antibody fragments

Antibody fragments & alternative binding proteins

Despite the huge success of monoclonal antibodies, there are some indications and disease targets which require an alternative antibody format. Full-length antibodies often show a poor tumor penetration, the bivalency sometimes causes receptor clustering and partial activation, while FcγR binding and complement activation can cause unwanted side effects such as thrombosis or inflammation. Furthermore, toxin conjugation to generate ADCs is inefficient and the production of complex antibody fusion proteins is challenging. PASylation® combined with antibody fragments like Fabs, single domain Ig fragments or alternative binding proteins such as Anticalins®, Darpins®, Adnectins® and i-bodies® can solve these issues, leading to long-acting, safer and more potent biologics.

  • Extended plasma half-life

    • Expanded hydrodynamic volume leading to extended circulation time
    • Reduced injection frequencies
  • Efficient & cheap production

    • Genetic fusion: high yield, homogenous product & reduced costs
    • Compatible with various industry standard expression systems
  • Biodegradable PEG alternative

    • PAS overcomes PEG hypersensitivity
    • No organ accummulation during chronic  treatment
  • PAS + binding protein enable:

    • Long-acting antagonists without Fc effector functions
    • Smart antibody drug conjugates (ADCs)
    • T-cell engagers
    • Bi-/Multispecifics
  • Related publications and press releases:

    Peplau, E., De Rose, F., Eichinger, A., Reder S., Mittelhäuser M., Scafetta G., Schwaiger M., Weber W.A., Bartolazzi A., D’Alessandria C., Skerra A. (2021) Effective rational humanization of a PASylated anti-galectin-3 Fab for the sensitive PET imaging of thyroid cancer in vivo. Sci. Rep. 11, 7358.

  • Brandl F., Busslinger S., Zangemeister-Wittke U., Plückthun A. (2020) Optimizing the anti-tumor efficacy of protein-drug conjugates by engineering the molecular size and half-life. J. Control Release 327, 86-197.

  • Eggenstein E., Richter A., Skerra A. (2020). FluoroCalins: engineered lipocalins with novel binding functions fused to a fluorescent protein for applications in biomolecular imaging and detection. Protein Eng. Des. Sel. 32, 289-296.

  • Aghaabdollahian S., Ahangari Cohan R., Norouzian D., Davami F., Asadi Karam M.R., Torkashvand F., Vaseghi G., Moazzami R., Latif Dizaji S. (2019) Enhancing bioactivity, physicochemical, and pharmacokinetic properties of a nano-sized, anti-VEGFR2 Adnectin, through PASylation technology. Sci. Rep. 9, 2978.

  • Griffiths K., Binder U., McDowell W., Tommasi R., Frigerio M., Darby W.G., Hosking C.G., Renaud L., Machacek M., Lloyd P., Skerra A., Foley M. (2019) Half-life extension and non-human primate pharmacokinetic safety studies of i-body AD-114 targeting human CXCR4. MAbs 11, 1331-1340.

  • Griffiths K., Habiel D. M., Jaffar J., Binder U., Darby W. G., Hosking C. G., Skerra A., Westall G. P., Hogaboam C. M., Foley M. (2018) Anti-fibrotic effects of CXCR4-targeting i-body AD-114 in preclinical models of pulmonary fibrosis. Sci. Rep. 8, 3212.

  • Längin M., Mayr T., Reichart B., Michel S., Buchholz S., Guethoff S., Dashkevich A., Baehr A., Egerer S., Bauer A., Mihalj M., Panelli A., Issl L., Ying J., Fresch A.K., Buttgereit I., Mokelke M., Radan J., Werner F., Lutzmann I., Steen S., Sjöberg T., Paskevicius A., Qiuming L., Sfriso R., Rieben R., Dahlhoff M., Kessler B., Kemter E., Klett K., Hinkel R., Kupatt C., Falkenau A., Reu S., Ellgass R., Herzog R., Binder U., Wich G., Skerra A., Ayares D., Kind A., Schönmann U., Kaup F.J., Hagl C., Wolf E., Klymiuk N., Brenner P., Abicht J.M. (2018) Consistent success in life-supporting porcine cardiac xenotransplantation. Nature 564, 430-433.

  • Hoffmann K., Milech N., Juraja S.M., Cunningham P.T., Stone S.R., Francis R.W., Anastasas M., Hall C.M., Heinrich T., Bogdawa H.M., Winslow S., Scobie M.N., Dewhurst R.E., Florez L., Ong F., Kerfoot M., Champain D., Adams A.M., Fletcher S., Viola H.M., Hool L.C., Connor T., Longville B.A.C., Tan Y.F., Kroeger K., Morath V., Weiss G.A., Skerra A., Hopkins R.M., Watt P.M. (2018) A platform for discovery of functional cell-penetrating peptides for efficient multi-cargo intracellular delivery. Sci. Rep. 8, 12538.

  • FREISING Germany, 13 November, 2017: AdAlta and XL-protein execute commercial license agreement