In Illumina, Inc. v. Ariosa Diagnositcs, Inc., (Fed. Cir. Slip Op. 2019-1419, March 17, 2020) the Federal Circuit held that process claims that exploit the discovered size differences between fetal and maternal DNA in serum or plasma are patent eligible. The Federal Circuit reversed the decision of the U.S. District Court for the Northern District of California (356 F. Supp. 3d 925 (N.D. Cal. 2018)) that the contested claims of U.S. Patent 9,580,751 (the “’751 patent”) and 9,738,931 (the “’931 patent”) are invalid under 35 U.S.C. § 101 as directed to an ineligible natural phenomenon. Judge Lourie wrote the panel opinion joined by Judge Moore. Judge Reyna dissented.

The Technology and Patent Claims

The ‘751 and ‘931 patents claim inventions from the 1996 discoveries of Drs. Dennis Lo and James Wainscoat that cell-free fetal DNA can be assayed in maternal plasma and serum. The ‘751 and ‘931 patents recognize that detection of the small amount of fetal DNA is difficult to distinguish from the more prevalent maternal DNA present in the maternal plasma and serum. The inventors discovered that despite the difference in relative quantity, one could detect the fetal DNA based on its size. Fetal DNA is approximately 500 base pairs or less as compared to maternal circulatory extracellular DNA in maternal plasma which has a size greater than approximately 500 base pairs. The ’751 and ’931 patents exploit that discovery.

Representative claim 1 of the ‘751 patent recites:

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).

Representative claim 1 of the ‘931 patent recites:

1. A method, comprising:

(a) extracting DNA comprising maternal and fetal DNA fragments from a substantially cell-free sample of blood plasma or blood serum of a pregnant human female;

(b) producing a fraction of the DNA extracted in (a) by:

(i) size discrimination of extracellular circulatory fetal and maternal DNA fragments, and

(ii) selectively removing the DNA fragments greater than approximately 300 base pairs,

wherein the DNA fraction after (b) comprises extracellular circulatory fetal and maternal DNA fragments of approximately 300 base pairs and less and a plurality of genetic loci of the extracellular circulatory fetal and maternal DNA fragments; and

(c) analyzing DNA fragments in the fraction of DNA produced in (b).

The 101 Analysis

In framing its decision, the Federal Circuit reiterated the current state of the law regarding patent eligibility. The Majority noted that while laws of nature and natural phenomena are not patentable, “applications and uses of such laws and phenomena may be patentable. A claim to otherwise statutory subject matter does not become ineligible by its use of a law of nature or natural phenomenon. See Diamond v. Diehr, 450 U.S. 101 at 187; Parker v. Flook, 437 U.S. 584, 590 (1978). On the other hand, adding ‘conventional steps, specified at a high level of generality,’ to a law of nature or natural phenomenon does not make a claim to the law or phenomenon patentable. Mayo, 566 U.S. at 82.” Slip Op. at 7.

The court then applied the Alice two-part test set forth by the Supreme Court to evaluate the patent eligibility of claims. “First, we examine whether the claims are “‘directed to’ a law of nature or natural phenomenon. Alice Corp. Pty. Ltd. v. CLS Bank Int’l, 573 U.S. 208, 217 (2014). If—and only if—they are, then we proceed to the second inquiry, where we examine whether the limitations of the claim apart from the law of nature or natural phenomenon, considered individually and as an ordered combination, ‘transform the nature of the claim’ into a patent-eligible application. Id. (quoting Mayo, 566 U.S. at 78).’” Slip Op. at 8.

The court then characterized the claims as neither diagnostic nor treatment claims. Rather, the claims are directed to methods of preparation. The court distinguished its prior decisions with similarly constructed claims. In contrast to the prior claims (diagnostic or treatment) and decisions that determined that they are patent ineligible (diagnostic) or eligible (treatment), the ‘751 and ‘931 claims focus on the discovery that cell-free fetal DNA tends to be shorter than cell-free maternal DNA in a mother’s bloodstream and the utilization of this natural phenomenon. The court focused on the process-specific steps of the methods, e.g., “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.” Slip Op at 10. The court determined that these process-specific steps distinguish the examined claims from claims that may solely focus on the observation that fetal DNA is present in maternal plasma or serum.

The court also looked to its prior CellzDirect opinion (see Rapid Litig. Mgmt. Ltd. v. CellzDirect, Inc., 827 F.3d 1042 (Fed. Cir.  2016)) as an additional basis for its current opinion. The inventors in CellzDirect discovered the natural phenomenon that some fraction of hepatocytes are capable of surviving multiple freeze-thaw cycles. The inventors 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.” Slip Op. at 12. These claims were held patent eligible by the court.

In sum, the Majority held:

Rather than focusing on what the inventors of the ’751 and ’931 patents did not invent, we focus our Alice/Mayo step one analysis on what the inventors did purport to invent and what they claimed in their patents: 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. Accordingly, we conclude 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.

Slip Op. at 14.

Dissent - The Claims Are Not Patent Eligible

Judge Reyna disagreed with the Majority’s characterization of the claims as distinguishable from diagnostic methods held to be patent ineligible. In his view, the “claims are directed to a natural phenomenon because the patent’s claimed advance is the discovery of that natural phenomenon” and the “[m]ajority disregards well-established precedent for conducting the Alice, step one, ‘directed to’ inquiry by failing to consider the patent’s claimed advance.” Dissent Slip Op. at 6. In this instance, Judge Reyna criticized the Majority for failing to identify the patents’ claimed advances.

Judge Reyna also criticized the Majority’s reliance on CellzDirect. In Judge Reyna’s opinion, CellzDirect is different because the inventors in CellzDirect created a new and useful cryopreservation technique comprising multiple freeze-thaw  cycles. In his opinion, the inventors there went beyond applying a known laboratory technique to a newly discovered natural phenomenon and, instead, created an entirely new laboratory technique. In his view, the claims were more similar to ineligible method claims¹ than eligible treatment claims.²

Personalized Medicine Diagnostics

The Federal Circuit’s decision indicates that certain discoveries that support personalized medicine diagnostics may be patent eligible. Claims that exploit discoveries with specific process steps that transform an observation of a natural phenomenon to defined steps that provide a new and useful result are more likely to withstand a Section 101 challenge. This decision, as well as the Federal Circuit’s CellzDirect decision are useful tutorials for patent practitioners.      

¹ See e.g., See Athena Diagnostics, Inc. v. Mayo Collaborative Servs., LLC, 927 F.3d 1333, 1352 (Fed. Cir. 2019); Athena Diagnostics, Inc. v. Mayo Collaborative Servs., LLC, 915 F.3d 743 (Fed. Cir. 2019); Cleveland Clinic Found. v. True Health Diagnostics LLC, 859 F.3d 1352 (Fed. Cir. 2017); and Cleveland Clinic Found. v. True Health Diagnostics LLC, 760 F. App’x 1013 (Fed. Cir. 2019).

² See e.g., Endo Pharm. Inc. v. Teva Pharm. USA, Inc., 919 F.3d 1347 (Fed. Cir. 2019); Natural Alternatives Int'l, Inc. v. Creative Com- pounds, LLC, 918 F.3d 1338 (Fed. Cir. 2019); and Vanda Pharm. Inc. v. West-Ward Pharm. Int’l Ltd., 887 F.3d. 1117 (Fed. Cir. 2018).