US Supreme Court Decision in Myriad: Are Genes Patentable?

The pharmaceutical and life sciences industries waited anxiously for the Supreme Court's decision in Association of Molecular Pathologists v. Myriad Genetics ("Myriad")¹ The high court's decision, handed down 13 June 2013, will have a significant impact on the pharma and device industries as they relate to human genes and genetic material. The decision found that naturally occurring genes cannot be patented, but synthetically produced genetic material remains patentable subject matter.  

Case Background

DNA, the building blocks of life, took center stage in the Myriad case. In the early 1990s, researchers at the University of California at Berkeley discovered genes on chromosome 17-later identified as the BRCA1 and BRCA2 genes-that led to an increased chance of developing breast cancer. It was quickly understood that if patients who exhibited the BRCA genes could be identified, this would offer a great indication of future risk for those patients more susceptible to the development of breast cancer.

Myriad Genetics Inc. (MGI), the defendant in the Supreme Court case, was founded in part to develop a diagnostic tool to assist practitioners in the detection of BRCA genes and associated mutations in patients. MGI filed several patent applications related to BRCA1 and BRCA2 and those mutations. The foci of the Myriad case were three patents (nine claims) issued to MGI related to BRCA1 and BRCA2. 

MGI spent years developing the diagnostic tests and tools related to the BRCA genes. Prior to MGI's development of its diagnostic tests, "Scientists knew that heredity played a role in establishing a woman's risk of developing breast and ovarian cancer, but they did not know which genes were associated with those cancers."² After the discovery of the BRCA1 and BRCA2 genes, practitioners were able to test their patients to determine potential cancer risk and assist in determining the most advantageous course of treatment.

The plaintiff in Myriad, the Association for Molecular Pathology, a collection of healthcare providers, researchers, institutions, patients and practitioners, provided genetic testing to its patients to determine the presence of the BRCA1 and BRCA2 gene mutations. MGI sent a cease-and-desist letter to several health practitioners threatening legal action if they did not stop testing patient samples for the BRCA genes, as that testing allegedly infringed upon MGI's patents. In response, the plaintiffs filed suit against MGI challenging MGI's patents as invalid on the grounds that they were not patentable subject matter under Section 101 of the United States Patent Code.³

As the case worked its way through the court system, the district court ruled in favor of the plaintiffs. MGI appealed to the federal circuit, which overturned the district court decision and ruled in favor of MGI. After a circuitous route, the Supreme Court agreed to hear the case and issued its ruling 13 June 2013.

Scientific Background

The Supreme Court offered a lengthy description, albeit with some discernible inaccuracies, about the science involving genes and DNA.⁴ As is generally known, DNA is a molecule that codes the genetic template found in living organisms. DNA is comprised of double-stranded helices that are chemically linked as nucleotides. Each nucleotide comprises one of four nucleobases (adenine, guanine, cytosine and thymine) that links the DNA helices through a sugar-based backbone. A nucleobase linked to a sugar is called a nucleoside, and a base linked to a sugar and one or more phosphate groups is called a nucleotide. It is the sequence of nucleotides that encodes genetic information such as amino acids that are used by the body to build proteins. However, not all nucleotides code for amino acids. The coding series of nucleobases are referred to as exons and the non-coding nucleobases that lie between the exons are referred to as introns.

Creation of proteins further involves the processes of translation and transcription. Transcription involves the separation of the bonds between the nucleotides and the unwinding of the DNA double helix into two single strands. One single strand is then used as a template to form a complementary RNA strand, with thymine being substituted for uracil in the RNA strand. The resulting RNA strand, referred to as pre-RNA, is a mirror image of the single corresponding DNA strand. The remaining strand contains only the coding exons from the original DNA strand. This exon-only strand is referred to as mRNA and is used to generate amino acids. (It was this exon-only strand that proved a critical element to the ruling in the Myriad case.) The generation of amino acids occurs through a process of translation, in which ribosomes read each triplet or three nucleobases, referred to as codons, to determine which amino acids to synthesize.

The process described above occurs naturally within the cells of living organisms. However, the development of science and technology now allows scientists to isolate specific segments within DNA, a human manipulated process, and replicate the transcription and translation processes. This replication can then be used in developing treatments for patients as well as advancing new research objectives.

Thus, the transcription and translation processes can be natural (i.e., occur naturally in the body) or through man-made or synthetic processes (i.e., manipulated by a scientist or physician). The court described one synthetic process that initiates an mRNA molecule and through natural bonding properties of nucleotides creates a synthetic DNA molecule known as cDNA. The cDNA molecule is DNA created from mRNA and thus lacks any of the naturally found introns.

Supreme Court Decision

With Justice Clarence Thomas delivering the unanimous opinion, the high court held in favor of the plaintiffs on the issue of whether isolated DNA was eligible for patent protection. A naturally occurring segment of DNA that has been isolated from the rest of the genetic material is not eligible for patent protection simply because of that isolation. Thus, naturally occurring genes and other genetic material are not eligible for patent protection.

However, the court found a distinction between the naturally occurring DNA and the exon-only developed cDNA which is free of the naturally occurring introns. It is important to consider the Patent Act regarding patentable subject matter, which states in relevant part:

"Whoever invents or discovers any new and useful…composition of matter, or any new and useful improvement thereof, may obtain a patent thereof, subject to the conditions and requirements of this [Act]."⁵ 

Drawing on previous case precedent, the court stated "[w]e have long held that this provision contains an important implicit exception [:] Laws of nature, natural phenomena, and abstract ideas are not patentable."⁶ However, the court was clear that the decision in Myriad does not offer an unconditional ban on "naturally occurring things" reiterating that, "All inventions at some level embody, use, reflect, rest upon, or apply laws of nature, natural phenomena, or abstract ideas," and, "Too broad an interpretation of this exclusionary principle could eviscerate patent law."⁷ The court emphasized a balance between "creating incentives that lead to creation, invention, and discovery" and "imped[ing] the flow of information that might permit, indeed spur, invention."⁸

Looking at MGI's patent claims in the isolated segments of natural DNA and consulting the language of the Patent Act (35 USC §101), it is clear that such segments existed naturally without any intervention by MGI. It was akin more to discovery than invention. The court did not diminish MGI's work in isolating the natural DNA segments, and stated "[t]o be sure, [MGI] found an important and useful gene, but separating that gene from its surrounding genetic material is not an act of invention."⁹ MGI may have found the BRCA genes "but that discovery, by itself, does not render the BRCA genes 'new…compositions[s] of matter,'" and thus eligible for patent protection.¹⁰ The court continued that "extensive effort alone is insufficient to satisfy the demands" for patentable subject matter.¹⁰

MGI tried to further argue that the isolated DNA only existed because of the severed bonds between the nucleotides. The court disagreed, as MGI's patent claims did not require chemical changes and was limited to the naturally occurring genes. MGI's patent claims focused only on the isolated DNA that coded for the BRCA genes.¹¹

The court's distinction, though, came in its analysis of cDNA. The decision stated that cDNA "does not present the same obstacles to patentability as naturally occurring, isolated DNA segments."¹² Since the cDNA sequences lack introns or the "non-coding" regions, the court reasoned that cDNA created in the lab retains the naturally occurring exons but is "distinct from the DNA from which it was derived."¹³ Thus, synthetically derived cDNA is eligible for patent protection.

Aftermath

Many commentators feel in its decision in Myriad, the Supreme Court was careful to avoid overreaching by expressly stating that the opinion excludes patent claims involving methods of use, "new applications of knowledge about the BRCA1 and BRCA2 genes" or "the patentability of DNA in which the order of the naturally occurring nucleotides has been altered."¹⁴ So while the decision confirmed that naturally occurring DNA is not patentable, it was careful not to overextend the ruling and did identify limitations.

Within hours of the decision, several companies announced the offering of lower-cost tests for the BRCA genes. The cost of some tests was 25% of MGI's original tests. MGI quickly filed infringement actions against two of the companies claiming that the tests infringe, in part, on patents for methods of testing owned by MGI that were not invalidated.¹⁵

Other actions in the aftermath of the court's decision involve legislators petitioning the National Institutes of Health (NIH) to enlist provisions of the Bayh-Dole Act to compel MGI to license its patents on cDNA, held to be valid by the court. The Bayh-Dole Act allows the NIH to exercise "march-in rights" related to patents developed with the assistance of federally funded research, such as MGI's BRCA gene technology. These rights allow the NIH to force patent holders like MGI to license patents on reasonable terms to third parties.

While the "march-in rights" outlined in Bayh-Dole have to date not been used against any patent holder, Sen. Patrick Leahy (D-VT), chairman of the Senate Judiciary Committee, made the argument in his 12 July 2013 letter to NIH that the exercise of these "march-in rights" could make what is now an unaffordable test for some women much more accessible. "The healthcare cost savings are equally clear. I am concerned, however, that the health needs of the public are not reasonably satisfied by the patentee [MGI] in this situation because testimony presented to the USPTO [US Patent and Trademark Office] made clear that many women are not able to afford the testing provided by [MGI]. I encourage you to consider using your march-in rights in this situation."¹⁶ Time will tell if this public access policy argument will compel the government to intervene for the first time against the rights of patent holders. 

Conclusion

The Myriad decision sent ripples through the pharma and life science industries as companies rushed to evaluate their patent portfolios and the effects of the decision on their intellectual property. It should not be shocking that naturally occurring genetic material was found not to be patent eligible, but the court's tortuous reasoning for patent-eligible cDNA will continue to be discussed long after this decision. 

References:

1. Association for Molecular Pathology, et al., v. Myriad Genetics, Inc., et al., No. 12-398 (U.S. June 13, 2013) (115 PTD, 6/14/13).
2. Association for Molecular Pathology, et al., v. Myriad Genetics, Inc., et al., No. 12-398 (U.S. June 13, 2013) (115 PTD, 6/14/13) (at 4).
3. See 35 USC sec 101.
4. This article gives a very cursory overview of the science involving DNA and readers are encouraged to seek outside materials and resources for a complete understanding of genetic science and technology.
5. Op cit. 3.
6. No. 12-398 (U.S. June 13, 2013) (115 PTD, 6/14/13) citing Mayo v. Prometheus 566 U.S. at (slip op., at 1)
7. No. 12-398 (U.S. June 13, 2013) (115 PTD, 6/14/13) citing Mayo v. Prometheus 566 U.S. at (slip op., at 2)
8. No. 12-398 (U.S. June 13, 2013) (115 PTD, 6/14/13) citing Mayo v. Prometheus 566 U.S. at (slip op., at 3)
9. Association for Molecular Pathology, et al., v. Myriad Genetics, Inc., et al., No. 12-398 (U.S. June 13, 2013) (115 PTD, 6/14/13) (at 12).
10. Association for Molecular Pathology, et al., v. Myriad Genetics, Inc., et al., No. 12-398 (U.S. June 13, 2013) (115 PTD, 6/14/13) (at 14).
11. Association for Molecular Pathology, et al., v. Myriad Genetics, Inc., et al., No. 12-398 (U.S. June 13, 2013) (115 PTD, 6/14/13) (at 15).
12. Association for Molecular Pathology, et al., v. Myriad Genetics, Inc., et al., No. 12-398 (U.S. June 13, 2013) (115 PTD, 6/14/13) (at 16).
13. Association for Molecular Pathology, et al., v. Myriad Genetics, Inc., et al., No. 12-398 (U.S. June 13, 2013) (115 PTD, 6/14/13) (at 17).
14. Association for Molecular Pathology, et al., v. Myriad Genetics, Inc., et al., No. 12-398 (U.S. June 13, 2013) (115 PTD, 6/14/13) (at 17-18).
15. Kendall, Brent, "Myriad Genetics Presses Ahead After High Court Ruling on Patents," Wall Street Journal, 12 July 2013 http://blogs.wsj.com/law/2013/07/12/myriad-genetics-presses-ahead-after-high-court-ruling-on-patents Accessed 13 August 2013.
16. Letter from Senate Judiciary Committee to NIH dated 12 December 2013. http://www.leahy.senate.gov/press/leahy-urges-action-to-ensure-access-to-affordable-life-saving-diagnostic-tests-for-breast-and-ovarian-cancer Accessed 13 August 2013.