Association for Molecular Pathology v. Myriad Genetics

Association for Molecular Pathology v. Myriad Genetics No. 11-725 is a case challenging the validity of gene patents in the United States, specifically challenging certain claims in issued patents owned or controlled by Myriad Genetics that cover isolated DNA sequences, methods to diagnose propensity to cancer by looking for mutated DNA sequences, and methods to identify drugs using isolated DNA sequences. Prior to the case, the US Patent Office accepted patents on isolated DNA sequences as a composition of matter. Diagnostic claims were already under question through the In re Bilski and Mayo v. Prometheus cases. Drug screening claims were not seriously questioned prior to this case.

The case was originally heard in the United States District Court for the Southern District of New York, which ruled that all the challenged claims were not patent eligible. Myriad then appealed to the United States Court of Appeals for the Federal Circuit. The Circuit court overturned the previous decision in part, ruling that isolated DNA which does not exist alone in nature can be patented and that the drug screening claims were valid, and confirmed in part, finding the diagnosic claims unpatentable. The plaintiffs appealed to the Supreme Court, which granted cert and remanded the case back to the Federal Circuit. The Federal Circuit did not change its opinion, so on September 25, 2012, the American Civil Liberties Union and the Public Patent Foundation filed a petition for certiorari with the Supreme Court with respect to the second Federal Circuit Decision. As of December 2012 isolated genes remain patentable in the US, although the Supreme Court on November 30, 2012, agreed to hear the plaintiffs' appeal of the Federal Circuit's ruling.

Proponents of the validity of these patents argue that they incentivize investment in biotechnology and promote innovation in genetic research by not keeping technology shrouded in secrecy. Opponents argued that these patents stifle innovation by preventing others from conducting cancer research, limit options for cancer patients in seeking genetic testing, and are not valid because they claim to patent genetic information that is intrinsic to all humans.

Background
The global search for a genetic basis for breast and ovarian cancer began in earnest in 1988. In 1990, at an American Society of Human Genetics Meeting, a team of scientists led by Mary-Claire King, Ph.D., from University of California at Berkeley announced the localization through linkage analysis of a gene associated with increased risk for breast cancer (BRCA1) to the long arm of chromosome 17. It was understood at the time that a test for these mutations would be a clinically important prognostic tool. Myriad Genetics was founded in 1994 as a startup company out of University of Utah, by scientists involved in the hunt for the BRCA genes. In August 1994, Mark Skolnick a founder of Myriad and scientist at University of Utah, and researchers at Myriad, along with colleagues at the University of Utah, the U.S National Institutes of Health (NIH), and McGill University published the sequence of BRCA1, which they had isolated. In that same year, the first BRCA1 U.S. patent was filed by the University of Utah, National Institute of Environmental Health Sciences (NIEHS) and Myriad. Over the next year, Myriad, in collaboration with University of Utah, isolated and sequenced the BRCA2 gene, and the first BRCA2 patent was filed in the U.S. by the University of Utah and other institutions in 1995. In 1996 Myriad launched their BRACAnalysis product, which detects certain mutations in the BRCA1 and BRCA2 genes, which put women at high risk for breast cancer and ovarian cancer.

Myriad's business model has been to exclusively offer diagnostic testing services for the BRCA genes. It was on the basis of the premium price that the patents would allow Myriad to set during the 20 year life of the patents, that investors put money into Myriad. These were the funds that allowed Myriad to rapidly sequence the BRCA2 gene and finalize a robust diagnostic test. The business model meant that Myriad would need to enforce its patents against competitors, which included diagnostic labs at universities, which function very much like for-profit businesses in addition to educating pathologists-in-training. The patents expire, starting in 2014. In 2012, Myriad—just a startup in 1994—employed about 1200 people, had revenue of around $500 million, and was a publicly traded company.

About 2000 isolated human genes had been patented in the United States before this case started. Gene patents have generated a great deal of controversy, especially when their owners or licensees have aggressively enforced them to create exclusivity. Clinical pathologists have been especially concerned with gene patents, as their medical practice of offering clinical diagnostic services is subject to patent law, unlike the practices of other doctors which are exempt from patent law. For example, in 1998, University of Pennsylvania's Genetic Diagnostic Laboratory received cease and desist letters on the basis of patent infringement from Myriad, which requested clinical pathologists to stop testing patient samples for BRCA. Similar cease and desist letters were sent to cancer centers in Canada as well. The Hereditary Cancer Program (HCP) received one in 2001 which required the HCP to refer all new patients to either Myriad Genetics or MDS Laboratory Services (one of Myriad’s licensees) for BRCA screening. Because of these kinds of legal threats to its members' medical practices, the Association for Molecular Pathology has actively lobbied against the existence of, and exclusive licensing of, gene patents and was the lead plaintiff in this litigation.

Litigants
Along with the AMP(Association for Molecular Pathology) and the University of Pennsylvania, other plaintiffs in the suit included researchers at Columbia, NYU, Emory, and Yale; several patient advocacy groups; and several individual patients.

The defendants in the suit were originally Myriad, the Trustees of the University of Utah, and the U.S. Patent and Trademark Office (USPTO), but the USPTO was severed from the case by the district court.

The American Civil Liberties Union(ACLU) and Public Patent Foundation represented the plaintiffs, and Jones Day represented Myriad.

Arguments
The complaint challenged specific claims on isolated genes, diagnostic methods, and methods to identify drug candidates, in seven of Myriad's 23 patents on BRCA1 and BRCA2.

The specific claims that were challenged were :
 * claims 1, 2, 5, 6, 7, and 20 of U.S. patent 5,747,282;
 * claims 1, 6, and 7 of U.S.patent 5,837,492;
 * claim 1 of U.S. patent 5,693,473;
 * claim 1 of U.S. patent 5,709,999;
 * claim 1 of U.S. patent 5,710,001;
 * claim 1 of U.S. patent 5,753,441; and
 * claims 1 and 2 of U.S. patent 6,033,857

The plaintiffs wanted these claims declared invalid on the grounds that they are not patentable subject matter under §101 of Title 35 of the United States Code&mdash;that the isolated genes are unpatentable products of nature, and that the diagnostic method claims are mere thought processes that do not yield any real world transformations, and that the drug screening claims were just describing the basic processes of doing science. This part of US law describes what is patent-eligible: "any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof". If the invention falls under one of several categories, however, including a "naturally occurring article" (a defined term in the law), then it is not patent eligible.

Plaintiffs further argued that Myriad's use of these patents—and the patents' very existence—restricted research for clinicians and limited scientific progress. They further argued that from a patient's perspective, Myriad's use of the patents not only made it impossible to obtain a second opinion on a patient's genetic predisposition to breast and ovarian cancer, but also kept the cost of BRCA1/2 testing high by preventing competition.

Myriad defended their patents to be valid because the USPTO issues patents for genes as "isolated sequences" in the same way it issues patents for any other chemical compound, since the isolation of the DNA sequence renders it different in character from that present in the human body, and they argued that their diagnostic tests were patentable subject matter.

District Court Decision
On March 29, 2010, Judge Robert W. Sweet of the United States District Court for the Southern District of New York declared all of the contested claims invalid.

With respect to claims to isolated DNA sequences, Judge Sweet's 152 page decision stated: "DNA's existence in an 'isolated' form alters neither this fundamental quality of DNA as it exists in the body nor the information it encodes. Therefore, the patents at issue directed to 'isolated DNA' containing sequences found in nature are unsustainable as a matter of law and are deemed unpatentable under 35 U.S.C. §101." The decision also found that comparisons of DNA sequences involved in these patents are abstract mental processes under the recent In re Bilski decision, therefore also not patent eligible, and that the drug screening claims were unpatentable as they merely cover a "basic scientific principle".

On June 16, 2010, Myriad filed its Notice of Appeal.

Federal Circuit Appellate Decision
Myriad's appeal was granted, and the case was heard in United States Court of Appeals for the Federal Circuit. Myriad, the defendant-appellant, was supported by at least 15 amicus (friend of the court) briefs and the plaintiff-appellees' position received support from 12 amicus briefs. The Department of Justice provided a surprising and unsolicited brief that in part supported the appellees but also suggested that claims covering isolated naturally-occurring human genetic sequences are not properly patentable. Oral arguments were held on April 4, 2011.

On July 29, 2011, the Federal Circuit overturned the district court's decision in part, (reversing that an isolated DNA sequence is patent-ineligible, and the district court's decision that methods for screening cancer therapeutics is patent-ineligible) and affirmed its ruling in part (agreeing that the district court's decision that Myriad's claims for comparing DNA sequences are patent-ineligible). Judge Alan Lourie, who wrote the majority ruling, reasoned that isolated DNA is chemically distinct from the natural state of a gene in the body. Judge Lourie cited the Supreme Court case Diamond v. Chakrabarty, which used the test of whether a genetically modified organism was "markedly different" from those found in nature to rule that genetically modified organisms are patent eligible. Thus, he concluded that since Myriad's patents describe DNA sequences that do not alone exist in nature, they are patent eligible.

1st certiorari petition and Supreme Court Ruling
After the Federal Circuit ruling, the Association for Molecular Pathology petitioned for a writ of certiorari to the Supreme Court, asking it to review this case. The Supreme Court granted the writ, and on March 26, 2012, it vacated the Federal Circuit decision, and remanded the case back to the Federal Circuit. In other words, the Supreme court revoked the original ruling of the Federal Circuit, and asked the lower court to re-hear the entire case again. These Supreme Court actions were made in light of its recent decision in Mayo Collaborative Services v. Prometheus Laboratories, Inc., where the Court ruled that certain kinds of claims in medical diagnostics patents, including natural phenomena, were not patentable. The Supreme Court expected the Federal Circuit to take this precedent into account in its new ruling.

Federal Circuit Decision: second hearing
On August 16, 2012, the Federal Circuit held its ground, ruling again in a 2–1 decision in favor of Myriad. The new court opinion was nearly identical to the original. The Federal Circuit again reversed the district court’s decision on isolated DNA molecules; the Federal Circuit found that such molecules are patent-eligible under § 101 because they are nonnaturally occurring compositions of matter. It also reversed the district court’s decision concerning assays to find drugs to treat cancer; the Federal Circuit again found that these assays are patentable. And again—now reinforced by the Prometheus decision—the Federal Circuit affirmed the lower court’s decision, that method claims directed to “comparing” or “analyzing” DNA sequences are patent ineligible. Such claims were held to include no transformative steps and therefore to cover only patent-ineligible abstract, mental steps.

With respect to the patentability of isolated genes, the majority opinion stated that the Mayo precedent was not particularly relevant to this case, because it did not deal with the patent eligibility of gene patents. Judge Lourie stated: "The remand of this case for reconsideration in light of Mayo might suggest, as Plaintiffs and certain amici state, that the composition claims are mere reflections of a law of nature. Respectfully, they are not, any more than any product of man reflects and is consistent with a law of nature."

Judge William Bryson wrote a dissent with respect to the non-patentability of isolated DNA sequences, applying the reasoning of the Supreme Court in the Mayo case with respect to methods involving "natural laws", to products of nature:


 * In Mayo, which involved method claims…the [Supreme] Court found that the method was not directed to patent-eligible subject matter because it contributed nothing “inventive” to the law of nature that lay at the heart of the claimed invention…In concluding that the claims did not add “enough” to the natural laws, the Court was particularly persuaded by the fact that “the steps of the claimed processes…involve well-understood, routine, conventional activity previously engaged in by researchers in the field.”


 * Just as a patent involving a law of nature must have an “inventive concept” that does “significantly more than simply describe…natural relations,”… a patent involving a product of nature should have an inventive concept that involves more than merely incidental changes to the naturally occurring product. In cases such as this one, in which the applicant claims a composition of matter that is nearly identical to a product of nature, it is appropriate to ask whether the applicant has done “enough” to distinguish his alleged invention from the similar product of nature. Has the applicant made an “inventive” contribution to the product of nature? Does the claimed composition involve more than “well-understood, routine, conventional” elements? Here, the answer to those questions is no.


 * Neither isolation of the naturally occurring material nor the resulting breaking of covalent bonds makes the claimed molecules patentable….The functional portion of the composition—the nucleotide sequence—remains identical to that of the naturally occurring gene.

2nd certiorari petition
On September 25, 2012, the American Civil Liberties Union and the Public Patent Foundation filed a petition for certiorari with the Supreme Court with respect to the second Federal Circuit Decision. On November 30, 2012, the Supreme Court agreed to hear the plaintiffs' appeal of the Federal Circuit's ruling.

Reactions
This is a landmark case on the practice of gene patenting. The District Court's decision was received as an unexpected ruling, because it contradicted the generally accepted practice of gene patents.

The Federal Circuit's decision was a return back to the status quo, in which the US Patent Office issues patents for isolated gene sequences. However, it still ignited much controversy and interest from the public. Many opponents of gene patents (including James Watson, one of the solvers of the structure of DNA) argue that §101 of Title 35 of the United States Code clearly allows for it, and that if DNA should be excluded from patent eligibility on the basis that it conveys special genetic information, then that should be done through an act of Congress, not under courts' powers to interpret that law.

In terms of the emotional impact of this case as it was portrayed in the media—the exclusive offering of a diagnostic test and the high price of the test—the real legal force on that issue arose in the outcome of other cases, In re Bilski and Mayo v. Prometheus, which rendered most diagnostic claims unpatentable, which will make it difficult for Myriad's business model (as described above in the Background section) to work going forward—difficult for R&D driven business and investors, potentially bad for patients as there may be fewer diagnostic tests brought to market, but potentially better for patients in that prices for tests may be lower and it will be easier to have a test re-done by an alternate lab.