On June 12, 2015, the Federal Circuit issued its eagerly anticipated decision in Ariosa v. Sequenom,1 which assessed the subject matter eligibility of claims directed to a diagnostic method under 35 U.S.C. § 101. The case involved U.S. Patent No. 6,258,540 ("the '540 patent") directed to methods of non-invasively measuring cell-free fetal DNA ("cffDNA") in maternal plasma and serum. Despite the discovery of unique diagnostic benefits in what had formerly been considered waste material, the court affirmed the invalidity of the asserted claims of the '540 patent, explaining that "[w]here claims of a method patent are directed to an application that starts and ends with a naturally occurring phenomenon, the patent fails to disclose patent-eligible subject matter if the methods [used to measure a sample] themselves are conventional, routine and well understood applications in the art."2 Ariosa repeats the Supreme Court's caution that "[g]roundbreaking, innovative, or even brilliant discovery does not by itself satisfy the § 101 inquiry."3 The decision adds to a spate of recent cases marking a shift in the law on patentable subject matter, a trend that started with the Supreme Court decisions in Mayo Collaborative Services v. Prometheus Laboratories, Inc.,4 and Association for Molecular Pathology v. Myriad Genetics, Inc.,5and continued more recently in Alice Corp. v. CLS Bank International.6 Here, we examine post-Alice USPTO guidance and case law addressing the subject matter eligibility of natural products and phenomena.
Shortly after Alice was decided, the USPTO issued a revised Guidance to examiners addressing patent subject matter eligibility.7 The Office emphasized the two-step analysis of Alice, requiring examiners to determine if a claim is "directed to" a natural law or product of nature by looking for "markedly different characteristics," and if no such marked difference is identified, to assess whether the claim recites additional elements that amount to "significantly more" than the judicial exception. The Guidance requires examiners to apply this analysis to all claims (product and process) that contain a judicial exception. The Office acknowledged the possibility that a marked difference could be shown by structure, function, or "other pertinent properties." And the Office emphasized that claims that clearly do not seek to "tie up" a judicial exception and preempt others from using it should be subject to a "streamlined" eligibility analysis. Various hypothetical examples were provided by the Office, and in several cases the conclusions backed away from a broader position on ineligibility. For example, the Guidance indicates that probes linked to a generic label, combinations of natural products, and methods of treatment should be considered patent eligible. District courts have begun to take note of the revised Guidance, citing it as persuasive reasoning when assessing the patent eligibility of challenged claims.8
One day after the USPTO issued its revised Guidance, the Federal Circuit addressed the patent eligibility of natural products and correlations in Myriad Genetics, Inc. v. Ambry Genetics Corp ("Ambry").9 That case, an appeal of a district court's denial of a preliminary injunction, involved a series of previously unasserted claims from the BRCA1 and BRCA2 patents at issue in the earlier Myriad Supreme Court decision. The asserted claims related to, inter alia, nucleotide primers for amplifying the BRCA1and BRCA2 genes, as well as methods of diagnosing breast cancer by comparing a patient's BRCA genotype against a wild-type sequence. In Ambry, the court held that neither the primer claims nor the method claims were patent eligible.
Addressing the primer claims, the court concluded that the "primers before us are not distinguishable from the isolated DNA found patent-ineligible in Myriad and are not similar to the cDNA found to be patent-eligible."10 The court stated that the primer nucleotide sequences were identical to those of naturally occurring DNA, and further that the intended use of the primers mimicked the natural DNA function of base pairing with complementary sequences.11 Nor did the single-stranded nature of the primers render them patent eligible. Rather, the court analogized the preparation of single-stranded primers to the ineligible act of "separating [DNA] from its surrounding genetic material."12 As such, because Myriad's claimed primers shared sequences and base-pairing function with naturally occurring nucleic acids, they were directed to patent-ineligible subject matter.
In addressing the method claims, the Ambry court applied the two-step analysis outlined in Alice: (1) determine whether a claim is directed to a patent-ineligible concept such as a product of nature, natural law, or abstract idea, and if so, (2) determine whether the remaining elements of the claims, alone or in combination, are sufficient to transform the claims into patent-eligible applications. The court explained that the method claims at issue were directed to "a patent-ineligible abstract idea of comparing . . . and determining the existence of alterations."13 The court then conducted the second part of the two-step test and found the "non-patent-ineligible elements" insufficient to support patentability.14 Rather, the physical interventions required by the claims — such as hybridizing gene probes, amplifying the BRCA1and BRCA2 loci, and sequencing those loci — were seen by the Court as "well-understood, routine and conventional activity engaged in by scientists at the time of Myriad's patent applications," not least because Myriad's own specification indicated that routine methods known to those of skill in the art could be used to detect and sequence the loci.15 Thus, when assessed "as a whole," the Court found that the asserted method claims were insufficient to rise to the level of patent-eligible subject matter.16 Although not before the court, Myriad's patent also contained narrower claims to determining a risk of breast cancer by detecting mutations in the BRCA1 andBRCA2 genes selected from a list of particular mutations reported in the specification. In dicta, the Federal Circuit suggested that these claims might be "qualitatively different from the [invalid] method claims at issue."17
Following Ambry, five district court cases have (to date) relied on the decision. In only one of those five cases, Ameritox, Ltd. v. Millennium Health, LLC, has a district court found a claim to a natural product or diagnostic method patent eligible.18 That case involved a claimed method of measuring metabolite levels in a patient's urine and comparing them to creatinine levels.
In the recent Ariosa decision, the Federal Circuit affirmed a grant of summary judgment issued by Judge Illston of the Northern District of California. The district court had held the claims of the '540 patent invalid. Claim 1 of the '540 patent, directed to a method of measuring cffDNA in maternal plasma or serum, states:
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.
The court noted that the dependent claims explain how to detect the cffDNA or how to use the detected cffDNA in prenatal diagnosis.19
Assessing these claims, the court reiterated the two-step analysis required by Mayoand Alice, namely "determin[ing] whether the claims at issue are directed to a patent-ineligible concept" and, if so, "consider[ing] the elements of each claim both individually and 'as an ordered combination' to determine whether additional elements 'transform the nature of the claim' into a patent-eligible application."20 While noting that the '540 patent recites method claims, which are "generally eligible subject matter," the court went on to point out that the claimed method "begins and ends with a natural phenomenon," i.e., the presence of cffDNA in maternal blood and the diagnostic implications that can be made by correlating that cffDNA with paternally inherited nucleic acid.21 Thus, the court concluded that the claims of the '540 patent satisfy the first step of the analysis laid out in Alice because they are "directed to matter that is naturally occurring."22
The Court next evaluated the second step of the analysis to determine whether the remaining elements of the claims in the '540 patent "transform" the natural phenomenon into a patent-eligible application.23 Despite the presence of claims to particular methods for amplifying, detecting, and correlating cffDNA with paternally inherited nucleic acid, the Court concluded that the claims were insufficient to integrate the naturally occurring material into a patent-eligible application. Rather, the specific methods recited in the claims were considered "routine and conventional," particularly in light of the guidance in the specification indicating that amplification, detection, and correlation could be done using "standard techniques."24 The decision then concluded by reiterating the Supreme Court guidance from Mayo that "appending routine, conventional steps to a natural phenomenon, specified at a high level of generality, is not enough to supply an inventive concept. Where claims of a method patent are directed to an application that starts and ends with a naturally occurring phenomenon, the patent fails to disclose patent eligible subject matter if the methods themselves are conventional, routine and well understood applications in the art."25 As such, the Federal Circuit found the claims of the ′540 patent at issue on appeal invalid.
The Federal Circuit rejected Sequenom's argument that the '540 patent claims were patent eligible because they did not preempt all uses of cffDNA.26 The court explained that "[w]hile preemption may signal patent ineligible subject matter, the absence of complete preemption does not demonstrate patent eligibility."27 The court further noted 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."28
Additional litigation will undoubtedly be required to further delineate the shifting standard for assessing patentable subject matter in view of Ariosa and Ambry. Interested stakeholders should continue to monitor the space, including whether either of these decisions will be subject to additional en banc review by the Federal Circuit or by the United States Supreme Court.