Merck Sharp & Dohme LLC v. Johns Hopkins University

1. Case Identification

• Case #: IPR2024-00625
• Patent #: 11,339,219
• Filed: March 4, 2024
• Petitioner(s): Merck Sharp & Dohme LLC
• Patent Owner(s): The Johns Hopkins University
• Challenged Claims: 1-8

2. Patent Overview

• Title: Treatment of Cancers with Microsatellite Instability
• Brief Description: The ’219 patent relates to methods of treating cancer in patients with microsatellite instability-high (MSI-H) or mismatch repair (MMR) deficient tumors by administering an effective amount of the anti-PD-1 antibody pembrolizumab.

3. Grounds for Unpatentability

Ground 1: Anticipation of Claims 1-4 and 6-8 by the MSI-H Study Record

• Prior Art Relied Upon: MSI-H Study Record (ClinicalTrials.gov identifier NCT01876511, 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 one year before the patent’s earliest effective filing date, disclosed every element of the claimed method. The protocol explicitly detailed a study for treating patients having MSI-H colorectal and non-colorectal cancer with a specific dose (10 mg/kg every 14 days) of pembrolizumab. Petitioner asserted that claimed functional outcomes, such as an "improved objective response rate" compared to a reference patient, are inherent results of practicing the disclosed treatment method. The petition cited Federal Circuit precedent holding that a prior art disclosure of a clinical trial protocol inherently anticipates a method of treatment claim, even if the trial’s results had not yet been published.

Ground 2: Obviousness of Claims 1-4 and 6-8 over MSI-H Study Record, Pernot, and Benson

• Prior Art Relied Upon: MSI-H Study Record, Pernot (a 2014 journal article on colorectal cancer and immunity), and Benson (a 2014 clinical practice guideline).
• Core Argument for this Ground:
  • Prior Art Mapping: This ground was presented as an alternative to anticipation. Petitioner argued that even if the MSI-H Study Record did not explicitly disclose that the trial patients had metastatic or unresectable cancer, Benson taught that patients with "measurable disease" in oncology clinical studies are, by standard of care, those with advanced or metastatic disease.
  • Motivation to Combine: A person of ordinary skill in the art (POSITA) would combine the teachings because the MSI-H Study Record proposed a clinical trial for which the broader scientific literature provided a strong rationale. Pernot taught that MSI-H cancers are "good candidates for immunotherapy," providing a clear motivation for a POSITA to conduct the trial outlined in the MSI-H Study Record.
  • Expectation of Success: A POSITA would have a reasonable expectation of success. The prior art established that MSI-H tumors are highly immunogenic due to numerous mutations, making them ideal targets for PD-1 inhibitors like pembrolizumab, which work by releasing the brakes on the immune system. Further, pembrolizumab had already been approved for another oncology indication, increasing the expectation of success for subsequent indications.

Ground 3: Obviousness of Claim 5 over MSI-H Study Record in view of Chapelle

• Prior Art Relied Upon: MSI-H Study Record (optionally combined with Pernot and Benson) and Chapelle (a 2010 journal article on MSI in colorectal cancer).

• Core Argument for this Ground:

  • Prior Art Mapping: Claim 5 is a dependent claim that specifies particular microsatellite markers (e.g., BAT-25, BAT-26) used to determine MSI-H status. Petitioner contended that Chapelle disclosed these markers as part of a "standard test" that had "stood the test of time" for identifying MSI-H tumors.
  • Motivation to Combine: A POSITA, seeking to implement the protocol of the MSI-H Study Record which required identifying MSI-H patients, would be motivated to use a well-known, standard, and reliable testing method. Chapelle provided exactly such a method, making its use to carry out the MSI-H Study Record’s protocol an obvious choice. A POSITA would have an expectation of success because the claimed testing method was known to be effective and its use would not alter the efficacy of the pembrolizumab treatment itself.

• Additional Grounds: Petitioner asserted additional obviousness challenges for claims 1-8 based on the MSI-H Study Record in view of combinations including Brown and Duval (to further support the biological rationale and expectation of success) and Hamid (to show intravenous infusion of pembrolizumab was standard).

4. Arguments Regarding Discretionary Denial

• Discretionary Denial Under Fintiv: Petitioner argued against discretionary denial under Fintiv, stating that the parallel district court litigation is in a very early stage, with significant investment in discovery and trial preparation yet to occur. Petitioner represented it would seek a stay of the litigation upon institution, and noted the district court’s median time to trial (mid-2026) is well beyond the statutory deadline for a Final Written Decision, mitigating concerns of inefficiency.
• Discretionary Denial Under §325(d): Petitioner argued that denial under 35 U.S.C. §325(d) is inappropriate. It contended that during prosecution of a related patent, the Examiner made a clear error of law by failing to properly apply the doctrine of inherent anticipation to the MSI-H Study Record. Furthermore, the Examiner did not consider the numerous additional prior art references or any of the obviousness combinations presented in the petition.

5. Relief Requested

• Petitioner requests institution of an inter partes review and cancellation of claims 1-8 of the ’219 patent as unpatentable.