CareDx, Inc. v. Natera, Inc.

563 F.Supp.3d 329

CAREDX, INC. and The Board of Trustees of the Leland Stanford Junior University, Plaintiffs,

v.NATERA, INC., Defendant.

CareDx, Inc. and The Board of Trustees of the Leland Stanford Junior University, Plaintiffs,

v.Eurofins Viracor, Inc., Defendant.

Civil Action No. 19-0567-CFC-CJB CONSOLIDATED

Civil Action No. 19-1804-CFC-CJB

United States District Court, D. Delaware.

Signed September 28, 2021

Brian Farnan, Michael Farnan, FARNAN LLP, Wilmington, Delaware; Derek Walter, Edward Reines, WEIL, GOTSHAL & MANGES LLP, Redwood Shores, California; Stephen Bosco, WEIL, GOTSHAL & MANGES LLP, Washington, District of Columbia, Counsel for Plaintiffs.

Jack Blumenfeld, Anthony Raucci, Derek Fahnestock, MORRIS, NICHOLS, ARSHT & TUNNELL LLP, Wilmington, Delaware; Kevin Johnson, QUINN EMANUEL URQUHART & SULLIVAN, LLP, Redwood Shores, California; Andrew Holmes, Carl Anderson, Felipe Corredor, QUINN EMANUEL URQUHART & SULLIVAN, LLP, San Francisco, California; Sandra Haberny, QUINN EMANUEL URQUHART & SULLIVAN, LLP, Los Angeles, California, Counsel for Defendant Natera, Inc.

John Shaw, Karen Keller, David Fry, Nathan Hoeschen, SHAW KELLER LLP, Wilmington, Delaware; J. Anthony Downs, GOODWIN PROCTER LLP, Boston, Massachusetts; Darryl Woo, GOODWIN PROCTER LLP, San Francisco, California; Beth Ashbridge, GOODWIN PROCTER LLP, New York, New York; Myomi Coad, GOODWIN PROCTER LLP, Washington, District of Columbia, Counsel for Defendant Eurofins Viracor, Inc.

MEMORANDUM OPINION

COLM F. CONNOLLY, CHIEF JUDGE

Plaintiffs CareDx, Inc. and the Board of Trustees of the Leland Stanford Junior University (collectively, CareDx) have sued Defendants Natera, Inc. (C.A. No. 19-0567) and Eurofins Viracor, Inc. (C.A. No. 19-1804) for patent infringement. On December 1, 2020, I denied Natera's and Eurofins's motions for summary judgment of invalidity of the asserted patents under 35 U.S.C. § 101. C.A. No. 19-0567, D.I. 115; C.A. No. 19-1804, D.I. 76. I subsequently decided, after identifying material facts that may not be genuinely in dispute, to reconsider summary judgment of invalidity of the asserted patents on my own pursuant to Federal Rule of Civil Procedure 56(f)(3) and the Court's inherent authority.¹ I held an evidentiary hearing and permitted the parties to submit briefing after the hearing. I have now determined, for the reasons set forth below, that there are no genuine disputes of material fact and that summary judgments in Defendants’ favor are warranted because the asserted patents claim patent-ineligible subject matter and are therefore invalid under § 101. See Fed. R. Civ. P. 56(a) ("The court shall grant summary judgment if the movant shows that there is no genuine dispute as to any material fact and the movant is entitled to judgment as a matter of law.").

I. THE ASSERTED PATENTS

CareDx has asserted three patents: U.S. Patent Numbers 8,703,652 (the #652 patent) (asserted against Natera and Eurofins); 9,845,497 (the #497 patent) (asserted against Natera); and 10,329,607 (the #607 patent) (asserted against Natera). As described by CareDx in the operative Amended Complaint against Natera, all three patents disclose "method[s] for determining organ transplant rejection" that "allow[ ] doctors to assess rejection through blood tests and without invasive biopsies." C.A. No. 19-0567, D.I. 74 ¶ 1.² An important determinant of the success or failure of an organ transplant is whether, and the extent to which, the recipient's body "rejects" the organ and attacks it with the body's immune system. Early detection of rejection is crucial to a transplant operation's success and the recipient's survival.

The methods disclosed in the patents, to use CareDx's words, "detect [ ] particular concentrations of donor-specific, cell-free DNA in the bodies of donor recipients ...." D.I. 15 at 3. The linkage between concentrations of the organ donor's cell-free DNA (cfDNA) found in the recipient's blood after the organ transplant and the likelihood that the recipient will reject the newly transplanted organ was "long-known" before 2009, when the applications for the asserted patents were filed with the United States Patent and Trademark Office (PTO). D.I. 176 at 2. According to CareDx, attempts to detect the concentration of donor-specific cfDNA as of 2009 were "deficient," and the methods claimed by the asserted patents "improved on these deficiencies [sic ] through the use of innovative, highly precise assays capable of detecting tiny increases in donor-specific DNA, thereby allowing doctors to recognize the onset of organ rejection before the damage becomes irreversible." D.I. 15 at 2.

The three asserted patents share a single written description and are all titled "Non-invasive Diagnosis of Graft Rejection in Organ Transplant Patients." Each patent has a priority date in November 2009. The shared written description states that the claimed "invention describes sensitive and non-invasive methods ... for diagnosing or predicting transplant status or outcome (e.g. transplant rejection)." #657 patent at 3:52–55.³ A detection method is said to be "sensitive" in two respects. Sensitivity can refer to the smallest absolute amount of change that can be detected by a method, Tr. of May 17, 2021 Hr'g at 96:25–97:14; or it can refer to the method's ability to correctly identify a patient with a particular disease, id. at 111:9–22.

CareDx alleged in its operative complaints that claim 1 of each asserted patent is "representative." See D.I. 74 ¶¶ 20, 23, 26; C.A. No. 19-1804, D.I. 1 ¶ 17. Defendants assert, and CareDx does not dispute, that claim 1 in each patent is sufficiently similar to the respective patent's other claims to be deemed a representative claim for determining whether the patent claims patent-eligible subject matter.

Claim 1 of the #652 patent recites:

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).

Claim 1 of the #497 patent recites:

A method of detecting donor-specific circulating cell-free nucleic acids in a solid organ transplant recipient, the method comprising:

(a) genotyping a solid organ transplant donor to obtain a single nucleotide polymorphism (SNP) profile of the solid organ transplant donor;

(b) genotyping a solid organ transplant recipient to obtain a SNP profile of the solid organ transplant recipient, wherein the solid organ transplant recipient is selected from the group consisting of: a kidney transplant, a heart transplant, a liver transplant, a pancreas transplant, a lung transplant, a skin transplant, and any combination thereof;

(c) obtaining a biological sample from the solid organ transplant recipient after the solid organ transplant recipient has received the solid organ transplant from the solid organ transplant donor, wherein the biological sample is selected from the group consisting of blood, serum and plasma, and wherein the biological sample comprises circulating cell-free nucleic acids from the solid organ transplant ; and

(d) determining an amount of donor-specific circulating cell-free nucleic acids from the solid organ transplant in the biological sample by detecting a homozygous or a heterozygous SNP within the donor-specific circulating cell-free nucleic acids from the solid organ transplant in at least one assay, wherein the at least one assay comprises high-throughput sequencing or digital polymerase chain reaction (dPCR), and

wherein the at least one assay detects the donor-specific circulating cell-free nucleic acids from the solid organ transplant when the donor-specific circulating cell-free nucleic acids make up at least 0.03% of the total circulating cell-free nucleic acids in the biological sample.

Claim 1 of the #607 patent recites:

A method of quantifying kidney transplant-derived circulating cell-free deoxyribonucleic acids in a human kidney transplant recipient, said method comprising:

(a) providing a plasma sample from said human kidney transplant recipient, wherein said human kidney transplant recipient has received a kidney transplant from a kidney transplant donor, wherein said plasma sample from said human kidney transplant recipient comprises kidney transplant-derived circulating cell-free deoxyribonucleic acid and human kidney transplant recipient-derived circulating cell-free deoxyribonucleic acid;

(b) extracting circulating cell-free deoxyribonucleic acid from said plasma sample from said human kidney transplant recipient in order to obtain extracted circulating cell-free deoxyribonucleic acid, wherein said extracted circulating cell-free

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