E! 7820 A novel platform for "Next Generation Kinome Profiling"

We have developed the "Next Generation Kinome Profiling" assay. We believe this technology is significantly superior to existing alternatives. The developed kinase activity profiling assay is based on mass-spectrometry detection. We have optimizaed glass slide coating in order to increase the signal to noise ratio. To obtain these results we have increased the thickness of the glass slide coatings to 20-25 nm. This thicker coating have resulted in significantly higher signal to noise ratios. For the peptide substrate design we have used rational design, based on newly developed software tools. This rational design gave highly specific and sensitive substrates. We are now capable of designing selective and specific substrates for a variety of protein kinases, both for use on peptide arrays as well as in mass-spectrometry assays. This design have been tested successfully using glioma as a model disease. We have developed an analysis software including several indexing algorithms and clustering methods. The new software support the following functionality: - Analysis and clustering based on status of the kinase activity in a patient file - Analysis to set status as tumor suppressor or oncogene. - Analysis and clustering of kinase activity in the patient file based on available and approved drugs. - Analysis and clustering focusing on statistical relevance to several types of medical concepts. In addition we have developed text mining and analysis algorithms for extraction and filtering of clinical trial in clinicaltrials.gov.

The aim of this project is to develop a novel protein kinase assay that allows a rapid identification of the activity of complete sets of protein kinases in a single patient sample. The proposed diagnostic assay developed using this technology can be used to determine the most optimal combination of kinase inhibitors for targeted and personalized treatment of patients, and to monitor treatment response. Three expert SME companies (Pepscope BV, PEPperPRINT GmbH and PubGene AS) and one academic partner (E rasmus Medical Center) will join forces to develop a "Next Generation Kinome Profiling" assay that is appropriate for such applications. To validate the prototype assay, the consortium will use colorectal cancer as a model. Despite recent advances in the field of cancer, this disease is a leading cause of death worldwide with 7.6 million casualties in 2008. For colorectal cancer, several kinase inhibitors have been identified. Some are already approved for clinical use and others are in phase II/III clini cal phases. If successful, this platform technology will also be suitable to determine kinase activity profiles in other types of cancer samples, and other diseases related to altered kinase activity. This tool will support and inform decision-making thro ughout the kinase drug development continuum.