Merck Sharp & Dohme LLC v. Johns Hopkins University

1. Case Identification

• Case #: IPR2024-00647
• Patent #: 11,649,287
• Filed: March 13, 2024
• Petitioner(s): Merck Sharp & Dohme LLC
• Patent Owner(s): The Johns Hopkins University
• Challenged Claims: 1-36

2. Patent Overview

• Title: Method of Treating Cancer with Mismatch Repair Deficiency
• Brief Description: The ’287 patent claims methods for treating colorectal cancer in patients whose tumors exhibit microsatellite instability-high (MSI-H) or DNA mismatch repair deficiency (dMMR). The claimed treatment involves administering a therapeutically effective amount of the anti-PD-1 antibody pembrolizumab.

3. Grounds for Unpatentability

Ground 1: Anticipation of Claims 1-2, 4-8, 11-12, 14-18, and 21-36 under §102

• Prior Art Relied Upon: MSI-H Study Record (a clinical trial protocol, NCT01876511, publicly available on ClinicalTrials.gov as of 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 effective filing date, discloses every limitation of the challenged claims. The protocol explicitly describes a method of treating human patients having MSI-H colorectal cancer with a specific dose of pembrolizumab (10 mg/kg every 14 days), which the ’287 patent itself identifies as therapeutically effective. The study’s eligibility criteria and design inherently require identifying patients with MSI-H tumors from biological samples (such as tumor tissue) before treatment, thus meeting all limitations of independent claims 1 and 11 and their asserted dependents.
  • Key Aspects: Petitioner contended that the claimed efficacy outcomes (e.g., increased progression-free survival, objective response rate) are inherent results of practicing the method disclosed in the MSI-H Study Record. Citing Federal Circuit precedent such as In re Montgomery, Petitioner argued that a prior art reference disclosing a clinical study protocol anticipates method of treatment claims, even if the treatment had not yet been practiced or its results published, because efficacy is inherent in carrying out the claimed steps.

Ground 2: Obviousness of Claims 1-2, 4-8, 11-12, 14-18, and 21-36 under §103

• Prior Art Relied Upon: MSI-H Study Record (NCT01876511) and Pernot (a 2014 journal article on colorectal cancer and immunity).
• Core Argument for this Ground:
  • Prior Art Mapping: Petitioner asserted that, at a minimum, the combination of the MSI-H Study Record and the state of the art as exemplified by Pernot rendered the challenged claims obvious. The MSI-H Study Record discloses the core method of treating MSI-H colorectal cancer patients with the anti-PD-1 inhibitor pembrolizumab.
  • Motivation to Combine: A Person of Ordinary Skill in the Art (POSITA) would combine the teachings of the references. The MSI-H Study Record described a plan to treat MSI-H colorectal cancer patients with immunotherapy. Pernot, published before the patent’s priority date, explicitly taught that MSI-H colorectal cancers are "good candidates for immunotherapy." This teaching would have provided a POSITA with a clear reason to implement the clinical trial described in the MSI-H Study Record to confirm the expected positive therapeutic outcome.
  • Expectation of Success: A POSITA would have had a reasonable expectation of success. The prior art widely taught that MSI-H tumors possess characteristics—such as a high number of mutations and infiltration by immune cells—that make them particularly susceptible to PD-1 inhibitors like pembrolizumab. This established scientific understanding, reinforced by Pernot's explicit suggestion, created a strong expectation that the treatment proposed in the MSI-H Study Record would be effective.

Ground 3: Obviousness of Claims 2, 9-10, 12, and 19-20 under §103

• Prior Art Relied Upon: MSI-H Study Record (NCT01876511), Pernot (a 2014 journal article), and Chapelle (a 2010 journal article on MSI in colorectal cancer).

• Core Argument for this Ground:

  • Prior Art Mapping: This ground focused on dependent claims requiring specific methods for testing biological samples to identify MSI-H status. The MSI-H Study Record required enrolling MSI-H positive patients, thus necessitating a determination of their MSI status.
  • Motivation to Combine: A POSITA seeking to implement the MSI-H Study protocol would need a method to test patients for MSI-H status. Chapelle taught standard, well-known methods for this purpose, including testing tumor tissue using techniques like polymerase chain reaction (PCR) and assessing specific genetic markers (e.g., BAT-25, BAT-26). A POSITA would combine the MSI-H Study Record with the routine testing methods described in Chapelle to carry out the study.
  • Expectation of Success: Success was expected because the methods in Chapelle were established and routine for determining MSI status, and applying these standard tests would not affect the efficacy of the subsequent pembrolizumab treatment.

• Additional Grounds: Petitioner asserted additional obviousness challenges for other claim groups based on the MSI-H Study Record combined with Steinert (for testing body fluids), Benson (for treating metastatic or previously treated cancer), and Hamid (for intravenous administration), relying on similar motivations to use known techniques to implement the clinical study protocol.

4. Arguments Regarding Discretionary Denial

• Petitioner argued that discretionary denial would be inappropriate under both Fintiv and 35 U.S.C. §325(d).
• Fintiv Factors: Denial under Fintiv was argued to be improper because the parallel district court litigation is in an early stage, a stay is likely upon institution, and a Final Written Decision (FWD) would issue long before a potential trial date.
• §325(d) Factors: Denial under §325(d) was argued to be improper because the Examiner for the ’287 patent never considered the MSI-H Study Record. Although an Examiner considered the reference during prosecution of a family member patent, that Examiner applied an incorrect legal standard by failing to consider whether the claimed efficacy was an inherent property of the disclosed method, contrary to controlling Federal Circuit precedent.

5. Relief Requested

• Petitioner requests institution of inter partes review and cancellation of claims 1-36 of the ’287 patent as unpatentable.