On 13 June 2013, the Supreme Court of the United States handed down its unanimous decision in the ongoing case of Association for Molecular Pathology et al v Myriad Genetics, Inc. et al 12-398, 569 US __ (2013). This case is the first brought in the US directly challenging the patentability of human genes and for that reason is extremely important to any entity involved in the biotechnology industry which relies on human genetics research as part of innovation strategy.
There has been a great amount of global coverage of this case since it kicked off back in May 2009 when the plaintiffs filed their complaint in the US District Court for the Southern District of New York. The plaintiffs comprising patient interest groups, medical organisations, researchers, pathologists and other interest groups were represented by the American Civil Liberties Union Foundation (ACLU) (an avid vocal follower of litigation in this human patent space). Although the key (commercial) defendant was Myriad (co-owner of one patent and exclusive licensee of the others), other defendants were the US PTO (for constitutional violations) and the directors of the University of Utah Research Foundation (co-owner of one patent and owner of the others licensed to Myriad). Not only were there multiple parties to this case but at every stage, there were multiple amici curiae briefs filed by third parties in support of both sides of the matter demonstrating the wide public interest in this case.
The patents and the science
The patents of interest are the highly valuable patents regarding the BRCA1 and BRCA2 gene sequences mutations of which may greatly increase a woman’s risk of breast and ovarian cancer. Some patent claims covered the sequence of the isolated genes themselves and others covered mutated versions of the isolated genes. Further claims covered synthetic version of those genes. There were also claims for methods of analysing and comparing the genes for mutations to determine risk, and for determining efficacy of certain therapeutic treatments.
Genes as they exist within animals are found within cellular DNA. The sequence of a gene is made of coding and non-coding regions. Naturally occurring genes contain both these regions. The DNA is a chemical sequence which via biological processes (which strip out the non-coding regions via transcription and translation to create an RNA template) determines the structure and composition of proteins to be produced which then go on to have their own functions within the body. Once the non-coding regions are stripped out, this complimentary DNA (cDNA) contains only the coding regions. This cDNA does not exist naturally in the body (not being a natural step in protein creation). However, Myriad determined which human DNA sequences within the entire human genome were significant in relation to a common type of breast and ovarian cancer (the BRCA1 and BRCA2 genes) if those sequences contained certain mutations. Myriad then determined which were the coding and non-coding regions and produced the sequence of the cDNA for those genes.
After patenting these BRCA1 and BRCA2 gene sequences and related medical testing methods, Myriad developed a very successful business in cancer screening (a famous patient being Angelina Jolie). This business was insulated from competition by the patents in issue.
The case and its travels
The ACLU argued that these patents prevent research and access by patients to vital tests and should be invalidated as the claims covering gene sequences were not eligible subject matter of a patent (under 35 USC §101) as these claims fall within the “product of nature” exception. Arguments were also made regarding the methods claims again based on another exception to patent eligibility being that they were comprised of a “mental process” only and therefore, failed the required legal tests (machine or transformation test).
The US District Court granted summary judgement to the plaintiffs in March 2010 and invalidated Myriad’s patent claims in issue. On appeal, the US Court of Appeals for the Federal Circuit reversed this decision in July 2011 in relation to the isolated natural DNA and cDNA gene sequences (Bryson J dissenting regarding isolated natural DNA gene sequences) and in relation to certain screening methods. However, it affirmed the US District Court’s decision to reject as patent eligible (as a mental process) the claims regarding methods of screening by comparing and analysing DNA sequences for changes only. The plaintiffs then obtained a writ of certiorari from the Supreme Court for the Federal Circuit to rehear the case in light of a recent Supreme Court decision on patentable subject matter. In August 2012, the Federal Circuit reached the same conclusions as its earlier (now vacated) decision.
The Supreme Court decision
The plaintiffs then filed a petition for a further writ of certiorari on the question on whether human genes are patentable which the Supreme Court granted. It is important to note that the writ was not filed in relation to the patentability of Myriad’s method claims. Oral arguments were made on 15 April 2013 which was just prior to the annual BIO convention in the USA being the largest international annual biotechnology meeting. Much commentary was made during this conference as well as in the press at the time regarding the Supreme Court’s apparent lack of ability to grasp the science involved with many jokes made in relation to analogies made as being completely inappropriate and misleading (for example, whether isolating DNA is like isolating a baseball bat from a tree or isolating a kidney from a body). In any event, the Supreme Court finally handed down its decision on 13 June 2013 and held that patent claims regarding isolated DNA sequences of genes are not patentable because Myriad did not alter or create that sequence information. All Myriad had done was identify and locate the genes as they occur in nature and isolate them (although the Supreme Court acknowledged that Myriad had spent much time and effort doing this and the discovery was groundbreaking but the technology in isolating genes was not inventive of itself). However, the cDNA sequences for the genes were patentable as that sequence did not appear in nature (the exception to this being where very short DNA sequences for genes do not contain non-coding regions and so the naturally occurring DNA would be the same as the cDNA).
Unpredictably both parties consider this decision a victory of sorts. The full impact is yet to be fully tested. Quickly after the decision was handed down, rival cancer screening companies including Ambry Genetics and Gene by Gene added BRCA1 and BRCA2 tests to their battery of genetic screening tests available in the USA at cheaper prices than those available from Myriad. However, Myriad has shot back by swiftly filing law suits alleging infringement of its method patents for testing. Ambry has now fired back arguing anticompetitive conduct by Myriad alleging that Myriad is relying on patent claims now ruled invalid by the Supreme Court. There are also calls by a US senator for the US Federal Government (through the National Institute of Health) to exercise its “march in rights” to the patents which cover the results of research assisted by federal funding.
Much has been made of these patents impeding research. The US does not have a general statutory research exemption but its case law prescribes a very narrow interpretation to the general experimental use exception in that the experimentation must have no or a very insubstantial commercial purpose. To soothe this argument, in July 2013, Myriad issued a statement that it would not impede non-commercial research using its patents (this is not a concern in many other jurisdictions including the UK which have legislated experimental use exceptions to patent infringement). This pledge reads similarly to the one given by Monsanto to farmers regarding accidental unauthorised use of Monsanto’s patented seeds.
However, Myriad’s trump card is its database of BRCA1 and BRCA2 sequence variants (mutations) that it has amassed in the years it has been undertaking screening and their clinical significance including companion diagnostic knowledge. This data is proprietary and inaccessible by its competitors but of great commercial value in terms of the advantages of seeking a test offered by Myriad as opposed to its competitors. In any event, the relevant patents are due to expire in the next few years so Myriad has had the benefit of many years of exclusivity to obtain its market lead.
The other query is even if naturally occurring gene sequences cannot be protected by patents in the USA, what value is this “free” information if the cDNA sequence can still be patentable thus preventing others from using it as the basis of genetic testing? The full impact of the Myriad decision on US genetic-based patents and the businesses that rely on them is yet to be seen.
Relevance to EU?
Significantly, the point to remember for those holding patents in EU countries is that Directive 98/44/EC on the legal protection of biotechnological inventions of 6 July 1998 (Biotech Directive) clarifies this area of law greatly. It provides specifically that elements isolated from the human body including gene sequences may still constitute a patentable invention even if the structure is identical that found in nature. Similar provision is made for all biological materials isolated from nature. Of course, patent applications covering such inventions will still need to satisfy other requirements of patent law (including novelty, inventive step and industrial application) and this is emphasised in the Directive. Therefore, Myriad and other gene patent holders may breathe a sigh of relief that at least their European gene sequence patents are not under threat from the reasoning in this US decision for the time being.