Merck Sharp & Dohme LLC v. Johns Hopkins University

1. Case Identification

• Case #: IPR2024-00623
• Patent #: 11,325,974
• Filed: March 4, 2024
• Petitioner(s): Merck Sharp & Dohme LLC
• Patent Owner(s): The Johns Hopkins University
• Challenged Claims: 1-7

2. Patent Overview

• Title: Methods of Treating Cancer with Mismatch Repair Deficiency
• Brief Description: The ’974 patent describes methods for treating cancer in patients whose tumors have a genetic instability known as microsatellite instability-high (MSI-H) or a deficiency in mismatch repair (dMMR). The method involves administering the anti-PD-1 antibody pembrolizumab.

3. Grounds for Unpatentability

Ground 1: Anticipation of Claims 1-3 and 5-7 under 35 U.S.C. §102

• Prior Art Relied Upon: MSI-H Study Record (ClinicalTrials.gov Identifier: NCT01876511), first published on 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, disclosed all limitations of the challenged claims more than a year before the patent’s earliest effective filing date. The protocol explicitly described a method of treating patients having MSI-H colorectal and non-colorectal cancers with pembrolizumab at a dose of 10 mg/kg every 14 days. It also specified inclusion criteria requiring patients to have measurable disease, which Petitioner contended corresponds to the claimed patient population.
  • Key Aspects: The central argument for anticipation relied on the legal principle of inherency. Petitioner asserted that the claimed "improved outcome" is an inherent result 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 planned clinical study inherently anticipates method-of-treatment claims, even if the clinical results or efficacy data have not yet been published. The performance of the disclosed protocol would necessarily result in the claimed therapeutic benefit.

Ground 2: Obviousness of Claims 1-3 and 5-7 under 35 U.S.C. §103

• Prior Art Relied Upon: MSI-H Study Record (NCT01876511), Pernot (a 2014 journal article), and Benson (a 2014 clinical practice guideline).
• Core Argument for this Ground:
  • Prior Art Mapping: This ground was presented as an alternative to anticipation. The MSI-H Study Record provided the foundational method of treating MSI-H cancer with pembrolizumab. Pernot taught that MSI-H colorectal cancers are "good candidates for immunotherapy," providing a strong rationale to pursue the study. Benson described the standard-of-care context for clinical trials, teaching that the patient population for such a study would typically have progressive and metastatic disease that had failed prior therapies, thus mapping to limitations in dependent claims 2, 5, and 6.
  • Motivation to Combine: A person of ordinary skill in the art (POSITA) would have been motivated to carry out the clinical trial protocol disclosed in the MSI-H Study Record. Pernot provided the scientific rationale, confirming the promise of immunotherapy for the specific MSI-H cancer subtype. Benson provided the established clinical context, informing the POSITA that the trial subjects would likely have advanced, treatment-refractory cancer, as is standard for Phase II oncology trials.
  • Expectation of Success: The combination of prior art established a strong expectation of success. The known immunogenic nature of MSI-H tumors (as taught by Pernot) combined with the known mechanism of PD-1 inhibitors like pembrolizumab would lead a POSITA to reasonably expect that the treatment outlined in the MSI-H Study Record would yield a positive clinical outcome.

Ground 3: Obviousness of Claim 4 under §103

• Prior Art Relied Upon: The MSI-H Study Record, optionally in view of Pernot and Benson, and further in view of Chapelle (a 2010 journal article).

• Core Argument for this Ground:

  • Prior Art Mapping: Claim 4 depends from claim 1 and adds limitations specifying the use of certain microsatellite markers (e.g., BAT-25, BAT-26) or mismatch repair markers to identify patients. While the MSI-H Study Record required identifying patients with MSI-H cancer, it did not specify the exact markers. Chapelle remedied this by teaching standard, well-known methods for determining MSI-H status, including the use of a panel of markers that included BAT-25 and BAT-26, which Chapelle noted had "stood the test of time."
  • Motivation to Combine: A POSITA, seeking to implement the protocol of the MSI-H Study Record, would need a method to identify eligible MSI-H patients. Chapelle provided these routine, standard-of-care testing methods. The motivation was straightforward: to use a known and reliable diagnostic test to select the patient population required by the primary reference's clinical trial.
  • Expectation of Success: Success was highly predictable, as Chapelle taught that these diagnostic tests were standard and reliable. The method of testing would not have been expected to interfere with the efficacy of the pembrolizumab treatment itself.

• Additional Grounds: Petitioner asserted additional obviousness challenges against claims 1-7 based on combinations including Brown (teaching PD-1 inhibitors work best in highly mutated tumors), Duval (teaching MSI-H tumors are highly mutated), and Hamid (teaching the standard intravenous administration of pembrolizumab).

4. Arguments Regarding Discretionary Denial

• Petitioner argued that discretionary denial under Fintiv is inappropriate because the parallel district court litigation is in an early stage, a stay will be requested upon institution, and a final written decision (FWD) from the PTAB would likely issue before a trial.
• Petitioner also argued that denial under §325(d) is inappropriate. It contended that the Examiner for the ’974 patent never considered the MSI-H Study Record. Furthermore, during prosecution of a related patent, the Examiner allegedly committed a legal error by failing to apply controlling precedent on inherency for anticipation and did not have the benefit of the numerous other prior art references and combinations presented in the petition.

5. Relief Requested

• Petitioner requests institution of an inter partes review and cancellation of claims 1-7 of the ’974 patent as unpatentable.