Personalis Inc v. Foresight Diagnostics Inc

I. Executive Summary and Procedural Information

• Parties & Counsel:
  • Plaintiff: Personalis, Inc. (Delaware)
  • Defendant: Foresight Diagnostics Inc. (Delaware)
  • Plaintiff’s Counsel: Weil, Gotshal & Manges LLP
• Case Identification: 1:23-cv-01623, D. Colo., 06/26/2023
• Venue Allegations: Venue is based on Defendant Foresight Diagnostics having its principal place of business in Aurora, Colorado.
• Core Dispute: Plaintiff alleges that Defendant’s personalized genetic assay, the "Solid Tumor Recurrence Test," infringes three U.S. patents related to methods for detecting and monitoring cancer by analyzing genetic variants.
• Technical Context: The technology lies in the field of personalized oncology diagnostics, specifically using liquid biopsy and whole genome sequencing to detect minimal residual disease (MRD) by identifying tumor-specific genetic mutations in a patient's blood.
• Key Procedural History: The complaint alleges that Plaintiff sent a "Patent Notice Letter" to Defendant on May 17, 2022, putting Defendant on notice of Plaintiff's patent portfolio, including the applications that would later issue as the patents-in-suit. This allegation forms the basis for the claims of willful infringement.

Case Timeline

Date	Event
2014-10-30	Earliest Priority Date for ’968 and ’507 Patents
2016-05-27	Earliest Priority Date for ’685 Patent
2021-01-01	Publication describing Accused Product's method referenced
2022-05-17	Plaintiff's Patent Notice Letter sent to Defendant
2023-02-21	U.S. Patent No. 11,584,968 Issues
2023-05-09	U.S. Patent No. 11,643,685 Issues
2023-05-16	U.S. Patent No. 11,649,507 Issues
2023-06-26	Complaint Filed

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

U.S. Patent No. 11,584,968 - "Methods For Using Mosaicism in Nucleic Acids Sampled Distal to Their Origin"

• Patent Identification: U.S. Patent No. 11584968, "Methods For Using Mosaicism in Nucleic Acids Sampled Distal to Their Origin," issued February 21, 2023.

The Invention Explained

• Problem Addressed: The patent's background describes the difficulty of detecting or monitoring diseases located in parts of the body that are hard to access without invasive surgery (Compl. ¶1; ’968 Patent, col. 1:19-25). While bodily fluids like blood contain nucleic acids from various tissues, it is difficult to determine the origin of a specific disease-indicating signal, which limits the sensitivity and utility of such tests (’968 Patent, col. 1:36-47).
• The Patented Solution: The invention proposes methods for improving the detection and monitoring of diseases by creating a "mutation map" for a subject to provide spatial or developmental localization for genetic mutations (’968 Patent, Abstract). This is achieved by comparing nucleic acid sequences from a tissue sample (e.g., a tumor) against sequences from a reference sample (e.g., leukocytes) to identify differential mutations, which can then be tracked in distal samples like blood to monitor a disease state (’968 Patent, col. 2:47-59).
• Technical Importance: This approach aims to improve the sensitivity of liquid biopsies by providing a method to trace circulating nucleic acid signals back to their specific tissue of origin within the body (’968 Patent, col. 2:1-3).

Key Claims at a Glance

• The complaint asserts independent claim 1 (Compl. ¶36).
• Essential elements of claim 1 include:
  • A method of analyzing a biological sample from a subject screened for cancer.
  • (a) Obtaining first and second sets of sequence reads via whole genome sequencing of nucleic acids extracted from (i) a tissue sample of the subject and (ii) leukocytes from a blood sample, respectively.
  • (b) Using the sequence reads to identify "mosaic variants" specific to the tissue sample that are not present in the leukocyte sequences.
  • (c) Subsequently identifying those specific mosaic variants in a first additional sample from a different source.
  • (d) Providing a report based on this identification to predict, diagnose, or prognose a cancer status or outcome.
• The complaint reserves the right to assert additional claims (Compl. ¶36).

U.S. Patent No. 11,649,507 - "Methods for Using Mosaicism in Nucleic Acids Sampled Distal to Their Origin"

• Patent Identification: U.S. Patent No. 11649507, "Methods for Using Mosaicism in Nucleic Acids Sampled Distal to Their Origin," issued May 16, 2023.

The Invention Explained

• Problem Addressed: The patent addresses the same technical challenge as the ’968 Patent: when nucleic acids are found in the body distal from their source tissue, there is no general method to identify that source, limiting the diagnostic utility of tests that analyze bodily fluids (’507 Patent, col. 1:36-42).
• The Patented Solution: The invention provides a method for detecting "differential mutations" within a single blood sample (’507 Patent, col. 2:4-5). The method involves separating the blood sample into at least two components—one containing cell-free or surface-bound nucleic acids and another containing leukocytes—and then independently sequencing and comparing them to identify mutations present in one component but not the other, thereby helping to identify the source tissue (’507 Patent, col. 2:5-14; Fig. 5).
• Technical Importance: This technique provides a method to de-convolve mixed nucleic acid signals within a single blood sample, which may improve the ability to detect and monitor localized diseases non-invasively (’507 Patent, col. 2:1-3).

Key Claims at a Glance

• The complaint asserts independent claim 1 (Compl. ¶42).
• Essential elements of claim 1 include:
  • A method for detecting differential mutations in a subject's blood sample.
  • (a) Separating the blood sample into at least a first component (with cell-free or surface-bound nucleic acids) and a second component (with leukocytes).
  • (b) Extracting nucleic acid molecules from both components.
  • (c) Independently sequencing the extracted nucleic acid molecules from both components.
  • (d) Comparing the nucleic acid sequences from the first and second components to identify differential mutations.
• The complaint reserves the right to assert additional claims (Compl. ¶42).

U.S. Patent No. 11,643,685 - "Methods and Systems For Genetic Analysis"

• Patent Identification: U.S. Patent No. 11643685, "Methods and Systems For Genetic Analysis," issued May 9, 2023.

Technology Synopsis

The patent describes a method for personalized genetic testing that aims to improve efficiency and reduce cost (’685 Patent, col. 4:36-47). The method involves analyzing a biological sample to determine a patient's specific genetic characteristics, using those characteristics to generate a personalized and smaller "probe set" (e.g., via array synthesis), and then using that custom probe set to track specific genetic variants in subsequent biological samples from the patient (Compl. ¶30; ’685 Patent, col. 4:54-65).

Asserted Claims

The complaint asserts independent claim 28 (Compl. ¶48).

Accused Features

The complaint alleges that Defendant’s test infringes by generating a patient-specific genetic signature, creating a personalized probe set based on that signature, and then using that probe set for tracking cancer in additional patient samples (Compl. ¶30, ¶33).

III. The Accused Instrumentality

Product Identification

• Defendant’s "Solid Tumor Recurrence Test" (the "Accused Product") (Compl. ¶31).

Functionality and Market Context

• The Accused Product is described as a personalized assay for detecting minimal residual disease (MRD) for solid tumors (Compl. ¶31). The complaint alleges the test involves a multi-step method: (a) performing whole genome sequencing of a tumor sample, (b) identifying genetic variants from the sequencing data, (c) creating probes designed to selectively enrich for those specific genetic variants, (d) using these probes to enrich a subsequent blood or plasma sample, and (e) sequencing the enriched sample to determine the presence or absence of the targeted genetic variants (Compl. ¶33). The complaint references a 2021 publication in Nature Biotechnology describing the test's methodology, positioning it as a sophisticated diagnostic tool (Compl. ¶31). No probative visual evidence provided in complaint.

IV. Analysis of Infringement Allegations

The complaint references infringement claim charts attached as Exhibits F, H, and I but does not provide them; therefore, the infringement theory is summarized below based on the narrative allegations in the complaint.

• '968 Patent Infringement Allegations:
  The complaint alleges that Foresight’s test directly infringes at least claim 1 of the ’968 Patent (Compl. ¶36). The theory of infringement appears to be that Foresight's method of performing whole genome sequencing on a tumor sample and comparing it to a "matching normal" sample to identify tumor-specific genetic variants constitutes the method claimed in claim 1(a) and 1(b) (Compl. ¶18, ¶33). The subsequent step of using probes to look for these variants in a later blood or plasma sample is alleged to meet the limitation of identifying the variants in an "additional sample" to prognose a cancer outcome, as recited in claim 1(c) and 1(d) (Compl. ¶18, ¶33).
• '507 Patent Infringement Allegations:
  The complaint alleges that Foresight infringes at least claim 1 of the ’507 Patent by performing a method of detecting somatic variants by comparing a patient's tumor sample to a reference sample and then tracking those variants over time (Compl. ¶24, ¶42). This allegation suggests that Foresight's process of identifying tumor-specific variants and then monitoring for them in the blood maps onto the patented method of identifying "differential mutations" by comparing different biological components.
• Identified Points of Contention:
  • Scope Questions: A primary question for the ’968 Patent will be whether Foresight's "matching normal" sample is derived from "leukocytes from a blood sample," as explicitly required by claim 1. A key question for the ’507 Patent will be whether Foresight’s process of sequencing a tumor tissue sample and later testing a blood sample maps onto the claim language requiring "separating the blood sample into at least a first component... and a second component" and "independently sequencing" molecules from each.
  • Technical Questions: What is the precise source of the "matching normal samples" that Foresight actually uses for its comparison against the tumor genome? Factual evidence on this point will be critical. Further, does Foresight's use of "probes to selectively enrich" a subsequent sample constitute "identifying said mosaic variants" in that sample in the manner required by the claims, or is there a functional or sequential mismatch between the accused process and the claim steps?

V. Key Claim Terms for Construction

• The Term: "leukocytes from a blood sample" (’968 Patent, claim 1)

• Context and Importance: This term specifies the required source for the reference ("normal") genome against which the tumor tissue genome is compared. Infringement of claim 1 hinges on whether the accused method uses this specific source. Practitioners may focus on this term because the choice of normal sample (e.g., blood leukocytes vs. a buccal swab vs. adjacent tissue) has technical implications for detecting somatic mosaicism.

• Intrinsic Evidence for Interpretation:

  • Evidence for a Broader Interpretation: The parties may argue the term should be given its plain and ordinary meaning without further limitation. The patent broadly discusses comparing different tissues to find differential mutations, which could suggest the specific choice of leukocytes is just one example. (’968 Patent, col. 2:47-52).
  • Evidence for a Narrower Interpretation: The claim explicitly recites "leukocytes from a blood sample." The patent specification also specifically depicts a flowchart where a blood sample is separated into leukocytes and cell-free nucleic acids for comparison, suggesting this specific source was integral to the invention. (’968 Patent, Fig. 5).

• The Term: "independently sequencing" (’507 Patent, claim 1)

• Context and Importance: This term is central to the claimed process. Its construction will determine whether the claim requires two physically separate sequencing runs for the cell-free and leukocyte components, or if it can be read on a process where components are barcoded, pooled, sequenced together, and then analyzed independently.

• Intrinsic Evidence for Interpretation:

  • Evidence for a Broader Interpretation: The purpose of the step is to enable a comparison that identifies "differential mutations." An interpretation focused on achieving this outcome might allow for computational independence rather than requiring physical separation of sequencing runs. (’507 Patent, col. 2:12-14).
  • Evidence for a Narrower Interpretation: The claim recites a sequence of steps: (a) separating, (b) extracting, (c) independently sequencing, and (d) comparing. This ordered structure may support an interpretation that the sequencing of the two components is a distinct and separate process step, not just a computationally distinct analysis of a pooled run.

VI. Other Allegations

• Willful Infringement: The complaint alleges willful infringement for all three patents-in-suit (Compl. ¶39, ¶45, ¶51). The allegations are based on pre-suit knowledge allegedly established by a "Patent Notice Letter" sent to Foresight Diagnostics on May 17, 2022, which purportedly made Foresight aware of Personalis's patent portfolio and the pending applications that matured into the asserted patents. The complaint alleges knowledge of the issued patents themselves since their respective issue dates in 2023 (Compl. ¶39, ¶45, ¶51).

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

• A core issue will be one of procedural mapping: Can Personalis establish that Foresight's alleged commercial process—which involves sequencing a tumor, creating custom probes, and then analyzing a subsequent blood sample—directly corresponds to the specific, ordered steps recited in the asserted method claims, which require particular biological sources for comparison (e.g., leukocytes) and actions (e.g., "independently sequencing" components from a single blood sample)?
• A key evidentiary question will be one of sourcing: What is the actual biological source of the "matching normal" reference genome used in Foresight's "Solid Tumor Recurrence Test"? This factual determination will be central to the infringement analysis for claims that explicitly require "leukocytes" as the source material.
• The case will also likely involve a question of temporal scope: Given that all three patents issued in 2023, a central dispute regarding damages and willfulness will be the extent to which Foresight's knowledge of the pending patent applications, allegedly established by the May 2022 notice letter, can support a finding of willful infringement for actions taken after the patents issued.