Last week saw the conclusion of the long-running gene patent lawsuit known as AMP v. Myriad Genetics, which pitted the US biotech company Myriad Genetics against the American Association for Molecular Pathology and others, including a group of cancer patients and campaign organisations with support from the American Civil Liberties Union (1). At stake was the patentability of isolated DNA sequences, such as those issued by the US Patent and Trademark Office (USPTO) to Myriad and the University of Utah on the BRCA1 and BRCA2 genes. Those genes play an important role in determining risk of breast cancer for a subset of women with a strong family history of the disease.
However, since the patents were granted in the late 1990s, Myriad has excluded other laboratories from offering testing services for patients while monopolising the US market from which most of their US$400 million revenue for BRCA testing is derived (2). The litigation, already attracting international media attention, was thrust even further into the spotlight when Hollywood star Angelina Jolie announced that she had undergone breast surgery after learning that she was at heightened risk of the disease as a result of her BRCA status. At the end of her media statement, the actress and activist expressed concern about the cost of BRCA testing in the USA and the fear that some women may have been unable to access the test as a consequence.
Critics of gene patents have long voiced this concern, as well as expressing fears that diagnostic monopolies limit different approaches to testing, which could detract from the quality of tests available, and that innovation will be hindered as the proliferation of patents creates thickets of intellectual property (3). While many companies hold patents on genes, and often develop products based on these without attracting much attention, the Myriad BRCA1/2 patents have been the lightning rod for concerns over gene patents for over a decade.
Over the years, the patents that Myriad's monopoly relies upon have been widely challenged in patent offices and courts in the USA, Australia and Europe, and in some countries they have been weakened and liberally infringed by hospital laboratories. However, it is only the vigour of the opposition to Myriad's tight grip on the US BRCA testing market that overcame prior court verdicts and forced the hearing of the case before the US Supreme Court (which had itself remanded the case to the lower Federal Circuit court once before).
In its acquiescence, the Supreme Court chose to hear arguments in relation only to a very specific point – the patentability of isolated gene sequences, which they ruled on earlier this month. Patent claims on gene sequences have for decades been accepted as a novel composition of matter by the USPTO when isolated and purified from their natural context, provided that the sequence has a specific and substantive industrial utility. This might mean that the sequence is useful for diagnostic or therapeutic purposes, for example. The ruling was therefore significant and much anticipated as it was set to overturn long standing accepted practice. And overturn established practice the Supreme Court judges duly did in a decisive manner, 9-0 in favour of making merely isolated gene sequences patent ineligible.
However the opinion is equally clear that where a nucleotide sequence claiming DNA or RNA differs from the natural sequence, then this may be considered as patentable subject matter, subject of course to the other conditions of patentability – these being: novelty of the subject matter, utility of the invention, sufficiency of the inventive step, and full disclosure of the invention. This leaves considerable latitude for the patenting of engineered genes such as might be used to produce modified proteins and enzymes with improved characteristics in therapeutic use or bioprocessing, as well as synthetic DNA and RNA probes and primers useful for diagnostic testing.
How does this decision change the biotech industry or impact healthcare? The answer is probably that this case will be an anti-climax with little visible change, other than on Myriad's share price. Indeed in the days since the ruling, much attention has focused on this financial gauge of how much the market will change and whether Myriad's monopoly will at last be broken in the USA (of course the patent position in other jurisdictions remains unchanged). Certainly, practitioners following the case expect competing tests will now be launched, so explaining the stock price decline which followed the decision. Yet Myriad has hundreds more patent claims still intact, and so competitors will still have to proceed with some caution. In fact, the invalidated patents would have expired soon anyway, given the limits of patent term so this is not a dramatic change in the patent landscape. Myriad also has an unprecedented database of BRCA 1/2 sequence variants and patient histories thus providing them with a significant advantage over other test providers when it comes to test results interpretation (4).
More dramatic is the sudden invalidation of hundreds, if not thousands, of patent claims similar in wording to those in the BRCA patents. These claims cover inventions in agricultural, industrial and health-related biotech sectors. Yet many of these patents will also expire in the near future. Indeed the type of broad patent claims on naturally occurring genes at stake in the Myriad case has been on the decline for over a decade, as the massive gene sequencing efforts by public and private organisations over the years have made it more difficult to meet patentability requirements (5). However, as noted above, it is still possible to patent non-naturally occurring sequences, and reading between the lines of the ruling, we can surmise it is still possible to obtain patent claims on a novel use of a naturally occurring molecule, be it a gene or a protein.
Finally outside the USA, the ruling will have little immediate impact other than providing a (perhaps politically unwelcome) reminder of the now relatively strong legal protections on patentability of genes and other nucleotide sequences enshrined in national laws across Europe, following the adoption of European Directive 98/44/EC.