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At Federal Circuit Hearing, Plaintiffs in Myriad Case Fight to Keep Gene Patentability Issue on the Table

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Originally published July 20.

WASHINGTON — Plaintiffs challenging Myriad's patents on isolated BRCA1 and BRCA2 gene sequences argued before the Court of Appeals for the Federal Circuit today that the firm's composition-of-matter claims related to its BRACAnalysis test are so broad — covering large stretches of gene sequences and "every conceivable form of DNA" — that, if upheld, would stop others from inventing new diagnostics and treatments based on that basic genetic knowledge.

The Supreme Court in March sent the case, known formally as Association for Molecular Pathology et al. vs. the United States Patent and Trademark Office et al. , back to the CAFC to be decided again in light of its decision in another case, Mayo Collaborative Services v. Prometheus Laboratories. In that case, the Supreme Court invalidated Prometheus's patent claims on gauging metabolites to dose thiopurine drugs, noting that merely using "well-understood, routine, conventional" methods to correlate naturally occurring biological processes to treatment decisions isn't patent eligible (PGx Reporter 3/21/2012).

In AMP v. USPTO, patients, healthcare providers, and researchers represented by the American Civil Liberties Union and the Public Patent Foundation are challenging Myriad's patent claims on methods of comparing isolated gene molecules and genomic DNA in the body, as well as claims on genomic DNA itself. The lawsuit 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" (PGx Reporter 5/13/2009).

After the Supreme Court remanded the case back to the CAFC in April, the appellate court asked Myriad and the plaintiffs to file supplemental briefs discussing the "applicability of the Supreme Court's decision in Mayo to Myriad's isolated DNA claims and the method claim 20 of the '282 patent."

The plaintiffs' brief stated that Mayo "reemphasized and gave new vigor" to three principles for establishing whether a product of nature has been "transformed" into patentable subject matter. First, in its Mayo decision, the Supreme Court restated that patent claims cannot preempt what is deemed unpatentable under Section 101 of the Patent Act; second, the patented product must have "markedly different characteristics" than things found in nature and have an "inventive concept;" and third, the courts should not decide the validity of patent claims based on whether an industry is reliant on the issuance of such patents or if the US Patent and Trademark Office has previously approved such patents.

Based on this reasoning, Chris Hansen, staff attorney with the ACLU representing the plaintiffs, attempted today to convince CAFC judges Kimberly Moore, Alan Lourie, and William Bryson that although the Supreme Court's decision in Mayo dealt with method patents, that decision has significance for the validity of Myriad's composition-of-matter claims on isolated BRCA1 and BRCA2 genes. According to Hansen, the legal principle that products of nature should remain in the "storehouse of knowledge for all men" is as true for method claims as it is for composition-of-matter claims.

Furthermore, noting that some of Myriad's patents on isolated gene sequences are so broad as to cover large stretches of DNA, Hansen argued that the patents would hinder research and the development of innovative products.

The breadth of Myriad's patents has been subject to some scrutiny in the scientific community. In 2010, Robert Cook-Deegan, director of Duke University's Center for Genome Ethics, Law & Policy and an outspoken critic of the USPTO's practice of granting patents claiming large chunks of DNA linked to disease susceptibility, conducted an analysis of the scope of Myriad's '282 patent by comparing the claims on a 15-mer oligonucleotide in the BRCA1 gene against gene sequences in GenBank. Cook-Deegan and colleagues discovered that 80 percent of cDNA and mRNA sequences in GenBank contain at least one oligonucleotide covered by the '282 claims. Additionally, around 300,000 oligonucleotides in chromosome 1, which does not contain the BRCA1 gene, would be covered by the claim, the researchers found (PGx Reporter 3/25/2010).

"The law of nature/product of nature doctrine is designed to be sure that natural things and natural laws are available to all of mankind, and are available to scientists," Hansen said before the CAFC today. "That's true whether we're talking about a composition that is preempting all scientific use, or we're talking about a method that's preempting all scientific use."

In its brief to the CAFC, the plaintiffs cited a study funded by the National Human Genome Research Institute that found that more than half of all labs surveyed decided "not to develop a new clinical [BRCA] test because of a gene patent or license." Although Myriad has maintained in AMP v. USPTO that it has not enforced its BRCA patents to restrict research, the question of whether its patents limit research "must be decided on the authority given Myriad by the patents, not Myriad's actions," the plaintiffs argue in their brief.

Judge Moore, however, wasn't convinced by Hansen's preemption arguments that Myriad's broad patent claims would hinder future research and innovation. "We're talking about something that will broadly exclude future innovation or something that will narrowly exclude future innovation. I think Prometheus v. Mayo has made it clear that breadth is irrelevant, too. They say, 'In any event our cases have not distinguished among different laws of nature according to whether or not the principles they embody are sufficiently narrow,' and this is understandable because courts and judges are not institutionally well suited to make these kinds of judgments," she said.

"So, I don't see any relevance to your point that this is going to broadly preempt because it's a broader claim. They said, 'if it's a product of nature, [then there is] a bright line prohibition,'" Moore continued. "So, your preemption story seems to be a waste of time."

Meanwhile, Myriad's lawyer tried to distance the Supreme Court's Mayo decision from the company's composition-of-matter claims on BRCA genes. "In its earlier decision … the court concluded that Myriad's composition claims were patent eligible because they reflected non-naturally occurring human-made inventions," Greg Castanias of Jones Day told the CAFC judges. "They were products of human ingenuity. That's the line that's drawn in Diamond v. Chakrabarty and nothing in the Supreme Court's recent Mayo decision changes that line."

More specifically, Castanias argued that it requires "enormous human judgment" to discern where to start and where to stop splicing a stretch of DNA so the sequence is meaningfully associated with disease. It was "man who decided which parts [of the DNA] to use and which parts to throw away" in making that gene-disease association, he said.

The plaintiffs, however, had support from the US government, represented by Justice Department lawyer Melissa Patterson, who drew the judges' attention to the fact that the Supreme Court expressed concern in Mayo "that patent law not inhibit future discovery by improperly tying up the use of laws of nature and the like."

"The problem here is that some of these claims preclude public access to a product of nature," Patterson said. "Everyone agrees that the native DNA is a product of nature. So the relevant question here is, 'Can the public still get at it? Can the public still use and exploit that in new and different ways?'"

Furthermore, in Mayo, while the Supreme Court acknowledged that applications of a law of nature may be patentable, the justices emphasized that the inventor must do more than merely apply that law. "As a general rule, when the only changes that someone has made to a product are those that are incidental to its extraction from its natural environment, you're almost always going to have a big preemption concern, because … in order to engage in a serious study or a serious exploitation of a product of nature you need to remove it from its natural environment," she added.

Judge Bryson probed Patterson about how much support there was from the different agencies under the executive branch for the DoJ's views on patenting isolated gene sequences. The DoJ, on behalf of the executive branch of the US government has written friend of the court briefs in the AMP v. USPTO. Patterson replied to Bryson that she was presenting the views of the US government and that she could not go into internal government deliberations.

It is well known by now that the USPTO isn't supportive of the DoJ's position in AMP v. USPTO. Cook-Deegan, who was present at the CAFC hearing, felt that the exchange was an attempt on Bryson's part to get it on the record that the solicitor general speaks for the executive branch. "Bryson just wanted to signal that [the judges] are fully aware of USPTO objections, and don't care much, since the solicitor general speaks for the US government when there are disputes and even when there aren't."

This is the second time that AMP v. USPTO has come before the CAFC. The first time the CAFC decided the case, in July 2011, Bryson wrote an opinion agreeing with Laurie and Moore on the patentability of cDNA and Myriad's method claims, but disagreed that isolated gene sequences were patentable (PGx Reporter 8/3/2011).

The lawsuit began in 2009, when the ACLU and PUBPAT first filed the suit with the Federal District Court of Southern New York. In 2010, federal district court Judge Robert Sweet invalidated 15 claims in seven patents held by Myriad, reasoning that isolated BRCA1/2 gene sequences were not markedly different from naturally occurring gene sequences in the body, particularly in the information they contain. Sweet also asserted in his decision that comparisons of isolated gene molecules and genomic DNA sequences are abstract mental processes, which (along with laws of nature and natural phenomena) are not patentable under Section 101 (PGx Reporter 03/31/2010).

Last July, partly reversing the federal district court's decision, the CAFC issued a two-to-one decision in which it upheld the validity of Myriad's composition claims on isolated DNA molecules, "since the molecules as claimed do not exist in nature." However, the appellate court deemed several of Myriad's method claims that describe "comparing" and "analyzing" gene sequences invalid.

The court also maintained claim 20 of Myriad's patent No. 5,747,282, describing a method of screening potential cancer therapeutics by gauging changes in cell growth rates, as patent eligible. According to the judges, claim 20 is patentable, unlike five other claims on "analyzing" and "comparing" DNA sequences, because it involves transformative steps.

Now that AMP v USPTO has returned to the CAFC via Supreme Court remand, it seems that the lower court will also reevaluate claim 20 of Myriad's patent No. 5,747,282.

With regard to this claim, Myriad's counsel Castanias argued that because the process described starts with a new "host cell" and then uses known methods of inserting the BRCA gene sequence associated with breast cancer, it is patent eligible. Additionally, he asserted that because plaintiffs didn't challenge the validity of claim 20 in their petition, it should not be reconsidered by CAFC. However, plaintiffs' lawyer Hansen countered that "the transformed eukaryotic host cell" that Myriad uses in the process described in the patent is "bought off the shelf" and is therefore "transformed" and "patented" by someone else.

Judge Bryson defended the CAFC's right to consider all aspects of the case as it originally came to the court last year, since the court has vacated its earlier decision. "We have the exact same case as last time," he said, characterizing the latest proceedings as a "do over" that is not limited by the issues that "the petitioners have chosen to raise."

Although at this stage it is impossible to gauge which way the judges may be leaning, Cook-Deegan felt that Judge Lourie appeared to be convinced that the Supreme Court's decision on Mayo was strictly about method patents and so only Myriad's claim 20 should still be up for consideration.

While Lourie didn't seem to think that Mayo was relevant to Myriad's composition-of-matter claims, "Patterson made the case clearer," Cook-Deegan said via e-mail. "It's about whether [Myriad] invented what they discovered and about a subject matter prohibition that blocks public access to a discovery. Discoveries are still patentable under the law, but is what Myriad … did 'different enough' to warrant patenting a discovery?"

In making this assertion, Patterson "could be right," Cook-Deegan believes. "If so, then, Prometheus v. Mayo is indeed relevant to Myriad's composition-of-matter claims."

The outcome of AMP v USPTO is being watched carefully by the life sciences community. Many industry players are concerned that if patents on isolated genes are outlawed it would invalidate thousands of such patents already issued by the USPTO and hinder investment in the molecular diagnostics and personalized medicine space.

During the hearing, Judge Moore verbalized this concern, saying that the USPTO has "considered isolated gene sequences to be patentable for decades … and industry has been build up on it, and a lot of money is at stake here. If it's so obvious these things are unpatentable, how come no one brought it up in 30-plus years?"

To this Patterson noted that with the Supreme Court's decision on Bilski v Kappos – a case focused on the patentability of innovation not tied to a physical instrument – invalidated many patents. "But nowhere in its statutory analysis did the court suggest that was a reason to alter the way it looks at [patent eligibility criteria under] Section 101," she said.

"Similarly, in Mayo, the court was careful to say … that 'We aren't here to make rules about a specific field. We need to make general rules and principles about Section 101,' and that's what we're asking the court to do here."

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