June 28, 2000

U.S. Hopes to Stem Rush Toward Patenting of Genes

By ANDREW POLLACK

	Tim Shaffer/Reuters (top); Agence France-Presse (bottom)
	Craig Venter, the founder of Celera Genomics, sits next to a DNA sequencer at a company lab in Rockville, Md. Below, a technician holds a plate that in turn holds DNA samples waiting to be analyzed for genome mapping.
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ong before scientists had completed the task of reading the human genome, parts of it had already been claimed for commerce. In what has often been compared to a land grab, companies and universities have filed for patents on hundreds of thousands of genes and gene fragments.

Amid concerns that such patents are being granted too liberally and that they could hinder innovation,the U.S. Patent and Trademark Office is about to implement new guidelines that will make it harder to patent genes. But critics say the new rules are still too lax.

Some opponents say that it is a moral affront to patent living things or parts of living things. They argue that a gene is not an invention, but something that exists in nature, which should be the common heritage of mankind.

"The notion that some company has a monopoly on my genes is like claiming ownership of the air," said Jonathan King, a professor of molecular biology at the Massachusetts Institute of Technology.

According to the Patent and Trademark Office, however, the law allows patenting of discoveries from nature, such as penicillin, if they are isolated and purified by the hand of man. "From a patent law standpoint, genes are treated just like any other chemical found in nature," said Q. Todd Dickinson, commissioner of the Patent Office. The patent office has now issued patents on 6,000 genes, more than 1,000 of them human genes.

Indeed, genes have been patented for years. Many of the first were for drugs. For example, erythropoietin, for anemia, was found by cloning genes that coded for particular proteins. In those early days, scientists knew the function of the protein and worked backwards, taking years to isolate a single gene.

But now high-speed gene sequencing and other techniques are allowing genes or fragments of genes to be discovered en masse, without knowing the functions of the proteins produced by the genes. These genes, rather than representing a product in themselves, are now guides to future product discovery. And there is concern that if these genes are patented it would discourage other scientists from doing research using the same genes. Some compare it to trying to gain ownership of the alphabet, rather than of a novel or play.

Earlier this year, for example, Human Genome Sciences, based in Rockville, Md., was granted a patent on a gene for a protein that turned out to serve as the entryway for the AIDS virus to infect cells, even though the company did not know what the gene did at the time. The gene's function was subsequently discovered by other researchers. Still, Human Genome can receive royalties on any drug that targets this entry portal -- or even block development of such a drug.

"You have people who haven't contributed to subsequent discovery being able to lay claim to those discoveries," said Rebecca S. Eisenberg, a professor of law at the University of Michigan.

Some doctors fear that genetic testing of patients could become prohibitively expensive if each gene is patented. Research scientists are already searching for clues to disease by seeing which genes are active in diseased cells. But the chips used to study the matter might become impractical if the rights to each gene had to be licensed.

Even some big drug companies, which normally preach the importance of patents for spurring innovation, have expressed concern about the ramifications of patenting genes.

Dr. Bob Levy, senior vice president for science and technology at American Home Products, calls the gene patenting situation a "minefield." Finding out who owns rights to what takes an increasing amount of time, Levy said at a health care conference earlier this year organized by Chase H&Q, an investment bank. Royalties paid to holders of patents on genes, research mice and other tools can total 12 percent to 14 percent for a single drug, he said, making some products uneconomical to produce.

As a result of these concerns, 10 big drug companies formed a consortium last year to study differences in the genome between one person and another. These differences, known as single nucleotide polymorphisms, or SNPs, could be important in testing susceptibility to disease. The consortium is putting them in the public domain to prevent other companies from patenting the SNPs before their function is known. "It's to ensure we have the basic alphabet," said Arthur Holden, chief executive of the consortium.

Some executives say concerns that innovation will be blocked are unwarranted, pointing out that patents are designed to encourage innovation, not retard it, by giving an incentive to inventors. Also, the contents of patents must be published so that others can learn from it.

William A. Haseltine, president of Human Genome Sciences, the leading patenter of human genes, said the electronics industry continues to innovate rapidly and reduce prices despite numerous patents.

Stephen P.A. Fodor, chairman and chief executive of Affymetrix Inc., which makes gene chips, said only one patent holder has refused to allow its gene to be placed on a chip. Most patent holders want people to do research on their genes in hopes of finding a drug, which would bring really big royalties, he said.

Scientists often make a distinction between the genome itself - the entire sequence of 3 billion chemical units in human chromosomes - and individual genes. It was a confusion between the two that caused the stocks of biotechnology stocks to plummet in March after President Clinton and British Prime Minister Tony Blair issued a statement saying the genome should be publicly available.

White House officials later emphasized that genes themselves should be eligible for patents.

The crucial issue for patent examiners has been how much of the gene's function must be known to satisfy the requirement that any patentable invention be useful. Until now, the companies have filed for patents in massive numbers without knowing the functions of many genes, claiming that, at a minimum, they can be used as animal feed. The patent office has granted some of these patents.

Applications are pending for more than half a million fragments of genes, which are known as expressed sequence tags, said John Doll, director of biotechnology at the Patent Office. Some applications claim that a fragment is useful because it can allow scientists to find the entire gene.

But now, in response to criticism, the patent office is raising the bar by requiring that more of the gene's function be known. "Nobody would go to the time and cost of isolating a protein from a diseased cell merely to put it in dog food," Doll said.

Under the new guidelines expected to take effect in the next few months, gene fragments will probably not qualify for patents. At the other extreme, fully characterized genes whose function is known - such as a gene that predisposes woman to breast cancer and can be used in a diagnostic test - will continue to be patentable.

There is still a vast ground in the middle, consisting of full-length genes whose function is not known for sure but is guessed at by computer analysis. The National Institutes of Health, the National Academy of Sciences and oppose patents on these genes.

With the technology in so much flux, gene patenting is likely to be the subject of numerous court battles and might be revisited by Congress. For companies that have staked their futures on owning the rights to genes, and for science in general, a lot is riding on the outcome.