The United States Supreme Court has denied Sequenom’s petition to review decisions by lower courts in which its patent directed to non-invasive prenatal screening was held to be invalid.
Many in the biotech and software industries hoped Sequenom’s petition would serve as a vehicle for the Supreme Court to step back from the strong language of Mayo v Prometheus (Mayo), a decision which has led to rejection and invalidation for many. The denial of the petition by the Supreme Court has effectively put an end to any such hope, at least in the short term.
Mayo concerned a dispute between Mayo Collaborative Services and Prometheus Laboratories over a diagnostic test.
Prometheus was the exclusive licensee of two US patents (6,355,623 and 6,680,302) directed to the use of thiopurine drugs in the treatment of autoimmune diseases. Different people metabolize these drugs differently. It is therefore difficult to get the dosage of these drugs right. US patent 6,355,623 detailed how to properly treat patients using thiopurine, the method including an administering step in which a doctor would administer the drug to the patient, a determining step in which the doctor measures metabolite levels in the patient’s blood, and a step to either increase or decrease the dosage based on the results. The diagnostic tests sold by Prometheus were based on this method. Mayo bought and used these kits until 2004, when it decided to offer its own diagnostic tests. Not surprisingly, Prometheus sued for infringement. Mayo responded by claiming the patents were invalid.
The dispute between Mayo and Prometheus reached the Supreme Court who held that the correlation between the naturally-produced metabolites of thiopurine drugs and therapeutic efficacy and toxicity was an unpatentable "natural law". The Court also stated that “… (1) a newly discovered law of nature is itself unpatentable and (2) the application of that newly discovered law is also normally unpatentable if the application merely relies upon elements already known in the art."[i]
The decision of the Supreme Court was controversial. Many felt it contained broad, sweeping assumptions with little critical analysis and thus, unclear conclusions. Nonetheless, the case has since been applied to hold invalid other patents directed to diagnostic methods. And this is where Sequenom fits into the picture.
Sequenom was an exclusive licensee to US patent 6,258,540 which was directed to a method of using cell-free fetal DNA (cffDNA) circulating in maternal plasma (cell-free blood) to diagnose fetal abnormalities. The method was based on the newly discovered natural phenomenon that cffDNA circulating in maternal plasma includes the presence of paternally inherited cffDNA. The method included the steps of amplifying and then detecting paternally inherited DNA from the plasma sample. Sequenom launched a test based on this method. Many other companies including Ariosa Diagnostics, Inc began to market similar tests and cut prices. A law suit ensued in which infringement was alleged and the validity of US patent 6,258,540 was called into question.
On application of the Supreme Court decision in Mayo, a majority of the Federal Circuit concluded that (1) the claims of US patent 6,258,540 were “directed to a patent-ineligible concept” because the “method begins and ends with a natural phenomenon” (i.e., cffDNA) and (2) the claimed method did not “‘transform’ the claimed naturally occurring phenomenon into a patent-eligible application” of the phenomenon.
The majority reasoned that the technology for amplifying and detecting DNA was already well known and generally used to detect DNA. Consequently, the claimed method did not include new and useful process steps. Rather, it added only “well-understood, routine, and conventional activity” to the natural phenomenon discovered, that of paternal DNA in a mother’s plasma originating from the fetus.
Senior Judge Linn concurred separately but with a critical assessment of the Supreme Court’s decision in Mayo. He felt that there was no reason “in policy or statute” why the claims of US patent 6,258,540 were not patent eligible. However, he was bound by the sweeping language of the test set out in Mayo to concur.
Sequenom sought a rehearing but was denied this on 15 December 2015. So, on 21 March 2016, Sequenom filed a petition for review of the invalidity ruling. We now know that this too has been denied.
Where to from here?
The petition provided the Supreme Court with an opportunity to differentiate a meritorious invention like that described in US patent 6,258,540 from that held to be patent-ineligible in Mayo. In Mayo, the natural phenomenon (the differential metabolism of thiopurine drugs and consequential impacts on dosing considerations and patient care) was well known. In contrast, the presence of paternally inherited cffDNA in maternal plasma was a newly discovered phenomenon. US patent 6,258,540 was an attempt to claim useful applications of the phenomenon.
The Supreme Court’s decision to refuse Sequenom’s petition equates to a determination that the bounds of the Mayo decision need no further clarification. Thus, the Court has refused to make any bright line distinctions between newly discovered natural phenomena and what is already known, which would have lent a degree of certainty to patent eligibility of diagnostic methods.
In the words of Sequenom CEO Dirk van den Boom, “the Supreme Court missed an ideal opportunity to clarify patent eligibility criteria not only to protect the significant investments made by Sequenom but also other innovative organisations to advance the standard of patient care and treatment.”[ii]
Four cases involving molecular diagnostics have come before the Federal Circuit since Mayo. In all cases, the challenged claims have been invalidated as a result of Mayo. While this trend is likely to continue with the Supreme Court’s denial of Sequenom’s petition, companies should not assume that new diagnostic methods they have developed cannot be patented in the United States. Patent protection is still a possibility in the US and must be assessed on a case-by-case basis. In May 2016, the U.S. Patent and Trademark Office released specific life science examples to supplement its Interim Guidance on Subject Matter Eligibility (2014). These examples provide some guidance on what types of diagnostic methods might be allowable. The Federal Circuit has also just released a favourable decision which gives more hope and some clarity around the sorts of biotech claims that might be allowable; more on this soon. And, don’t underestimate the skill of a good patent attorney in overcoming or avoiding some of the road blocks.
We recommend seeking advice before making any commercial decision to file (or not) a patent application for a new diagnostic method. A skilled patent attorney will be able to help companies navigate the currently turbulent waters on the path to achieving grant.