The Federal Circuit Opens a Window: Another Claiming Option for Molecular and Biological Inventions

Overview
The Federal Circuit has just provided a window in the seemingly impenetrable wall of patent ineligibility under 35 U.S.C. § 101 for diagnostic uses of molecular and biological inventions.

Perhaps seeking to break the contradictory impasse of patent-ineligible diagnostic claims on the one hand, and patent-eligible method of treatment claims on the other, the Federal Circuit has introduced a third category of claims into the § 101 mix: the method of preparation claims. While it is unclear whether this holding will increase the contradictory nature of § 101 jurisprudence or improve upon it, or whether the U.S. Patent and Trademark Office (USPTO) will interpret this case narrowly or more broadly, practitioners facing § 101 rejections in the molecular diagnostics space at least have another claim strategy to consider.

The case, Illumina, Inc., v. Ariosa Diagnostics, (Fed. Cir. Mar. 17, 2020), was appealed from a decision of the United States District Court for the Northern District of California. Claims 1, 2, 4, 5, 9 and 10 of U.S. Patent No. 9,580,751 (the '751 Patent) and claims 1, 2, and 10-14 of U.S. Patent No. 9,738,931 (the '931 Patent) were held invalid by the District Court on a motion for summary judgment. On appeal, a divided Federal Circuit Court reversed the District Court's decision, and concluded that the claims are directed to "patent-eligible subject matter."

Background
In Ariosa v. Sequenom, (Fed. Cir. June 12, 2015), the Federal Circuit held that claims directed to detecting paternally inherited cell-free fetal DNA (cffDNA) in maternal plasma or serum samples was patent-ineligible subject matter under 35 U.S.C. § 101 because the claims were directed to "matter that is naturally occurring." The U.S. Supreme Court denied a petition for certiorari on June 27, 2016.

Patents at Issue
The subject matter of the patents at issue in this case (the '751 patent and the '931 patent) is related to the subject matter of the patents contested in Ariosa, but the patents are unrelated in family lineage.

Claim 1 is the only independent claim in both the '751 patent and the '931 patent. Each claim 1 is reproduced below for comparison:

• Claim 1 of the '751 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).
• Claim 1 of the '931 Patent:
• 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).

Claims Analysis
At the outset, the Court made clear that this case concerns a new category of claims outside of the settled § 101 law. "This is not a diagnostic case. And it is not a method of treatment case. It is a method of preparation case."

The Court applied the two-part Alice/Mayo test, stating as follows: "First, we examine whether the claims are 'directed to' a law of nature or a natural phenomenon," and "[i]f–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."

The Court defined the natural phenomenon as the finding that "cell-free fetal DNA tends to be shorter than cell-free maternal DNA in a mother's bloodstream," and stated that "it is undisputed that the inventors…discovered a natural phenomenon."

The Court then asked, pursuant to step 1 of the Alice/Mayo test, "whether the claims of the … patents are 'directed to' the natural phenomenon, i.e., whether they claim the discovered natural phenomenon itself versus eligible subject matter that exploits the discovery of the natural phenomenon." The answer to this question was "no."; The Court held that "the claims are not directed to a natural phenomenon, but rather to a patent-eligible method that utilizes it." Specifically, the Court held that the claims were directed "to methods for preparing a fraction of cell-free DNA that is enriched in fetal DNA" (emphasis added).

In addition, the Court emphasized that the present claims "change the composition of the mixture, resulting in a DNA fraction that is different from the naturally-occurring fraction in the mother's blood," and that "this achieves more than simply observing that fetal DNA is shorter than maternal DNA or detecting the presence of the phenomenon," (emphasis added).

In distinguishing its rationale in the present case from that in Ariosa, the Court noted that the only operative steps claimed in Ariosa were directed to amplifying the cffDNA and detecting it so that one could see that a natural phenomenon exists. The Court contrasted the present claims, stating that they are directed to "more than just the correlation between a DNA fragment's size and its tendency to be either fetal or maternal," and that "the claims do not merely cover a method for detecting whether a cell-free DNA fragment is fetal or maternal based on its size." The Court again emphasized that the claimed methods remove "some maternal DNA from the mother's blood to prepare a fraction of cell-free DNA that is enriched in fetal DNA."

To distinguish the present method claims from the claims directed to purified nucleic acid sequences contested in Myriad, the Court noted that "the claims here are not directed to the cell-free fetal DNA itself," and pointed out that the Supreme Court in Myriad made clear that method claims were not at issue. The Court reiterated that the Myriad claims "were ineligible because they covered a gene rather than a process for isolating it," and that the current case covers the opposite, "the claims do not cover cell-free fetal DNA itself but rather a process for selective removal of non-fetal DNAs to enrich a mixture in fetal DNA."

Practice Tips
While it is unclear how the USPTO and individual examiners will implement this holding, ideas for consideration are presented below:

1. Draft claims directed to methods of preparation of materials needed for diagnostic methods to:

a) include more than just amplification and detection steps;

b) include, if possible, an "enrichment" step or point out an enrichment–or depletion–of some component of the sample;

c) assure that the specification provides support for the methods of preparation; and

d) be prepared for, and consider arguments to counter, obviousness rejections.

2. Remember that while claims directed to enriched or purified products are still patent-ineligible, methods of purification and enrichment may pass muster under § 101.

3. In arguments and/or when drafting a specification, consider emphasizing the change in a composition due to the "preparation" steps and identify physical (e.g., structural, biochemical) characteristics that would distinguish the "prepared" composition from the natural composition. Ask the question: what changes? For example, a target antigen is no longer active when bound by its antibody, thus the sample is "transformed" compared to the subject's natural state, and preparing a sample to determine DNA methylation is arguably "transformative."

4. Argue that claims are not directed to the natural phenomenon but rather are directed to "a patent-eligible method that utilizes it" as asserted by the majority:

• consider outlining arguments in a "problem/solution style" as the Federal Circuit did in this case;
• then, emphasize that the claims are directed to a patent-eligible technical solution.

5. During prosecution, be wary of § 101 rejections alleging that the steps in your method claims are "routine or conventional." Be certain that your claims FAIL step 1 of the Alice/Mayo test before acquiescing to this rejection.

6. For method claims, lean on CellzDirect-styled arguments to address § 101 rejections and argue that the claims are drawn to new and useful methods for preparing a useful product.

7. If financially feasible, consider keeping an application pending via continuation filings. Given the unpredictable nature of § 101 jurisprudence, the Federal Circuit may open additional "windows" through the § 101 wall.

For more information about method of preparation claims or the patent-eligibility process, contact your local Quarles & Brady attorney, or:

• Stephanie Vavra: (414) 277-5454 / stephanie.vavra@quarles.com