TRYBE®: an Fc-free antibody format with three monovalent targeting arms engineered for long in vivo half-life

MAbs. 2023 Jan-Dec;15(1):2160229. doi: 10.1080/19420862.2022.2160229.

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.

Keywords: Fc-free; TrYbe®; albumin binder; monovalent; multi-specific; multivalent antigen; targeting.

MeSH terms

  • Animals
  • Half-Life
  • Immunoglobulin Fc Fragments* / chemistry
  • Immunoglobulin Fragments*
  • Mammals / metabolism

Substances

  • Immunoglobulin Fc Fragments
  • Immunoglobulin Fragments

Grants and funding

The author(s) reported that there is no funding associated with the work featured in this article.