PIRS Anticalins
The technology lends itself to bispecifics, and indeed, much of their pipe consists of them. One example, wholly owned, is this CD137/Her2 bispecific (note CD137=4-1BB, which is how it's shown in their pipeline chart):
Costimulatory T cell engagement via a novel bispecific anti-CD137/anti-HER2 protein based on Anticalin® technology
Hot of the presses is this piece regarding Anticalins targeting VEGFR-3. This is probably one of several of undisclosed targets in its pipe, but since it's not a bispecific, that narrows it to two ownership possibilities: might be partnered with Roche, might be wholly owned.
>> Biol Chem. 2017 Jan 1;398(1):39-55. doi: 10.1515/hsz-2016-0195.
Anticalins directed against vascular endothelial growth factor receptor 3 (VEGFR-3) with picomolar affinities show potential for medical therapy and in vivo imaging.
Richter A, Skerra A.
Abstract
Members of the vascular endothelial growth factor receptor (VEGFR) family play a central role in angiogenesis as well as lymphangiogenesis and are crucial for tumor growth and metastasis. In particular, VEGFR-3 expression is induced in endothelial cells during tumor angiogenesis. We report the design of anticalins that specifically recognize the ligand-binding domains 1 and 2 of VEGFR-3. To this end, a library of the lipocalin 2 scaffold with 20 randomized positions distributed across its binding site was subjected to phage display selection and enzyme linked immunosorbent assay (ELISA) screening using the VEGF-C binding fragment (D1-2) or the entire extracellular region (D1-7) of VEGFR-3 as target proteins. Promising anticalin candidates were produced in Escherichia coli and biochemically characterized. Three variants with different receptor binding modes were identified, and two of them were optimized with regard to target affinity as well as folding efficiency. The resulting anticalins show dissociation constants down to the single-digit picomolar range. Specific recognition of VEGFR-3 on cells was demonstrated by immunofluorescence microscopy. Competitive binding versus VEGF-C was demonstrated for two of the anticalins with Ki values in the low nanomolar range. Based on these data, VEGFR-3 specific anticalins provide promising reagents for the diagnosis and/or therapeutic intervention of tumor-associated vessel growth.<<
Cheers, Tuck |
