Ariosa Diagnostics v. Sequenom: A Groundbreaking Diagnostic Falls to the Mayo Rule

Ariosa Diagnostics, Inc. v. Sequenom, Inc., 788 F.3d 1371 (Fed. Cir. 2015), is the case that showed how far Mayo reached into diagnostic medicine. Sequenom held a patent on a genuinely important discovery: that cell-free fetal DNA (cffDNA) circulates in a pregnant woman’s blood, permitting prenatal genetic testing without the risks of invasive procedures like amniocentesis. Yet in an opinion by Judge Reyna, the Federal Circuit held the claims patent-ineligible under 35 U.S.C. § 101, reasoning that they were directed to a natural phenomenon and added only conventional detection steps. The decision — accompanied by a reluctant concurrence and later an unusually pointed denial of en banc review — became the emblem of concern that the Mayo/Alice framework invalidates valuable diagnostic inventions.

At a glance

• Case: Ariosa Diagnostics, Inc. v. Sequenom, Inc., 788 F.3d 1371 (Fed. Cir. 2015), Docket Nos. 2014-1139, 2014-1144
• Court: U.S. Court of Appeals for the Federal Circuit, on appeal from the Northern District of California
• Decided: June 12, 2015
• Opinion: Judge Reyna, for the panel (joined by Judge Wallach); Judge Linn concurring
• Subject matter: Methods for detecting paternally inherited cell-free fetal DNA in maternal blood or serum for noninvasive prenatal diagnosis (U.S. Patent No. 6,258,540)
• Holding: Claims directed to detecting a natural phenomenon using well-understood, routine, and conventional techniques lack an inventive concept and are patent-ineligible under § 101

The discovery and the claims

For years, prenatal genetic testing meant invasive sampling — amniocentesis or chorionic villus sampling — that carried a risk of harm to the fetus. In the 1990s, the inventors named on Sequenom’s ‘540 patent discovered that cffDNA, DNA of fetal origin, is present in the plasma and serum of pregnant women, portions of maternal blood that had previously been discarded as medical waste. That discovery meant a fetus’s paternally inherited genetic material could be detected from a simple maternal blood draw, avoiding the risks of invasive procedures entirely.

The ‘540 patent claimed methods of using this insight. The representative claims recited amplifying the cffDNA found in a maternal serum or plasma sample — for example, by the polymerase chain reaction — and then detecting the paternally inherited fetal DNA. Sequenom’s commercial test built on the method transformed noninvasive prenatal testing. Ariosa and other competitors sought declaratory judgments of noninfringement and invalidity; the district court granted summary judgment that the claims were patent-ineligible, and Sequenom appealed.

Applying Mayo’s two steps

The Federal Circuit analyzed the claims under the two-step Mayo/Alice framework. At step one, the court asked whether the claims were directed to a patent-ineligible concept. It concluded they were. The existence and location of cffDNA in maternal blood is a natural phenomenon — Sequenom did not create or alter the fetal DNA; it discovered that the DNA is naturally present in the mother’s plasma. “The method begins and ends with a natural phenomenon,” the court observed, so the claims were directed to naturally occurring matter.

At step two, the court searched for an inventive concept — something in the claims, beyond the natural phenomenon itself, sufficient to transform the claim into a patent-eligible application. It found none. The steps the claims added to the natural discovery — amplifying DNA and detecting it — were, on the record, well-understood, routine, and conventional activities that scientists had long performed. The patent itself described the amplification and detection techniques as known in the art. Applying Mayo Collaborative Services v. Prometheus Laboratories, Inc., 566 U.S. 66 (2012), the court held that appending conventional steps, specified at a high level of generality, to a natural phenomenon does not supply an inventive concept. The claims therefore failed step two.

Sequenom argued that no one had previously used the discarded maternal plasma to detect fetal DNA, so the specific application was new. The court answered that the novelty of the natural discovery does not itself confer eligibility: what matters at step two is whether the additional steps are inventive, and here they were conventional. The court also rejected the argument that the claims did not improperly preempt the natural phenomenon, explaining that while preemption underlies the eligibility exceptions, the absence of complete preemption does not make an otherwise ineligible claim eligible once Mayo’s two-step test is failed.

A concurrence written in protest

The most striking feature of Ariosa is Judge Linn’s concurrence. He agreed the panel was bound to invalidate the claims, but only because he believed Mayo’s “sweeping language” compelled that result. Judge Linn wrote that the invention was a genuine breakthrough — it “effectuated a practical result and benefit not previously attained,” transforming prenatal care by making testing safe and noninvasive — and that in his view it was “deserving of patent protection.” He stressed that the combination the inventors claimed had never been done: “the amplification and detection of cffDNA had never before been done” from maternal plasma, because the medical community had discarded that plasma as waste.

Judge Linn’s objection was that Mayo directs courts to disregard exactly that kind of inventive application. Mayo had refused to credit the conventional post-solution steps in Prometheus’s diagnostic claims, and its logic, mechanically applied, swept in Sequenom’s method too — even though, Linn argued, the two inventions differed in their contribution to the art. The concurrence became a rallying point for critics who contended that the eligibility doctrine had grown detached from the purpose of the patent system. When the full court later declined to rehear the case en banc, several judges wrote separately to voice similar unease while acknowledging that only the Supreme Court could recalibrate the Mayo framework.

Open questions

Ariosa crystallized a debate that remains unresolved. Does the Mayo/Alice framework, as applied to diagnostics, invalidate the very inventions the patent system should reward — methods that translate a newly discovered natural relationship into a life-changing test? Where is the line between an ineligible “discovery of a natural phenomenon plus conventional detection” and an eligible “new and useful application” of that phenomenon? The Federal Circuit’s later diagnostic decisions have continued to struggle with these questions, and repeated calls — from judges, the USPTO, and commentators — for the Supreme Court or Congress to clarify § 101’s application to diagnostics have not yet produced a definitive answer. Ariosa stands as the leading illustration of the tension.

Implications

• Detecting a natural phenomenon is not enough. A claim that discovers a naturally occurring correlation or substance and then applies only conventional detection steps is likely ineligible, however important the discovery.
• The inventive concept must lie in the added steps. Novelty in the underlying natural discovery does not satisfy step two; the claim’s additional elements — the how — must be more than routine and conventional.
• Draft diagnostics with a technological hook. Where possible, claim a specific, unconventional technique, a new laboratory method, or a treatment step, rather than a bare “detect the natural marker” method.
• The doctrine’s reach is contested. Even judges who apply Ariosa have criticized the result; practitioners should watch for legislative or Supreme Court intervention that could reshape diagnostic eligibility.

Frequently asked questions

Why did Sequenom’s patent fail under Section 101? Applying Mayo v. Prometheus, the Federal Circuit held the claims were directed to a natural phenomenon — the presence of paternally inherited cell-free fetal DNA (cffDNA) in maternal blood — and that the additional steps of amplifying and detecting that DNA were well-understood, routine, and conventional. With no inventive concept beyond the natural discovery, the claims were ineligible.

Was the invention actually valuable or non-obvious? Yes, and the court acknowledged as much. The method enabled safe, noninvasive prenatal testing where earlier methods risked harm to the fetus. But the Federal Circuit held that practical value and even revolutionary utility do not, by themselves, make a claim eligible if it is directed to a natural phenomenon applied through conventional steps.

What did the concurrence say about the case? Judge Linn concurred only because he felt bound by the Supreme Court’s Mayo decision. He wrote that the invention was truly groundbreaking and deserving of protection, and that Mayo’s sweeping language forced an unsound result by disregarding the novelty of combining a newly discovered natural phenomenon with detection steps that had never before been applied to it.

Authorities and sources

• Ariosa Diagnostics, Inc. v. Sequenom, Inc., 788 F.3d 1371 (Fed. Cir. 2015), Docket Nos. 2014-1139, 2014-1144 (decided June 12, 2015). BitLaw full-text opinion; Patent Docs case report.
• Judge Reyna’s authorship and Judge Linn’s concurrence corroborated by Wikipedia: Ariosa v. Sequenom.
• Governing framework from Mayo Collaborative Services v. Prometheus Laboratories, Inc., 566 U.S. 66 (2012), via Justia.