An Improved Step in a Diagnostic Method is Patentable Subject Matter

In Illumina, Inc., v. Ariosa Diagnostics, Inc., [2019-1419] (March 17, 2020) the Federal Circuit reversed the district court’s determination that claims of U.S. Patent Nos. 9,580,751 and 9,738,931 were invalid under 35 U.S.C. § 101 as directed to an ineligible natural phenomenon.

Illumina’s related U.S. Patent 6,258,540, which claimed a method for detecting the small fraction of paternally inherited cell-free fetal DNA in the plasma and serum of a pregnant woman, were famously held invalid under 35 U.S.C. § 101 back in 2015 because they were directed to “matter that is naturally occurring”—i.e., the natural phenomenon that cell-free fetal DNA exists in maternal blood.  The ‘751 and ‘931 patents presently at issue were based upon the “surprising” discovery that the majority of the circulatory extracellular fetal DNA has a relatively small size of approximately 500 base pairs or less, which meant that fetal DNA could be amplified by separating extracellular DNA fragments which are smaller than approximately 500 base pairs.

The Federal Circuit noted that this was not a diagnostic invention, or a treatment invention, but a method of preparation invention, and applied the two step Alice/Mayo test.  At Step 1, the Federal Circuit said it was undisputed that the inventors of the ’751 and ’931 patents discovered a natural phenomenon. But at step one of the Alice/Mayo test, “it is not enough to merely identify a patent-ineligible concept underlying the claim; we must determine whether that patent-ineligible concept is what the claim is ‘directed to.’”   After noting the parties difficulty in identifying the natural phenomenon involved, the Federal Circuit identified the natural phenomenon: that cell-free fetal DNA tends to be shorter than cell-free maternal DNA in a mother’s bloodstream. Turning to the crucial question of whether the claims are “directed to” that natural phenomenon, the Federal Circuit concluded that the claims are not directed to that natural phenomenon but rather to a patent-eligible method that utilizes it.

The Federal Circuit explained the claims in this case are directed to methods for pre-paring a fraction of cell-free DNA that is enriched in fetal DNA. The methods include specific process steps—size dis-criminating and selectively removing DNA fragments that are above a specified size threshold—to increase the relative amount of fetal DNA as compared to maternal DNA in the sample.  These process steps change the composition of the mixture, resulting in a DNA fraction that is different from the naturally-occurring fraction in the mother’s blood. Thus, the process achieves more than simply observing that fetal DNA is shorter than maternal DNA or detecting the presence of that phenomenon.

Roche insisted that the claims in this case are no more eligible than the claims at issue in Ariosa, but the Federal Circuit disagreed, noting that in Ariosa, the relevant independent claims were directed to a method “for detecting a paternally inherited nucleic acid” or a method “for performing a prenatal diagnosis,” and the only operative steps in the claims were “amplifying” (i.e., making more of) the cell-free fetal DNA and then “detecting [it],” “subjecting [it] . . . to a test,” or “performing nucleic acid analysis on [it] to detect [it].” The claims were ineligible because, like the invalid diagnostic claims at issue in Mayo, Athena, and Cleveland Clinic, they were directed to detecting a natural phenomenon.

This case shows the importance of how the invention is characterized to the 101 analysis