Three Reasons Why the Supreme Court Should Grant Cert in Critical Biotech Case

In Ariosa Diagnostics, Inc. v. Sequenom, Inc.,^[1] the Federal Circuit, relying on Mayo Collaborative Servs. v. Prometheus Labs., Inc.,^[2] held that diagnostic methods reciting novel steps of amplifying and detecting cell-free fetal DNA are not patent eligible because cell-free fetal DNA is a natural phenomenon and amplification and detection of DNA, in general, was “conventional.” Sequenom petitioned for a writ of certiorari, which was supported by almost two dozen amici briefs.^[3] 

Arent Fox filed an amici brief on behalf of the Wisconsin Alumni Research Foundation, the Indiana University Research and Technology Corporation, and San Diego Intellectual Property Law Association. Our brief focused on the following three errors in the Federal Circuit’s rationale.

First, the Federal Circuit misconstrued the meaning of the term “conventional” used in Mayo. In Mayo, the Court reviewed the patent eligibility of claims reciting a two-step method of optimizing therapeutic efficiency comprising first “administering” a drug providing 6-thioguanine (6-TG) to a subject, and second “determining” the level of 6-TG in the subject. Both of these steps were known in the prior art. The point of novelty lay in a “wherein” clause that set forth a correlation between levels of 6-TG in a subject and the need to increase or decrease the amount of drug subsequently administered. The Court held that the claims were not statutory because, other than the correlation, which is a law of nature, the method only involved “well-understood, routine, conventional activity previously engaged by researchers in the field.”^[4] Accordingly, the claimed method steps were “conventional,” i.e., already known in the prior art. 

Unlike Mayo, Sequenom involves claims that recite unconventional steps. Prior to the invention, researchers separated blood samples from pregnant women into cellular and non-cellular fractions, and discarded the non-cellular portion. The inventors of Sequenom’s patent, however, surprisingly discovered that fetal DNA was contained in the cell-free maternal serum and plasma, and applied known amplification and detection techniques to a subset of this DNA (i.e., paternally inherited DNA). Since the presence of cell-free fetal DNA in maternal serum and plasma was unknown, it was not “conventional” to amplify and detect such DNA. Accordingly, in stark contrast to Mayo, none of the instantly claimed method steps had ever been performed, let alone suggested by the prior art.

The Federal Circuit, relying on Mayo, held that the claims were non-statutory because methods of “amplifying” and “detecting” DNA were known in the art and thus conventional. In our brief, we contend the Federal Circuit took an overly broad view on the meaning of “conventional” within its eligibility analysis. Instead of asking whether the method employs techniques that were generally known, the proper inquiry under Mayo is to determine whether the specifically claimed steps — amplifying and detecting a paternally inherited nucleic acid from maternal serum or plasma — were conventional. They were not. Indeed, while the general techniques of amplifying and detecting DNA were known in the art, there is no dispute that such techniques had never been applied to paternally inherited nucleic acids from maternal serum or plasma. In fact, the court agreed that the inventors “combined and utilized man-made tools of biotechnology in a new way that revolutionized prenatal care.”^[5] Accordingly, the Federal Circuit erred by improperly expanding Mayo’s definition of “conventional” to encompass novel, i.e., unconventional, steps.

Second, the Federal Circuit ignored Supreme Court precedent that the application of an obvious solution to the cause of an unknown problem is a “new and useful” discovery deserving patent protection. In Eibel Process Co. v. Minn. & Ontario Paper Co.^[6],the Court reviewed the patent eligibility of paper making machines that used gravity to increase the flow of paper stock. Eibel discovered that existing paper machines produced defective paper because the paper stock and wire traveled at different speeds in the prior art machines. To solve this problem, Eibel simply increased the pitch of the wire so that, through gravity, the paper stock traveled at a faster speed corresponding to the wire’s speed. The Court of Appeals ruled against Eibel, holding that the invention was no more than a combination of the prior art and the “obvious” application of a natural principle.^[7] The issue presented by the Supreme Court was “whether Eibel’s discovery was invention rather than the mere obvious and simple application of known natural forces.”^[8] The Court held that “[t]he invention was not the mere use of a high or substantial pitch to remedy a known source of trouble,” but rather “the discovery of the source not before known, and the application of the remedy, for which Eibel was entitled to be rewarded in his patent.”^[9] 

Similarly in Sequenom, the invention is not merely the amplification and detection of a “known source” of fetal DNA. Rather, it is “the discovery of the source not before known,” i.e., maternal plasma and serum containing paternally inherited DNA, and “the application of the remedy,” for which the inventors are entitled to a patent.^[10] The inventors surprisingly discovered that fetal DNA was present in maternal plasma and serum—previously discarded as medical waste—and applied known techniques to the newly identified DNA. While it may have been obvious to perform these techniques once cell-free fetal DNA was discovered, Eibel confirms that the solution to an unknown problem is patent eligible even if the technique used in the solution was well known. Accordingly, under Eibel, the instant claims are statutory.^[11]

Finally, the Federal Circuit erred in failing to conduct a meaningful preemption analysis. The Supreme Court has made clear that preemption is “the concern that drives” the exclusion of natural phenomena from patent eligibility.^[12] The Federal Circuit concluded that any such “concerns” are “moot” because the claims failed the two-part Mayo test.^[13] We argued in our brief that the Federal Circuit’s preemption analysis was flawed because (1) it did not perform a preemption analysis similar to that done in Mayo; and (2) if it had, the court would have concluded that the claims do not tie up all future uses of cell-free fetal DNA. The claims do not merely recite the natural phenomena of cell-free fetal nucleic acids, or a general application of the phenomena. Rather, the claims are limited to methods that, at a minimum, amplify a paternally inherited nucleic acid from maternal serum or plasma—i.e., genetic material distinguishable from maternally inherited nucleic acids and a subset of all cell-free nucleic acids.  Accordingly, the natural phenomenon related to the invention is not preempted by the specifically claimed application. 

In sum, the Federal Circuit misapplied and ignored Supreme Court precedent by expanding the ineligibility doctrine to encompass unconventional methods. In doing so, it has unnecessarily excluded from patent protection a practical application of an important discovery, and threatens to eviscerate protection for other novel and potentially lifesaving applications of newly discovered scientific principles. Here, the invention provides physicians with the ability to diagnose fetal abnormalities using non-invasive techniques — a goal long sought by the scientific community. Tomorrow, it may be the discovery of a marker that enables early detection and treatment for a rare cancer. Without reasonable certainty of patent protection, biotechnology companies and research universities have little incentive to continue their valuable research. The Federal Circuit’s overly broad and inconsistent approach with the Supreme Court’s precedent, if left unchanged, will have a chilling effect on research and adversely affect the current and future state of healthcare in this country.