Science Editor

Patent challenges - long a favorite parlor game in the biotech industry, at least for plaintiffs - received a new twist recently with a lawsuit brought by the American Civil Liberties Union and a number of co-plaintiffs against Utah biotechnology company Myriad Genetics and the University of Utah Research Foundation.

The suit alleges that patents they hold on BRCA 1 and BRCA 2 genes infringe on women's civil liberties because those patents "stifle research that could lead to cures and limit women's options regarding their medical care."

The lawsuit has raised concerns that, if successful, they could knock loose the underpinnings of the life sciences field. The fear is that patent protection is what draws investment money, which is the lifeblood of biotech drug development

Richard Gold, professor of law at McGill University, is skeptical that the lawsuit will be successful, at least as a test case for the larger issue of whether genes are patentable. "No one has brought up the constitutional issues, so there is the possibility" that the ACLU's argument will prevail, he told BioWorld Financial Watch.

But "courts have been granting these patents for 30 years," and have held fast to the idea that genes are patentable in the face of repeated challenges. In addition, the patent may well be expired by the time the suit winds its way through the court system, and that other factors are leading to fewer attempts to patent genes.

Given these circumstances, the specifics of the suit at first blush seem to take on a whiff of much ado about nothing. But in the bigger sense, patents - or at least, the way they are seen and the way they are used - may be changing.

Intellectual property is a cornerstone of drug discovery. And there is a common belief that developments such as the Bayh-Dole Act, which enabled the patenting of federally funded inventions, and the Supreme Court's Diamond v. Chakrabarty decision, which allowed for the broad patenting of genes in 1980, have been instrumental to moving drug discovery forward.

The Biotechnology Industry Organization's position is that "patents add value to laboratory discoveries, providing incentives for private sector investment into biotechnology development of new medicines and diagnostics for treatment and monitoring of intractable diseases . . ., to meet global needs."

Patent attorney Patrick Higgins told BioWorld Financial Watch that patents encourage innovation by functioning as a "reward to the inventor for teaching everybody how to use this new invention."

Harry Glorikian, managing partner of the life sciences consulting firm Scientia Advisors, added that "the point of filing is to make information public and encourage others" to use that information for further innovation.

And because the inventor's monopoly is temporary, it encourages both the inventor and possible competitors to come up with something better than the invention that can be brought to market after the patent expires.

Certainly, patents are important to venture capitalists, and because of this, are valuable to biotech companies. They serve as a biomarker of sorts to determine whether a company is innovative.

But like with so many biomarkers, whether what is being measured is relevant is open to debate. Gold and others studying the issue are agnostic as to whether patents enhance innovative drive, or impede it.

At its heart, Gold said, whether to believe the arguments made by the ACLU is "a judgment call. The central argument is that [patents] decrease innovation. And the question is, how do you know?"

Gold stressed that to speak of the patent system as a whole "misses the subtlety of the question" of whether patents are useful. In a report on intellectual property last year, Gold and his co-authors argue that there is a sea change underway in how patents are used. The report was authored by the nonprofit organization The Innovation Partnership, which describes itself as "an independent non-profit consultancy specializing in use and management of intellectual property." Gold is the organization's director.

The report argues that there is growing recognition that, as opposed to material goods, "many IP rights are only valuable . . . because of our relationships with others" and that as a consequence of that recognition, "we are entering a new IP era in which IP is used to sustain and maintain collaborations and partnerships," rather than being "hoarded."

The data on whether patents currently further or stifle innovation, Gold said, are ambiguous. For diagnostics tests what data there is suggests that patents are more likely to stifle innovation than to further it. "When a new gene is announced, laboratories are pretty quick to produce a diagnostic test - it's not rocket science," he said. Later, when a patent is announced, those same diagnostic labs shut down, leaving the monopoly decried by several co-plaintiffs in the ACLU suit.

For drug discovery, things are murkier; examples exist for drugs that would not be on the market were it not for strong patent protection, but there also is the counterexample of drugs being prevented from reaching the market due to patent issues.

Overall, the report concludes that "the analysis of data linking patents to increased innovation is ambiguous," that "IP rights have only a marginal role in encouraging research," and that "according to one study, IP and licensing together account for less than 20 percent of the dissemination of research ideas originating in universities." The other 80 percent, Gold said, include management and finances, but also such intangibles as having good contacts and being in the right place at the right time.

Aled Edwards also thinks that the current patent system is misguided both in its scope and its targets. Edwards is a professor at the University of Toronto, co-founder of Affinium Pharmaceuticals Inc., and director of the Structural Genomics Consortium, a nonprofit whose goal is to "determine the three dimensional structures of proteins of medical relevance, and place them in the public domain without restriction."

Edwards believes that the patenting of the very beginning of a potential drug - in the form of a gene, or even a chemical - does more harm than good.

The reason is that "the problem in discovering medicines is not to find a chemical and patent it," he said. "The fundamental problem is that we don't know enough about human biology. That is what cripples every drug discovery program."

Gene patents, he said, contribute to the problem by "impeding the free flow of information," while patents on chemotypes are often "a study in obfuscation" to prevent potential competitors from determining which of many patented chemotypes is the important one for a given application.

Edwards said that a better alternative would be to have open-access, government-supported research through Phase II, with patents coming later in the process to protect more specific molecules that are actually promising in clinical trials.

And it's an approach that is gaining support in at least some corners of the drug discovery industry. Last fall, GlaxoSmithKline plc entered into a public-private partnership with Edwards' Structural Genomics Consortium, the National Institutes of Health and Oxford University with the goal of generating small molecule inhibitors of epigenetic signaling and placing them into the public domain.

Tim Willson, who is a scientist at GSK, told BioWorld Financial Watch that the company had long put compounds for orphan steroid receptors into the public domain retrospectively. And such release "greatly stimulated research in the area, which in turn gave us better insight" into promising targets as well as compounds, leading the company to consider that moving from retroactive to proactive release of compounds for epigenetics research. Epigenetics, he said, exemplifies the vast unknowns of basic biology that hamper drug discovery research. "It's a hot area of research - but of the 300 potential targets, which one do you work on?"

In the collaboration, he said, GSK synthesizes and screens compounds, and releases promising ones into the public domain. From there, the idea is that academic researchers will test different targets, and that the information from those experiments will help GSK determine the best target for which an optimized compound can then be generated, patented and entered into clinical development.

Willson acknowledged that the approach is "a double-edged sword." But, he added, the company believes that the benefits of extra information outweigh the risks of having chemotypes in the public domain, especially since pharmaceutical companies tend to patent more narrowly anyhow. "You only really need a patent on the compound that you are going to take into the clinic," he said. And in terms of the defensibility of a patent in the courts, "You have a stronger patent if you patent very narrowly."

The Structural Genomics Consortium's Edwards said that "GSK is being quite forward-thinking on this, because it is addressing an industry-wide problem by itself." But GSK's motives are not altruistic: Despite the risks, "probabilistically, there is more value in releasing [the information] than in keeping it close to their chests."

Edwards thinks that the collaboration heralds the way of the future. "There's a large part of the scientific community that would be happy to put their discoveries into the public domain," he asserted. "There's a dawning realization that universities taking on an aggressive stance on patents is not beneficial . . . . There is a whole group of people who think that Bayh-Dole is an anachronism, or has been misinterpreted."

That belief about Bayh-Dole, perhaps unsurprisingly, is not shared by industry; Scientia's Glorikian told BioWorld Financial Watch that he, as well as others at Scientia, "have never seen any data connecting the two," and instead related the decline in drug discovery productivity to "a host of other factors" including patient stratification and a changing regulatory landscape.

Edwards readily admits that he cannot prove his belief that drug discovery would be better off without the sorts of patents he criticizes. "It's tough to say that patents don't encourage innovation - because there is no system without patents," and so no way of knowing what such a system would look like.

But, he said, you don't need a control group to tell you that the state of drug discovery is bad, and getting worse.

"The productivity of the sector has been going down for 30 years," he said. "If we were making more drugs for less money, I wouldn't be talking. But we're not."