Call it the Clinton administration's parting gift to biotechnology, or a triumph of government regulation. The new gene-patenting guidelines, released January S by the U.S. Patent and Trademark Office (PTO), drew high praise from one of biotech's biggest barons and from one of its chronic critics.

"I think this could be the Magna Carta of biotechnology," says William Haseltine, Ph.D., chairman and CEO of Human Genome Sciences (Rockville, MD). "This is probably the most systematic review of this field that has ever been done. It acknowledges every comment and lays out a rational, clear response to each one."

"The document is commendable for demystifying much of the complexity of patent law applied to genomic sequences," adds Sheldon Krimsky, Ph.D., professor of urban and environmental policy at Tufts University (Medford, MA).

The guidelines' systematic clarity should result in stronger patents, according to Lila Feisee, director for intellectual property at the Biotechnology Industry Organization (1310), adding that the PTO's response to comments provides perspective on their positions, an "insight into their decisionmaking process."

The guidelines "outline the criteria for patentability," and those criteria, comments Dr. Haseltine, mirror his company's mission. Other companies may suffer as a result, but he predicts that Human Genomic Sciences will prosper.

The guidelines' approach is one of strict constructionism. Responding to critics' comments, the PTO hewed to the classic criteria of utility, novelty, and nonobviousness. Objections to patentability based on concerns that had nothing to do with patent law, such as the potential to "exacerbate tensions between indigenous peoples and western academic/ research communities" were accordingly dismissed.

Similarly, gross generalizations, like the notion that ESTs (express sequence tags) should not be patentable because intrinsically they lack utility or novelty, did not impress the PTO. "ESTs that meet the criteria for utility, novelty, and nonobviousness are eligible for patenting when the application teaches ...how to make use of the invention," according to the guidelines.

It is not necessary to know the function of the gene or EST in order to obtain a patent, according to the guidelines: function and utility are not necessarily synonymous. Take prostate-specific antigens, says Dr. Haseltine. "It was not put in the human body to allow us to determine if somebody has prostate cancer."

The guidelines lay to rest the notion that products from nature, in general, and human genes, in particular, should lie outside of the realm of patent law. The guidelines "establish clearly and in the most dramatic fashion the patentability of human genes," says Dr. Haseltine. "If anything, the document reinforces the move toward economic colonization of the human genome and other biochemical substances found in nature," says Dr. Krimsky. It has been protested the no one should be able to own or control something so fundamentally linked to "what it means to be human," such as sequences of the human genome.

But the PTO glossed over this philosophical objection to control, stating that "patents do not confer ownership of genes, genetic information, or sequences," but merely time-limited control.

The guidelines also clearly torpedo the notion that, while inventions are patentable, genes are discoveries and, as such, should not be patentable. "The U.S. Constitution uses the word "discoveries" where it authorizes Congress to promote progress made by inventors," according to the guidelines. In a 1911 decision in which the Supreme Court ruled that adrenaline could be patented, Justice Learned Hand wrote that Japanese chemist Jokichi Takamine "was the first to make it available for any use by removing it from the other gland tissue in which it was found, and, while it is of course possible logically to call this a purification of the principal, it became for every practical purpose a new thing commercially and therapeutically."

But Dr. Krimsky contends that there is too low a burden of proof insofar as the guidelines specify that "discoveries from nature which are transformed into useful products are eligible for patents." Furthermore, despite their general clarity, Dr. Krimsky contends that the guidelines have some loose ends and rough edges. They have been widely praised by Dr. Haseltine and others for raising the bar on utility, but Dr. Krimsky maintains that the bar has dropped.

"An application need only provide one credible utility assertion of specific and substantial utility for each claimed invention to satisfy the utility requirement," the documents state.

"Some may view the phrase `specific and substantial' as tightening the utility requirement over what it was for several years when general claims were accepted," says Dr. Krimsky. But the burden is on the PTO "to explain and justify any rejection of the patent applications based on substantial and credible utility. This burden would tend to liberalize patents issued:' And although the guidelines clarify the right of a patent holder to control uses of patented gene sequences other than those for which the patent was issued, Dr. Krimsky claims, "they do not clarify what happens when someone develops a use for the `composition of matter,' or gene sequence, which, the guidelines state, may qualify for its own process patent, notwithstanding that the DNA composition itself is patented. This may easily lead to a conflict between the original patent holder of a gene sequence and the inventor of a new use for that same sequence:'

The guidelines are not the last word on gene patenting at the dawn of the new millennium. "We really won't know all that much about how much impact they will have until we look at the training materials," says Feisee, who spent ten years at the patent office before coming to BIO. In the meantime, she says, the accompanying training materials available provide examiners with case-by-case guidance to questions and issues.

More information on the U.S. PTO's new gene-patenting guidelines can be found at their Website: www.uspto.gov
http://www.mindfully.org/GE/Biotech-Magna-Carta.htm

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