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. 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.
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 specific claims that were challenged were: • 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. ==Decision of the District Court==