Maria Lai ’17, THURJ Staff

Before a landmark Supreme Court decision in 2013, naturally occurring human gene sequences, defined here as “nucleotide sequences that correspond to coding regions from the genomes of natural organisms” (Graff et al 2013), were eligible for patents. Patent owners defending this practice claimed that their purification methods transformed the information carrier DNA into an unnatural chemical form. Tides turned in the Supreme Court case Association for Molecular Pathology (AMP) v. Myriad Genetics, Inc., which settled on June 13, 2013 with a win in the Association’s favor: the Judges voted 9-0 against the patentability of naturally occurring human genes (Torrance 2013). Reactions to the decision have ranged from positive, which came from patent holders’ competitors and those who believe in the unpatentability of human genes, to negative, which came from patent owners and professionals who believe a lack of intellectual protection may stagnate biotechnology innovation. The decision may have profound ramifications for the future of genetics research, diagnostics development, and the biotechnology landscape.

History

A patent gives an inventor legal monopoly over his invention and prevents others from using, making, and selling that invention for a period of time (Gold and Carbone 2010). The US Patent Act grants patents to “any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement” (Powlick 2012). This clause is often interpreted as anything man-made, as long as it is a novel invention. Even though patentability was defined so broadly, not everything is patentable. Laws of nature, natural phenomena, and abstract ideas cannot be patented (Torrance 2013); however, the application of these laws and natural phenomena is eligible for patent, but the degree of application needed to turn an unpatentable natural phenomenon into a patentable innovation is a gray area often debated.

Before 1980, applications for patents of living things would be rejected. This was changed in the famous Diamond v. Chakrabarty case, where Chakrabarty argued that his genetically modified bacterium, even though a living organism, was patentable because it did not exist in nature.  The Supreme Court ruled 5-4 that a living organism was patentable if it contained a human-manufactured composition of matter. This ruling gave law protection to gene sequences as well, on the basis that the isolation of DNA molecules gave it a chemical form that does not exist naturally. The US Patent and Trademark Office (USPTO) began to approve any patent on DNA sequences as long as they were rightfully claimed as isolated DNA. (Kevles 1994)

While supporters of gene patent insisted that the protection of innovation in the form of gene patents pose no harm and actually stimulate more innovations, opponents raised two main concerns in the decades following the revolutionary Chakrabarty decision: the commercialization of a natural product of the human body and that this commercialization may hinder research and discoveries (Gold and Carbone 2010). The gene sequences are products of nature and contain characteristics that are the culmination of evolution (Graff et al 2013). The information that these genes contain are not the result of human innovation and may not be appropriate for legal monopoly. With more than 20% of all human genes had been patented (Jensen and Murray 2005), this concern rang true. Overly broad patents can inhibit follow-up research and subsequent scientific innovations because the patent holders hold legal ownership of the gene sequences and the essential knowledge of those genes; they can block the research they perceived as competition by exercising ownership rights. Many laboratories that had worked on patented genes received cease-and-desist warning letters and lost the ability to perform more research on those patented genes (Gold and Carbone 2010). In short, the exclusivity of patents may prevent utilization of innovation and further research on the patented inventions and does not align with their proclaimed mission to stimulate innovation.

Monopoly over a human product may bring complications to many issues. Many genetic diagnostic tests employ patented genes; in fact, the personalized genetic testing industry promotes and thrives on the culture of monopoly because exclusivity deters competitors from entering the market, which generates more lucrative profit. For example, genetic tests can reveal an individual’s predisposition for breast cancer because breast cancer shows a strong association to the BRCA1 and BRCA2 genes; the patents of both genes belong to Myriad Genetics. Patents on these gene sequences make diagnostic tests expensive for patient consumers and prevent them from seeking a second opinion because the patent owner, in this case Myriad, is the sole provider in the market (Gold and Carbone 2010; Nature Medicine 2013). The expensive cost set in place by legal monopoly also creates challenges to public health and the goal to provide equal health care access (Gold and Carbone 2010).

patentpending
Image source: pixabay.com

Gene patent supporters responded to these concerns by arguing that no significant negative impact was made to public health nor innovation. Few studies have tried to verify claims made by both sides, and often times, data presented by one side may still be refuted by the other. For example, one impact study of US gene patents on genetic testing in the UK showed no significant negative impact on public health, and no significant lack of access was detected; though the study noted that this was due to the lack of enforcement of patent rights (Hawkins 2011). Opponents countered that it remains true that patent holders have legal monopoly and could at any time choose to enforce their patent rights, which not only affect innovation and health care but also conflict with the fundamental human right to the knowledge of one’s body (Graff et al 2013).

 

The Supreme Court case

The Association for Molecular Pathology (AMP) is a scientific society that aims to “advances the science and excellence of molecular and genomic laboratory medicine through education, innovation, and advocacy.” AMP frequently lobbies against gene patents and their exclusive rights holders. Myriad Genetics is a publicly traded company that employ 1200 people and the owner of the BRCA1 and BRCA2 gene patents. Technology based on these patented genes took 17 years to develop and $500 million to break even.

Along with the AMP, the plaintiffs on the AMP v. Myriad Genetics case include the University of Pennsylvania, Columbia University, New York University, Emory, Yale University, patient advocacy groups, and individual patients. The University of Pennsylvania had a previous encounter with Myriad before this case: Myriad requested that the University of Pennsylvania’s Genetic Diagnostic Laboratory to cease performing tests for BRCA on patient samples. The defendants are Myriad Genetics and The Trustees of the University of Utah, who held the BRCA2 gene patent with Myriad.

Chris Hansen, the representative attorney for the plaintiffs, revealed in a talk given at Harvard College in November 2013 that it was against his common sense that biotechnology companies could own patents on naturally occurring human genes. He said, “If you can’t patent a product of nature, an abstract idea, nor law of nature, you can’t patent human genes.” AMP used this reasoning and science to argue its case: it aimed to convince the judges that the isolation process of DNA does not change its integrity and the information it carried, which is a product of nature.

The legal battle garnered a lot of public attention to Myriad and its practices. Myriad responded to the public criticism it received by providing evidence of social impact: it claimed that its test had promoted research. 18000 scientists worked on the gene; their work resulted in more than 10,000 publications. Against the criticism that its genetic test price was too high, Myriad said 95% of its customers were covered by insurance, and that it often conducted the test at no cost for those who cannot afford it. (Meldrum, accessed 2014)

The case lasted from 2010-2013 and went through two petitions before appearing in front of the Supreme Court. This Supreme Court case was the first judicial decision that recognized DNA as a carrier of information that is not changed even after it is isolated. Judge Robert Sweet 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,” in the first hearing before the US District Court for the Southern District of New York. The Supreme Court upheld that decision in June 2013 and declared that “a naturally occurring DNA segment is a product of nature and not patent eligible merely because it has been isolated.” (Torrance 2013; Nature Medicine 2013)

Reactions

An analysis revealed that the Supreme Court decision can invalidate about 8,073 patents involving genes. 3,535 (41%) of those patents involved human genes; the rest involved sequences from other animals, plants, and microorganisms (Graff et al 2013). A study about the actual number of patents invalidated as a result of the decision has not been completed.

chromosomes-154668_640
Image source: pixabay.com

Scientists and experts who oppose gene patents rejoiced with the unanimous decision from the court. A month after the decision in July 2013, Nature Medicine published an editorial titled “A victory for genes” that reflects how most gene patent opponents were reacting: human gene patents were seen as costly to both researchers and patients, and legal monopoly reduced competition in the market, which increased costs for patients and may have decreased innovation. This Supreme Court decision is expected to open up research, allowing scientists to research things previously were disallowed and conduct follow-up research to patented discoveries; it also increases choices for patients both in terms of prices and the number of sellers. The editorial called the decision a win-win-win situation for science, patients, and the industry. (Nature Medicine 2013)

While many gene patent opponents celebrated this decision, some were dissatisfied, deeming the Court’s definition of what is unpatentable too narrow. Bloomberg ran an article entitled “The Supreme Court’s Bad Science on Gene Patents” right after the conclusion of the court case. In the article, Bloomberg raised concern for an important caveat in the decision: “cDNA is patent eligible because it is not naturally occurring” (Feldman 2013). cDNA is synthetic DNA that is made by coping mRNA, and is an altered form of its template DNA; it codes for the same sequence as its template DNA, just with introns spliced out. In other words, even though cDNA is synthetic, cDNA and DNA contain the same information. The author of the article argued that if the court believed the isolated BRCA genes did not have their information altered, it should have believed the same with cDNA. Because most of gene patents now involve synthetic DNA, some raised doubts about the actual impact of this decision on research: even though the decision is a landmark case, its actual effect on research may be moderate (Nature Medicine 2013).

The gene patent field reacted to the Supreme Court decision with product copiers and patent invalidations. In October 2013, a California district court invalidated the biotechnology company Sequenom’s patent on a test that detects Down syndrome in the fetus using DNA from the mother’s blood, a safer approach than the previous approach of taking a sample from the womb. The court stated that, considering the recent AMP v. Myriad Genetics decision, Sequenom should never have received that patent. In response to the patent invalidation, Sequenom’s stock dropped 23%. The company’s executives commented that Sequenom will appeal. However, not all biotechnology companies were upset. Three other companies in California were planning to offer similar blood tests to those of Sequenom’s in light of Sequenom’s patent annulment. In fact, Sequenom’s patent annulment was the result of a legal battle with another company called Ariosa Diagnostics, who commented “It’s a huge victory for us and for the entire field” and most likely initiated this legal battle in response to AMP v. Myriad Genetics. Thanks to this recent court decision, Ariosa Diagnostics will now be able to run the similar genetic tests as the ones developed by Sequenom. (Marshall 2013) Indeed, even though the Supreme Court decision may cause losses for some patent owners, it may also generate more business and stimulate competition, which is expected to decrease the prices of genetic diagnostic tests for patient consumers.

The Future

Fewer protections from the law for genetic discoveries as the result of the decision of the Supreme Court to defend the patent ineligibility of human genes may be seen as a blow to the biotechnology industry in some ways. Some biotech companies may incur losses, and investment for some genetics research may be reduced due the naturally occurring human genes being ineligible for patent. But the biotechnology industry is expected to survive this landmark law (Cho 2010). In addition, the caveat regarding cDNA is good for companies desiring patent protection: since cDNA is patent eligible, companies may focus resources on developing innovations that involve cDNA instead of normal DNA. In fact, patent applications involving human genes have been in the decline since 1999 (Nature Medicine 2013), and by 2010, the largest proportion of gene patents were those involving synthetic sequences (Graff et al 2013).

Plus, the old argument that innovations are motivated by intellectual property protection may not hold true in today’s genomic era. The patent ineligibility of human genes can lead to greater contributions to genetic discoveries and diagnosis tests because researchers have discovered that many genetic conditions have complex genetic bases, which means they involved many genes (Cho 2010). Diagnosis tests for those genetic conditions would have to make use of multiple genes, so an exclusive right on a certain gene would inhibit research and development of diagnostic tests of those complex genetic conditions. While this Supreme Court decision may harm prospects for some biotechnology companies in the short run; in the long run, it should not only encourage innovation, but also create a more vibrant and innovative trend in the biotechnology industry.

 

References

Cho, Mildred. “Patently Unpatentable: Implications of the Myriad Court Decision on Genetic Diagnostics.” Trends in Biotechnology 28, no. 11 (November 2010): 548–51. doi:10.1016/j.tibtech.2010.08.005.

Feldman, Noah. “The Supreme Court’s Bad Science on Gene Patents.” Bloomberg. (June 2013). Accessed April 8, 2014. http://www.bloomberg.com/news/2013-06-13/the-supreme-court-s-bad-science-on-gene-patents.html.

Gold, E. Richard, and Julia Carbone. “Myriad Genetics: In the Eye of the Policy Storm.” Genetics in Medicine : Official Journal of the American College of Medical Genetics 12, no. 4 Suppl (April 2010): S39–S70. doi:10.1097/GIM.0b013e3181d72661.

Graff, Gregory D., Devon Phillips, Zhen Lei, Sooyoung Oh, Carol Nottenburg, and Philip G. Pardey. “Not Quite a Myriad of Gene Patents.” Nature Biotechnology 31, no. 5 (May 2013): 404–10. doi:10.1038/nbt.2568.

Hawkins, Naomi. “The Impact of Human Gene Patents on Genetic Testing in the UK.” Genetics in Medicine : Official Journal of the American College of Medical Genetics 13, no. 4 (April 2011): 320–24. doi:10.1097/GIM.0b013e3181fc50bc.

Jensen, Kyle, and Fiona Murray. “Intellectual Property Landscape of the Human Genome.” Science 310, no. 5746 (October 14, 2005): 239–40. doi:10.1126/science.1120014.

Kevles DJ. Ananda Chakrabarty wins a patent: biotechnology, law, and society. Hist Stud Phys Biol Sci. 1994;25(Pt 1):111-35.

Marshall, Eliot. “California Moves Shake Up Prenatal Gene Testing Market.” Science 342, no. 6159 (November 8, 2013): 680–680. doi:10.1126/science.342.6159.680.

Meldrum, Peter. “Myriad Genetics (Ft. Peter D. Meldrum) – Patents On Your DNA.” News Genius. Accessed April 8, 2014. http://news.rapgenius.com/Myriad-genetics-patents-on-your-dna-annotated.

Nature Medicine. “A Victory for Genes.” Nature Medicine 19, no. 7 (July 2013): 792–792. doi:10.1038/nm.3279.

Powlick, Jill T. “Patents and Laboratory Medicine: What Is Required to Turn an Unpatentable Natural Phenomenon or Law of Nature into a Patentable Invention?” Clinical Chemistry 58, no. 8 (August 1, 2012): 1205–7. doi:10.1373/clinchem.2012.187534.

Torrance, Andrew W. “The Unpatentable Human Being.” Hastings Center Report 43, no. 5 (September 1, 2013): 10–11. doi:10.1002/hast.203.

Comments:

NO COMMENTS

LEAVE A REPLY