In Illumina, Inc. v. Ariosa Diagnostics, Inc., a divided panel of the Federal Circuit found claims directed to methods of preparing DNA samples for analysis satisfy the patent eligibility requirement of 35 USC § 101. Although the claimed methods could be practiced in conjunction with a diagnostic method, the majority decision emphasizes that “this is not a diagnostic case.” Still, stakeholders in the diagnostic space may find hope—and take note—that the court identified eligible subject matter. 

The Patents At Issue

As described in the Federal Circuit opinion, the patents at issue addressed a problem encountered in practicing the diagnostic method found ineligible in Sequenom relating to the detection of “extracellular fetal DNA … in maternal plasma,” namely, the need “to distinguish and separate the tiny amount of fetal DNA from the vast amount of maternal DNA.” As quoted in the opinion, the patents explain:

An examination of circulatory extracellular fetal DNA and circulatory extracellular maternal DNA in maternal plasma has now shown that, surprisingly, 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.

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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 patents at issue were U.S. Patent 9,580,751 and U.S. Patent 9,738,931. The court focused on claim 1 of each patent.

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).

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 district court invalidated the claims under 35 USC § 101 on summary judgment. 

The Federal Circuit Decision

The Federal Circuit decision was authored by Judge Lourie and joined by Judge Moore. Judge Reyna dissented. 

Judge Lourie’s opinion sets up the § 101 analysis as follows:

Laws of nature and natural phenomena are not patentable, but 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 Diehr, 450 U.S. 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. 

To distinguish claims to patent-eligible applications of laws of nature and natural phenomena from claims that impermissibly tie up such laws and phenomena, we apply the two-part test set forth by the Supreme Court. 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)

Judge Lourie next acknowledges the eligibility divide between “diagnostic” cases and “method of treatment” cases: 

Under Mayo, we have consistently held diagnostic claims unpatentable as directed to ineligible subject matter. …. In contrast, we have held that method of treatment claims are patent-eligible. 

As to the claims at issue, the opinion finds: 

This is not a diagnostic case. And it is not a method of treatment case. It is a method of preparation case.

Turning to the first step of the Alice/Mayo framework, the opinion frames and answers the inquiry as follows:

[W]e adopt Illumina’s articulation 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. We thus turn to the crucial question on which this case depends: whether the claims are “directed to” that natural phenomenon. We conclude that the claims are not directed to that natural phenomenon but rather to a patent-eligible method that utilizes it.

The majority opinion explains further: 

The claims in this case are directed to methods for preparing a fraction of cell-free DNA that is enriched in fetal DNA. The methods include 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 majority opinion finds some similarity to the claims at issue in CellzDirect, and emphasizes that claims directed to “a method for determining whether a fragment of cell-free DNA is fetal or maternal based on its length” would not be eligible. 

Judge Reyna’s Dissent 

Judge Reyna’s dissenting opinion provides a detailed analysis of his disagreement with the majority. Overall, he finds:

The claims are directed to a natural phenomenon because the patent’s claimed advance is the discovery of that natural phenomenon.

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This conclusion is bolstered by the fact that the claimed method steps begin and end with a naturally occurring substance …. 

Judge Reyna disagrees with the majority’s analogy to CellzDirect (“Here, the claimed advance is not an improvement in the underlying DNA-processing technology, as hinted by the Majority.”) and instead cites Genetic Technologies for the proposition that “[a] process that merely changes the composition of a sample of naturally occurring substances, without altering the naturally occurring substances themselves, is not patent eligible.”