The United States Court of Appeals for the Federal Circuit issued its decision in Ariosa Diagnostics Inc. et al. v. Sequenom Inc. (PDF), case number 14-1139 and concluded, in view of the framework established by the U.S. Supreme Court's Myriad[1] and Mayodecisions, that Sequenom's U.S. patent number 6,258,540 for prenatal DNA tests is not patent-eligible because it is directed to a natural phenomenon[2]. This decision is likely to have significant long-term implications and has the potential to undermine the validity of many existing U.S. patents in biotechnology, particularly in the fields of personalized medicine and medical diagnostics.

In 1996 two scientists, Drs. Lo and Wainscoat, discovered that cell-free fetal DNA (cffDNA) in maternal plasma and serum. cffDNA circulates freely in the blood stream of a pregnant woman. Some of that cffDNA is paternally inherited and the two scientists applied known laboratory techniques to detect that paternally inherited DNA and to determine fetal characteristics such as gender and certain genetic defects. The scientists' discovery was surprising and unexpected considering that maternal plasma was routinely discarded by investigators studying non-invasive prenatal diagnosis using fetal cells in maternal blood. Drs. Lo and Wainscoat's major contribution was published in Lancet in 1997 and their publication has since been cited over a thousand times. The invention is commercialized by Sequenom as its MaterniT21® test as a noninvasive prenatal test that detects fetal chromosomal abnormalities such as trisomies 21, 18 and 13. Therefore, the invention created an alternative for prenatal diagnosis of fetal DNA that avoids the risks of widely-used techniques that took samples from the fetus or placenta. The claims of the '540 patent recite methods of using cffDNA and making a diagnosis of certain fetal characteristics by amplifying the cffDNA obtained from the maternal serum or plasma sample.

Applying Mayo, the Federal Circuit held all the claims in suit ineligible. Applying the first part of the eligibility test set in Mayo, the Court noted that cffDNA was naturally occurring and circulated freely in the blood stream of a pregnant woman and, as a result, the existence of cffDNA in maternal blood was a natural phenomena. Since the method ended with paternally inherited cffDNA, which was also a natural phenomena, the method began and ended with natural phenomenon. Regarding the second part of the test, because methods of amplifying DNA were well-known at the time of the invention, the Court determined that the method claims did not result in an inventive concept that transformed the natural phenomenon into a patentable invention. According to the Court: "The method at issue here amounts to a general instruction to doctors to apply routine, conventional techniques when seeking to detect cffDNA. Because the method steps were well-understood, conventional and routine, the method of detecting paternally inherited cffDNA is not new and useful. The only subject matter new and useful as of the date of the application was the discovery of the presence of cffDNA in maternal plasma or serum".

At the end of the opinion, the Court addressed Sequenom's arguments that "before the '540 patent, no one was using the plasma or serum of pregnant mothers to amplify and detect paternally-inherited cffDNA". The Court agreed that Drs. Lo and Wainscoat's contribution was significant and that it revolutionized prenatal care but it, nevertheless, put aside these arguments in view of the Supreme Court comments in Myriad that "[g]roundbreaking, innovative, or even brilliant discovery does not by itself satisfy the 101 inquiry". The Federal Court stated: "While Drs. Lo and Wainscoat's discovery regarding cffDNA may have been a significant contribution to the medical field, that alone does not make it patentable. We do not disagree that detecting cffDNA in maternal plasma or serum that before was discarded as waste material is a positive and valuable contribution to science. But even such valuable contributions can fall short of statutory patentable subject matter, as it does here".

In a concurring opinion, Circuit Judge Richard Linn said he joined with his colleagues in invalidating the claims of the '540 patent only "because I am bound by the sweeping language of the test set out in Mayo". According to Judge Linn's concurrence, the Sequenom's invention is truly meritorious and the steps of the method were new because no one was amplifying and detecting paternally-inherited cffDNA using the plasma or serum of pregnant mothers. In his view, this case represents the consequence - perhaps unintended - of the broad language of the Mayo decision in depriving Sequenom from the patent protection it deserves and should have been entitled to retain: "Sequenom effectuated a practical result and benefit not previously attained, so its patent would traditionally have been valid" Judge Linn said. "But for the sweeping language in the Supreme Court's Mayo opinion, I see no reason, in policy or statute, why this breakthrough invention should be deemed patent-ineligible".

Comment: Although it clarifies several aspects of the patent-eligibility inquiry of Mayo, the decision will likely have significant long-term implications for patent eligibility, not only in biotechnology, but in other fields. In this case, the Federal Circuit has supported a highly restrictive interpretation of the test for patentability set in Mayo, indicating that the individual steps of the process must be new and useful. Considering that natural laws cannot be bypassed and that most inventions are based on rearrangements of known elements, it is getting more and more difficult to foresee what novel and inventive additional features might be required to transform an otherwise invalid claim in a patentable invention.