HAMBURG, Germany - Atugen Biotechnology AG, the Berlin-based target discovery and validation spin-off of Ribozyme Pharmaceuticals Inc. (RPI), entered a collaboration with Roche Bioscience.

In addition, a North American research center was founded as a subsidiary in Boulder, Colo. The center will serve existing and future collaborations with U.S. pharmaceutical companies.

When Atugen formally opened in January it was celebrated as the first example of technology transfer from a U.S. biotechnology company to a German biotech start-up. Two factors contributed to this development: excellent federal and state funding conditions in Germany, and the newly founded RiNA RNA Network, which was established to speed up the development of therapeutic and diagnostic applications of RNA. (See BioWorld International, Aug. 5, 1998, p. 4.)

Atugen received initial financing of more than $20 million for the first three years of operations and obtained exclusive worldwide licenses to RPI's entire technology portfolio for target discovery and validation.

"We offer a unique solution," Klaus Gies, Atugen's vice president, technology, told BioWorld International. "Our GeneBloc technology includes ribozymes that directly cleave or modify RNA, and oligonucleotide chimeras that indirectly activate cellular nucleases as RNase H. That way, expression of a target sequence or an expressed sequence tag is inhibited in a very specific way by at least 70 percent.

"We then quantify the inhibition using high-throughput mRNA assays and study the phenotypic effects so that we can establish the relative importance of a given sequence to disease pathology," he said.

Using special lipids as vehicles for the inhibiting substances, the blocking works both in vitro and in vivo and lasts at least four days with a single application, Gies said. "The technology has been established now in more than 50 cell lines and has been automated for high-throughput screening."

To get access to early and rapid in vivo assessments of gene expression inhibition in whole animals, Atugen recently acquired Transgenics Berlin-Buch GmbH, of Berlin, a company specialized in producing transgenic animals. In addition, Atugen cooperates with the microarray manufacturer Clondiag, of Jena, Germany, to obtain oligonucleotide arrays for highly automated, high-throughput target validation and functional genomics studies.

In the collaboration with Palo Alto, Calif.-based Roche Bioscience, Atugen will provide its technology to knock down, or inhibit, genes in inflammatory pathways to validate or invalidate putative therapeutic targets. Atugen will develop and perform assays to evaluate attenuation levels, differential expression and phenotypic endpoints of the target genes and transfer the technology to Roche Bioscience for internal use. Financial details were not disclosed.

Separately, Atugen has collaborations with Chiron Corp., of Emeryville, Calif.; Glaxo Wellcome plc, of London; the Parke-Davis unit of Warner-Lambert Co., of Morris Plains, N.J.; and Berlin-based Schering AG, along with its U.S. affiliate, Berlex Pharmaceuticals. Founding of the U.S. subsidiary, which employs a staff of 16 formerly employed by RPI, was designed to help serve partners.

"Berlin will remain our headquarters," Gies said. "The U.S. subsidiary will be self-sustaining as a result of revenues from the collaborations." Further partnerships are soon to follow, he said. "In Europe, we are in an advanced state of negotiations with several pharmaceutical companies."