Detecting Natural Phenomena Using Conventional Techniques Found “Directed to” Natural Phenomena at Alice/Mayo Step One
| September 16, 2022
CAREDX, INC. v. NATERA, INC.
Lourie, Bryson, and Hughes. Opinion by Lourie.
Summary
The CAFC held that genetic diagnostic method claims are ineligible for patent, finding that the claims reciting conventional laboratory techniques to perform diagnosis using a naturally occurring correlation are directed to natural phenomena under Alice/Mayo step one, and also lack additional elements to constitute enough inventive concept under Alice/Mayo step two.
Details
CareDx sued Natera and Eurofins in the U.S. District Court for the District of Delaware, asserting that their products infringed one or more patents licensed to CareDx. The district court awarded summary judgment for the defendants, holding that the patents are ineligible for patent under 35 U.S.C. §101. CareDx appealed the district court’s grant of the summary judgment motions of ineligibility.
The patents at issue, U.S. Patents 8,703,652, 9,845,497, and 10,329,607, relate to diagnosis of organ transplant status by detecting a donor’s cell-free DNA (“cfDNA”) circulating in a recipient’s body. The specification, common to all three patents, depicts prior findings that the existence of cfDNA in blood is mostly attributed to dead cells, and had been used for various diagnostic purposes, such as cancer diagnostics and prenatal testing. The specification notes that the cfDNA-based diagnostic scheme is applicable to organ transplant situations, where the recipient’s immune system kills incompatible donor’s cells which in turn release their nucleic acids into the recipient’s stream, such that an increased level of the donor-derived cfDNA may allow for detection of the transplant rejection.
Claim 1 of ‘652 patent recites:
1. A method for detecting transplant rejection, graft dysfunction, or organ failure, the method comprising:
(a) providing a sample comprising cell-free nucleic acids from a subject who has received a transplant from a donor;
(b) obtaining a genotype of donor-specific polymorphisms or a genotype of subject-specific polymorphisms, or obtaining both a genotype of donor-specific polymorphisms and subject-specific polymorphisms, to establish a polymorphism profile for detecting donor cell-free nucleic acids, wherein at least one single nucleotide polymorphism (SNP) is homozygous for the subject if the genotype comprises subject-specific polymorphisms comprising SNPs;
(c) multiplex sequencing of the cell-free nucleic acids in the sample followed by analysis of the sequencing results using the polymorphism profile to detect donor cell-free nucleic acids and subject cell-free nucleic acids; and
(d) diagnosing, predicting, or monitoring a transplant status or outcome of the subject who has received the transplant by determining a quantity of the donor cell-free nucleic acids based on the detection of the donor cell-free nucleic acids and subject cell-free nucleic acids by the multiplexed sequencing, wherein an increase in the quantity of the donor cell-free nucleic acids over time is indicative of transplant rejection, graft dysfunction or organ failure, and wherein sensitivity of the method is greater than 56% compared to sensitivity of current surveillance methods for cardiac allograft vasculopathy (CAV).
The representative claims of the three patents recite somewhat similar procedures, which may be summarized as:
- collecting a bodily sample from the recipient,
- “genotyping” or identifying genetic features that allow for distinction between the donor and recipient,
- “sequencing” or determining the makeup of cfDNA included in the sample, and
- determining, using the genetic features, the amount of cfDNA originating from the donor in the sample.
The specification depicts that the methods are performed using specific techniques that are “standard,” “well-established” and/or reported in prior patents and scientific articles, including sophisticated polymerase chain reaction (“PCR”), such as digital PCR and selective amplification, and next-generation sequencing (“NGS”), all of which are advanced, but already known, techniques in the field.
The district court held that that the asserted claims were patent ineligible as they were “directed to the detection of natural phenomena, specifically, the presence of donor cfDNA in a transplant recipient and the correlation between donor cfDNA and transplant rejection” and also, “recited only conventional techniques.”
On appeal, the CAFC performed the two-step Alice/Mayo analysis to determine patent-eligibility.
- Are the claims “directed to” laws of nature or natural phenomena? – Yes.
CareDx sought to characterize the claimed invention as directed to “improved measurement methods,” in particular, patent-eligible “use of digital PCR, NGS, and selective amplification” allowing for improved accuracy in cfDNA measurement, as opposed to “discovery of a natural correlation between organ rejection and the donor’s cfDNA levels in the recipient’s blood.” CareDx also asserted that the district court improperly considered conventionality of the claimed techniques at step one, essentially merging the two steps into a single-step analysis centered on conventionality.
The CAFC found that the claims satisfy the step one. Two contrasting precedents are notable: Illumina, Inc. v. Ariosa Diagnostics, Inc., 952 F.3d 1367, opinion modified by 967 F.3d 1319, 1327 (Fed. Cir. 2020), and Ariosa Diagnostics, Inc. v. Sequenom, Inc., 788 F.3d 1371 (Fed. Cir. 2015). The CAFC noted that this case is different from Illumina, where the claimed improvement was a patent-eligible “method for preparing” a cfDNA fraction that would not occur naturally without manipulation of a starting sample; rather, the asserted claims are akin to those in Ariosa, wherein the claimed diagnostic methods, including the steps of “amplifying” (i.e., making many copies of) a cfDNA sample using PCR and “detecting” a certain type of cfDNA, so as to perform diagnosis using a natural correlation between certain conditions and the level of cfDNA, were found to be “directed to a natural phenomenon.”
The CAFC noted that the conventionally considerations are not limited to step two, and precedents have routinely performed overlapping conventionality inquiry at both stages of Alice/Mayo. The CAFC found that the use of specific laboratory techniques relied on by CareDx only amounts to “conventional use of existing techniques to detect naturally occurring cfDNA.” The CAFC added that the conventionality is supported by the specification’s numerous remarks characterizing the claimed techniques as “any suitable method known in the art” and similar boilerplate language.
- Do the claims recite additional elements, aside from the natural phenomena, which transform the nature of the claim’ into a patent-eligible application? – No.
CareDx’s main argument at step two was that the inventive concept resides in the use of the specific advanced techniques to identify and measure donor-derived cfDNA.
The CAFC disagreed, concluding that the claimed methods lack requisite inventive concept. In reaching the conclusion, the CAFC again pointed to the specification’s admissions of the conventionality of the individual techniques recited in the claims. The CAFC went on to state that “[t]he specification confirms that the claimed combination of steps … was a straightforward, logical, and conventional method for detecting cfDNA previously used in other contexts,” which adds nothing inventive to the detection of natural phenomena.
Takeaway
This case provides a reminder that conventionality of claimed elements may affect both steps of Alice/Mayo test. At step one, the effort to characterize the claim as being “directed to” a patent-eligible subject matter can be thwarted where the claimed elements are undisputedly conventional, in the absence of an unconventional element that is not a judicial exception to eligibility. And at step two, the conventionality of the individual elements and their combination prohibits finding of inventive concept.
