Caredx Inc., the Board of Trustees of the Leland Stanford Junior University v. Natera, Inc. and Eurofins Viracor, Inc.

• Publication year: 2022
• Author: D. Benjamin Borson

CAREDX INC., THE BOARD OF TRUSTEES OF THE LELAND STANFORD JUNIOR UNIVERSITY V. NATERA, INC. AND EUROFINS VIRACOR, INC.

D. Benjamin Borson
Borson Law Group P.C.

CAREDX INC., THE BOARD OF TRUSTEES OF THE LELAND STANFORD JUNIOR UNIVERSITY V. NATERA, INC. AND EUROFINS VIRACOR, INC.

United States Court of Appeals for the Federal Circuit, Slip. Op. 2022-1027.

BACKGROUND

CareDx, Inc. is the owner of U.S. Patent Nos. 8,703,652 (the ''652 patent'), 9,845,497 (the '497 patent) and 10,329,607 (the '607 patent). These 3 patents share the same specification. The claims are drawn to methods for diagnosing transplant rejections by using methods to detect a donor's cell-free DNA ("cfDNA"). According to the description in the Federal Circuit's decision by Judges Lourie, Bryson, and Hughes, Judge Lourie explained:

When an organ transplant is rejected, the recipient's body, through its natural immune response destroys the donor cells, thus releasing cfDNA from the donated organ's dying cells into the blood. These increased levels of donor cfDNA—which occur naturally as the organ's condition deteriorates—can be detected and then used to diagnose the likelihood of an organ transplant rejection. Slip Op at 2.

A representative claim of the '652 patent is:

1. A method for detecting transplant rejection, graft dysfunction, or organ failure, the method comprising:
(a) providing a sample comprising [cfDNA] 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

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donor cfDNA], 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 [cfDNA] in the sample followed by analysis of the sequencing results using the polymorphism profile to detect donor [cfDNA] and subject [cfDNA]; 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 [cfDNA] based on the detection of the donor [cfDNA] and subject [cfDNA] by the multiplexed sequencing, wherein an increase in the quantity of the donor [cfDNA] 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). '652 patent at col. 27 l. 39-col. 28 l. 40.

The other 2 patents have different limitations on the methods used to detect cfDNA, but they all share the same problems under 35 U.S.C. § 101. As Judge Lourie explained:

In summary, the methods disclosed in the representative claims have four steps for detecting cfDNA in a transplant recipient:
1) "obtaining" or "providing a "sample" from the recipient that contains cfDNA;
2) "genotyping" the transplant donor and/or recipient to develop "polymorphism: or "SNP" profiles;
3) "sequencing" the cfDNA from the sample using "mutltiplex" or "high-throughput" sequencing; or performing "digital PCR"; and
4) "determining" or "quantifying" the amount of donor cfDNA. Id. at 8.

CareDx is the exclusive licensee of these patents and sued Natera for infringement of the claims. CareDx also sued Eurofins, alleging that their transplant rejection tests infringed one or more claims of CareDx's licensed patents. The case was heard in the district court of Delaware. The magistrate judge held that the claims were a "purportedly new, unconventional combination of steps" to detect natural phenomena." Id. However, the magistrate judge reasoned: "language in the written description of the asserted patents suggested that the patented steps are neither new nor unconventional" and that the "specifications raised doubts about the patent's validity." Id. at 9.

The district court vacated the magistrate judge's recommendation and permitted the parties to conduct limited discovery and develop the record on conventionality.

After the limited discovery, Natera and Eurofins moved for summary judgment of ineligibility. According to Judge Lourie:

[F]ollowing reconsideration, the district court granted the summary judgment motions of ineligibility, because "the claims 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. The court concluded that the specification's admissions, the claims recited only conventional techniques." Id.

CareDx appealed to the Federal Circuit. Judge Lourie discussed Section 101, as "anything under the sun made by man" (citing Diamond v. Chakrabarty 447 US 303, 308-09 (1980)). He went on to describe "implicit exceptions "[l]aws of nature, natural phenomena, and abstract ideas are not patentable." Citing Mayo v. Prometheus 566 US 66 at 70 (2012)." Id. at 10.

Judge Lourie noted that "a claim to otherwise eligible statutory subject matter does not become ineligible by its use of a law of nature of natural

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phenomenon. (citing Diamond v. Diehr, 450 U.S. 175 at 187 (1981)).

CareDx argued that the claims are directed to improved methods for detecting transplant rejection using a novel combination of methods that are "superior to inadequate prior art measurement techniques." Id. at 11.

However, Judge Lourie found that this case is not like that of Illumina, Inc. v. Ariosa Diagnostics, Inc. 952 F.3d at 1367 (2020)), which held that "a new and improved 'method for preparing' an unnaturally enriched fetal cfDNA fraction was unlike claims merely directed to starting with a sample that contains' cfDNA and 'seeing that the cfDNA exists.'" Id. at 13.

Further, Judge Lourie found admissions in the specification asserting that "the patents' written description expressly states that the techniques referred to in the claim steps are, "unless otherwise indicated, conventional techniques of immunology biochemistry, chemistry, molecular biology, microbiology, cell biology, genomics and recombinant DNA, which are well within the skill of art." Id. at 13 bridging to 14, emphasis added.

In light of the above, Judge Lourie held "the claimed methods are indistinguishable from...