HAMBURG, Germany - Atugen AG signed a research collaboration with Boehringer Ingelheim group, of Ingelheim, Germany, for the validation of gene targets using Atugen's proprietary gene block technology.

Zisi Fotev, Atugen's vice president of business development, told BioWorld International the deal was the preparatory step for a bigger collaboration. "Boehringer will deliver less than 10 targets in this first step, but if the validation process is successful, the collaboration might well be extended to several hundred targets in autumn this year."

Financial details were not disclosed.

This collaboration marks the ninth corporate partner to join with Berlin-based Atugen and the fifth agreement completed since Atugen was spun off from Ribozyme Pharmaceuticals Inc., of Boulder, Colo. When Atugen was formed, Atugen/RPI had signed five corporate partners for its target discovery and validation programs including Schering AG and its U.S. Berlex subsidiary; Chiron Corporation; the Parke-Davis unit of Warner-Lambert Co.; Glaxo Wellcome; and Roche Biosciences. Since then Millennium Pharmaceuticals Inc., AstraZeneca, Roche Bioscience (formerly partnered for target discovery only) and Axys Pharmaceuticals Inc. have initiated gene target validation collaborations, most of them spanning several hundred targets each.

Three of the collaborations are serviced through the Atugen USA subsidiary in Boulder. Earlier this year, Atugen and the German biotech company GPC AG, of Martinsried, initiated a strategic biotech-biotech alliance to combine their technology to a fully integrated functional genomics and proteomics platform.

"In addition, we are about to close a deal with a big German company," Fotev said. He said Atugen had initiated a second financing round, and was planning an initial public offering on Germany's Neuer Markt in the first quarter of 2001.

"So far, we have concentrated mostly on gene target validation; however, recently we have been able to demonstrate that our GeneBloc technology is able to inhibit the expression of certain genes involved in cancer in vivo as well," he said. "We are already negotiating with a big U.S. company about a collaboration to develop these molecules into therapeutic drugs. This business segment will become much more important for us in the near-term future - there's much more money in it than in services."

The process offered by Atugen to determine gene function and to validate appropriate therapeutic targets is conceptually simple. The function and relevance of genes involved in disease processes are analyzed using proprietary oligonucleotides designed to inhibit gene expression by hybridizing to the mRNA of the targeted gene. "This process is very specific and very effective in preventing the synthesis of the gene product," Fotev said. "In addition, we use ribozymes that directly cleave or modify RNA, or oligonucleotide chimeras that indirectly activate cellular nucleases."

The inhibitory molecules are delivered by a proprietary lipid technology. "It allows a 100 percent transfection of the cells under investigation." Expression of the targeted gene is then blocked for at least four days.

The effects of the inhibition in terms of gene expression can be quantified with robotized high-throughput mRNA assays, oligonucleotide-based arrays and phenotypic endpoints. "The relative importance of a particular gene sequence to disease pathology can then be established by correlating the inhibition of gene expression with phenotypic results," Fotev said. "With a step-by step process, we are able to reassemble every step of the disease process, as if we were able to travel back into the past."

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