Section 101 Love in the Time of COVID-19, with Apologies to Gabriel García Márquez

It is a good bet that everyone has a heightened appreciation for diagnostic technology right now. The countries that have fared reasonably well during the ongoing pandemic are those with meticulous testing regimens. After initial missteps in the U.S., there are reasons to be hopeful. The FDA just approved a rapid, point-of-care test, and increasing our testing capability is critical to flattening the curve.

If you are a patent owner in the diagnostic space, there is another reason to be hopeful. Since the Supreme Court’s decisions in Mayo, Myriad, and Alice, it has been increasingly difficult to protect diagnostic technology. Claims are not eligible for patent protection when they recite a law of nature, and add nothing more than well-understood, routine, and conventional steps. Patent protection is also unavailable for naturally occurring molecules and for comparative steps that can be practically performed in the human mind. Practitioners have learned to claim diagnostic steps as part of method of treatment claims. The Federal Circuit’s recent decision in Illumina, Inc. v. Ariosa Diagnostics, Inc. opens up some additional avenues for clever claim drafting.

The underlying technology is a form of prenatal diagnostic testing and was previously addressed in a case between Ariosa Diagnostics and Sequenom in 2015. In that case, the claims focused on paternally inherited DNA that is detectable in the maternal bloodstream (also referred to as “cell-free, fetal DNA” or “cffDNA”):

1. A method for detecting a paternally inherited nucleic acid of fetal origin performed on a maternal serum or plasma sample from a pregnant female, which method comprises amplifying a paternally inherited nucleic acid from the serum or plasma sample and detecting the presence of a paternally inherited nucleic acid of fetal origin in the sample.

The additional claim steps related to amplifying and detecting cffDNA, but the panel found these methods were well understood and routine. Consequently, while the panel acknowledged that detecting cffDNA in maternal plasma was “a positive and valuable contribution to science,” that contribution fell short of patentable subject matter.

Now, five years later, Illumina has prevailed (at least for now) with claims that are also directed to detecting cffDNA. The patents acknowledge that cffDNA was known in the art, but report an allegedly surprising observation, which is that there is a size differential between cffDNA and extracellular maternal DNA. While the former tends to be under 500 base pairs in length, the latter tends to be longer. With that discovery in hand, the inventors claimed a solution. Specifically, they claimed a method for preparing a fraction of cell-free DNA that is enriched in fetal DNA, which facilitates genetic analysis:

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).

Illumina asserted its patents against Ariosa Diagnostics, and lost on a §101 summary judgment challenge. On appeal, Illumina successfully convinced the Federal Circuit that “[t]his is not a diagnostic case. . . . It is a method of preparation case.” Here, the observed natural phenomenon was that cffDNA tends to be shorter than cell-free maternal DNA. The question was then whether Illumina’s claims were directed to that phenomenon, or to a patent-eligible application of the same.

In determining that Illumina’s claims were patent eligible, the Federal Circuit noted that the claimed methods reflected not simply observing a phenomenon but concrete steps for exploiting it, involving extracting and fractionating a DNA sample, and then excluding DNA over a certain length prior to any analysis.

The court was not unanimous in its view. In dissenting, Judge Reyna notes that the patent specification highlighted the discovery of a natural phenomenon, which is the size differential between cell-free maternal DNA and cffDNA. Just as in the earlier Ariosa case, Illumina’s claims began and ended with naturally-occurring DNA molecules. Separating the DNA sample by size in no way altered the DNA molecules that are naturally found in the maternal bloodstream. The patent specification identified no improvement in DNA processing technology, but rather relied upon well-known and commercially available tools and kits. Thus, in his view, and just as in Ariosa, the additional claim steps—DNA extraction, fractionation, and analysis— provided nothing new.

Stay tuned, as a petition for rehearing is likely.