Isolated DNA: unpatentable. Synthetic cDNA: patentable.
In the much awaited Myriad decision (Association for Molecular Pathology v Myriad Genetics Inc) on the patentability of gene sequences, the US Supreme Court unanimously held that a naturally occurring DNA segment is a 'product of nature' and is not patentable subject matter merely because it has been isolated. However, it was held that cDNA is patentable subject matter because it is not naturally occurring - it is distinguishhable from the natural DNA.
This decision is a significant change in US patent law and reverses the US Patent and Trade Mark Office's (USPTO's) practice of granting patents on naturally occurring substances as long as they are 'isolated' from nature.
As discussed below, we are still faced with uncertainties over the patentability of proteins and other naturally occurring substances and what constitutes sufficient modification for a sequence to be considered patentable subject-matter. It seems that we need to wait and see how US practice develops. In the meantime, below we suggest some courses of actions which you may wish to consider at this stage.
Myriad Genetics Inc (Myriad) obtained several patents after determining the precise location and sequence of the BRCA1 and BRCA2 genes – mutations of which can significantly increase the risk of breast and ovarian cancer. Myriad did not create or alter the genetic information encoded by these genes.
Some of the claims of some of Myriad's patents were challenged by the Association for Molecular Pathology (AMP).
The District Court held that the challenged claims were invalid because they covered products of nature. On appeal, this decision was reversed with the Federal Court finding that both isolated DNA and cDNA was patentable subject matter. Whilst the Federal Court judges were unanimous concerning the patentability of cDNA, the judges were not unanimous with regard to the patentability of isolated DNA.
The decision was then appealed to the US Supreme Court which, as mentioned above, has reversed the Federal Court's decision in part. In this case, the US Supreme Court considered nine composition claims from three of Myriad's patents.
Under US patent practice (35 USC paragraph 101) laws of nature, natural phenomena and abstract ideas are not patentable. The US Supreme Court considers that they are basic tools of scientific and technological research that lie beyond patent protection and a balance needs to be created between "incentives that lead to creation, invention and discovery" and "impeding the flow of information which might permit, indeed spur, invention".
The question posed was whether Myriad's patents claim a "new and useful composition of matter" or "a naturally occurring phenomenon".
Two previous judicial decisions (Diamond v Chakrabarty and Funk Brothers Seed Co v Kalo Inoculant Co) have influenced the Supreme Court in this case.
Chakrabarty claimed a bacterium which had been modified so that it contained four plasmids which enabled it to breakdown components of crude oil. In this case, the Supreme Court held that non naturally occurring genetically modified microorganisms are patentable.
Funk Brothers Seed Co claimed a mixture of naturally occurring strains of nitrogen fixing bacteria to help leguminous plants take nitrogen from the air and fix it in the soil.
The Supreme Court held that in this case the composition was not patentable subject-matter because the bacteria had not been altered in any way.
Isolated DNA claims
Myriad's patents describe the extensive efforts which they had taken to identify the BRCA1 and BRCA2 genes.
The Supreme Court held that extensive effort alone is not sufficient. Moreover, isolating the DNA from the genome, thereby creating a non-naturally occurring molecule, does not save the claims. Further, the past practice by the USPTO of awarding gene patents is not sufficient reason to hold that isolated DNA is patentable subject matter.
In summary, the Supreme Court held that a naturally occurring DNA segment is a "product of nature" and is not patentable subject matter merely because it has been isolated.
The Supreme Court noted that the creation of cDNA results in an exon only molecule which is not naturally occurring. Therefore cDNA is patentable subject matter because it is not naturally occurring.
An exception to this is the situation where the DNA does not have an intervening intron which is removed when creating the cDNA. Here the cDNA is indistinguishable from the natural DNA and therefore is not patentable subject matter. This point could impact on claims to short cDNA fragments.
In this decision, the Supreme Court did not consider any method claims or new applications of the BRCA1 and BRCA2 genes (eg, diagnostics). Further, the Supreme Court did not consider the patentability of nucleotide sequences in which the order of naturally occurring nucleotides has been altered.
It is unclear from this decision alone as to the minimal number of modifications and the nature of the modifications which need to be made to a sequence for it to be considered not naturally occurring and therefore patentable subject matter.
Further, the impact of this decision on other naturally found biological molecules (such as antisense DNA, microDNA, siRNA, viruses, proteins, antibodies and stem cells) has yet to be established.
Changes to USPTO practice
The USPTO has issued preliminary guidance to its examiners.
Unsurprisingly, in view of the Supreme Court's decision, examiners have been instructed to reject "product claims directed solely to naturally occurring nucleic acids or fragments thereof, whether isolated or not". However, claims clearly directed to "non-naturally-occurring nucleic acids, such as a cDNA or a nucleic acid in which the order of the naturally-occurring nucleotides has been altered (eg, man made variant sequence)" remain patentable subject matter.
The USPTO will issue more comprehensive guidance to examiners at a later date.
Until the USPTO issues this further guidance, it seems that we will be faced with uncertainty on how method claims and claims to proteins and other naturally occurring biomolecules will be treated. We may find that different examiners will take different stances on the same facts. Further, we may find that we need to wait for further developments in US case law.
On the day that the Supreme Court issued its decision, a number of companies announced that they would provide genetic diagnostic testing for the BRCA1 and BRCA2 genes. Interestingly, Myriad has now started infringement proceedings against two of these companies, Ambry Genetics and Gene by Gene.
In brief, amongst the claims which Myriad alleges are infringed, are isolated DNA claims, claims directed to single-stranded DNA primers and claims directed to methods for screening/detecting a germline alteration of a BRCA1/BRCA2 gene.
These will most certainly be cases to watch.
No change to EPO practice
This development in the US should have no effect on the current situation in Europe where gene sequences isolated from their natural environment can be patented (Directive 98/44/EC) if the sequences fulfil the requirements of patentability (novelty, inventive step, industrial applicability, etc). Under European patent practice, the function of the gene must be known and disclosed in the specification in order to meet with industrial applicability requirements. It is interesting to note that, in Europe, a claim directed to a DNA sequence may only cover that sequence when it is "performing" its stated function (CJEU Monsanto Technology LLC v Cefetra BV and others).
Actions to take
There has been much speculation and debate about the impact of this decision on the biotechnology industry.
Some commentators suggest that the impact on future biotechnology business interests in the US will not be as restrictive as initially thought by many with the claims of pending applications being drafted with this decision in mind. Nevertheless, this decision will undoubtedly undermine the validity of patents with isolated DNA claims affecting both the business plans of patentees and potential infringers.
Patentees may find that some of their patents are invalid at least in part. Potential infringers may find that they now have more freedom in which to operate.
It will take some time before we can truly evaluate the impact of this decision on US practice. In the meantime, we suggest you review your US cases to determine if you have any applications or patents with 'isolated DNA' claims. If you are concerned about any of your US cases then you may wish to contact your attorney for advice.
Pending US applications with 'isolated DNA' claims
Obviously, if you have pending applications with claims to 'isolated DNA' then we would suggest amending these claims in light of the Myriad decision.
US patents with 'isolated DNA' claims
If there is a pending sister divisional or continuation application to a US patent which has 'isolated DNA' claims then you could consider pursuing 'synthetic DNA' claims (if such claims have not already granted) in a divisional or continuation application.
If there are no further pending US applications then you could consider using the US reissue procedure in order to strengthen key US patents with 'isolated DNA' claims. Under the US reissue procedure, a narrowing amendment can be filed at any time during the life of the patent and a broadening amendment may be filed within two years after the patent is granted. Nevertheless, there is no requirement for you to take such action because of the Myriad decision.
US freedom to operate opinions/licences/infringement actions
Since 'isolated DNA' claims are no longer valid, you might wish to review any US freedom to operate opinions you may have obtained to determine if any of your business plans require alteration.
Similarly, you may need to review any licensing arrangements you have made or are considering making.
Further, you should review any infringement actions which you have made, that you were considering taking or which have been made against you.
Supreme Court decision of 13 June 2013: http://dycip.com/opinionmyriad0613
D Young & Co article, 2 June 2010, author Anthony Albutt, 'ECJ Considers Monsanto Technology LLC v Cefetra BV Case Following Advocate General Mengozzi Opinion of March 2010': http://dycip.com/monsantocefetra