DCT

1:23-cv-00629

Natera Inc v. NeoGenomics Laboratories Inc

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I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 1:23-cv-00629, M.D.N.C., 12/10/2024
  • Venue Allegations: Venue is alleged to be proper based on Defendant operating a regular and established place of business, a CAP/CLIA-certified laboratory, in Durham, North Carolina, where acts of infringement have allegedly occurred.
  • Core Dispute: Plaintiff alleges that Defendant’s RaDaR™ Minimum Residual Disease Assay infringes patents related to methods for preparing and analyzing cell-free DNA to detect and monitor cancer-specific genetic mutations.
  • Technical Context: The technology at issue is in the field of non-invasive genetic testing, or "liquid biopsies," which analyze trace amounts of circulating tumor DNA in a patient's blood to monitor for cancer recurrence.
  • Key Procedural History: The complaint notes that Defendant’s earlier "RaDaR 1.0" assay was subject to a permanent injunction in separate litigation. In that context, Defendant allegedly agreed not to contest that RaDaR 1.0 infringed claims of the ’454 Patent and that the claims were valid and enforceable. The current complaint accuses both RaDaR 1.0 and a modified version, "RaDaR 1.1," which was allegedly developed after the initial injunction.

Case Timeline

Date Event
2014-04-21 ’596 Patent Priority Date
2015-04-15 ’454 Patent Priority Date
2017-01-01 Natera launches Signatera test
2019-05-06 FDA grants first "Breakthrough Device" designation for Signatera
2022-05-03 ’596 Patent Issued
2022-12-20 ’454 Patent Issued
2022-12-20 Natera files lawsuit against Defendant's affiliates asserting the '454 Patent
2023-03-16 Defendant begins selling RaDaR 1.0 in the U.S.
2023-07-27 RaDaR 1.0 obtains Medicare coverage for breast cancer recurrence
2023-12-27 RaDaR 1.0 assay is preliminarily enjoined
2024-03-01 Defendant enters feasibility stage of development for "RaDaR 1.1"
2024-09-23 RaDaR 1.0 assay is permanently enjoined
2024-12-10 First Amended Complaint Filed

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

U.S. Patent No. 11,530,454 - "Detecting Mutations and Ploidy in Chromosomal Segments"

  • Patent Identification: U.S. Patent No. 11,530,454, "Detecting Mutations and Ploidy in Chromosomal Segments," issued December 20, 2022 (the "’454 Patent").

The Invention Explained

  • Problem Addressed: The patent addresses the technical difficulty of non-invasively detecting cancer markers, which requires measuring extremely small quantities of circulating-tumor DNA (ctDNA) within a much larger background of normal cell-free DNA (cfDNA) in a blood sample (Compl. ¶5; ’454 Patent, col. 44:48-56).
  • The Patented Solution: The invention provides a personalized, two-stage method. First, a patient’s tumor tissue is sequenced (e.g., whole genome sequencing) to identify a set of single nucleotide variant (SNV) mutations unique to that patient's cancer. Second, a highly sensitive "targeted multiplex amplification" process is performed on cfDNA from the patient's plasma to simultaneously search for many of those specific tumor mutations at once, followed by deep sequencing to confirm their presence (Compl. ¶27; ’454 Patent, Abstract; ’454 Patent, col. 97:28-44).
  • Technical Importance: This patient-specific approach to cfDNA analysis enables the creation of a personalized "liquid biopsy" for monitoring cancer recurrence or treatment response with high sensitivity (Compl. ¶17-18).

Key Claims at a Glance

  • The complaint asserts at least one claim and recites independent claim 1 (Compl. ¶27, 57).
  • Essential elements of independent claim 1 include:
    • Performing whole exome or whole genome sequencing on a subject's tumor sample to identify a plurality of tumor-specific SNV mutations.
    • Performing targeted multiplex amplification on cfDNA from a plasma sample to amplify 10 to 500 target loci, each containing a different identified tumor-specific SNV.
    • The amplification must produce amplicons of 50-150 bases and occur for all target loci together in the same reaction volume.
    • Sequencing the amplicons to a depth of read of at least 50,000 per target locus to detect the tumor-specific SNVs.

U.S. Patent No. 11,319,596 - "Detecting Mutations and Ploidy in Chromosonal Segments"

  • Patent Identification: U.S. Patent No. 11,319,596, "Detecting Mutations and Ploidy in Chromosonal Segments," issued May 3, 2022 (the "’596 Patent").

The Invention Explained

  • Problem Addressed: Similar to the ’454 Patent, this invention targets the challenge of detecting and monitoring cancer by identifying minuscule amounts of ctDNA in a patient's blood (Compl. ¶5; ’596 Patent, col. 1:35-2:56).
  • The Patented Solution: The patent claims a method for monitoring cancer progression over time. The process involves sequencing a tumor biopsy to identify patient-specific mutations, defining target loci based on those mutations, and then assaying cfDNA from blood samples taken at different time points. The assay step uses targeted multiplex PCR and high-throughput sequencing with sufficient sensitivity to detect SNV mutations that are present at extremely low frequencies (e.g., 0.015% or less of the total cfDNA) (Compl. ¶31; ’596 Patent, col. 172:42-173:7).
  • Technical Importance: The claimed method provides a framework for highly sensitive, longitudinal monitoring of a patient's cancer, potentially allowing clinicians to detect recurrence much earlier than with traditional imaging methods (Compl. ¶18).

Key Claims at a Glance

  • The complaint asserts at least one claim and recites independent claim 1 (Compl. ¶31, 62).
  • Essential elements of independent claim 1 include:
    • (a) Performing sequencing on a tumor biopsy sample to identify a plurality of tumor-specific SNV mutations.
    • (b) Evaluating the sequencing results to determine a plurality of subject-specific target loci.
    • (c) Assaying cfDNA from a plurality of biological samples obtained from the subject at different time points.
    • The assaying step includes performing targeted multiplex PCR to amplify the target loci together in the same reaction volume.
    • The assaying step also includes performing high-throughput sequencing where an SNV mutation present at a level of less than or equal to 0.015% of the cfDNA is detected.

III. The Accused Instrumentality

Product Identification

  • The accused instrumentality is the "RaDaR™ Minimum Residual Disease Assay," which includes versions identified as "RaDaR 1.0" and "RaDaR 1.1," as well as any other similar products or assays from the Defendant (Compl. ¶11, 43).

Functionality and Market Context

  • The RaDaR assay is described as a "liquid biopsy test for MRD [minimal residual disease]" used for cancer detection and monitoring (Compl. ¶11, 47). The complaint alleges the test is performed on a blood sample in Defendant's laboratory (Compl. ¶45). Plaintiff positions the RaDaR assay as a direct competitor to its own Signatera® product in the market for personalized, tumor-informed cancer recurrence monitoring (Compl. ¶50).

IV. Analysis of Infringement Allegations

The complaint incorporates by reference Exhibits 2 and 3, described as "preliminary and exemplary claim charts" for the ’454 and ’596 Patents, respectively; however, these exhibits were not included with the provided complaint document (Compl. ¶38). In their absence, the infringement theory is summarized from the complaint's narrative allegations.

  • ’454 Patent Infringement Allegations: The complaint alleges that Defendant, by performing or directing the performance of the RaDaR assay, practices a method that meets every element of at least one claim of the ’454 Patent (Compl. ¶36, 57). The narrative suggests that the RaDaR assay is a process that begins with sequencing a patient's tumor to identify unique SNV mutations, which are then used to design a personalized panel for a subsequent blood test. That blood test allegedly involves targeted multiplex amplification of cfDNA from plasma and high-depth sequencing to detect the previously identified tumor markers, mirroring the steps of claim 1 (Compl. ¶27).
  • ’596 Patent Infringement Allegations: The complaint alleges that the process for the RaDaR assay practices every element of at least one claim of the ’596 Patent (Compl. ¶37, 62). The narrative theory suggests that the RaDaR assay is used for longitudinal monitoring by testing blood samples over time. This process allegedly involves an initial tumor sequencing step to define patient-specific targets, followed by a highly sensitive multiplex PCR and sequencing assay on cfDNA from blood samples to detect mutations at frequencies as low as the claimed 0.015% threshold (Compl. ¶31).

No probative visual evidence provided in complaint.

  • Identified Points of Contention:
    • Numerical and Functional Limitations: A central dispute may concern whether the accused RaDaR assay consistently meets the specific numerical parameters of the claims, such as the number of target loci ("10 to 500"), amplicon length ("50-150 bases"), and sequencing depth ("at least 50,000") in the ’454 Patent, or the functional sensitivity threshold ("less than or equal to 0.015%") in the ’596 Patent.
    • Scope of Prior Agreement: For the ’454 Patent, a key issue may be the technical differences between the enjoined "RaDaR 1.0" assay and the accused "RaDaR 1.1" assay. The litigation may focus on whether any modifications to the assay are sufficient to place it outside the scope of the claims that Defendant previously agreed it infringed (Compl. ¶42-43).

V. Key Claim Terms for Construction

  • The Term: "depth of read of at least 50,000 per target locus" (’454 Patent, Claim 1)

    • Context and Importance: This term sets a high, specific, and quantitative requirement for the sequencing step. The viability of the infringement allegation may depend on how "depth of read" is calculated and whether the accused process consistently achieves this minimum threshold for each targeted locus.
    • Intrinsic Evidence for Interpretation:
      • Evidence for a Broader Interpretation: The specification discusses various sequencing depths, including examples of "at least 1,000 reads" or "at least 3,000 reads," which may suggest that the claimed number is one possible embodiment of a more general principle of deep sequencing needed for high sensitivity (’454 Patent, col. 100:2-4).
      • Evidence for a Narrower Interpretation: The claim uses the explicit "at least 50,000" language, which suggests a hard floor. The specification links high sequencing depth to the ability to detect very low-frequency mutations, indicating that this specific, high number is integral to the claimed method’s performance and not merely illustrative (’454 Patent, col. 99:43-62).

  • The Term: "assaying cell-free DNA isolated from a plurality of biological samples obtained from the subject at different time points" (’596 Patent, Claim 1)

    • Context and Importance: This phrase is critical for establishing the temporal element of the claimed monitoring method. Practitioners may focus on this term because its construction will determine whether performing a single RaDaR test can infringe, or if infringement requires a course of conduct involving multiple tests on the same patient over time.
    • Intrinsic Evidence for Interpretation:
      • Evidence for a Broader Interpretation: The patent title and the claim's preamble, which states the method is for "monitoring the progression of cancer," support an interpretation where an assay designed and intended for serial use infringes, as the context is longitudinal monitoring (’596 Patent, col. 172:43-45).
      • Evidence for a Narrower Interpretation: The plain language requires assaying a "plurality of...samples" obtained at "different time points." This could support an argument that infringement only occurs when a party actually performs or controls the performance of tests on at least two separate samples from the same patient taken at different times.

VI. Other Allegations

  • Indirect Infringement: The complaint alleges that Defendant induces infringement by its corporate affiliate, Inivata, to perform the RaDaR assay (Compl. ¶66, 70). Knowledge of the ’454 Patent is alleged to have been established by at least December 20, 2022, via a prior lawsuit, while knowledge of the ’596 Patent is alleged from the date of service of the current complaint (Compl. ¶66, 70). Specific intent is alleged based on Defendant offering the assay for sale with the specific intention that Inivata would perform the test in Defendant's Durham laboratory (Compl. ¶66, 70).
  • Willful Infringement: Willfulness is alleged for both patents. For the ’454 Patent, the claim is based on alleged knowledge from the December 20, 2022 lawsuit against Defendant's affiliates (Compl. ¶74). For the ’596 Patent, willfulness is based on knowledge gained from the service of this complaint (Compl. ¶78). For both, Plaintiff alleges Defendant's conduct has been "deliberate and willful" and constitutes "egregious misconduct" or, alternatively, willful blindness (Compl. ¶74, 78).

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

  • A core issue will be one of product modification and estoppel: in light of Defendant’s agreement not to contest infringement of the ’454 Patent by its "RaDaR 1.0" assay, to what extent do the technical specifications of the accused "RaDaR 1.1" assay differ? The case may turn on whether the alleged modifications are merely "colorable" or represent a substantive technical departure from the scope of the asserted claims.
  • A key evidentiary question will be one of quantifiable performance: can Plaintiff produce evidence that the RaDaR assay, as practiced, meets the precise numerical and functional limitations of the asserted claims, particularly the "at least 50,000" depth of read required by the ’454 Patent and the "less than or equal to 0.015%" detection sensitivity required by the ’596 Patent?
  • A third central question may be one of attribution of conduct: as the claims recite multi-step methods involving both tumor and blood samples taken over time, the court may need to resolve whether Defendant is a single actor that "directs or controls" all claimed steps, or if proving infringement will require navigating complex legal standards for divided and indirect infringement involving Defendant, its affiliates, and prescribing physicians.