Foresight Diagnostics Inc v. Personalis Inc

1. Case Identification

• Case #: IPR2024-00170
• Patent #: 11,584,968
• Filed: November 22, 2023
• Petitioner(s): Foresight Diagnostics Inc.
• Patent Owner(s): Personalis, Inc.
• Challenged Claims: 1-13

2. Patent Overview

• Title: Methods for Using Mosaicism in Nucleic Acids Sampled Distal to Their Origins
• Brief Description: The ’968 patent describes methods for cancer screening and monitoring by performing whole genome sequencing (WGS) on a patient's tumor tissue sample and a matched normal sample (e.g., leukocytes from blood). The method identifies tumor-specific "mosaic variants" which are then monitored in subsequently obtained samples to predict, diagnose, or prognose a cancer status.

3. Grounds for Unpatentability

Ground 1: Claims 1-13 are unpatentable over Chan

• Prior Art Relied Upon: Chan et al., “Cancer Genome Scanning in Plasma...” (a 2013 journal article).
• Core Argument for this Ground: Petitioner argued that Chan, which describes using WGS to identify and monitor tumor markers in plasma, anticipates claims 1-4, 7, and 9-12 and renders all challenged claims (1-13) obvious under 35 U.S.C. §102 and §103.
  • Prior Art Mapping: Chan disclosed performing WGS on matched hepatocellular carcinoma (HCC) tumor tissue and normal buffy coat DNA (containing leukocytes) to identify tumor-specific single-nucleotide variants (SNVs), which align with the claimed "mosaic variants." Chan then identified these same SNVs in subsequent pre- and post-operative plasma samples containing cell-free DNA (cfDNA). The results were presented in a table comparing pre- and post-surgery fractional concentrations of the SNVs, constituting a report that prognoses the outcome of the surgical intervention. This method was argued to meet every limitation of independent claim 1.
  • Motivation to Combine (for §103 grounds): For claims not directly anticipated (e.g., claim 13), Chan itself motivated obvious modifications. Chan suggested that after identifying mosaic variants via shotgun WGS, one could use "solution-phase hybridization-based capture approaches" for serial monitoring. Petitioner contended this teaching would have made it obvious for a person of ordinary skill in the art (POSA) to use capture probes to identify the variants in additional samples, as recited in claim 13.
  • Expectation of Success (for §103 grounds): A POSA would have had a high expectation of success, as Chan noted that capture approaches had already been successfully used to enrich plasma DNA for other diagnostic purposes, such as noninvasive prenatal testing.

Ground 2: Claims 1-13 are obvious over Ley

• Prior Art Relied Upon: Ley et al., “DNA sequencing of a cytogenetically normal acute myeloid leukaemia genome” (a 2008 journal article), in view of the knowledge of a POSA.
• Core Argument for this Ground: Petitioner asserted that Ley established the foundational method of using paired tumor/normal WGS to discover tumor-specific mutations for cancer monitoring. By the ’968 patent’s priority date, applying Ley’s well-known method for leukemia to solid tumors was a routine, obvious, and predictable extension.
  • Prior Art Mapping: Ley disclosed performing WGS on an acute myeloid leukemia (AML) patient's tumor sample and a matched normal skin sample to identify tumor-specific somatic mutations (i.e., mosaic variants). Ley subsequently identified these same variants in a relapse tumor sample taken at a later time point, demonstrating the principle of serial monitoring.
  • Motivation to Combine (for §103 grounds): A POSA would combine Ley’s teachings with established techniques for solid tumors. This would involve the simple and obvious substitution of sample types: using a solid tumor biopsy instead of Ley's AML sample, and using leukocytes from a blood sample as the normal control instead of Ley's skin sample. This adaptation was a common practice documented in numerous subsequent studies. Furthermore, a POSA would have been motivated to monitor the identified variants non-invasively using cfDNA from plasma, a known technique to avoid repeated invasive biopsies.
  • Expectation of Success (for §103 grounds): A POSA would have had a high expectation of success because the principles of WGS for mutation discovery are universal across cancer types, and multiple successor studies (e.g., Chan, Dawson) had already successfully demonstrated this exact approach for solid tumors.

Ground 3: Claims 1-13 are unpatentable over Okosun-II

• Prior Art Relied Upon: Okosun et al., “Integrated genomic analysis identifies recurrent mutations and evolution patterns...” (a 2014 journal article).
• Core Argument for this Ground: Petitioner contended that Okosun-II, which details serial WGS analysis of follicular lymphoma, anticipates claims 1, 8-9, and 11-13 and renders all challenged claims (1-13) obvious.
  • Prior Art Mapping: Okosun-II disclosed performing WGS on matched follicular lymphoma (FL) tumor tissue from lymph node biopsies and paired germline samples from peripheral blood (which contains leukocytes). This analysis identified tumor-specific mosaic variants (SNVs and indels). The study then analyzed subsequent, sequential tumor biopsies from the same patients to track the evolution of these variants over time, anticipating the core steps of claim 1. Okosun-II also provided a report (in its figures) on the identified variants and recommended therapeutic strategies based on mutations in the NF-kB signaling pathway, anticipating claims 8 and 12.
  • Motivation to Combine (for §103 grounds): Okosun-II’s reliance on repeated invasive biopsies would have motivated a POSA to use known non-invasive techniques, such as analyzing cfDNA from plasma, for serial monitoring. This modification, combined with Okosun-II’s teachings, would render claim 2 and its dependents obvious.
  • Expectation of Success (for §103 grounds): A POSA would have expected success in applying non-invasive monitoring, as the art already established that FL tumors release circulating tumor DNA into the blood and that cfDNA was a useful tool for tracking tumor-associated mutations.

4. Key Claim Construction Positions

• “mosaic variants”: Petitioner argued for adopting the Patent Owner’s own infringement litigation position that the term encompasses any somatic mutation (causal or non-causal) present in a cancer sample that is not present in a matched normal sample.
• Reporting/Recommending Steps (Claims 1(d), 8, 12): Petitioner contended these limitations are directed to non-functional "printed matter" and should be given no patentable weight. The argument is that they merely recite the mental step of conveying information (a diagnosis or recommendation) that is not functionally related to a substrate.
• “capture probe” (Claim 13): Based on the patent’s specification and prior Board decisions in related cases, Petitioner argued this term should be construed to include both PCR primers and solution-based hybridization baits.

5. Arguments Regarding Discretionary Denial

• Petitioner argued that discretionary denial under 35 U.S.C. §325(d) is inappropriate. The petition relies on three primary references. Okosun-II was never cited during prosecution. While Chan and Ley were listed in an Information Disclosure Statement (IDS), they were among hundreds of references and were never substantively analyzed by the Examiner or used as the basis for a rejection. Petitioner asserted that the Examiner overlooked the key teachings of these references and that the petition raises arguments materially different from those considered during prosecution.

6. Relief Requested

• Petitioner requests institution of an inter partes review and cancellation of claims 1-13 of Patent 11,584,968 as unpatentable.