DCT
1:20-cv-00038
Natera Inc v. CareDx Inc
I. Executive Summary and Procedural Information
- Parties & Counsel:
- Plaintiff: Natera Inc (Delaware)
- Defendant: CareDx Inc (Delaware)
- Plaintiff’s Counsel: Quinn Emanuel Urquhart & Sullivan LLP
- Case Identification: 1:20-cv-00038, D. Del., 01/03/2023
- Venue Allegations: Venue is alleged to be proper in the District of Delaware because Defendant CareDx Inc is a Delaware corporation and therefore resides in the district.
- Core Dispute: Plaintiff alleges that Defendant’s cell-free DNA (cfDNA) based genetic testing services infringe a patent related to methods for analyzing genetic data in mixed biological samples.
- Technical Context: The technology involves non-invasive analysis of cfDNA from blood samples to distinguish between DNA from two different individuals, a technique critical for monitoring organ transplant rejection.
- Key Procedural History: The complaint notes that the parties have been engaged in separate patent litigation since 2019. Plaintiff Natera Inc previously filed a complaint on May 13, 2022, alleging infringement of the same patent-in-suit, which was subsequently consolidated into the present action.
Case Timeline
| Date | Event |
|---|---|
| 2005-07-29 | U.S. Patent No. 11,111,544 Priority Date |
| 2017-01-01 | Accused AlloSure Product Launch |
| 2019-01-01 | Accused AlloSeq Product Launch |
| 2021-01-01 | Accused KidneyCare and HeartCare Product Launch |
| 2021-09-07 | U.S. Patent No. 11,111,544 Issue Date |
| 2021-09-29 | Date Defendant allegedly became aware of the ’544 Patent |
| 2022-05-13 | Plaintiff filed initial complaint alleging infringement of the ’544 Patent |
| 2023-01-03 | First Amended 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 describes the technical challenge of obtaining accurate genetic data from very small quantities of biological material, such as a single cell or fragments of DNA from mixed sources ('544 Patent, col. 3:5-9). Such "noisy" measurements are prone to errors like "allele drop out (ADO)," which complicates genetic analysis ('544 Patent, col. 3:12-16).
- The Patented Solution: The invention claims to solve this problem by using statistical methods to "clean" the noisy genetic data from a target individual (e.g., a fetus or an organ donor) by using the known, more complete genetic data of genetically related individuals (e.g., parents or the organ recipient) as a reference ('544 Patent, Abstract). This process allows for the reconstruction of incomplete or incorrect genetic data, thereby increasing the fidelity of the final analysis ('544 Patent, col. 1:57-67).
- Technical Importance: This analytical approach enables more reliable non-invasive diagnostic testing from minute biological samples, offering a significant potential improvement over more invasive, higher-risk procedures like biopsies or amniocentesis (Compl. ¶3).
Key Claims at a Glance
- The complaint asserts independent claims 1, 18, 21, and 38 ('544 Patent, col. 83:12-86:37; Compl. ¶¶24-27).
- Independent Claim 1 includes the core elements:
- A method for determining genetic data for DNA from a first individual in a biological sample of a second individual.
- Amplifying target loci on cell-free DNA (cfDNA) from the sample.
- Sequencing the amplified products via "sequencing-by-synthesis."
- Determining the most likely genetic data for the first individual based on allele frequencies in the sequenced data.
- Independent Claim 18 adds further specificity to the method, including:
- Performing "targeted PCR" to amplify a plurality of "SNP loci" on cfDNA.
- Specifying that the SNP loci are on a plurality of chromosomes.
- Requiring that the "sequencing-by-synthesis" comprises "clonal amplification" of the products and measurement of the clonally amplified DNA sequences.
III. The Accused Instrumentality
Product Identification
- The accused instrumentalities are Defendant’s AlloSure, AlloSeq, KidneyCare, and HeartCare products and services (Compl. ¶13).
Functionality and Market Context
- The complaint alleges that the accused products are genetic testing services used for post-transplant surveillance (Compl., Ex. A, p. 22). The AlloSure test is described as a "donor derived cell-free DNA (dd-cfDNA) test developed for transplant patients" which determines the percentage of dd-cfDNA in a blood sample to monitor for potential organ rejection (Compl., Ex. A, p. 22).
- The AlloSeq HCT product is alleged to perform "amplification and sequencing of 202 single nucleotide polymorphisms (SNPs) across all autosomal chromosomes" to calculate the percentage of recipient and donor DNA in post-transplant samples (Compl., Ex. A, p. 23). The complaint includes a workflow diagram illustrating the accused AlloSeq process, which involves steps of DNA extraction, PCR amplification, sequencing, and analysis (Compl., Ex. A, p. 24).
IV. Analysis of Infringement Allegations
U.S. Patent No. 11,111,544 Infringement Allegations
| Claim Element (from Independent Claim 1) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| A method for determining genetic data for DNA from a first individual in a biological sample of a second individual... | The Accused Products are described as methods for determining genetic data from a transplant donor (the first individual) in a blood sample from a transplant patient (the second individual) (Compl., Ex. A, p. 22). | ¶37; Ex. A, p. 22 | col. 1:57-67 |
| amplifying a plurality of target loci on cell-free DNA extracted from the biological sample to generate amplified products; | The AlloSure test is alleged to involve "targeted amplification and sequencing of a set of carefully selected and validated single nucleotide polymorphisms (SNPs)" from cfDNA (Compl., Ex. A, p. 23). | ¶37; Ex. A, p. 23 | col. 6:55-60 |
| sequencing the amplified products by sequencing-by-synthesis to obtain genetic data of the plurality of target loci; | The Accused Products are alleged to use next-generation sequencing (NGS), specifically Illumina MiSeq and NextSeq systems, which employ sequencing-by-synthesis (SBS) technology, to measure SNPs (Compl., Ex. A, p. 25, 35). | ¶37; Ex. A, p. 25 | col. 7:25-30 |
| determining the most likely genetic data for DNA from the first individual based on allele frequencies in the genetic data at the plurality of target loci. | The AlloSure bioinformatics software is alleged to calculate the percent dd-cfDNA based on an algorithm that uses "known population frequencies of the SNPs sequenced and expected distribution of alleles" (Compl., Ex. A, p. 26). An exemplary analysis output shows calculated DNA percentages (Compl., Ex. A, p. 28). | ¶37; Ex. A, p. 26 | col. 9:1-10 |
- Identified Points of Contention:
- Scope Questions: The infringement analysis may focus on the construction of "determining the most likely genetic data for DNA from the first individual based on allele frequencies." A question for the court will be whether the defendant’s proprietary algorithm, which allegedly uses "known population frequencies of the SNPs" to quantify dd-cfDNA, performs the claimed step of "determining... genetic data" for the donor.
- Technical Questions: A potential point of dispute could be whether the specific next-generation sequencing technologies allegedly used by the defendant, such as Illumina's systems, meet the claim limitation of "sequencing-by-synthesis." The complaint alleges a direct correspondence, but the technical specifics of both the claimed term and the accused process will likely be scrutinized.
V. Key Claim Terms for Construction
- The Term: "determining the most likely genetic data for DNA from the first individual based on allele frequencies"
- Context and Importance: This term recites the central computational step of the asserted claims. The outcome of the infringement analysis may depend on whether the defendant’s method of quantifying donor-derived DNA is found to practice this specific claimed step of "determining genetic data."
- Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: The specification describes various statistical approaches for making predictions from genetic data, including Maximum a Posteriori (MAP) estimation and Bayesian inference, suggesting the term is not limited to a single algorithm ('544 Patent, col. 9:11-10:46).
- Evidence for a Narrower Interpretation: The patent’s abstract and background repeatedly frame the invention in the context of "cleaning" noisy data or reconstructing incomplete data by using "expected similarities between the target genome and the genome of genetically related individuals" ('544 Patent, Abstract; col. 3:1-4). A party could argue that an algorithm based on general population frequencies, rather than specific data from a related individual, falls outside this narrower scope.
VI. Other Allegations
- Indirect Infringement: The complaint alleges that CareDx induces and contributes to infringement by, among other things, instructing others to use the Accused Products (Compl. ¶13, ¶40).
- Willful Infringement: The complaint alleges willful infringement based on pre-suit knowledge of the ’544 Patent. It specifically alleges that a member of CareDx's legal team became aware of the patent on September 29, 2021, "in connection with ongoing patent analysis," and that CareDx also had knowledge via a prior complaint filed by Natera on May 13, 2022 (Compl. ¶33, ¶39, ¶42).
VII. Analyst’s Conclusion: Key Questions for the Case
- A core issue will be one of definitional scope: Can the claim phrase "determining the most likely genetic data...based on allele frequencies," which is described in the patent in the context of "cleaning" noisy data using related individuals' genomes, be construed to cover the accused method, which allegedly uses population-level allele frequencies to quantify the percentage of donor DNA in a recipient's blood sample?
- A key factual question will concern pre-suit knowledge: What was the nature and extent of the "ongoing patent analysis" that allegedly made CareDx aware of the '544 patent on September 29, 2021, and does this evidence support the knowledge and intent required for a finding of willful infringement?