"A Method of Preparation" and Patent Eligibility Under Section 101

March 30, 2020

Before LOURIE, MOORE, and REYNA, Circuit Judges.

Illumina, Inc. and Sequenom, Inc. (“Illumina”) filed suit against Ariosa Diagnostics, Inc., Roche Sequencing Solutions, Inc., and Roche Molecular Systems, Inc. (“Roche”) alleging infringement of U.S. Patents 9,580,751 and 9,738,931. Roche moved for summary judgment that the asserted claims were invalid under 35 U.S.C. § 101. The district court granted Roche’s motion holding that the claims of the ’751 and ’931 patents were directed to ineligible subject matter. Illumina appealed. The Federal Circuit (“the Court”) reversed the district court’s grant of summary judgment and remanded for further proceedings.

The Court pointed out that “although it was known that cell-free fetal DNA existed in the mother’s blood-stream, there was no known way to distinguish and separate the tiny amount of fetal DNA from the vast amount of maternal DNA.” The majority of the circulatory extracellular fetal DNA has a relatively small size of approximately 500 base pairs or less, whereas the majority of circulatory extracellular maternal DNA in maternal plasma has a size greater than approximately 500 base pairs. “Having made that discovery, they [the inventors] used it to develop a solution to the identified problem of distinguishing fetal DNA from maternal DNA in the mother’s bloodstream.” “This surprising finding forms the basis of the present invention according to which separation of circulatory extracellular DNA fragments which are smaller than approximately 500 base pairs provides a possibility to enrich for fetal DNA sequences from the vast bulk of circulatory extracellular maternal DNA.” The Courted noted that the claims of the ’751 and ’931 patents were directed to that solution. Specifically, the claimed methods are for preparing a fraction of cell-free DNA that is enriched in fetal DNA.

Claim 1 of the ‘751 patent reads:

1. 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).

The Court noted that the focus of the dispute in this case was whether the claims of the ’751 and ’931 patents were “directed to” the natural phenomenon, i.e., whether they claimed the discovered natural phenomenon itself versus eligible subject matter that exploits the discovery of the natural phenomenon. The Court pointed out that “[t]his is not a diagnostic case. And it is not a method of treatment case. It is a method of preparation case.”

The district court appeared to find that the relevant natural phenomenon was the “testable quantity” of fetal DNA or “test results” obtained from that fetal DNA. However, the Court adopted Illumina’s interpretation of the natural phenomenon, i.e., that cell-free fetal DNA tends to be shorter than cell-free maternal DNA in a mother’s bloodstream, and concluded that the claims were not directed to that natural phenomenon but rather to a patent-eligible method that utilizes it.

The Court pointed out that the claimed methods included specific process steps—size discriminating 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. Those 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.

The Court distinguished this case from Ariosa, where the inventors discovered that cell-free fetal DNA exists, and obtained patent claims covered only the knowledge that it exists and a method to see that it exists. The Court stated that here, “in contrast, the claims were directed to more than just the correlation between a DNA fragment’s size and its tendency to be either fetal or maternal. And the claims do not merely cover a method for detecting whether a cell-free DNA fragment is fetal or maternal based on its size. Rather the claimed method removes some maternal DNA from the mother’s blood to prepare a fraction of cell-free DNA that is enriched in fetal DNA.”

The Court further said that the Supreme Court’s decision in Myriad was not on point here, as in Myriad, the claims were ineligible because they covered a gene rather than a process for isolating it. “Here, we encounter the opposite situation, i.e., the claims do not cover cell-free fetal DNA itself but rather a process for selective removal of non-fetal DNA to enrich a mixture in fetal DNA.”

The Court also noted that “CellzDirect, while not directly on point, is instructive.” In CellzDirect, the inventors discovered the natural phenomenon “that some fraction of hepatocytes are capable of surviving multiple freeze-thaw cycles” and then patented an “improved process of preserving hepatocytes,” that comprises freezing hepatocytes, thawing the hepatocytes, removing the non-viable hepatocytes, and refreezing the viable hepatocytes. The Court in CellzDirect found that the “inventors in CellzDirect did not invent hepatocytes or impart to hepatocytes an ability to survive cycles of freezing and thawing. Rather, they discovered that hepatocytes naturally have that ability, and they exploited that phenomenon in a patent-eligible method. So too here, the inventors of the ’751 and ’931 patents obviously did not invent cell-free fetal DNA or the relative size distribution of fetal and maternal cell-free DNA in maternal blood. And, like in CellzDirect, the inventors used their discovery to invent a method of preparing a fraction of DNA that includes physical process steps to selectively remove some maternal DNA in blood to produce a mixture enriched in fetal DNA.” Thus, the Court focused on what the inventors did purport to invent and what they claimed in their patents, i.e., methods for preparing a fraction of cell-free DNA by the physical process of size discriminating and selectively removing DNA fragments longer than a specified threshold. Those methods are “directed to” more than merely the natural phenomenon that the inventors discovered. The Court concluded at step one of the Alice/Mayo test that the claims are not directed to a patent-ineligible concept, and “we need not reach step two of the test.”

Judge REYNA dissented, finding the claims to be directed to a natural phenomenon and that the method steps are routine and conventional and as such, insufficient to transform the patent ineligible natural phenomenon to a patent eligible invention.

When drafting claims that may be rejected as reciting law of nature or a natural phenomenon, consider adding various types of claims that are directed not only to a diagnostic method and/or a method of treatment (with specific elements in view of Vanda), but also to a method of preparation.

Illumina, Inc. v. Ariosa Diagnostics, Inc., 356 F. Supp. 3d 925 (N.D. Cal. 2018).
Illumina, Inc. v. Ariosa Diagnostics, Inc., No. 2019-1419 (Fed. Cir. Mar. 17, 2020).
Alice Corp. Pty. Ltd. v. CLS Bank Int’l, 573 U.S. 208, 217 (2014).
Rapid Litig. Mgmt. Ltd. v. CellzDirect, Inc., 827 F.3d 1042 (Fed. Cir. 2016).
Ariosa Diagnostics, Inc. v. Sequenom, Inc., 788 F.3d 1371 (Fed. Cir. 2015).
Vanda Pharm. Inc. v. West-Ward Pharm. Int’l Ltd., 887 F.3d. 1117 (Fed. Cir. 2018).