Merck Sharp & Dohme LLC v. Johns Hopkins University

1. Case Identification

• Case #: IPR2024-00240
• Patent #: 11,591,393
• Filed: November 30, 2023
• Petitioner(s): Merck Sharp & Dohme LLC
• Patent Owner(s): The Johns Hopkins University
• Challenged Claims: 1-42

2. Patent Overview

• Title: Methods of Treating Cancer
• Brief Description: The ’393 patent claims methods for treating colorectal cancer patients by administering the PD-1 inhibitor drug pembrolizumab. The claimed methods are limited to patients whose tumors have been identified as having microsatellite instability-high (MSI-H) or DNA mismatch repair deficient (dMMR) characteristics.

3. Grounds for Unpatentability

Ground 1: Anticipation over the MSI-H Study Record - Claims 1-2, 4-7, 11-12, 14-15, 17-20, 24-25, and 27-42 are anticipated by the MSI-H Study Record under 35 U.S.C. §102.

• Prior Art Relied Upon: MSI-H Study Record (ClinicalTrials.gov identifier NCT01876511, first published June 10, 2013).
• Core Argument for this Ground:
  • Prior Art Mapping: Petitioner argued that the MSI-H Study Record, a publicly available clinical trial protocol published more than a year before the patent’s earliest possible priority date, explicitly disclosed every element of the claimed methods. It described a clinical study for treating patients having MSI-H colorectal cancer with a therapeutically effective amount of pembrolizumab (10 mg/kg every 14 days), which is the same dosage described in the ’393 patent.
  • Key Aspects: The core of the argument rested on the doctrine of inherent anticipation. Petitioner contended that even though the MSI-H Study Record did not publish the results of the study, the claimed efficacy outcomes (e.g., an objective response rate of 40% or progression-free survival of 78% at 20 weeks) were the necessary and inherent result of practicing the disclosed treatment method. Citing Federal Circuit precedent such as In re Montgomery, Petitioner asserted that a prior art reference disclosing a planned clinical study inherently anticipates method of treatment claims, as efficacy is inherent in carrying out the claimed steps.

Ground 2: Obviousness over MSI-H Study Record in view of Pernot - Claims 1-2, 4-7, 11-12, 14-15, 17-20, 24-25, and 27-42 are obvious over the MSI-H Study Record in view of Pernot under 35 U.S.C. §103.

• Prior Art Relied Upon: MSI-H Study Record (ClinicalTrials.gov, NCT01876511) and Pernot (a journal article titled Colorectal Cancer and Immunity: What We Know and Perspectives, published April 2014).
• Core Argument for this Ground:
  • Prior Art Mapping: The MSI-H Study Record provided the foundational method of treating MSI-H colorectal cancer patients with pembrolizumab. Pernot provided the scientific rationale and motivation for pursuing such a treatment.
  • Motivation to Combine: Petitioner argued that even if the MSI-H Study Record did not inherently anticipate the claims, a person of ordinary skill in the art (POSITA) would have been motivated to perform the clinical trial it described and would have expected it to be successful. Pernot explicitly taught that colorectal cancers with microsatellite instability are "good candidates for immunotherapy." This teaching, along with general knowledge that MSI-H tumors are highly immunogenic, would have provided a POSITA with a clear reason to combine the teachings and pursue the treatment protocol outlined in the MSI-H Study Record to achieve the claimed results.
  • Expectation of Success: The established knowledge that PD-1 inhibitors work by enhancing the immune response against tumors, combined with Pernot’s teaching that MSI-H tumors were particularly susceptible to immunotherapy, created a reasonable expectation of success for the treatment protocol.

Ground 3: Obviousness over MSI-H Study Record and Chapelle - Claims 2, 8, 15, and 21 are obvious over the MSI-H Study Record (optionally with Pernot) in view of Chapelle under §103.

• Prior Art Relied Upon: MSI-H Study Record (ClinicalTrials.gov, NCT01876511), Pernot (optional), and Chapelle (a journal article titled Clinical Relevance of Microsatellite Instability in Colorectal Cancer, published 2010).

• Core Argument for this Ground:

  • Prior Art Mapping: This ground specifically addressed dependent claims requiring that the MSI-H status be determined by testing a tumor tissue sample, including by immunohistochemistry (IHC). The MSI-H Study Record required enrolling MSI-H patients, and Chapelle taught standard, routine methods for determining a tumor's MSI-H status from a tumor tissue sample, including IHC.
  • Motivation to Combine: A POSITA, seeking to implement the protocol of the MSI-H Study Record, would have been motivated to use a conventional and reliable method for identifying the required patient population. Chapelle provided exactly such a method, making its combination with the Study Record a matter of applying a known technique for its intended purpose.
  • Expectation of Success: The methods for testing tumor tissue for MSI-H status described in Chapelle were well-established and predictable, providing a high expectation of success in identifying the correct patients for the study.

• Additional Grounds: Petitioner asserted additional obviousness challenges for various claims based on the MSI-H Study Record in combination with other references, including Steinert (for testing body fluids), Benson (for establishing patient criteria in clinical trials), Salipante (for PCR and next-generation sequencing tests), and Hamid (for teaching intravenous administration of pembrolizumab). These grounds relied on similar theories of combining the primary treatment protocol with known, conventional techniques to arrive at the specific limitations of various dependent claims.

4. Arguments Regarding Discretionary Denial

• Fintiv Factors: Petitioner argued against discretionary denial under Fintiv, stating that the parallel district court litigation was in an early stage, a stay would be sought upon institution, and a final written decision (FWD) from the Board would likely issue before a trial date.
• §325(d) Factors: Petitioner argued that denial under §325(d) was inappropriate because the Examiner did not consider the MSI-H Study Record at all during prosecution of the ’393 patent. Furthermore, while the reference was considered for a related patent, the Examiner committed legal error by failing to properly apply the doctrine of inherent anticipation. Petitioner also noted that the specific obviousness combinations presented in the petition were never considered by the Examiner.

5. Relief Requested

• Petitioner requests institution of an inter partes review and cancellation of claims 1-42 of the ’393 patent as unpatentable.