Odyssey Thera granted pathway-based drug discovery patent
single-and multi-colour protein-fragment complementation assays
(PCA), which can be applied to high throughput drug discovery.
The assays present a new method to drug discovery, addressing the need for a universal approach to study the dynamics of biochemical pathways.
Drug discovery has long been in need for assays that accurately reflect the activity of drug targets in their native context, resulting in screening hits of greater quality and likelihood of success.
Odyessy's patent (7,062,219) is based on an assay that selects an interacting protein pair that is combined with an appropriate PCA reporter such as monomeric enzymes and fluorescent proteins.
The assays may be run in high-throughput or high-content mode and may be used in automated screening of libraries of compounds.
"The assay achieves three key goals: first, a massive increase in the scope of cell-based, biologically relevant screens for drug discovery and profiling. Importantly, the claims are not limited to particular targets, cell types or assay formats, and we've constructed assays for all major target classes," said John Westwick, patent co-author and >Odyssey Thera President and CSO.
"Second, we describe how these tools are applied to high throughput drug discovery, enabling the screening of large compound libraries."
"Finally, we demonstrate that the assays accurately reflect the activity of drug targets in their native context, resulting in screening hits of greater quality and likelihood of success."
There is currently a need in drug discovery and development for rapid and robust methods for performing biologically relevant assays in high throughput.
In particular, cell-based assays are critical for assessing the biological activity of chemical compounds and the mechanism-of-action of new biological targets.
In addition, there is a need to quickly and inexpensively screen large numbers of chemical compounds. This need has arisen in the pharmaceutical industry where it is common to test chemical compounds for activity against a variety of biochemical targets, for example, receptors, enzymes and signalling proteins.
These chemical compounds are collected in large libraries, sometimes exceeding one million distinct compounds.
Most screening of chemical libraries is performed with in vitro assays. Techniques such as scintillation proximity, fluorescence polarization and time-resolved fluorescence resonance energy transfer (FRET) or surface plasmon resonance spectroscopy have enabled large-scale screening of diverse biochemical processes such as ligand-receptor binding and protein kinase activity.
Cell-based HTS and HCS assays could represent the fastest approach to screening poorly characterised targets.
The increased numbers of drug targets that are derived from genomics approaches has driven the development of multiple `gene to screen` approaches to interrogate poorly defined targets, many of which rely on cellular assay systems.
