LONDON Proteome Sciences plc has signed a deal in the area of cardiovascular disease with Rhtne-Poulenc Rorer Inc. (RPR) to identify proteins which are characteristic of failing human myocardium.

For an initial period of two years, the research program will be funded by RPR. Proteome will retain all rights relating to discoveries with diagnostic applications, while RPR, of Collegeville, Pa., will have rights to discoveries relevant to the treatment of heart disease or heart failure. Samples of diseased heart tissue will be supplied by Proteome¿s academic partner, the Heart Sciences Research Centre of Harefield Hospital, in London. Harefield and Proteome will receive a royalty on any drugs developed as a result.

Christopher Pearce, managing director of Proteome, based in Cobham, Surrey, told BioWorld International the deal with RPR and a previous agreement with diaDexus, of Santa Clara, Calif., are expected to open the door to ¿a steady flow of license agreements. A year ago, proteomics didn¿t really exist as a discipline. We now expect pharmaceutical companies to do deals in the same way as they have moved into platform technologies like combinatorial chemistry and functional genomics.¿

DiaDexus is a joint venture between SmithKline Beecham plc, of London, and Incyte Pharmaceuticals Inc., of Palo Alto, Calif.

Proteomics may be a new discipline, but Proteome Sciences was founded in 1984, as Electrophoretics International plc. It changed its name in June 1998 to reflect its focus on proteomics, in which gel electrophoresis is combined with mass spectrometry and bioinformatics to search for novel protein markers in bodily fluids and tissue to identify specific disease states and develop associated diagnostic, prognostic and therapeutic applications.

¿Electrophoresis is still the best way to separate proteins, but improvements in the technology since the mid-1990s, in terms of reproducibility and the level of detail it is possible to achieve, have transformed the art,¿ Pearce said. ¿We are now able to visualize protein fragments and low-molecular-weight proteins down to 600 molecules. It is like the difference between looking at the stars with one eye through an old-fashioned telescope, and looking at them through the Hubble telescope. You can see enormous amounts of differences and focus faster on the proteins of importance.¿

Detecting Changes In Protein Expression

Pearce said that, while humans are estimated to have approximately 100,000 genes encoding 100,000 proteins, post-translational modification (which modulates the function of the protein, but is not directly encoded by genes) may expand the original number of proteins to greater than 5 million proteins or protein fragments.

¿Our technology is able to detect the changes in patterns of protein expression in disease down to levels of low-abundance proteins and protein fragments,¿ he said.

An example is in lung cancer, where, Pearce said, the company is able to differentiate between diseased lung tissue and controls and identify the type of lung cancer. Proteins overexpressed in lung cancer relative to normal tissue are then purified and sequenced, and monoclonal antibodies are developed. Under the deal with diaDexus, announced in April 1998, Proteome was provided with blinded lung cancer samples. It now is developing monoclonal antibodies that will be available for testing by the end of the year, as the basis for immunoassays.

¿The major objective of our program in oncology is to identify proteins from readily accessible body fluids or tissue that could serve as novel markers for particular forms of cancer,¿ Pearce said. ¿These could be used for screening, diagnosis, for deciding on a treatment plan and for predicting the outcome of treatment. The same markers may be useful in therapy.¿

Proteome Sciences announced the RPR deal as it released results for the six months ended June 30 which showed a loss of #886,000, up from #760,000 in the same period of 1997. The company, which is listed on London¿s Alternative Investment Market, had #2.2 million in cash.

¿Even if we have no revenue at all, this will last until 2000,¿ Pearce said. ¿Because most of our work is in collaboration with academics, we have a highly predictable burn rate. In fact, we have been inside expectations for the past few years.¿

During the period, Proteome generated its first U.K. revenue from its protein separation and analysis service. ¿This is making a useful contribution to overheads, but our business is not to be a contractor,¿ Pearce said. Instead, the company plans to commercialize its research through licensing novel proteins.

¿We have built up a considerable patent portfolio, and pharmaceutical companies will have to come to us in due course for licenses,¿ he said.