In Ariosa Diagnostics, Inc. v. Sequenom, Inc., Slip Op. 2014-1139, 2014-114 (Fed. Cir. June 12, 2015), the U.S. Court of Appeals for the Federal Circuit held that Sequenom’s U.S. Patent No. 6,258,540 (the ‘540 Patent) was invalid under 35 U.S.C. § 101, for failing to claim patent-eligible subject matter. The Court’s decision is yet another application of the U.S. Supreme Court’s recent interpretation of patent-eligibility and confirms the raised bar for patents claiming diagnostic methods – even for “ground-breaking” inventions.

The ‘540 Patent

The ‘540 Patent was awarded to inventors Yuk-Ming Dennis Lo and James Stephen Wainscot for “Non-invasive prenatal diagnosis.” The invention of the patent is based on the discovery that maternal blood contains cell-free fetal DNA (“cffDNA”) which can be used to determine fetal characteristics, such as gender and genetic defects. Appellant Sequenom commercialized the technology in its “MaterniT21” test. The test was an important improvement over then state-of-the art invasive techniques that took samples from the fetus or placenta.

Twenty-seven claims issued. Claims 1, 2, 4, 5, 8, 19-22, 24 and 25 of the ‘540 Patent were at issue in this appeal. Claims 1, 21, 24 and 25 are reproduced below.

1. A method for detecting a paternally inherited nucleic acid of fetal origin performed on a maternal serum or plasma sample from a pregnant female, which method comprises amplifying a paternally inherited nucleic acid from the serum or plasma sample and detecting the presence of a paternally inherited nucleic acid of fetal origin in the sample.

21. A method of performing a prenatal diagnosis, which method comprises the steps of:

(i) providing a maternal blood sample;

(ii) separating the sample into a cellular and a non-cellular fraction;

(iii) detecting the presence of a nucleic acid of foetal origin in the non-cellular fraction according to the method of claim 1;

(iv) providing a diagnosis based on the presence and/or quantity and/or sequence of the foetal nucleic acid.

24. A method for detecting a paternally inherited nucleic acid on a maternal blood sample, which method comprises: removing all or substantially all nucleated and anucleated cell populations from the blood sample, amplifying a paternally inherited nucleic acid from the remaining fluid and subjecting the amplified nucleic acid to a test for the Paternally inherited fetal nucleic acid.

25. A method for performing a prenatal diagnosis on a maternal blood sample, which method comprises  obtaining a non-cellular fraction of the blood sample  amplifying a paternally inherited nucleic acid from the non-cellular fraction  and performing nucleic acid analysis on the amplified nucleic acid to detect paternally inherited fetal nucleic acid.

Appellee Ariosa makes and sells a competing test – the “Harmony Test.” Similar to Sequenom’s MaterniT21 test, Ariosa’s test is a non-invasive test for prenatal fetal diagnosis. Co-Appellee Natera, Inc. also makes and sells a non-invasive test to confirm the paternity of a gestating fetus from fetal DNA in the mother’s blood. Diagnostics Center, Inc. is a licensee of Natera.

In response to letters threating claims of infringement, Ariosa, Natera and Diagnostics Center, Inc. each filed separate declaratory judgment actions alleging that they did not infringe the ‘540 Patent. Sequenom counterclaimed alleging patent infringement. During the first appeal to the Federal Circuit, the court declined to address the issue of whether the claims raised a substantial issue of patent-eligibility. After remand to the district court, appellees then alleged that the claims-in-suit were invalid under 35 U.S.C. § 101 for failing to claim a patent-eligible invention. The district court agreed, holding that the asserted claims of the ‘540 Patent were patent-ineligible for being directed to the natural phenomenon of paternally inherited cffDNA. The court also found that the additional elements of the claims (e.g., analyzing the samples) did not add enough to the natural phenomenon (cffDNA) to make the claims patent-eligible. The court further noted that the claimed processes also posed a risk of preempting the use of the natural phenomenon cffDNA. Sequenom disagreed and appealed.

Patent-Eligibility – Federal Circuit’s View

In analyzing the claims, the Federal Circuit looked to the U.S. Supreme Court’s interpretations of the judicial exceptions to patent-eligibility under Section 101 – laws of nature, natural phenomena, and abstract ideas as set forth in Alice Corp. v. CLS Bank Int’l, 234 S. Ct. 2347 (2014) and Mayo Collaborative Services v. Prometheus Laboratories, Inc., 132 S. Ct. 1289 (2012)(“Mayo”).

The court began its analysis by noting that all asserted claims are directed to a multistep method that starts and ends with cffDNA taken from a sample of maternal blood. The existence of cffDNA was undisputed by the parties to be a natural phenomenon. The claims, therefore, were determined to be directed to mattter that is naturally occurring.

The court then analyzed the steps of the method claims to determine if the steps as a whole, recite something more than the judicial exception itself. The court analogized the claims to those under consideration in Mayo, in that the steps of analyzing the cffDNA utilized well-understood, routine, and conventional activity at the time the invention was made. In the court’s view, the “only subject matter new and useful as of the date of the application was the discovery of the presence cffDNA in maternal blood or serum.” Slip Op. at page 11. This conclusion was supported by the patent’s specification, Sequenom’s declaration evidence, and the prosecution history of the patent.

The court also dismissed Sequenom’s arguments that the claimed methods should be patent-eligible because they do not preempt all uses of cffDNA. Sequenom argued that there are numerous other uses of cffDNA and other methods for analyzing cffDNA outside the scope of the patent claims. While the court acknowledged that the Supreme Court made clear that the principle of preemption is the basis for the judicial exceptions to patentability, it also summarily concluded that the “absence of complete preemption does not demonstrate patent eligibility.” Slip Op. at page 14. Importantly, the court stated that “[w]here a patent’s claims are deemed only to disclose patent ineligible subject matter under the Mayo framework, as they are in this case, preemption concerns are fully addressed and made moot.” Slip Op. at pages 14-15.

What Now?

The Federal Circuit’s decision is yet another in a recent line of decisions holding diagnostic claims patent-ineligible under 35 U.S.C. § 101 (e.g., In re BRCA1- and BRCA2-Based Hereditary Cancer Test Patent Litigation Slip Op. 2014-1361, -1366, (Fed. Cir. Dec. 17, 2014), wherein the Federal Circuit determined that diagnostic claims to screen for alterations in the BRCA gene also were not patent-eligible because they claim nothing more than a judicial exception, in this case an abstract idea). In view of the Supreme Court’s Mayo decision, the Federal Circuit’s application of Mayo and holdings invalidating diagnostic method claims, there has been little guidance on what remains patent-eligible when a claimed method is directed to the analysis of a naturally occurring product such as a biological specimen. Therefore, patent applicants may need to pivot and look to whether the diagnostic method analyzes an altered, naturally occurring product, and seek patent protection on the modified or altered product itself.