By Lisa Seachrist

Washington Editor

Reaching across the ocean for a partnership once again, Human Genome Sciences Inc. (HGS) announced a collaboration with Tel Aviv-based Compugen Ltd. to delve into HGS¿ collection of genes and develop a human gene map, a large collection of single nucleotide polymorphisms and a description of human gene organization.

On Wednesday, HGS entered a collaboration with England-based Cambridge Antibody Technology plc for access to CAT¿s phage display technology.

The financial terms of the deal weren¿t disclosed, but HGS did say it would pay Compugen a fixed multi-million dollar fee for the work, which is expected to take a year. HGS will retain the exclusive rights to commercialize the results of the collaboration.

¿This is really a look at our post-July 2001 strategy to strengthen our position,¿ said William Haseltine, the Rockville, Md.-based company¿s chairman and CEO. ¿First and foremost, this is to help us discover our own drugs. Our secondary objective is to support our current and future partners.¿

Until July 2001, Middlesex, U.K.-based SmithKline Beecham plc has exclusive rights to develop drug candidates based on certain gene discovery projects at HGS. Haseltine said HGS intends to have the information generated from the Compugen collaboration up and ready when the exclusivity deal expires.

The basis for the collaboration is Compugen¿s Leads technology, which allows direct comparison of DNA sequences. All of the work will be conducted at HGS, with a team of Compugen scientists collaborating with HGS scientists.

In establishing the deal with Compugen, of Tel Aviv, Israel, HGS will rely only on the information generated by the federally sponsored Human Genome Project and the company¿s collection of more than 95 percent of all human genes. Haseltine noted HGS had isolated more than 2.5 million messenger RNAs (mRNAs) from a representative sample of all human organs and tissues from 800 different people. The mRNAs serve as the template for producing proteins in the body.

¿Once we have the genome sequence from the Human Genome Project, getting a map of human genes is very easy, it¿s just matching up the DNA sequence to the mRNAs,¿ Haseltine said.

While the Human Genome Project aims to create a map of the human genome as well, Haseltine believes HGS has a leg up. For example, when HGS analyzed the newly sequenced Chromosome 22, the scientists found over 300 genes on that chromosome alone missed by the federally funded researchers.

¿I believe we will be the first to achieve a virtually complete map of the human genome,¿ Haseltine said. ¿The biggest untold secret of the Human Genome Project is that you can¿t find genes from the sequence. That¿s why mRNA is so uniquely valuable.¿

Once a map is completed, Haseltine said researchers will be able to determine associations between individual genes and inherited disease relatively quickly.

In addition to using its collection of mRNAs to locate genes on chromosomes, HGS will use Compugen¿s considerable computing power to identify single nucleotide polymorphisms in expressed genes ¿ referred to as cSNPs. These individual variations are thought to be important in determining a person¿s susceptibility to certain diseases and reactions to certain medications.

¿The SNPs found in mRNAs are valuable because those variations point to genes,¿ Haseltine said. ¿The minimum estimate of the number of SNPs found in mRNA is half a million.¿

Finally, the collaborators intend to look at the organizations of genes in the human genome. Rather than a cohesive whole, genes are scattered about a chromosome in segments. On the mRNAs the pieces needed for a functional gene are called exons and the intervening sequences between the exons are called introns. In different organs and tissues the final structure of the mRNA varies depending on how the exons are spliced together. Splicing variants of the same gene may have profoundly different activities in a cell.

¿I liken it to having the commandment Thou shalt not commit adultery¿ and removing the word not ¿ it¿s an entirely different meaning,¿ Haseltine said. ¿We¿ve seen things like this where a growth hormone gene becomes a growth hormone antagonist as a result of its splicing pattern.¿

Haseltine noted information on splicing variants was vital for understanding the function and medical use of human genes. Such information will ultimately strengthen patent claims.

¿This is a nice bonus for our partners,¿ Haseltine said. ¿We also are very open to academic collaboration. We will make this information available to those who want to use it for research purposes. We have a precedent for this ¿ we¿ve already made available more than 2,000 genes and proteins for academic scientists for free.¿

HGS¿ stock (NASDAQ:HGSI) closed Thursday at $214.125, down $11.125.

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