Whether or not genes can be patented has been debated since the inception of the Human Genome Project. At the heart of the debate have been questions about whether discovery of a gene is sufficient to claim an invention and whether gene patents encourage or stifle research and the clinical use of genomics. In a landmark decision in June 2013, the Supreme Court determined that DNA in its natural form cannot be patented.
The earliest genetic patents were issued in 1982, following the U.S. Supreme Court case of Diamond vs. Chakrabarty, which opened the door to patenting biotechnology discoveries. Since then, the core of the debate over gene patents has been whether or not the discovery of a gene or sequence of DNA rises to the level of invention required by Title 35 of the United States Code [gpo.gov], which lays out the criteria that must be satisfied for a patent to be granted. According to the Code, a patent may only be granted on “any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof.” Laws of nature, natural phenomena, and abstract ideas cannot be patented. Even if this first hurdle is passed, the invention must be novel; the existence of ‘prior art’ shows that someone else invented it first, of course. Also, the invention cannot be obvious to “a person having ordinary skill in the art to which said subject matter pertains.”
In the case of gene patents, critics have pointed out that such patents fail to meet most or all of these criteria. Firstly, genes are naturally occurring, and while much intellectual effort may have gone into discovering them within the DNA sequence, discovery is not the same as invention. Secondly, with the completion of the Human Genome Project in 2003 all of the human gene sequences were in the public domain and, therefore, prior art. And, finally, many argued that discovering the location of a gene never rose above the bar for being non-obvious; certainly by the late 1990s the practice was common place. DNA patenting has proven to be a very active area, despite the controversy of patenting genetic information that was discovered and not created. Although it is difficult to determine a precise number, some estimates assert that a fifth of the human genome is subject to patent claims.
Patents are issued to encourage innovation, and provide protection to allow those investing in an innovation the opportunity to maximize the profit from their investment. Patents issued for genetic technologies such as new methods of DNA sequencing are no different and their issuance has been extremely valuable to those developing products based on genetic discoveries. However, when patents limit the use of basic genetic information, they threaten to inhibit or unduly constrain biomedical research, and the translation of research discoveries to clinical applications.
Indeed, one of the early principles agreed upon by leaders of the Human Genome Project was that the DNA sequence generated should be freely available to the public. This principle was codified in the 1997 Bermuda Principles, which set forth the expectation that all DNA sequence information should be released into publicly available databases within 24 hours of being generated. This policy of open access to the genome has been a core ethos of genomics ever since.
Over the years that this debate has occurred, there have been concerns that large numbers of patents associated with the human genome would limit the integration of genomic medicine into health care because of either restrictive patents or prohibitive costs. Diagnostic tests on patented genes cannot be invented around, as is possible with other patents. This is because the actual DNA sequence to be tested is claimed in the patent, not the method of analyzing the gene to determine its sequence, and so only the patent holder, or their licensees, have the rights to sequence that DNA during the patent’s life.
In addition, so-called “patent thickets,” where multiple patent holders stake their claims across the genome, could have the potential to inhibit the translation of genetic discoveries into health care benefits. Patent thickets have occurred in other technological domains when multiple patent holders have related claims; for example in consumer electronics or standards for digital video and music.
In April 2010 the Secretary’s Advisory Committee on Genetics, Health and Society published a report, Gene Patents and Licensing Practices and Their Impact on Patient Access to Genetic Tests [oba.od.nih.gov]. Resting on the underlying assumption that patents on human genes were acceptable, the report recommended that diagnostic (but not therapeutic) genetic tests, be exempted from patent infringement, along with a research use exemption. Exempting diagnostic patents from infringement while still recognizing that diagnostic gene patents could exist was greeted with controversy at the time, especially considering that the case studies that accompanied the report showed mixed evidence of harm to patients as a result of gene patents.
NHGRI and Patent Policy
The debate about gene patents was already a hot topic at the time of the early Congressional deliberations about the U.S. involvement in the Human Genome Project. Congressional worries about the potential effects of gene patents resulted in a statutory mandate [gpo.gov] to the National Human Genome Research Institute to research ‘legal issues regarding patents’ as part of the then Center’s research into the ethical, social, and legal implications of human genome research.
Indeed, such were the concerns over the patenting of human genes that, in 2001, then-NIH Director Harold Varmus, and then-NHGRI Director Francis Collins wrote to the U.S. Trademark and Patent Office (USPTO) urging them to implement stricter criteria for biotechnology patents. USPTO raised their bar for issuing such patents, with new guidelines stating that identification of a gene’s sequence alone is not patentable, but that a gene isolated from its natural state may be patentable if the applicants can demonstrate “specific, substantial and credible utility” for the discovery. See: United States Patent and Trademark Office Utility Examination Guidelines [uspto.gov] (2001).
How patent holders license the gene patents they have been issued has also been a critical component of the ethical discussions about genetic intellectual property. A patent that is widely or, in some cases, even freely licensed does not pose the same types of impediments to the implementation of genomic medicine as a patent that is exclusively licensed. To explore the range of issues implicated in consideration of genetic intellectual property practices, NHGRI, in partnership with other NIH institutes, commissioned the 2005 National Academies report Reaping the Benefits of Genomic and Proteomic Research: Intellectual Property Rights, Innovation, and Public Health [nap.edu].
NHGRI worked extensively with the NIH Office of Technology Transfer to develop Best Practice Guidelines for the Licensing of Genomic Inventions [gpo.gov], published in 2005. The institute, in partnership with other organizations, has worked actively on these issues in an effort to maintain a level of access to basic genomic data able to achieve maximum public benefit through freedom to operate for researchers and care providers.
The Courts and Gene Patents
In 2009, the questions regarding gene patents finally went to court when the Association of Molecular Pathologists, the American Civil Liberties Union, and a coalition of other groups, filed a lawsuit against Myriad Genetics, the USPTO, and the University of Utah Research Foundation. The suit challenged the constitutionality and validity of the BRCA1 and BRCA2 gene patents. Myriad Genetics had been particularly active in enforcing their exclusive license to these breast cancer genes, sending cease and desist letters to other labs and even researchers it felt were infringing its intellectual property. Critics of the company also pointed to the test’s high price and the fact that it created a health disparity between those who could afford to be tested and those who could not.
The case was first heard in the United States District Court for the Southern District of New York and in March 2010, District Judge Robert Sweet ruled in favor of the plaintiffs [graphics8.nytimes.com] and against Myriad Genetics, finding that the BRCA1 and BRCA2 genes were products of nature and therefore not patentable material. Judge Sweet’s ruling made the important point that it is the information encoded in a gene, and not just the molecular structure, that makes them valuable to the patent holder. Since the raw information encoded in a gene is a product of nature, Judge Sweet asserted that it was not patentable under section 101 of Title 35 of the U.S. Code.
Myriad and the other defendants appealed Judge Sweet’s decision, and so the lawsuit over gene patents moved on to the Court of Appeals for the Federal Circuit. This court affirmed part of Judge Sweet’s ruling but the ruling on Myriad’s claims to the isolated genes [cafc.uscourts.gov] were reversed in a 2-1 ruling (in favor of allowing Myriad to hold the patents). Writing the opinion, Judge Alan Lourie rejected Judge Sweet’s argument about the information content of a gene, and focused on the fact that isolating a gene broke the covalent bonds between the molecules within the DNA, thereby creating a new substance. Judge Kimberly Moore concurred in part with Judge Lourie, also finding Myriad’s claims to the isolated BRCA genes patent-eligible, not because they were new substances but because USPTO had been granting such patents since the 1980s, and she believed that throwing them out would be too disruptive to the biotech industry.
The plaintiffs appealed this decision to the U.S. Supreme Court, but following their 2012 ruling in another diagnostic patent case [supremecourt.gov], the Supreme Court returned it to the Federal Circuit for reexamination. upon reexamination, the Federal Circuit arrived at the same decision as in their first ruling, upholding Myriad’s core claim on the isolated gene sequence information. The case again was appealed to the Supreme Court, who heard oral arguments [supremecourt.gov] on the question of whether isolated human genes are patent-eligible subject matter in April 2013.
On June 13th 2013, the Supreme Court published their ruling [supremecourt.gov] in the case, unanimously finding that isolated but otherwise unmodified genes were products of nature and therefore not patent eligible subject matter. However, the court did find that cDNA, synthetic DNA molecules that contain only the exons of a gene, do involve an inventive step, and thus remain patent eligible. The opinion, written by Justice Clarence Thomas, agreed with Judge Sweet’s 2010 argument that the information content of a gene was as important as its chemical structure.
The court’s opinion also agreed with a friend of the court brief, filed by the U.S. Department of Justice on behalf of the federal government when the case was before the Federal Circuit in 2011 (and again in a modified form when the case went before the Supreme Court in 2013). In this brief, the government took the position that isolated, but otherwise unmodified DNA should not be patent eligible, but that cDNA should be patent eligible. NIH and NHGRI are very pleased with the Supreme Court’s ruling in this case, and the removal of serious potential roadblocks that could impede the widespread adoption of genomic medicine.