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'Isolated DNA' Definition May Be Biggest Barrier to Summary Judgment at Anti-Gene Patenting Hearing

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Following the publication of this article, the ruling judge on the case chose not to make a decision ‘from the bench’ at a Feb. 2 hearing and said he would wait to decide whether the case should go to trial or be dismissed. Originally published on Jan. 29.

By Turna Ray

Divergent definitions of "isolated DNA" may be what cause the ruling judge to decide against granting summary judgment in the American Civil Liberties Union's anti-gene patenting case.

The ACLU on Jan. 20 filed a counterstatement against defendant Myriad Genetics' claims that isolated DNA molecules are patentable chemical compounds. In addition, Robert Nussbaum, chief of the division of medical genetics at the University of California, San Francisco, and other genetics experts have filed statements challenging many of Myriad's scientific claims, specifically with regard to their definitions of isolated DNA and complementary DNA.

Association for Molecular Pathology, et al. v. United States Patent and Trademark Office, et al. — filed in May by the ACLU on behalf of scientific organizations representing numerous medical professionals, researchers, women's health groups, and individual women — alleges that the BRCA gene patents held by the University of Utah Research Foundation and exclusively licensed to Myriad "stifle research that could lead to cures and limit women's options regarding their medical care." Specifically, the lawsuit challenges the patentability and constitutionality of Myriad's patents on the BRCA1 and BRCA2 genes, linked to increased hereditary risk for breast and ovarian cancer [see PGx Reporter 05-13-2009].

At a Feb. 2 hearing at the New York Southern District Court, the ACLU and Myriad will both argue for summary judgment before Judge Robert Sweet. Both sides are asserting that there are undisputed facts in the case and that summary judgment is appropriate because the case rests on legal questions, such as whether Myriad's exercise of its exclusive licenses to certain BRCA gene mutations restricts research, limits thought, and violates the First Amendment. Concurrently, the USPTO will argue that the judge should dismiss the ACLU's charges against it on the basis of "constitutional avoidance," which recommends courts to attempt to decide a case on statutory grounds first before interpreting the Constitution [see PGx Reporter 01-20-2010].

However, as a rejoinder to Myriad's claims of material fact for summary judgment, the ACLU has filed a document with 59 counterstatements. The disputes of material fact between the two sides center on their divergent definitions and functional descriptions of "isolated DNA" and "cDNA."

This dispute, according to John Conley, a law professor at the University of North Carolina, Chapel Hill, who specializes in intellectual property and civil litigation, "could be a barrier to summary judgment."

Conley pointed out to Pharmacogenomics Reporter this week that in 1991, in Amgen v. Chugai Pharmaceutical, the Federal Circuit Court of Appeals allowed patents on "isolated and purified" DNA. The question in the ACLU case that the court must decide is "just what do Myriad's patents claim?" Conley noted. "Now patents have come to cover only genes in isolation. Is that enough of a distinction from the natural versions?"

Separately, the ACLU has also filed a memo deeming "irrelevant" Myriad's assertion that its gene patents promote research, rather than stifle it. Furthermore, the ACLU reasserted allegations that Myriad's patents restrict access and bar patients from getting a second opinion.

DNA vs. cDNA

In Myriad's motion for summary judgment, the company maintains that isolated DNA has long been a patentable composition of matter. "The law is clear, and has been for a hundred years or more, that isolated or purified products, even if they originate from 'natural' sources, are patent eligible," Myriad claims. Furthermore, the company holds that its BRCA patents do not violate the First Amendment and do not impede the progress of science, since "isolated DNA" claims cover chemical compositions and diagnostic methods, which, according to Myriad, do not constitute just information.

Essentially, the ACLU and plaintiffs hold that isolated DNA, or cDNA, does not functionally differ from DNA occurring in the body, and thus is a natural phenomena that is not patentable.

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In response, the defendants have claimed that cDNA is not naturally occurring because it is created outside of the body by a scientist. To support this assertion, Myriad pointed out that the functional interaction between DNA and chromosomal proteins is eliminated from an isolated DNA molecule. Mark Kay, director of the program in human gene therapy at Stanford University, has provided the definitions of isolated DNA in support of Myriad and other defendants.

One of the experts on the plaintiffs' side is UCSF's Nussbaum, who counters in his statement to the court that in claiming that isolated DNA is functionally different from DNA occurring naturally in a cell, the defendants are "blurring the distinction" between DNA isolated form the cell and synthetic DNA used as primers made from chemical reactions and biochemical procedures.

"Although separation may be accomplished by biochemical methods, such as excising that segment or amplifying it by PCR, it is also possible to use biological methods to separate the DNA containing a gene away from other genes without extracting it," Nussbaum points out.

According to Nussbaum, the distinction between DNA in a cell and isolated DNA is a mischaracterization by the defendants' expert, whose definition actually describes the separation of DNA from chromatin, which packages DNA inside the cell. As such, Nussbaum argues "that isolated DNA is not made by the hands of a molecular biologist, but is instead simply extracted from the chromatin."

Research and Access

Beyond arguments over the definition of isolated DNA — perhaps the most salient factual dispute between the parties that might cause the judge to deny summary judgment — the ACLU has also filed a memo calling "irrelevant" the defendants' claims and examples that patents enhance scientific knowledge and don't hinder access.

Just as the ACLU is representing many researchers who allege that Myriad's exclusive licenses to BRCA gene patents have restricted their research, Myriad has gathered statements from researchers asserting the opposite — that they have engaged in research involving BRCA1/2 mutations and have not been sued by Myriad.

"First, that Myriad has not enforced its patents against these researchers does not mean that it cannot," the ACLU states. "Under the law, Myriad has the authority to stop all research on the BRCA1/2 genes." This authority is what many researchers on the plaintiffs' side claim deters research and stifles free speech.

In its motion for summary judgment, Myriad argues that the ability to patent the BRCA gene associations allowed it to add to the body of scientific knowledge about hereditary breast and ovarian cancer, the company points out. "The availability of patents incentivized Myriad not only to discover the BRCA genes but also to invest heavily in disseminating BRCA testing to the public," the company states. "Moreover, since publishing its discoveries, Myriad has consistently promoted and subsidized research on the BRCA genes."

The company claims that more than 18,000 scientists have researched BRCA1 and BRCA2, and published over 7,000 papers on the genes. And Myriad further said it has invested more than $200 million in promoting patient access to BRCA testing, resulting in 400,000 people being tested for BRCA mutations throughout the US. Furthermore, Myriad claims in court documents that 90 percent of BRACAnalysis tests are covered by insurers at an average rate of 90 percent.

"Even if some research has been permitted, there is strong, empirical evidence that patents on genes inhibit the production of follow-on knowledge," the ACLU states.

"Defendants point to the publication of a number of papers relating to the BRCA1/2 genes. However, this is meaningless because they offer no control group to show how many papers would have been published if the BRCA1/2 sequences had not been patented," the ACLU notes. "Furthermore, many of the published papers do not involve research that requires isolating or sequencing the genes. Scientists who do want to engage in this type of BRCA1/2 research are reluctant to do so because it would infringe upon the patents."

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On the issue of access, the ACLU claims that only 130 million out 308 million people in the US can receive coverage for testing with Myriad's BRACAnalysis test from insurers. For the 200 million whose insurance companies don't cover this type of testing, and for Medicare beneficiaries in states that do not cover the technology, Myriad has provided 3,000 free tests in the last four years, the ACLU alleges.

"Other labs provide up to 10 percent of their tests for free, which would have meant they would have done 40,000 rather than 3,000," the ACLU notes. "These statistics reinforce plaintiffs’ assertion that the patents have prevented some (indeed many) women from obtaining critical information about their own health."

Researchers from Duke University's Center for Genome Ethics, Law & Policy and experts on the HHS Secretary's Advisory Committee on Genetics, Health, and Society studied the impact of gene association patents and exclusive licenses, and reported that such practices have harmed patient access to genetic testing in geographically isolated and poor populations [see PGx Reporter 10-14-2009].

Finally, many individual women who have signed on the lawsuit against Myriad and other defendants assert that Myriad's exclusive licenses on BRCA gene patents essentially restrict them from getting a second opinion on their BRCA mutation status.

"Myriad's assertion that 'second opinion' means solely having a second physician interpret the results of a test, rather than re-run the test or perform a different test, is simply wrong," the ACLU said. In addition, Myriad’s claim that second opinions can be obtained from Yale University or the University of Chicago is not entirely true, according to the ACLU, since those academic institutions "do only the most limited testing for individual mutations. Myriad is not permitting those labs to do full sequencing of the genes."

In its motion for summary judgment, Myriad asserted that the "plaintiffs' anecdotal allegations" about its patents restricting access and scientific progress "ring hollow in the face of all the scientific progress that has been spurred by the BRCA patents."

On the defendants' side, the Biotechnology Industry Organization, Genetic Alliance, and others have filed amicus briefs asserting that the ACLU's lawsuit is too broad and that invalidating gene patents would harm innovation in the medical and technology fields overall.

Myriad cites two cases, Prometheus Labs v. Mayo Collaborative and Bilski v. Kappos, in its defense. The Federal Circuit court's decision last year in Prometheus found that diagnostic claims using a correlation occurring in nature — in this case involving methods for identifying metabolites of a drug for gastrointestinal disorders — were patentable.

"As to the method claims, the Supreme Court and the Federal Circuit have held that the key to determining the patent-eligibility of a method or process is that it transforms an article 'to a different state or thing,'" Myriad states in its filing. "In Prometheus, the Federal Circuit found that claims to a diagnostic method that utilized a correlation were not a mere 'law of nature,' but a patent-eligible application of a law of nature in a transformative fashion."

In the pending Supreme Court case Bilski, justices are deciding to what extent they will uphold or overturn a Federal Circuit Court's decision that a so-called machine-or-transformation test is necessary for a process to be patentable. The justices' comments during a November hearing suggest they are struggling to narrowly uphold a lower court's machine-or-transformation test and minimize the impact to other sectors, mainly the technology and medical device industries [see PGx Reporter 11-18-2009]. The Supreme Court justices are expected to issue a ruling on Bilski this year.

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