PTAB

IPR2025-01435

Tempus Ai Inc v. Guardant Health Inc

Log In
Key Events
Petition
petition

1. Case Identification

2. Patent Overview

  • Title: Method for Detecting Genetic Variation in Microsatellite Regions
  • Brief Description: The ’916 patent discloses methods for detecting genetic variations in microsatellite regions of cell-free nucleic acid (cfDNA) from a subject with cancer. The methods involve ligating molecular barcodes to cfDNA molecules, amplifying the tagged molecules, sequencing them, and quantitatively analyzing the resulting sequence reads to detect microsatellite changes.

3. Grounds for Unpatentability

Ground 1: Obviousness over Schmitt, Forshew, and Porreca - Claims 13-30 are obvious over Schmitt in view of Forshew and Porreca.

  • Prior Art Relied Upon: Schmitt (Patent 9,752,188), Forshew (a May 2012 article in Science Translational Medicine), and Porreca (Application # 2012/0165202).
  • Core Argument for this Ground:
    • Prior Art Mapping: Petitioner argued that the combination of Schmitt and Forshew taught the core method of independent claim 13. Schmitt disclosed a high-accuracy method, Duplex Consensus Sequencing (DCS), that uses molecular barcodes ligated to DNA fragments to correct for amplification and sequencing errors. Schmitt’s method explicitly enables the "quantitative detection of sites of DNA damage" by "mutation counting" from consensus sequences, directly mapping to the "quantitative measure" limitation. Forshew taught the application of deep sequencing to detect rare "cancer mutations present in circulating [cell-free] DNA" from patient plasma. Petitioner contended that applying Schmitt’s superior error-correction technique to Forshew’s cfDNA liquid biopsy was an obvious improvement for detecting low-frequency cancer mutations. Porreca was argued to supply the final piece: the explicit motivation to target microsatellite regions. Porreca taught that "cancer... has been associated with microsatellite instability (MSI)" and disclosed "methods for detecting nucleic acid deletions or insertions in regions containing nucleic acid sequence repeats," providing the rationale to apply the combined Schmitt/Forshew method to these specific, clinically relevant regions.
    • Motivation to Combine: A Person of Ordinary Skill in the Art (POSA) would combine Schmitt and Forshew to improve the accuracy of detecting rare mutations in cfDNA, a known goal in the art. The POSA would be further motivated to incorporate Porreca's teachings to apply this highly sensitive method to detect MSI, a well-known and powerful biomarker for cancer diagnosis and prognosis. The combination would predictably yield a method that provides not just a qualitative MSI status but a "quantitative measure of microsatellite change," offering improved clinical resolution for patient care.
    • Expectation of Success: Petitioner asserted a high expectation of success because the combination involved the predictable application of established techniques. It required only routine molecular biology and sequencing methods, as described in all three references, to address a recognized problem.

Ground 2: Obviousness over Schmitt, Forshew, and Sacko - Claims 13-30 are obvious over Schmitt in view of Forshew and Sacko.

  • Prior Art Relied Upon: Schmitt (Patent 9,752,188), Forshew (a May 2012 article in Science Translational Medicine), and Sacko (Application # 2010/0264331).
  • Core Argument for this Ground:
    • Prior Art Mapping: This ground presented a similar argument, leveraging the core combination of Schmitt's high-accuracy DCS method and Forshew's cfDNA sequencing application. The key difference was the substitution of Sacko for Porreca to provide the motivation for targeting microsatellite regions. Sacko taught that cfDNA from cancer patients contains "microsatellite alterations" and that these alterations, known as MSIs, could be a "new potential marker" for monitoring tumors. Petitioner argued that this teaching would have made it obvious to a POSA to focus the powerful analytical method of Schmitt/Forshew on detecting MSIs in cfDNA. Petitioner noted that the Examiner in the ’916 patent’s prosecution had previously relied on Sacko for the same purpose: to find it obvious to apply a general genetic detection method to the specific "species" of microsatellite changes.
    • Motivation to Combine: The motivation was again to improve non-invasive cancer diagnostics. A POSA would combine the high-sensitivity framework taught by Schmitt and Forshew with Sacko's disclosure on the clinical utility of MSIs in cfDNA. This combination would create a powerful and accurate clinical tool for quantifying microsatellite changes, directly addressing the goals of all three references.
    • Expectation of Success: Petitioner argued for a high expectation of success, as the combination involved applying established detection principles (DCS from Schmitt) to a known analyte (cfDNA from Forshew) and a well-characterized clinical target (MSIs from Sacko). The approach relied on conventional tools and presented a predictable path to achieving the claimed method.

4. Relief Requested

  • Petitioner requests institution of an inter partes review (IPR) and cancellation of claims 13-30 of Patent 10,793,916 as unpatentable under 35 U.S.C. §103.