Jan Terje Andersen, Professor in Biomedical Innovation , University of Oslo and Oslo University Hospital

Design of protein-based biologics with better performance

The number of approved antibodies for therapeutic use has substantially grown and reached more than 100 in the US while record numbers of additional candidates are under regulatory review. To tailor-design the next-generation antibody modalities, plasma half-life is a commercially competitive differentiator, which dictates dosing and the frequency of administration. In addition, albumin is increasing explored as a fusion partner for therapeutics.

The plasma half-life of the two most abundant proteins in blood, albumin and the antibody IgG, is roughly 3 weeks at average. Remarkably, the plasma half-life of these structurally and functionally unrelated proteins is prolonged by a common cellular receptor, FcRn. In this talk, I will discuss the key role of FcRn in design of antibody and albumin based formats with favourable binding and transport properties.

The talk is relevant for all disciplines aiming for improved pharmacokinetic properties of protein-based biologics, including both invasive and non-invasive delivery strategies across a broad range of applications.  

Relevant references:

1. Potent TRIM21 and complement-dependent intracellular antiviral immunity requires the IgG3 hinge. Foss S, Jonsson A, Bottermann M, Watkinson R, Lode HE, McAdam MB, Michaelsen TE, Sandlie I, James LC, Andersen JT. Science Immunol. 2022 Apr 29;7(70):eabj1640.
2. An engineered human albumin enhances half-life and transmucosal delivery when fused to protein-based biologics. Bern M, Sand KMK, Bækkevold ES, Foss S, Grevys A, Nilsen J, Dalhus B, Christianson GJ, Roopenian DC, Schlothauer T, Michaelsen TE, Sandlie I, Andersen JT*. Science Trans Med. 12, 565 (2020).
3. A human endothelial cell-based recycling assay for screening of FcRn targeted molecules. Grevys, A, Nilsen, J, Sand, KMK, Daba, MB, Øynebråten, I, Bern, M, McAdam, MB, Foss, S, Schlothauer,T, Michaelsen, TE, Christianson, GC, Roopenian, DC, Blumberg, RS, Sandlie, I, Andersen JT*. Nature Com, 9, 621 (2018).