One of the many benefits of genetic testing is the ability to carry out prenatal diagnosis of genetic disorders, most notably including (but certainly not limited to) Downs Syndrome. This can be particularly valuable when one or both parents are known to be carriers of a genetic mutation such that the baby may be at significant risk of developing a serious condition or abnormality. The conventional method of obtaining foetal DNA in order to conduct such tests is via amniocentesis, which is an invasive procedure in which a small amount of amniotic fluid is sampled from the amniotic sac surrounding the developing foetus using a needle. Unfortunately, amniocentesis presents a risk to both foetus and mother.A test that would enable screening of foetal DNA in a noninvasive manner would therefore be an important breakthrough. Fortunately, just such a breakthrough was made in 1997 at Oxford University, when researchers Stephen Wainscoat and Dennis Lo discovered the presence of cell-free foetal DNA (cffDNA) in maternal blood serum, and developed techniques to isolate this DNA for testing. Their discovery led to the grant of patents in a number of countries, including US patent no. 6,258,540 and Australian patent no. 727,919. Oxford University, through its commercialisation arm Isis Innovation (now renamed as Oxford Innovation, for sadly obvious reasons), licensed the technology exclusively to US company Sequenom, Inc.
Last year, the US Court of Appeals for the Federal Circuit (CAFC) found the US patent to be invalid on the basis that the claimed invention was essentially the discovery of the pre-existing, but hitherto unknown, natural phenomenon of cffDNA being present in maternal blood: Ariosa Diagnostics, Inc.v. Sequenom, Inc. (Fed. Cir. 2015). The claims were therefore considered to be directed to ineligible subject matter under the standards established by the US Supreme Court in its Myriad and Mayo decisions. The CAFC subsequently declined to rehear the case en banc. However a number of the Federal Circuit judges, including Judge Linn on the original panel, and Judges Lourie and Dyk in the decision refusing en banc rehearing, indicated that they felt bound by the Supreme Court precedents, but did not agree with the result in this case. Judge Newman went further, stating her view that the case had been wrongly decided, and was distinguishable from the facts in Myriad and Mayo.
Many observers therefore felt that the Sequenom case was ripe for review by the Supreme Court, which would then have an opportunity to further develop and clarify its Myriad and Mayo guidance. However, on 27 June 2016 the Supreme Court denied Sequenom’s petition, sealing the US patent’s demise once and for all.
However, in the meantime (on 7 June 2016) Sequenom has commenced proceedings in the Federal Court of Australia, also against Ariosa Diagnostics, Inc, for infringement of the equivalent Australian patent. This raises the question of whether the invention that was found ineligible for patent protection in the US may nonetheless be upheld under Australian law. This will be the second time in recent history (the other being the Myriad BRCA breast cancer gene case) that subject-matter eligibility has been considered for corresponding patents in the US and Australia.
The US and Australian Patent Claims
The Australian cffDNA patent is broader in scope than its US counterpart. Claim 1 of US patent no. 6,258,540 defined the inventions as follows:1. A method for detecting a paternally inherited nucleic acid of fetal origin performed on a maternal serum or plasma sample from a pregnant female, which method comprises
amplifying a paternally inherited nucleic acid from the serum or plasma sample and
detecting the presence of a paternally inherited nucleic acid of fetal origin in the sample.
Claim 1 of Australian patent no. 727,919, by comparison, recites:
1. A detection method performed on a maternal serum or plasma sample from a pregnant female, which method comprises detecting the presence of a nucleic acid of foetal origin in the sample.
The differences between the claims are essentially that the Australian claim lacks the ‘paternal inheritance’ and ‘amplification’ limitations of the US claim. The first of these is important in practice, because it is the presence of features of the father’s genetic inheritance that distinguishes foetal DNA from the mother’s own DNA. ‘Amplification’ refers to a well-known practice of multiplying copies of the DNA of interest to facilitate detection and further analysis.
These features are, however, also present in the Australian claims – specifically in claims 9 and 2 respectively – and thus the differences in claim 1 should not affect any final decision as to whether the patent as a whole discloses and claims valid subject matter.
Will Australia Prove to Be More Friendly to Sequenom?
The prospects of the cffDNA patent being upheld in Australia are, in my view, considerably better than in the US. As I have already noted, the primary basis on which the US patent was found to invalid was that the invention did not amount to substantially more than the application of a newly-discovered natural phenomenon or ‘law of nature’. There is no question – particularly following the Supreme Court’s Mayo and Myriad decisions – that laws of nature and natural phenomena constitute excluded subject matter in the US.In Australia, however, the courts have generally declined to find that there is a ‘laws of nature’ exclusion in our ‘manner of manufacture’ eligibility test. As Justices Gageler and Nettle stated (at [137]) in D'Arcy v Myriad Genetics Inc [2015] HCA 35:
Of course, as NRDC implies, the application of naturally occurring phenomena to a particular use may be a manner of manufacture if it amounts to a new process or method of bringing about an artificially created state of affairs of economic significance. Even so, the inventor cannot claim to have invented the naturally occurring product as opposed to the process of application. In NRDC, the patentee could not claim to have invented, and therefore there was no suggestion of it laying claim to a monopoly over, the commonplace herbicides which were used in the course of the patentable process. Similarly, in Shell Oil Co v Commissioner of Patents, the patentee could not claim to have invented, and therefore there was no suggestion of laying claim to a monopoly over, the known compounds which were applied as part of the patentable process to a new use of plant growth regulation. So too here, insofar as the invention consists in the application of a naturally occurring phenomenon to a particular use, the inventor cannot claim to have invented the naturally occurring phenomenon as opposed to the method of use and has no claim to a monopoly over the naturally occurring phenomenon as opposed to the method of use.
In the Australian Myriad case, the challenged claims were found to be invalid because, in effect, they were directed to the naturally-occurring genetic information content of DNA exhibiting the BRCA mutation. The court did not dispute that considerable effort and ingenuity might be required to make the original discovery of the mutation, and to determine its significance as a predictor of cancer risk. Nor did it appear to dispute that a practical application of this new discovery, such as a diagnostic test, could be patent-eligible, regardless of how routine the implementation of that application may be.
In the seminal NRDC case itself, for example, the chemicals used in the patented process were known, as were techniques for applying chemicals to crops. What was new was the discovery of the particular utility of the chemicals used in the claimed process. As the High Court said in that case (at [9]):
There is a clear assertion of a discovery that a useful result can be attained by doing something which the applicant's research has shown for the first time to be capable of producing that result. ... It is irrelevant, even if true, that once the discovery was made that the chemicals produce a lethal reaction when applied to the weeds and produce no such reaction when applied to the crops there was no more ingenuity required in order to show how the process might be performed.
In contrast to the circumstances in Myriad, there is no attempt in the cffDNA patent to claim rights over the foetal DNA itself, or any of the genetic information that it encodes. The claims are limited to methods of detecting foetal DNA in maternal serum or plasma samples, (as in claim 1), and to methods of performing prenatal diagnoses using the detected foetal DNA. Similarly to the NRDC case, prior to the work of Wainscoat and Lo it had not been suspected that cffDNA was present in maternal blood – on the contrary, the evidence in the US Sequenom case was that maternal serum was typically discarded as biological waste. The inventors were thus the first to discover that a useful result could be attained by detecting the presence of a nucleic acid of foetal origin in a maternal serum or plasma sample, as is claimed.
Conclusion – A Long Road Ahead
The Sequenom case is proceeding number VID611/2016 in the Victorian Division of the Federal Court of Australia, and it appears at this stage that it will be heard by Justice Beach.It is obviously very early days yet. Depending upon how the case plays out, in terms of evidence and other preparations for trial, it is entirely possible that we will not see a decision until the first half of 2018. Whatever the outcome, an appeal to the Full Bench of the Federal Court would then seem to be a virtual certainty, with a subsequent application for leave to appeal to the High Court also being on the cards.
As I see it, Sequenom is in a considerably better position in Australia than (as things turned out) it was in the US. However, there could be a very long road ahead, and anything can happen in the course of complex and protracted litigation.
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