format's broad functionality by co-targeting of soluble and cell surface antigens. The benefit of monovalent target binding is illustrated by the lack of formation of large immune complexes when co-targeting multivalent antigens. TrYbes® are manufactured using standard mammalian cell culture and protein A affinity capture processes. TrYbes® have been formulated at high concentrations and have favorable drug-like properties, including stability, solubility, and low viscosity. The unique functionality and inherent developability of the TrYbe® makes it a promising multi-specific antibody fragment format for antibody therapy.