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MorphoSys Antibodies by Design, ProQinase and Natural and Medical Sciences Institute (NMI) receive BMBF-promotion for Kinome-project

Martinsried/Munich, Freiburg and Reutlingen, June 17, 2005

ASK-chip shall enable targeted functional analysis of the human kinome

ProQinase, a division of KTB Tumorforschungs GmbH at the Tumor Biology Center, Freiburg, the NMI Natural and Medical Sciences Institute at the University of Tübingen, and Antibodies by Design, a division of MorphoSys AG, Munich, today announced the start of a joint project which could revolutionize the analysis of all human protein kinases – the human “kinome”. The project combines the established protein kinase platform of ProQinase with the know-how of Antibodies by Design in the field of custom-made antibody generation and the experience of NMI with siRNA and Biochip technologies. The goal of the project is to develop an adenoviral siRNA-kinome-chip (ASK chip) which enables the parallel inhibition of all human protein kinases by means of RNA interference on a miniaturized Biochip. This technology allows simultaneous determination of the function of all protein kinases, e.g. growth of tumor cells to identify starting points for new therapies. Members of the protein kinase family are considered as promising targets for therapy of different diseases. In the coming three years, the project will be supported by approximately EUR 2.0 million within the scope of the BioChancePLUS Program of the German Federal Ministry of Research (BMBF).

More than 500 protein kinases, which pass on cell signals and affect almost all biological processes, are currently known. A number of these kinases are suspected to play a central role in various diseases such as cancer, inflammation, or cardiovascular disease. “Protein kinases function as a complex network which often is altered in human diseases, but can be affected therapeutically by drugs that block individual protein kinases”, stated Dr. Michael Kubbutat, Head of Research & Development at ProQinase. “Until now, however, an overall picture and understanding of this network that would allow e.g. to determine the effects of drugs on the interaction of the protein kinase network is still missing. The expertise of ProQinase in this field will support this project to find a remedy.”

Drug research in this field requires optimized reagents. Sufficient quantities of recombinant protein kinases, methods for specific manipulation of protein expression in suitable cell lines, and kinase-specific antibodies for the entire kinome play a central role. At present, there are no antibodies available for the majority of kinases. This bottleneck in the project will be resolved by the use of MorphoSys’ HuCAL® technology. Antibodies by Design will generate recombinant antibodies against up to 250 protein kinases. “By combining Biochip, siRNA, and antibody technologies, this project represents a new scientific approach and validates the efficiency of our automation systems for high-throughput antibody generation”, stated Dieter Lingelbach, General Manager of Antibodies by Design and Senior Vice President of MorphoSys.

Targeted blocking of the expression of selected protein kinases will be achieved using short interfering RNA molecules (siRNA) in the form of short hairpin RNAs (shRNA). These shRNA vectors will be produced by NMI and MorphoSys. ProQinase will use kinase-specific antibodies from Antibodies by Design to confirm successful deactivation of the protein kinases by specific shRNA vectors. The combination of all components to create a complete analysis system in chip format will take place at the NMI, where adenoviruses expressing functionally validated shRNA sequences will be arranged on a miniaturized biochip. A patent application protecting the procedure to produce and apply ASK chips has been submitted to the German Patent Office by NMI. “A new approach enabling parallel functional analysis of all human protein kinases in living cells in combination with miniaturization via chip technology has not yet been developed”, commented Dr. Enzio Müller, Director of the institute at the NMI. “We therefore predict a good potential market for the products developed out of this partnership.”

Antibodies by Design
NMI – Natural and Medical Sciences Institute

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