On August 3, 2020, the Federal Circuit (Judges Lourie, Moore, and Reyna (dissenting)) (“the Court”) granted a petition for panel rehearing and issued a modified opinion (“Mod. Op.”) that maintained its prior patent-eligibility determination in Illumina, Inc. v. Ariosa Diagnostics, Inc., Case No. 19-1419. Specifically, the modified majority opinion again held that the challenged claims of U.S. Patent Nos. 9,580,751 (the “’751 patent”) and 9,738,931 (the “’931 patent”), generally directed to methods of preparing cell-free fetal DNA from maternal blood for genetic analysis, are not invalid under 35 U.S.C. § 101 as directed to a natural phenomenon under the Alice/Mayo test, and are differentiated from other cases where the Court held claims ineligible.
Illumina asserted the ’751 and the ’931 patent claims against Ariosa. Claim 1 of the ʼ751 patent recites selectively enriching for fetal DNA in samples extracted from maternal blood, by removing DNA fragments larger than 500 base pairs in length:
A method for preparing a deoxyribonucleic acid (DNA) fraction from a pregnant human female useful for analyzing a genetic locus involved in a fetal chromosomal aberration, comprising:
(a) extracting DNA from a substantially cell-free sample of blood plasma or blood serum of a pregnant human female to obtain extracellular circulatory fetal and maternal DNA fragments;
(b) producing a fraction of the DNA extracted in (a) by:
(i) size discrimination of extracellular circulatory DNA fragments, and
(ii) selectively removing the DNA fragments greater than approximately 500 base pairs,
wherein the DNA fraction after (b) comprises a plurality of genetic loci of the extracellular circulatory fetal and maternal DNA; and
(c) analyzing a genetic locus in the fraction of DNA produced in (b).
Compared to the original opinion issued in March 2020, the Court’s modified opinion emphasized the inventors’ observation “that 70% of all DNA fragments smaller than 300 base pairs were fetal.” Mod. Op. at 4. The Court concluded that including size limits to enrich for fetal DNA in the claims amounted to a “human-engineered parameter … not dictated by any natural phenomenon” and instead “optimize[d] the amount of maternal DNA that is removed from the mixture and the amount of fetal DNA that remains in the mixture.” Id. at 11.
In its modified opinion, the Court rejected comparisons to the claims in Ariosa Diagnostics, Inc. v. Sequenom, Inc., 788 F.3d 1371, 1373 (Fed. Cir. 2015). The Court explained that the ʼ751 and ʼ931 patents
begin by acknowledging the natural phenomenon that was at issue in Ariosa. . . . The patents then identify a problem that . . . although it was known that cell-free fetal DNA existed in the mother’s bloodstream, there was no known way to distinguish and separate the tiny amount of fetal DNA from the vast amount of maternal DNA. The inventors of the ’751 and ’931 patents attempted to find a solution to that problem. . . . Specifically, they claim methods of preparing a fraction of cell-free DNA that is enriched in fetal DNA.
Mod. Op. at 3.
The Court drew the distinction that performing the methods of the ’751 and ’931 patent claims, which include conventional separation technologies used in unconventional ways, increased the relative amount of cell-free fetal DNA in the processed sample compared to maternal DNA, thereby “chang[ing] the composition of the mixture, resulting in a DNA fraction that is different from the naturally-occurring fraction in the mother’s blood.” Id. at 11. Moreover, since the ’751 and ’931 patent claims require more than simply observing the natural phenomenon that fetal DNA circulating in a mother’s serum is shorter than the mother’s circulating DNA, the claims “include physical process steps that change the composition of the mixture.” Id. at 8. In other words, the ’751 and ’931 patent claims are directed to methods of exploiting a natural phenomenon – size distribution of fetal DNA and maternal DNA circulating in maternal serum – during sample preparation, for the purpose of isolating shorter fetal DNA from longer maternal DNA, instead of simply detecting or observing a property of the natural phenomenon. According to the majority, this differs from Association for Molecular Pathology v. Myriad Genetics, Inc., 569 U.S. 576 (2013), where the claims at issue were directed to isolating DNA itself. The claims also include the step of analyzing a genetic locus, thereby shifting the focus of the claims even further from Ariosa, Myriad, and Mayo Collaborative Services v. Prometheus Laboratories, Inc., 566 U.S. 66 (2012) — “[t]his is not a diagnostic case. And it is not a method of treatment case. It is a method of preparation case.” Id. at 8.
Judge Reyna continued to dissent from the majority by asserting that the claims are directed to a natural phenomenon. According to Judge Reyna, the “sole claimed advance is the discovery of that natural phenomenon, and the application of the natural phenomenon utilizes routine steps and conventional procedures that are well known in the art.” Mod. Op., Dissent at 1-2. The claimed steps of (a) DNA extraction and (b) production of a fraction of the extracted DNA fragments that is limited by their nucleotide length, are nothing more than commonly used techniques that still result in a composition having the same naturally occurring nucleotides present in their naturally occurring forms. Mod. Op., Dissent at 5.
Illumina provides further guidance to practitioners drafting method claims to characterize the invention by “human-engineered” parameters when possible.