Ariosa Diagnostics, Inc. v. Sequenom, Inc.[1]  - Another Blow to the Patentability of Diagnostic Method Claims

The question of what constitutes patentable subject matter lies in an uncertain and evolving area of U.S. patent law, primarily due to three recent U.S. Supreme Court decisions: Alice Corp. Pty. Ltd. v. CLS Bank Int'l, 134 S. Ct. 2347 (2014); Ass'n for Molecular Pathology v. Myriad Genetics, Inc., 133 S. Ct. 2107 (2013); and Mayo Collaborative Servs. v. Prometheus Labs., Inc., 132 S. Ct. 1289 (2012). In light of these rulings, the federal courts, U.S. Patent and Trademark Office, and patent practitioners are all struggling to apply new legal principles of patent eligibility, often with respect to patent claims that were drafted and prosecuted under a very different interpretation of the law. Claims directed to diagnostic methods seem particularly vulnerable, and were the subject of a case decided June 12, 2015 by the U.S. Court of Appeals for the Federal Circuit in Ariosa Diagnostics, Inc. v. Sequenom, Inc.

The Ariosa court considered the patentability of claims directed to methods of detecting fetal nucleic acid in the plasma or serum of a pregnant woman. The claims were based on the indisputably groundbreaking discovery that cell-free fetal DNA (cffDNA) is present in maternal plasma or serum, a blood component that theretofore had been routinely discarded as waste. Detection of cffDNA makes it possible to conduct prenatal diagnoses of genetic defects with a simple blood test of the pregnant mother. Prior to this innovation, such testing was only achievable through invasive means, such as amniocentesis which poses risks to both the mother and fetus. The inventors published their discovery in a 1997 journal article that has since been cited over a thousand times.

In 2001, the invention was patented as a diagnostic method in U.S. Patent No. 6,258,540 and then subsequently commercialized by Sequenom, the exclusive patent licensee, as the MaterniT21 test for prenatal diagnosis of fetal DNA. Sequenom also threatened claims of patent infringement against Ariosa and two other makers of competitive diagnostics, all of which filed declaratory judgment actions against Sequenom that were later consolidated into a single lawsuit.

District Court Decision: All of the independent claims at issue in the lawsuit were distilled down by the District Court to two basic steps: (i) amplifying cffDNA in the blood component of interest (serum, plasma, or a non-cellular blood fraction); and (ii) detecting cffDNA. The dependent claims included additional details of how these steps can be performed – e.g., amplification by polymerase chain reaction or detection by a sequence specific probe.

The U.S. District Court for the Northern District of California began its claim analysis by quoting 35 U.S.C. § 101, the statute that defines eligible subject matter, and reviewing several Supreme Court decisions concerning the judicial exceptions to this statute. Section 101 states:

Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title..

For over 150 years, the Supreme Court has repeatedly held that laws of nature, natural phenomena, and abstract ideas (e.g., bacterial species, mathematical formulas, methods of hedging risk, data correlations, naturally occurring DNA, etc.) cannot themselves be patented; and that “[i]f there is to be invention from such a discovery, it must come from the application of the law of nature to a new and useful end.”[2] Even if a judicial exception such as a mathematical formula is applied for a narrow purpose, it can still be unpatentable if the only novel feature of the claimed application is the formula itself.

This point is slightly better understood by comparing the Ariosa District Court’s discussion of two Supreme Court cases involving claims to mathematical formulas – Parker v. Flook, 437 U.S. 584 (1978) and Diamond v. Diehr, 450 U.S. 175 (1981). In Flook, claims to a method of using a mathematical formula to update alarm limits in response to temperature data were found unpatentable because the only difference between conventional alarm limit updating and the claimed method was the use of the formula. In contrast, claims in Diehr directed to a method of using a mathematical formula (the Arrhenius equation) to calculate cure time in a rubber molding process were found patentable because the claims did not preempt others from using the formula in different applications, called for an article to be transformed to a different state, and arguably included other novel aspects beyond the formula itself.

The Ariosa District Court also reviewed the Supreme Court’s recent Mayo and Myriad decisions. In Mayo, claims to a method of using a data correlation to determine if a drug dose is toxic or ineffective based on certain metabolite levels measured in a patient after drug administration were found unpatentable because they recited a law of nature in the context of conventional patient dosage titration routinely performed by doctors. In Myriad, claims to isolated sequences of two genes, mutations of which substantially increase the risks of breast and ovarian cancer, were found unpatentable because the Court considered naturally occurring DNA to be a product of nature even when isolated from its natural state. The Myriad Court did, however, hold that claims to synthetically created cDNA were patentable, essentially because such sequences are not found in nature.

Returning to the facts of Ariosa, the District Court characterized the claims at issue as methods of detecting a naturally occurring phenomenon (cffDNA in maternal plasma or serum), and considered whether any additional elements transformed the claims into something significantly more than a claim to the naturally occurring phenomenon itself – i.e., the District Court sought to identify an “inventive concept” other than the presence of cffDNA in maternal plasma or serum. Sequenom admitted that amplifying and detecting are both routine techniques, and thus not the basis for the invention. Instead, Sequenom argued that it was the use of maternal plasma or serum that was inventive because this material had previously been considered waste and not a potential source of cffDNA. The court disagreed with this reasoning, and concluded that using a newly discovered natural phenomenon does not render a claim patentable if that use is the only innovation in the claims, as the court considered it to be in Ariosa.

Additionally, in response to Sequenom’s argument that the claims do not preempt others from using different methods of detecting cffDNA, the court found the alternative methods to be commercially unviable, which was sufficient to effectively preempt all methods of detecting cffDNA and thus all uses of the natural phenomenon. Ultimately, the District Court held the claimed subject matter unpatentable.

Federal Circuit Decision: On appeal, a three-judge panel at the Federal Circuit unanimously affirmed the District Court decision. In arriving at this conclusion, the Federal Circuit relied heavily on the Supreme Court decision in Mayo and its two-step framework for assessing patent eligibility. Following the Mayo analysis, the Federal Circuit first determined whether the claims were directed to a patent-ineligible concept, concluding that the answer is yes – the claimed method “begins and ends with a natural phenomenon” and  is “generally directed to detecting the presence of a naturally occurring thing.” In the second step, the Federal Circuit considered whether the claims contained an inventive concept by ascertaining if the additional steps in the claimed method were new and useful. According to the Federal Circuit, since methods for amplifying and detecting cffDNA are well-understood and routine, the only new and useful subject matter in the claims was the discovery of the presence of cffDNA in maternal plasma or serum – i.e., the natural phenomenon itself, according to the Federal Circuit. Consequently, the court affirmed that the claimed subject matter is not patentable. The Federal Circuit supported its decision by referencing the principle of preemption, which it cited as the basis for the Supreme Court’s judicial exceptions to patentability, and asserting that “patent claims should not prevent the use of the basic building blocks of technology.”

In a single judge concurrence, Judge Linn joined in the court’s decision, but only because he felt “bound by the sweeping language of the test set out in Mayo.” In Judge Linn’s view, the claimed invention deserved patent protection but was blocked by the Mayo “Supreme Court’s blanket dismissal of conventional post-solution steps,” which disregarded the recitation of all process steps routinely performed by those in the field. According to Judge Linn, Mayo left no room to distinguish the facts of Ariosa, in which the use of maternal plasma was a breakthrough since that material had been routinely discarded before the claimed invention. And although amplification and detection were routine techniques, they had never before been conducted on maternal plasma or serum in a method of detecting cffDNA. Nevertheless, Mayo precluded a finding of patentability, according to Judge Linn.

Conclusion: Going forward, patent applicants interested in pursuing diagnostic method claims may benefit from drafting claims that include features directed to a transformation of material, the use of non-naturally occurring components, and/or the use of non-conventional techniques, steps or sequences of steps. Additionally, the Ariosa decision, and particularly the concurrence, suggest that legislation may be the only way to reign in the scope of the Supreme Court’s most recent decisions on patent eligible subject matter. Accordingly, patent applicants may also benefit from filing continuation applications on their most important cases in order to maintain pendency if and when such legislation is passed.