Association for Molecular Pathology v. Myriad Genetics, Inc.

The lawsuit in question challenged the validity of gene patents in the United States, specifically questioning 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 U.S. Patent Office accepted patents on isolated DNA sequences as a composition of matter. Diagnostic claims were already under question through the Supreme Court's prior holdings in Bilski v. Kappos and Mayo v. Prometheus. Drug screening claims were not seriously questioned prior to this case.

Notably, the original lawsuit in this case was not filed by a patent owner against a patent infringer, but by a public interest group (American Civil Liberties Union) on behalf of 20 medical organizations, researchers, genetic counselors, and patients as a declaratory judgement.

The case was originally heard in Southern District Court of New York. The District Court ruled that none of the challenged claims were patent eligible. The majority opinion called patenting isolated or purified natural products a “lawyer's trick” to circumvent the prohibitions on the direct patenting of products of nature.

Myriad then appealed to the United States Court of Appeals for the Federal Circuit (CAFC). The Federal Circuit reversed the district court in part and affirmed in part, ruling that isolated DNA, which does not occur by itself in nature, can be patented, and that the drug screening claims were valid, but that Myriad's diagnostic claims were not patentable. The CAFC considered the valid gene claims as directed toward compositions of matter rather than toward information, like the District Court did.

On appeal, the Supreme Court vacated and remanded the case back to the Federal Circuit to reconsider the issues in light of Mayo v. Prometheus. On remand, the Federal Circuit held that Mayo v. Prometheus did not affect the outcome of the case, so the American Civil Liberties Union and the Public Patent Foundation filed a petition for certiorari. The Supreme Court granted certiorari and unanimously invalidated Myriad's claims to isolated genes. The Supreme Court held that merely isolating genes (even with introns removed), which are found in nature, does not make them patentable. However, the SCOTUS agreed with the "friend of the court" brief submitted by the USPTO, that complementary DNA should be patent eligible, because it does not exist in Nature but rather was "engineered by man", even though this decision lacks scientific consistency. A prominent US biotech patent lawyer commented on the SCOTUS decision: "It is inconsistent to conclude that isolated DNA and naturally occurring DNA are not markedly different because their information content is the same, and at the same time find that cDNA is patent eligible despite having virtually identical information content to naturally occurring mRNA."

This decision was not devastating for Myriad Genetics, since the Court only "invalidated five [of its 520] patent claims covering isolated naturally occurring DNA, ... thereby reducing [its] patent estate to 24 patents and 515 patent claims." Myriad continued suing its competitors. However, it was unable to get preliminary injunctions per eBay Inc. v. MercExchange, L.L.C., and most of these lawsuits were settled out of court.

Background

The global search for a genetic basis for breast and ovarian cancer began in earnest in 1988. In 1990, at a meeting of the American Society of Human Genetics, a team of scientists led by Mary-Claire King, from the University of California, 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 the 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 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 that 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 were to 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.

The USPTO patent examination guidelines in 2001, allowed patenting of DNA sequences:

Like other chemical compounds, DNA molecules are eligible for patents when isolated from their natural state and purified or when synthesized in a laboratory from chemical starting materials. A patent on a gene covers the isolated and purified gene but does not cover the gene as it occurs in nature.

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, the 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. 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.

Relevant case law precedents

Prior to Myriad the question of whether isolation or purification of a product of Nature from its natural environment is a patentable invention or a non-patentable discovery had a long history of contradictory judgements in the USA and elsewhere. In an 1889 case, ex parte Latimer, the inventor applied for a patent on fiber derived from Pinus australis tree. The Commissioner of Patents concluded that “alleged invention is unquestionably very valuable, it nonetheless was a natural product and can no more be the subject of a patent in its natural state when freed from its surroundings than wheat which has been cut by a reaper.” However, the Commissioner suggested, that “If applicant's process had another final step by which the fiber ... were changed, ... [it would probably be patentable] ... because the natural fiber ... would ... become something new and different from what it is in its natural state.” This statement is very important, because after over a century of turmoil, the US case law returned to exactly this idea.

However, soon after Latimer the US courts decided that molecules (which are claimed as composition of matter, unlike the natural fibers, which were claimed as articles of manufacture) were patentable, if the chemicals were "purified and isolated" from their natural environment(s). The "purified and isolated" doctrine was used to validate valuable patents on aspirin in 1910, on adrenaline in 1912, on vitamin B12 in 1958 and on prostaglandins in 1970. Although the SCOTUS invalidated in 1948 a patent on a naturally occurring mixture of bacterial strains (see Funk Bros. Seed Co. v. Kalo Inoculant Co.), US courts thought that "purified and isolated" doctrine still applied to molecules, and that Funk Bros. affected only living things.

The 1980 US Supreme Court decision in Diamond v. Chakrabarty opened a floodgate in patenting isolated genes, purified proteins, and cell lines. The practice of patenting isolated genes was affirmed in 1991 by the CAFC in Amgen v. Chugai Pharmaceutical. It is estimated that between 1980 and 2013 the USPTO allowed patent claims on up to 40,000 natural DNA sequences.

The SCOTUS had a chance to reverse Amgen in 2006, when it granted a writ of certiorari in LabCorp v. Metabolite, Inc.. However, the Court quickly dismissed the writ as improperly granted. Eventually, the practice of patenting "purified and isolated" products of nature came to an end in 2013, when the SCOTUS announced its decision in Association for Molecular Pathology v. Myriad Genetics.

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, with attorney Chris Hansen arguing the case. The law firm of Jones Day represented Myriad.

Proponents of the validity of these patents argued that recognizing such patents would encourage investment in biotechnology and promote innovation in genetic research by not keeping technology shrouded in secrecy. Opponents argued that these patents would stifle innovation by preventing others from conducting cancer research, would limit options for cancer patients in seeking genetic testing, and that the patents are not valid because they relate to genetic information that is not inventive, but is rather produced by nature.

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, arguing that they are not patentable subject matter under §101 of Title 35 of the United States Code—that the isolated genes are not patentable products of nature, that the diagnostic method claims are mere thought processes that do not yield any real world transformations, and that the drug screening claims were merely describing the basic processes of doing science. This part of U.S. 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 excluding categories, however, including a "naturally occurring article" (a defined term in the law), then it is not patent eligible.

The Plaintiffs 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, arguing that 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. Myriad argued that their diagnostic tests were patentable subject matter.