DNA-encoded chemical libraries: The isolation of specific binding molecules is a formidable challenge in the drug discovery process. DNA-encoded chemical libraries promise to revolutionize the way organic ligands to pharmaceutical targets are isolated. Such libraries consist of a collection of organic molecules each covalently coupled to a distinctive DNA tag that serves as an amplifiable identification bar code. No screening assay is required, which allows tackling of historically difficult target proteins, such as components involved in protein-protein interactions.
a) Schematic representation of the Philochem DNA-encoded chemical libraries. b) Typical graphical representations of the library after selection and high-throughput sequencing characterization.
Discovery of Vascular Targets:The development of novel therapeutic antibodies and other vascular targeting agents crucially relies on the identification of novel vascular antigens, abundantly expressed and/or selectively accessible in diseased tissue compared to normal tissues. In collaboration with the ETH Zurich, Philochem has developed a perfusion-based chemical proteomic technique for the selective enrichment of proteins accessible from the vasculature and pioneered the area of label-free MALDI-MS-based protein quantification.
Antibody Libraries: Recombinant antibody technology has revolutionized the way monoclonal antibodies are isolated, both for research applications and for the development of pharmaceutical products. Philochem has developed ‘single-pot’ libraries containing billions of antibodies, suitable for the isolation of high-quality binders against virtually any protein target of interest. A number of human monoclonal antibodies isolated from Philochem’s libraries have progressed to advanced clinical trials.
The selected high affinity antibody specific for the desired antigen is reformatted from scFv to different antibody or immunocytokine formats.
Antibody Derivatives: Philochem is active in innovative projects, focused on the modification of antibodies for pharmaco-delivery applications. The main areas of activity include the fields ofantibody-drug conjugates, immunocytokines and radio-labelled antibodies.
Schematic representation of antibody-drug conjugate effect: Long residence time of specific antibodies on the tumor neo-vasculature is ideally suited for a slow release of a potent cytotoxic drug by virtue ofjudiciously chosen linker lability, leading to drug-indiced cell death.