CareDx Inc v. Tai Diagnostics Inc

I. Executive Summary and Procedural Information

• Parties & Counsel:
  • Plaintiff: CareDx, Inc. (Delaware) and The Board of Trustees of The Leland Stanford Junior University (California)
  • Defendant: Tai Diagnostics, Inc. (Delaware)
  • Plaintiff’s Counsel: Farnan LLP; Weil, Gotshal & Manges LLP
• Case Identification: 1:20-cv-00486, D. Del., 04/08/2020
• Venue Allegations: Venue is asserted in the District of Delaware based on Defendant Tai Diagnostics, Inc. being a Delaware corporation.
• Core Dispute: Plaintiffs allege that Defendant’s non-invasive heart transplant rejection test infringes a patent related to methods for detecting donor-specific nucleic acids in a transplant recipient.
• Technical Context: The technology involves using quantitative analysis of donor-derived cell-free DNA (dd-cfDNA) in a recipient's blood as a biomarker to non-invasively monitor the health of a transplanted organ.
• Key Procedural History: The patent-in-suit is exclusively licensed from Stanford to CareDx. The complaint notes that the patent shares a common specification with two related patents (U.S. Patent Nos. 9,845,497 and 8,703,652) that were the subject of a prior judicial opinion finding the claims were not directed to a natural law or phenomenon.

Case Timeline

Date	Event
2009-11-06	U.S. Patent No. 10,494,669 Priority Date
2019-01-01	Alleged commercial launch of myTAIHEART test (stated as "in 2019")
2019-12-03	U.S. Patent No. 10,494,669 Issue Date
2020-01-13	Tai-affiliated scientists publish PLOS One article on myTAIHEART test
2020-04-08	Complaint Filed

II. Technology and Patent(s)-in-Suit Analysis

U.S. Patent No. 10,494,669 - "Non-Invasive Diagnosis of Graft Rejection in Organ Transplant Patients"

• Patent Identification: U.S. Patent No. 10494669, "Non-Invasive Diagnosis of Graft Rejection in Organ Transplant Patients", issued December 3, 2019.

The Invention Explained

• Problem Addressed: The patent describes the monitoring of organ transplant patients for rejection as difficult, expensive, and often reliant on invasive procedures like biopsies, which lack adequate sensitivity and carry risks (’669 Patent, col. 1:36-39, col. 5:9-12). Current surveillance methods for cardiac allograft vasculopathy (CAV), a major cause of late graft failure, are noted as being costly and resource-intensive ('669 Patent, col. 6:40-43).
• The Patented Solution: The invention provides a non-invasive method for detecting transplant rejection by quantifying donor-derived genetic material in the recipient’s bloodstream ('669 Patent, col. 1:49-57). The method involves first genotyping both the donor and recipient to identify a set of distinguishing polymorphic markers, such as single nucleotide polymorphisms (SNPs) ('669 Patent, col. 9:15-23). After transplantation, a biological sample (e.g., blood plasma) is taken from the recipient, and the amount of donor-specific cell-free DNA is quantified using these pre-identified markers, with an increase in this amount indicating potential graft rejection ('669 Patent, FIG. 5; col. 14:41-48).
• Technical Importance: This approach provides a universal, non-invasive method for monitoring allograft health that is independent of the gender of the donor and recipient, aiming to circumvent issues with prior art methods and provide a more sensitive and cost-effective tool than traditional biopsies ('669 Patent, col. 9:3-14).

Key Claims at a Glance

• The complaint asserts independent claim 1 (Compl. ¶19).
• Essential elements of claim 1 include:
  • (a) genotyping a heart transplant donor to obtain a single nucleotide polymorphism (SNP) profile;
  • (b) genotyping a heart transplant recipient to obtain a SNP profile;
  • (c) obtaining a biological sample (blood, serum, or plasma) from the recipient post-transplant containing circulating cell-free nucleic acids;
  • (d) performing quantitative polymerase chain reaction (qPCR) on the cell-free DNA to amplify at least 10 different DNA targets that comprise at least 10 informative SNPs; and
  • (e) quantifying the amount of heart transplant-derived cell-free DNA, wherein the quantified amount comprises at least 0.03% of the total circulating cell-free DNA in the sample.
• The complaint alleges infringement of "multiple claims" and reserves the right to modify its allegations, which may suggest an intent to assert additional or dependent claims later in the proceedings (Compl. ¶21, ¶28).

III. The Accused Instrumentality

Product Identification

• The accused instrumentality is Defendant Tai's "myTAIHEART test" (Compl. ¶10). No probative visual evidence provided in complaint.

Functionality and Market Context

• The "myTAIHEART test" is described as a non-invasive test for heart transplant rejection performed at Tai's CLIA-certified laboratory (Compl. ¶10).
• The test's methodology, as alleged in the complaint by reference to a PLOS One article, involves taking initial donor and recipient samples to establish a "baseline signature of 94 SNPs in genomic DNA" (Compl. ¶17). Post-transplant, the test uses "multiplexed, high-fidelity amplification followed by allele-specific qPCR of 94 SNP targets" on the recipient's blood plasma to detect and quantify the donor DNA fraction (Compl. ¶17, ¶20).
• The complaint alleges that rising levels of this donor fraction are used as a biomarker indicating a potential for transplant rejection (Compl. ¶17). The test was allegedly launched commercially in 2019 (Compl. ¶18).

IV. Analysis of Infringement Allegations

10,494,669 Infringement Allegations

Claim Element (from Independent Claim 1)	Alleged Infringing Functionality	Complaint Citation	Patent Citation
(a) genotyping a heart transplant donor to obtain a single nucleotide polymorphism (SNP) profile of said heart transplant donor;	The myTAIHEART test is alleged to develop a SNP profile of the donor by taking an initial donor sample to establish a "baseline signature of 94 SNPs."	¶17, ¶20	col. 9:15-18
(b) genotyping a heart transplant recipient to obtain a SNP profile of the heart transplant recipient;	The myTAIHEART test is alleged to develop a SNP profile of the recipient by taking an initial recipient sample to establish a "baseline signature of 94 SNPs."	¶17, ¶20	col. 9:15-18
(c) obtaining a biological sample from said heart transplant recipient after said heart transplant recipient has received a heart transplant..., wherein said biological sample is selected from the group consisting of blood, serum and plasma...	The complaint alleges that "Blood samples are collected from a heart transplant recipient" and that the myTAIHEART test quantifies changes in the "cell-free DNA donor fraction (DF) of blood plasma samples."	¶16, ¶20	col. 2:1-2
(d) performing one or more quantitative polymerase chain reaction (PCR) reactions... wherein said one or more quantitative PCR reactions amplify at least 10 different deoxyribonucleic acid targets, and wherein said at least 10 different deoxyribonucleic acid targets comprise at least 10 informative SNPs; and	The complaint alleges the myTAIHEART test uses "multiplexed, high-fidelity amplification followed by allele-specific qPCR of 94 SNP targets," which satisfies the requirement for at least 10 targets and at least 10 informative SNPs.	¶20	col. 14:30-34
(e) quantifying an amount of heart transplant-derived circulating cell-free deoxyribonucleic acid... wherein said quantified amount... comprises at least 0.03% of the total circulating cell free deoxyribonucleic acid from said biological sample...	The complaint alleges that the myTAIHEART test "can then detect and quantify donor DNA in the transplant recipient’s blood and calculate a donor fraction," and asserts that performance of the test leads to infringement of this claim element.	¶17, ¶20	col. 18:47-54

• Identified Points of Contention:
  • Technical Questions: A primary technical question is whether the accused myTAIHEART test meets the quantitative threshold of the final claim element. The complaint alleges infringement but does not provide specific facts showing that the "quantified amount" of donor-derived DNA in an accused test "actually comprises" "at least 0.03% of the total circulating cell free deoxyribonucleic acid." The litigation may focus on whether this limitation requires the result to always be above 0.03% for infringement, or if it defines the method's sensitivity or capability.
  • Scope Questions: The definition of "informative SNPs" may be disputed. The court may need to determine if this term encompasses any SNP that distinguishes a donor from a recipient, or if it implies a more specific set of markers with particular characteristics (e.g., homozygosity in both individuals, as described in the patent's specification) that must be proven.

V. Key Claim Terms for Construction

• The Term: "informative SNPs"

• Context and Importance: This term appears in claim 1, elements (d) and (e), and defines the specific genetic markers used for both amplification and quantification. Its construction is critical because it dictates the universe of markers that can be used in an infringing method. Practitioners may focus on this term because its precise meaning will determine whether the 94 SNPs allegedly used by Defendant qualify under the claim.

• Intrinsic Evidence for Interpretation:

  • Evidence for a Broader Interpretation: The specification suggests a broad purpose of identifying markers that are "distinguishable between the transplant donor and the subject receiving the transplant" ('669 Patent, col. 2:19-21). This could support a construction where any SNP that allows for such differentiation is "informative."
  • Evidence for a Narrower Interpretation: The specification also provides more specific examples, noting that "Usable SNPs must be homozygous for the recipient and ideally homozygous for the donor as well" to allow for a direct read to distinguish donor from recipient DNA ('669 Patent, col. 14:12-18). This language could support a narrower construction requiring proof of specific zygosity characteristics for a SNP to be considered "informative."

• The Term: "wherein said quantified amount ... comprises at least 0.03% of the total circulating cell free deoxyribonucleic acid"

• Context and Importance: This limitation in claim 1, element (e), sets a quantitative floor. Its interpretation is central to the infringement analysis. Practitioners may focus on this term because it appears to be a condition on the outcome of the method step, and the complaint lacks specific factual allegations that the accused test produces results meeting this threshold.

• Intrinsic Evidence for Interpretation:

  • Evidence for a Broader Interpretation (e.g., as a capability): The specification describes the method's high sensitivity, stating that it should have a sensitivity "capable of detecting donor molecules when the donor fraction is as low as 0.03%" ('669 Patent, col. 18:50-54). This may support an argument that the claim recites the capability of the method, rather than a condition that must be met in every instance of infringement.
  • Evidence for a Narrower Interpretation (e.g., as a required result): The claim language uses the phrase "wherein said quantified amount ... comprises," which directly modifies the result of the "quantifying" step. This phrasing may support an interpretation that for infringement to occur, the specific act of quantification must yield a result that is, in fact, at least 0.03%.

VI. Other Allegations

• Indirect Infringement: The complaint does not contain separate counts for indirect or induced infringement. The core allegation is that Tai itself performs the patented method, pointing to direct infringement under 35 U.S.C. § 271(a) (Compl. ¶28).
• Willful Infringement: The complaint does not contain allegations of willful infringement or pre-suit knowledge of the patent-in-suit.

VII. Analyst’s Conclusion: Key Questions for the Case

1. A central evidentiary question will be one of quantitative proof: Does the myTAIHEART test, in practice, result in a "quantified amount" of donor-derived DNA that "comprises at least 0.03% of the total circulating cell free deoxyribonucleic acid," as required by claim 1? The case may turn on whether this is interpreted as a required outcome for every infringing act or as a statement of the method's potential sensitivity.

2. A key legal question will be one of definitional scope: How will the court construe the term "informative SNPs"? The outcome will determine whether the 94 SNPs allegedly used in the accused test meet this limitation, potentially hinging on whether the term requires specific homozygosity characteristics as suggested by the patent's examples.

3. A foundational issue will be the link between public documents and the accused product: The complaint's infringement theory relies heavily on a PLOS One article and press releases to describe the myTAIHEART test. A key question for discovery will be whether the commercially practiced test operates identically to the methods described in those public-facing documents.