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, USDC Colorado, 08/31/2023
• Venue Allegations: Venue is alleged to be proper in the District of Colorado because Defendant Foresight Diagnostics has its principal place of business in the state.
• Core Dispute: Plaintiff alleges that Defendant's personalized "Solid Tumor Recurrence Test," a liquid biopsy assay for detecting cancer recurrence, infringes three patents related to methods for identifying and tracking patient-specific genetic variants.
• Technical Context: The technology lies in the field of personalized oncology diagnostics, specifically using a "tumor-informed" liquid biopsy approach to monitor patients for minimal residual disease (MRD) and cancer recurrence.
• Key Procedural History: The complaint alleges that the asserted patents were granted by the USPTO over prior art references that Defendant recently relied upon in four unsuccessful inter partes review (IPR) filings directed at related patents. It also references an ongoing related litigation between the parties. Plaintiff alleges it provided Defendant with notice of the patent applications that led to the patents-in-suit via a letter dated May 17, 2022, forming a basis for its willfulness allegations.

Case Timeline

Date	Event
2014-10-30	Earliest Priority Date for '968 and '507 Patents
2016-05-27	Earliest Priority Date for '685 Patent
2021-05-20	Publication date of Kurtz abstract describing accused methodology
2022-05-17	Plaintiff sends patent notice letter to Defendant
2023-02-21	'968 Patent issues
2023-05-09	'685 Patent issues
2023-05-16	'507 Patent issues
2023-08-31	Complaint Filing Date

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. 11,584,968, issued February 21, 2023.

The Invention Explained

• Problem Addressed: The patent's background describes the difficulty in detecting and monitoring diseases when the source tissue is inaccessible, as nucleic acids sampled distally (e.g., in blood) are a mixture from many bodily sources, which limits sensitivity and makes it difficult to identify the tissue of origin '968 Patent, col. 1:21-47
• The Patented Solution: The invention provides methods to discriminate between combined nucleic acid signals in the body. It proposes separating a blood sample into a cell-free component and a leukocyte component, sequencing nucleic acids from both, and comparing them to identify "differential mutations" that are present in the cell-free DNA but not the leukocytes, thereby helping to identify the source of the cell-free signal '968 Patent, col. 2:3-15 '968 Patent, Fig. 5 This allows for improved sensitivity and localization of disease signals.
• Technical Importance: This method provides a framework for using a patient's own non-cancerous cells (leukocytes) as a matched normal control, enabling highly sensitive detection of tumor-derived cell-free DNA against a background of normal DNA.

Key Claims at a Glance

• The complaint asserts independent claim 1 Compl. ¶48
• The essential elements of claim 1 include:
  • A method for analyzing a biological sample from a subject being screened for cancer.
  • Obtaining a first set of sequence reads and a second set of sequence reads by sequencing nucleic acid molecules from a first set and second set of nucleic acid molecules.
  • The first set of sequence reads corresponds to a first set of nucleic acid molecules extracted from a tissue sample.
  • The second set of sequence reads corresponds to a second set of nucleic acid molecules extracted from leukocytes from a blood sample.
  • Both sets of sequence reads are generated using whole genome sequencing.
  • Using the sequence reads to identify mosaic variants specific to the tissue sample that are not present in the leukocytes.
  • Subsequently identifying those mosaic variants in an additional sample from a source different than the tissue sample.
  • Providing a report based on the identification of the mosaic variants.
• The complaint reserves the right to assert additional claims Compl. ¶48

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. 11,649,507, issued May 16, 2023.

The Invention Explained

• Problem Addressed: As with the related '968 patent, the technology addresses the challenge of detecting and monitoring diseases using distally sampled nucleic acids, where signals from multiple sources are mixed and the origin is often unknown '507 Patent, col. 1:21-47
• The Patented Solution: The invention describes a method for creating a "mutation map" for a subject by obtaining and sequencing nucleic acid samples from different tissues to identify differential mutations. This map then serves as a reference to determine the origin of a nucleic acid sequence found in a subsequent, distally collected sample, such as blood '507 Patent, col. 2:47-56 '507 Patent, abstract
• Technical Importance: This approach systematizes the creation of a personalized genetic blueprint for tracking disease, which is foundational to tumor-informed MRD monitoring.

Key Claims at a Glance

• The complaint asserts independent claim 1 Compl. ¶54
• The essential elements of claim 1 include:
  • A method for detecting, diagnosing, or monitoring a human cancer patient.
  • Obtaining a first and second set of nucleic acid molecules from a first and second tissue of the patient, respectively.
  • Sequencing the nucleic acid molecules from both sets.
  • Identifying a subset of mosaic variants specific to the patient that are known to be associated with cancer.
  • Tracking the presence or absence of the subset of mosaic variants in one or more additional samples over the life of the patient.
• The complaint reserves the right to assert additional claims Compl. ¶54

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

• Patent Identification: U.S. Patent No. 11,643,685, issued May 9, 2023.
• Technology Synopsis: The patent addresses personalized genetic testing by claiming a method that involves generating a patient-specific "genetic signature" from a first assay, creating a "personalized probe set" based on that signature, and then using that probe set to track cancer or other diseases in additional samples from the patient over time Compl. ¶30
• Asserted Claims: The complaint asserts independent claim 28 Compl. ¶60
• Accused Features: The complaint alleges that Foresight's Solid Tumor Recurrence Test infringes by performing a first assay (whole genome sequencing of a tumor) to generate a genetic signature, creating a personalized probe set, and using it in subsequent assays (on plasma cfDNA) to monitor for recurrence Compl. ¶45

III. The Accused Instrumentality

• Product Identification: The accused instrumentality is Foresight Diagnostics' "Solid Tumor Recurrence Test," a service referred to as the "Accused Product" (Compl. ¶¶35; Compl. ¶47).
• Functionality and Market Context: The complaint alleges the Accused Product is a personalized liquid biopsy assay for detecting minimal residual disease (MRD) for solid tumors Compl. ¶35 The technology is marketed as "PhasED-Seq" and is described as a "highly sensitive and extremely advanced cancer surveillance technology" capable of detecting tumor-derived DNA at levels below one part-per-million Compl. p. 11 A screenshot from Defendant's website describes the PhasED-Seq technology as lowering the error profile of mutation detection by requiring the concordant detection of two separate events in an individual DNA molecule Compl. p. 11 The complaint alleges the test operates by first performing whole genome sequencing on a patient's tumor to identify patient-specific "phased variants," then creating a personalized panel to enrich for these variants, and finally using that panel to perform targeted sequencing on subsequent cfDNA samples from the patient's plasma to monitor for cancer recurrence (Compl. ¶¶42; Compl. ¶45). The complaint includes a screenshot from Defendant's website for its "Solid Tumor Recurrence Test" which states the test is "personalized based on patient-specific phased variants that are identified with whole-genome sequencing" Compl. p. 12

IV. Analysis of Infringement Allegations

The complaint does not include the referenced claim chart exhibits. The following summary is based on the narrative infringement allegations provided in the body of the complaint.

'968 Patent Infringement Allegations

Claim Element (from Independent Claim 1)	Alleged Infringing Functionality	Complaint Citation	Patent Citation
a method of analyzing a biological sample obtained from a subject being screened for a cancer...	Foresight performs the Solid Tumor Recurrence Test for cancer patients.	¶35	col. 5:6-8
(a) obtaining a first set of sequence reads... by sequencing nucleic acid molecules derived from a first set of nucleic acid molecules... extracted from a tissue sample of said subject...	Foresight performs a "first assay" involving whole genome sequencing of a patient's tumor biopsy to identify phased variants.	¶45	col. 3:50-52
...and a second set of sequence reads... by sequencing... a second set of nucleic acid molecules... extracted from leukocytes from a blood sample...	The complaint alleges this element is met but describes the accused "second assay" as sequencing of cfDNA from a plasma sample, not sequencing of DNA from leukocytes.	¶45	col. 2:5-12
wherein said first set of sequence reads and said second set of sequence reads are generated using whole genome sequencing;	The "first assay" on the tumor biopsy is described as whole genome sequencing.	¶45	col. 3:21-22
(b) using said first set of sequence reads and said second set of sequence reads to identify mosaic variants specific to said tissue sample of said subject that is not present in said second set of nucleic acid molecules...	Foresight compares the sequence data from the tumor biopsy with a reference to identify tumor-specific variants, which the complaint alleges are a type of mosaic variant.	¶¶42-44	col. 2:12-15
(c) subsequent to (b), identifying said mosaic variants specific to said tissue sample of said subject in a first additional sample of said subject, wherein said first additional sample is obtained from a source that is different than said tissue sample...	Foresight performs a "second assay" by sequencing cfDNA from a later-collected plasma sample to detect the presence of the previously identified tumor-specific variants.	¶45	col. 4:57-64

'507 Patent Infringement Allegations

Claim Element (from Independent Claim 1)	Alleged Infringing Functionality	Complaint Citation	Patent Citation
A method for detecting, diagnosing, or monitoring a human cancer patient...	Foresight offers the Solid Tumor Recurrence Test for detecting and monitoring cancer.	¶35	col. 2:57-59
(a) obtaining a first set of nucleic acid molecules from a first tissue of the human cancer patient and a second set of nucleic acid molecules from a second tissue of the human cancer patient;	Foresight obtains a tumor biopsy sample ("first tissue") and a reference sample (e.g., normal blood) ("second tissue").	¶18	col. 3:49-51
(b) sequencing nucleic acid molecules in said first set of nucleic acid molecules and said second set of nucleic acid molecules;	Foresight performs whole genome sequencing on the tumor sample.	¶42	col. 3:51-53
(c) identifying with a programmed computer processor a subset of mosaic variants specific to the human cancer patient that are known to be associated with cancer...	Foresight identifies tumor-specific "phased variants" by comparing the tumor sequence data to a reference, which the complaint alleges are a type of mosaic variant.	¶¶43-44	col. 4:51-56
(d) tracking the presence or absence of said subset of the mosaic variants in one or more additional samples over the life of the patient.	Foresight uses the identified variants to create a personalized panel for sequencing subsequent plasma samples to monitor for recurrence over time.	¶45	col. 5:57-61

• Identified Points of Contention:
  • Scope Questions: The case may turn on whether the "phased variants" (PVs) identified by the accused test fall within the scope of the term "mosaic variants" as used and defined in the asserted patents. The complaint argues they are a type of mosaic variant, citing scientific literature and the patents' own claim language Compl. ¶43 Compl. ¶44, but this definitional scope is a potential point of dispute.
  • Technical Questions: A significant question arises regarding the infringement analysis of claim 1 of the '968 patent. The claim recites comparing sequences from a "tissue sample" to sequences from "leukocytes from a blood sample." The complaint alleges Foresight's test involves a first assay on a "tumor biopsy" and a second assay on "cfDNA a plasma sample" Compl. ¶45 This raises the question of whether comparing sequences from a tumor biopsy to a reference sample (to identify variants) and then searching for those variants in cfDNA meets the claim limitation requiring a comparison between a tissue sample and leukocytes from a blood sample.

V. Key Claim Terms for Construction

• The Term: "mosaic variants"

• Context and Importance: This term is central to all three asserted patents and appears in the asserted independent claims. The infringement case hinges on whether the "phased variants" identified by Foresight's test are properly characterized as "mosaic variants." Practitioners may focus on this term because the dispute is not just over the method steps, but over the fundamental nature of the genetic markers being tracked.

• Intrinsic Evidence for Interpretation:

  • Evidence for a Broader Interpretation: The patents explain that somatic variants commonly seen in cancer are a type of mosaic variant '968 Patent, col. 18:6-9 Dependent claims in the '507 patent explicitly state that "mosaic variants identified in a cancer patient comprise somatic mosaicism" '507 Patent, claim 21 This language may support an interpretation that includes any tumor-specific somatic variation.
  • Evidence for a Narrower Interpretation: A defendant may argue that the term should be limited by the patents' broader discussion of developmental biology and cell lineage mapping '968 Patent, Fig. 1 '968 Patent, col. 8:52-64, suggesting "mosaic variants" must have a demonstrable developmental or spatial origin beyond simply being a somatic tumor mutation.

• The Term: "a blood sample" (from claim 1 of the '968 Patent)

• Context and Importance: This term is critical for the '968 patent because the claim requires separating "a blood sample" into a cell-free component and a leukocyte component for comparative sequencing. The accused method allegedly compares a tumor biopsy to cfDNA from plasma. Practitioners may focus on this term as it goes to a direct potential mismatch between the claim language and the accused method's structure.

• Intrinsic Evidence for Interpretation:

  • Evidence for a Broader Interpretation: A plaintiff might argue that the term should be read in the context of the overall invention, which is about comparing tumor-derived material to normal material from the same patient, and that a rigid single-draw interpretation would improperly limit the claim.
  • Evidence for a Narrower Interpretation: The specification explicitly describes a method of separating "the blood sample" into a cell-free component and a leukocyte component, and then comparing them '968 Patent, col. 2:3-15 Figure 5 of the patent shows a flowchart where a single "Blood Sample" is the input for two separate processing paths (leukocytes and cell-free acids) that are later compared. This provides strong evidence for an interpretation requiring both components to be derived from a single sample.

VI. Other Allegations

• Indirect Infringement: The complaint focuses on direct infringement and does not plead specific facts to support claims for induced or contributory infringement.
• Willful Infringement: The complaint alleges that Defendant had pre-suit knowledge of the applications leading to the patents-in-suit as of a notice letter sent on May 17, 2022 Compl. ¶51 Compl. ¶57 Compl. ¶63 It further alleges knowledge of the issued patents as of their respective issue dates and that Defendant's continuing infringement is therefore willful, deliberate, and with knowledge, warranting enhanced damages.

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

• A core issue will be one of definitional scope: can the term "mosaic variants," which the patents root in the context of developmental and spatial mutation mapping, be construed to cover the specific "phased variants" identified and tracked by Defendant's accused cancer monitoring test?
• A second key issue will be a question of method step equivalence: does Defendant's process-which compares variants from a tumor biopsy to sequences from a later-drawn plasma sample-meet the literal requirements of claim 1 of the '968 patent, which recites a method of deriving and comparing sequences from the cell-free and leukocyte components of the same "blood sample"?
• An evidentiary question will concern patent strength and willfulness: to what extent does the USPTO's allowance of the asserted patents over prior art Defendant previously cited in IPR proceedings, combined with the pre-suit notice letter, support the Plaintiff's position on patent validity and willful infringement?