Natera v. CareDx Inc

I. Executive Summary and Procedural Information

• Parties & Counsel:
  • Plaintiff: Natera, Inc. (Delaware)
  • Defendant: CareDx, Inc. (Delaware)
  • Plaintiff’s Counsel: Morris, Nichols, Arsht & Tunnell LLP
• Case Identification: 1:22-cv-00642, D. Del., 05/13/2022
• Venue Allegations: Venue is asserted in the District of Delaware based on Defendant's incorporation in that state, establishing corporate residence.
• Core Dispute: Plaintiff alleges that Defendant’s transplant diagnostic products infringe a patent related to methods for non-invasively analyzing cell-free DNA from a first individual within a biological sample of a second individual.
• Technical Context: The technology at issue involves the analysis of cell-free DNA (cfDNA), a field with significant market importance for non-invasive diagnostics in organ transplantation, oncology, and reproductive health.
• Key Procedural History: The complaint notes that Defendant has previously filed separate actions against Plaintiff in the same judicial district, which Plaintiff cites in support of the court's personal jurisdiction over the Defendant.

Case Timeline

Date	Event
2005-07-29	U.S. Patent No. 11,111,544 Earliest Priority Date
2017-01-01	Accused Product AlloSure Launch Date (approx.)
2019-01-01	Accused Product AlloSeq Launch Date (approx.)
2021-01-01	Accused Products KidneyCare and HeartCare Launch Date (approx.)
2021-09-07	U.S. Patent No. 11,111,544 Issue Date
2022-05-13	Complaint Filing Date

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

U.S. Patent No. 11,111,544 - "System and Method for Cleaning Noisy Genetic Data and Determining Chromosome Copy Number"

• Patent Identification: U.S. Patent No. 11,111,544, "System and Method for Cleaning Noisy Genetic Data and Determining Chromosome Copy Number," issued September 7, 2021.

The Invention Explained

• Problem Addressed: The patent's background section describes the technical challenges of obtaining reliable genetic data from a very small sample, such as a single cell or from fragmentary DNA, noting that such measurements are often "highly error-prone, or noisy" (’544 Patent, col. 3:10-12). It specifically identifies issues like Allele Drop Out (ADO) as a significant problem in techniques like pre-implantation genetic diagnosis (PGD) ('544 Patent, col. 5:55-67).
• The Patented Solution: The invention provides methods for analyzing and determining genetic data from a "target individual" (e.g., a fetus or an organ donor) when its DNA is mixed in a biological sample from a "second individual" (e.g., a pregnant mother or a transplant recipient) ('544 Patent, Abstract). The core method involves amplifying specific genetic locations ("target loci") from the mixed cell-free DNA, sequencing the amplified products, and then computationally determining the genetic data of the target individual by analyzing the frequencies of the different genetic variants ("alleles") present in the sequencing data ('544 Patent, col. 16:26-42).
• Technical Importance: This technological approach is designed to enable more accurate and non-invasive genetic testing from samples containing minuscule amounts of target DNA, a key advancement for clinical diagnostics ('544 Patent, col. 1:21-27; Compl. ¶15).

Key Claims at a Glance

• The complaint asserts independent claims 1, 18, 21, and 38 (Compl. ¶¶ 24-27).
• Claim 1 recites a three-step method:
  • amplifying a plurality of target loci on cell-free DNA extracted from the biological sample to generate amplified products;
  • sequencing the amplified products by sequencing-by-synthesis to obtain genetic data; and
  • determining the most likely genetic data for DNA from the first individual based on allele frequencies in the genetic data.
• Claim 18 is similar to claim 1 but specifies:
  • the biological sample is a blood sample;
  • the amplification is "targeted PCR" on a plurality of "SNP loci"; and
  • the sequencing-by-synthesis comprises "clonal amplification."
• Claim 21 recites a method for preparing a preparation of amplified DNA, comprising:
  • extracting cell-free DNA from the sample;
  • preparing a preparation of amplified DNA by amplifying target loci; and
  • analyzing the preparation by sequencing and "determining the most likely genetic data... based on allele frequencies."
• Claim 38 is similar to claim 21 but specifies:
  • the biological sample is a blood sample;
  • the amplification is "targeted PCR to amplify a plurality of SNP loci"; and
  • the sequencing includes clonal amplification.
• The complaint states its infringement allegations are "exemplary and without prejudice," suggesting the right to assert additional claims may be reserved (Compl. ¶29).

III. The Accused Instrumentality

Product Identification

• The complaint identifies the accused instrumentalities as Defendant’s "AlloSure, AlloSeq, KidneyCare, HeartCare, and any other CareDx products that use similar technologies" (Compl. ¶13).

Functionality and Market Context

• The complaint alleges these are transplant diagnostic testing products used to non-invasively assess the health of a transplanted organ (Compl. ¶¶ 3, 20-21). The central allegation is that these products function by analyzing cfDNA from a transplant recipient's blood sample, which contains a mixture of DNA from the recipient and the donated organ (Compl. ¶22). This analysis allegedly allows for the measurement of donor-derived DNA to monitor for potential organ rejection, a function Plaintiff alleges is of significant clinical value (Compl. ¶3).

IV. Analysis of Infringement Allegations

The complaint references an "exemplary claim chart detailing CareDx's infringement" as Exhibit A, but this exhibit was not provided with the complaint (Compl. ¶33). The narrative infringement theory presented in the complaint is that CareDx's Accused Products practice the patented methods for analyzing mixed DNA samples (Compl. ¶31). The complaint alleges that the Accused Products are used to measure DNA from a "first individual" (the organ donor) within a biological sample taken from a "second individual" (the organ recipient) (Compl. ¶22). This process is alleged to involve amplifying target loci from cfDNA, sequencing the amplified products, and analyzing allele frequencies to determine genetic information about the donor DNA, thereby mapping to the core steps of the asserted claims (Compl. ¶¶ 24-28, 31).

No probative visual evidence provided in complaint.

• Identified Points of Contention:
  • Scope Questions: The patent's specification frequently discusses the problem of prenatal diagnosis (a fetus's DNA within a mother's blood sample) ('544 Patent, col. 3:1-12). A potential point of contention may be whether claim terms such as "first individual" and "second individual," developed in that context, can be construed to cover the distinct clinical scenario of an organ donor and a transplant recipient as alleged by the Plaintiff.
  • Technical Questions: The complaint alleges infringement on "information and belief" and does not provide specific technical details about the internal workings of the Accused Products (Compl. ¶22). A central evidentiary question will be what proof Plaintiff can provide that the Accused Products perform each claimed step, especially the computational step of "determining the most likely genetic data... based on allele frequencies," and whether Defendant's proprietary algorithms function in a manner covered by the claims.

V. Key Claim Terms for Construction

• The Term: "determining the most likely genetic data... based on allele frequencies"

• Context and Importance: This phrase appears in all four asserted independent claims and describes the core analytical step of the invention. The construction of this term will be critical to the infringement analysis, as it will define the scope of computational or statistical methods covered by the patent. Practitioners may focus on this term because the dispute could turn on whether the specific algorithms used by Defendant's Accused Products fall within its scope.

• Intrinsic Evidence for Interpretation:

  • Evidence for a Broader Interpretation: The specification discusses multiple statistical approaches for analysis, including "maximum a posteriori (MAP) estimation" and "Bayesian inference," which may support an interpretation that the term is not limited to a single, specific algorithm but covers a class of statistical methods that use allele frequency data as an input ('544 Patent, col. 17:15-21, col. 23:9-25).
  • Evidence for a Narrower Interpretation: The patent provides detailed mathematical derivations for certain statistical methods, such as MAP estimation ('544 Patent, col. 17:15-67). Language from these specific embodiments could be used to argue that the term should be construed more narrowly to encompass only those methods, or methods substantially similar to those, explicitly detailed in the patent.

• The Term: "sequencing-by-synthesis"

• Context and Importance: This term, also present in all asserted independent claims, defines the type of DNA sequencing technology used in the claimed method. Its construction is important for establishing the range of accused technologies.

• Intrinsic Evidence for Interpretation:

  • Evidence for a Broader Interpretation: "Sequencing-by-synthesis" is a widely understood technical term referring to a class of next-generation sequencing technologies. The patent does not appear to provide a special definition for the term, which suggests it should be given its plain and ordinary meaning to one of skill in the art, thereby covering various commercial sequencing platforms that operate on this principle ('544 Patent, col. 7:15).
  • Evidence for a Narrower Interpretation: A party could argue that the scope of the term should be limited by the technological context at the time of the invention, as reflected in the patent's disclosure. However, the specification does not appear to contain explicit language that would limit the term to a particular instrument or vintage of technology.

VI. Other Allegations

• Indirect Infringement: The complaint alleges that CareDx "induces others to use" the accused products, which suggests a claim for induced infringement (Compl. ¶13). The factual basis for this is not detailed but would typically involve allegations that Defendant provides instructions, marketing, or support that encourage and enable its customers to perform the patented method.
• Willful Infringement: The complaint does not contain an explicit count for willful infringement. However, it requests a finding that the case is "exceptional" under 35 U.S.C. § 285 and an award of attorneys' fees, alleging that "CareDx has made extensive use of Natera's patented technology" (Compl. ¶34, Prayer for Relief ¶4). This allegation implies knowledge but does not specify whether it is based on pre- or post-suit conduct.

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

• A core issue will be one of definitional scope: How broadly will the court construe the analytical claim limitation "determining the most likely genetic data... based on allele frequencies"? The outcome will likely depend on whether this phrase is interpreted as a broad category of statistical analysis or is limited more closely to the specific algorithms detailed in the patent's examples.
• A second key issue will be one of evidentiary proof: As the complaint is based on "information and belief," the case will turn on the factual evidence Natera can produce through discovery to demonstrate that the specific, proprietary processes inside CareDx's Accused Products actually perform each step of the asserted claims, establishing a technical correspondence between the accused methods and the patent's claims.