By Chyreene Truluck and Waheed Mahomed

The decision of the United States (US) Supreme Court in Association for Molecular Pathology, et al. v Myriad Genetics, Inc., et al 569 U.S. 133 S.Ct. 2107 (2013) (the US Myriad case) was a landmark case on the patentability of biotechnological inventions. In particular the US Myriad case dealt with the issue of patentability of naturally occurring genes or nucleotide sequences, which have been isolated and characterised. Myriad Genetics, Inc. is a molecular diagnostic company specialising in predictive and personalised cancer diagnostic methods centred on the isolated BReast CAncer (BRCA) genes and was founded as a spinoff company out of the University of Utah. In August 1994 the first BRCA1 gene US patent was filed followed by the BRCA2 gene US patent in 1995. In 1996, Myriad launched their BRCA Analysis product, which detects certain mutations in the BRCA1 and BRCA2 genes that put women at high risk for breast cancer and ovarian cancer. Their discovery of the breast cancer gene, BRCA1 was universally acclaimed as a monumental achievement, but sparked controversy regarding the patentability of DNA molecules and their use in diagnosis and drug identification. Prior to the case against Myriad Genetics, the US Patent and Trademark Office (USPTO) had granted numerous patents in respect of technologies containing isolated DNA sequences as a composition of matter.

In the US Myriad case, a number of US courts, and finally the US Supreme Court, considered whether claims directed to isolated genes, diagnostic methods and methods for identifying drug candidates were valid under 35 U.S.C. § 101 which states that: ‘Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.’ The judicial exceptions to this section include laws of nature, natural phenomena, and abstract ideas.

The Association for Molecular Pathology, along with several medical associations, researchers and doctors challenged the resulting BRCA1 and BRCA2 patents, granted by the USPTO. In its landmark decision, the US Supreme Court held that naturally occurring DNA sequences and natural derivative products from such sequences are not patentable as they are natural phenomena, or products of nature. However, it was held that synthetically produced complementary DNA (cDNA) and gene sequences modified by synthetic processes, and their products are patentable. It was also emphasised by the US Supreme Court that the claims of the BRCA1 and BRCA2 patents, which were directed to new applications of knowledge for naturally occurring DNA sequences, were not challenged and as a result these in all likelihood are valid.

This decision, although welcomed by many, created some confusion, as it only related to human DNA sequences, and raised questions about how proteins and non-human DNA would be treated. In December 2014 the USPTO published the 2014 Interim Guidance on Subject Matter Eligibility, which was updated in July 2015 (the guidelines). These documents set out the USPTO’s interpretation of subject matter eligibility requirements of 35 U.S.C. § 101 in view of the US Myriad case and others. The primary guidance provided is that naturally occurring substances and substances that do not have ‘markedly different’ characteristics to what occurs in nature are not patentable under 35 U.S.C. § 101. In other words, the primary test is whether the claimed product, or product of a claimed process is markedly different from its naturally occurring counterpart.

In 2015, the issue of patentability of the BRCA1 gene by Myriad arose again in Australia in D’Arcy v Myriad Genetics Inc [2015] HCA 35 (the Australian Myriad case). In the Australian Myriad case the Australian High Court decided that claims directed to an isolated nucleic acid coding for a mutant BRCA1 protein is not patentable. Under Australian patent law, in order to be patentable an invention must be ‘a manner of manufacture’, which has been preserved as the threshold test for patentability, and interpreted by the courts over time. In the Australian Myriad case, the court stated that an isolated nucleic acid is not ‘made’ by human action as contemplated by Australian law, but rather it is discerned. The Australian High Court further held that a nucleic acid bearing certain mutations or polymorphisms depends on the characteristics of the person from which it is isolated and has nothing to do with the person isolating it. The court also reiterated the warning that a patent over a single gene may prove to set up a barrier against its use in a genetic procedure for a different condition. It thus held that claims to the gene or nucleic acid sequences themselves are too broad. It was noted in the decision that: ‘For the primary judge, the issue of patentability turned on … whether an isolated nucleic acid, which may be assumed to have precisely the same chemical composition and structure as that found in the cells of some human beings, constitutes an artificial state of affairs’, which was held not to be the case.

In light of the decision the Australian Patent Office has issued a note on updated examination practices, which was released in January 2016, following the Australian Myriad case. In an interesting move, and perhaps in an effort to inspire confidence in the biotech sector, the Australian Patent Office proposed in December 2015 to retain patentability of most naturally occurring products, with the exception of coding nucleic acid sequences. However, the finalised examination practice note states that naturally occurring nucleic acids, whether human or non-human, coding or non-coding, are excluded from patentability based on the decision in the Australian Myriad case. Claims to cDNA, synthetic nucleic acids, probes, primers and isolated inhibitory nucleic acids will be excluded where they merely replicate the genetic information of a naturally occurring organism. However, it would seem that other biological inventions such as regulatory DNA, isolated bacteria, viruses, polypeptides, chemical molecules, cells and transgenes will still be patentable, provided they fulfil all the other requirements for patentability, namely, they are not naturally occurring, or do not merely replicate the genetic information of a naturally occurring organism.

The Australian and US Myriad decisions reach the same conclusion with regard to naturally occurring genes and DNA sequences but differ with regard to the patentability of cDNA, due to the differing approaches of the two courts. The US Supreme Court held that BRCA cDNA has no natural existence and, is therefore, patent eligible. The Australian High Court focused on the information contained within the DNA molecule rather than the ‘form’ of the molecule and concluded that cDNA represents the same information as its complementary genomic DNA (and expresses the same protein) and was thus held to be patent ineligible.

It is worth noting that in contrast to the approach adopted in the USA and Australia, the patentability of isolated genetic sequences is expressly recognised under European law. Article 5 of the EU Biotechnology Directive provides that: ‘An element isolated from the human body or otherwise produced by means of a technical process, including the sequence or partial sequence of a gene, may constitute a patentable invention, even if the structure of that element is identical to that of a natural element’ provided that the industrial application of such sequence is disclosed in the patent application. However, ‘[t]he human body … and the simple discovery of one of its elements, including the sequence or partial sequence of a gene, cannot constitute patentable inventions.’

The current South African Patents Act 57 of 1978 does not define an invention but rather lists a number of exclusions as to what would constitute a patentable invention. In particular, s 25(2)(a) provides that a discovery is not an invention for the purposes of this Act. This is in contrast to the previous South African Patents Act where the definition of an ‘invention’ included a ‘composition of matter’. This is similar to the wording of 35 U.S.C. § 101. Furthermore, the previous Patents Act 37 of 1952 provided that a claim for a new substance does not include that substance when found in nature.

Although South Africa has no case law on the meaning of ‘discovery’ or the patentability of biotech inventions, the abovementioned international cases will have persuasive value if a patent with claims to an isolated gene or nucleotide sequence is challenged in our courts. Therefore, we postulate that from the cases discussed, as well as the both the current and repealed Patents Acts, naturally occurring nucleic acid sequences and proteins, and synthetic versions which replicate these, will likely be held not to be patentable by our courts as they will be considered to be discoveries of substances found in nature. However, this will likely not preclude the patentability of synthetic nucleic acids or proteins which are significantly different from naturally occurring sequences or new applications of nucleic acid sequences and proteins.

Chyreene Truluck MSc Genetics (Wits) LLB (Unisa) and Waheed Mahomed PhD Biotechnology (UP) are candidate attorneys at Spoor & Fisher in Pretoria.

This article was first published in De Rebus in 2016 (June) DR 26.