Ass'n for Molecular Pathology v. Myriad Genetics, Inc.

Association for Molecular Pathology v. Myriad Genetics,^[1] No. 12-398 (569 U.S. ___ June 13, 2013), was 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 U.S. 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 Southern District Court 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 diagnostic claims unpatentable. The plaintiffs appealed to the Supreme Court, which granted certiorari and remanded the case 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.

On November 30, 2012, the Supreme Court agreed to hear the plaintiffs' appeal of the Federal Circuit's ruling. On June 13, 2013, in a unanimous decision, the Supreme Court invalidated Myriad's claims to isolated genes. The Court held that merely isolating genes that are found in nature does not make them patentable.

Proponents of the validity of these patents argued that they encourage 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 genetic information that is not inventive, but is rather produced by nature.

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, from 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.^[2] 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 National Institutes of Health (NIH), and McGill University published the sequence of BRCA1, which they had isolated.^[3] 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.^[4] 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.^[5] 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.^[6]

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.^[7] 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.^[7] 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.^[8]

About 2000 isolated human genes had been patented in the United States before this case started.^[9][10] 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.^[11] 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.^[7] 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.^[12][13]

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.^[7]

The American Civil Liberties Union (ACLU) and Public Patent Foundation represented the plaintiffs, with attorney Chris Hansen arguing the case, 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.^[14]

The specific claims that were challenged were:^[7]

• claims 1, 2, 5, 6, 7, and 20 of U.S. patent 5,747,282;^[4]
• claims 1, 6, and 7 of U.S. patent 5,837,492;^[5]
• claim 1 of U.S. patent 5,693,473;^[15]
• claim 1 of U.S. patent 5,709,999;^[16]
• claim 1 of U.S. patent 5,710,001;^[17]
• claim 1 of U.S. patent 5,753,441;^[18] and
• claims 1 and 2 of U.S. patent 6,033,857^[19]

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—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.^[7] 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 excluding categories, however, including a "naturally occurring article" (a defined term in the law), then it is not patent eligible.^[7]

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.^[7]

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.^[7]

Decision of the District Court

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.^[7]

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."^[7] 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".^[7][14][20]

On June 16, 2010, Myriad filed its Notice of Appeal.^[9][10]

First hearing in the Court of Appeals for the Federal Circuit

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 briefs and the plaintiff-appellees' position received support from 12 amicus briefs.^[21][22] 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.^[23][24] Oral arguments were held on April 4, 2011.^[25]

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.^[26] 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.^[27]

First petition to the Supreme Court

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.^[28] 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.^[29] 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.

Second hearing in the Court of Appeals for the Federal Circuit

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.^[30] 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.^[31] 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."^[32]

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.^[33]

Second petition to the Supreme Court

On September 25, 2012, the American Civil Liberties Union and the Public Patent Foundation filed another petition for certiorari with the Supreme Court with respect to the second Federal Circuit Decision.^[34] On November 30, 2012, the Supreme Court agreed to hear the plaintiffs' appeal of the Federal Circuit's ruling.^[35]

Oral arguments were heard before the Supreme Court on April 15, 2013.^[36]

Decision of the Supreme Court

Justice Clarence Thomas, on June 13, 2013, delivered the opinion of the Court,^[37][38][39] in which all other members of the Supreme Court joined, except Justice Antonin Scalia, who concurred in part and concurred in the judgment. The majority opinion delivered by Thomas held, "A naturally occurring DNA segment is a product of nature and not patent eligible merely because it has been isolated, but cDNA is patent eligible because it is not naturally occurring."^[40] In Part III of the majority opinion, Thomas wrote:

It is important to note what is not implicated by this decision. First, there are no method claims before this Court. Had Myriad created an innovative method of manipulating genes while searching for the BRCA1 and BRCA2 genes, it could possibly have sought a method patent. But the processes used by Myriad to isolate DNA at the time of Myriad's patents "were well understood, widely used, and fairly uniform insofar as any scientist engaged in the search for a gene would likely have utilized a similar approach," 702 F. Supp. 2d, at 202–203, and are not at issue in this case.

Similarly, this case does not involve patents on new applications of knowledge about the BRCA1 and BRCA2 genes. Judge Bryson aptly noted that, "[a]s the first party with knowledge of the [BRCA1 and BRCA2] sequences, Myriad was in an excellent position to claim applications of that knowledge. Many of its unchallenged claims are limited to such applications." 689 F. 3d, at 1349.

Nor do we consider the patentability of DNA in which the order of the naturally occurring nucleotides has been altered. Scientific alteration of the genetic code presents a different inquiry, and we express no opinion about the application of §101 to such endeavors. We merely hold that genes and the information they encode are not patent eligible under §101 simply because they have been isolated from the surrounding genetic material.^[40]

In his concurring opinion, which relates to the scientific details in the majority opinion,^[39] Scalia wrote:

I join the judgment of the Court, and all of its opinion except Part I–A and some portions of the rest of the opinion going into fine details of molecular biology. I am unable to affirm those details on my own knowledge or even my own belief. It suffices for me to affirm, having studied the opinions below and the expert briefs presented here, that the portion of DNA isolated from its natural state sought to be patented is identical to that portion of the DNA in its natural state; and that complementary DNA (cDNA) is a synthetic creation not normally present in nature.^[40]

Reactions to the decision

Molecular Pathology v. Myriad Genetics was 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.^[41][42] The Federal Circuit's decision was a return to the status quo, in which the U.S. Patent Office issues patents for isolated gene sequences. However, it still ignited much controversy and interest from the public. The plaintiff's argument that DNA should be excluded from patent eligibility was widely echoed in popular media.^[43][44] Jim Dwyer, a reporter for The New York Times, wrote: "But for many people, it is impossible to understand how genes—the traits we inherit from our parents and pass along to our children—could become a company’s intellectual property."^[45] James Watson, one of the discoverers of the structure of DNA, agreed and submitted a brief in the case. He argued that DNA conveys special genetic information, that human genetic information should not be the private property of anyone, and that developing a patent thicket of gene sequences could prevent easy commercialization of genetic diagnostics.^[46]

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 from the outcome of other cases, In re Bilski and Mayo v. Prometheus, which rendered most diagnostic claims unpatentable, making 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.^[47][48]

The same issue, namely the patentability of the DNA sequence in the BRCA1 gene, was considered in a February 2013 case in the Federal Court of Australia where the validity of Myriad's patent was upheld.^[49] This was also a landmark ruling, and an appeal to the Full Court of the Federal Court of Australia is to be heard in August 2013.^[50] The submissions for that appeal were due on June 14, 2013, the day after the U.S. Supreme Court ruling was published, and the appellants in the Australian case have stated that the U.S. ruling has been referenced within their submission.^[51]

In an unanimous decision in October 2015, the High Court of Australia (the equivalent of the U.S. Supreme Court) found that an isolated nucleic acid, coding for a BRCA1 protein, with specific variations from the norm that are indicative of susceptibility to breast cancer and ovarian cancer was not a “patentable invention”. ^[52]

References

Further reading

• Abbott, Laurie E. (2012). "Incentive for Innovation or Invitation to Inhumanity?: A Human Rights Analysis of Gene Patenting and the Case of Myriad Genetics". Utah Law Review 2012 (1): 497–525. 
• Rogers, Douglas L. (2013). "After Prometheus, are Human Genes Patentable?". Duke Law & Technology Review 11 (2): 434–508. SSRN 2185984. 

External links

• Slip opinion from the U.S. Supreme Court