Merck Sharp & Dohme LLC v. Johns Hopkins University

1. Case Identification

• Case #: IPR2024-00650
• Patent #: 11,634,491
• Filed: March 13, 2024
• Petitioner(s): Merck Sharp & Dohme LLC
• Patent Owner(s): The Johns Hopkins University
• Challenged Claims: 1-38

2. Patent Overview

• Title: Treatment of Cancer Using PD-1 Inhibitors in Patients with Microsatellite Instability
• Brief Description: The ’491 patent claims methods of treating cancer patients by administering the PD-1 inhibitor drug pembrolizumab. The method is directed to a specific sub-population of patients whose cancers are identified as having high microsatellite instability (MSI-H) or being mismatch repair deficient (dMMR).

3. Grounds for Unpatentability

Ground 1: Anticipation of Claims 1-2, 4-7, 11-17, 19-22, and 26-38 under §102

• Prior Art Relied Upon: MSI-H Study Record (a clinical trial protocol identified as NCT01876511, published on ClinicalTrials.gov 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 published more than one year before the patent’s earliest possible priority date, explicitly taught every limitation of the independent claims. The protocol described a method of treating cancer in human patients by: (1) identifying patients with MSI-H non-colorectal cancer (which required testing a biological sample), and (2) administering the same drug (pembrolizumab) at the identical dosage (10 mg/kg every 14 days) claimed in the patent. Petitioner asserted that any claimed therapeutic efficacy was an inherent result of performing the disclosed method, and that under controlling Federal Circuit precedent (In re Montgomery), a prior art document disclosing a planned clinical study inherently anticipates method of treatment claims, even if the treatment had not yet been practiced or its results published.
  • Key Aspects: The core of this ground rested on the principle of inherency, contending that the Patent Owner improperly secured a patent on the foreseeable results of a publicly disclosed research plan. Petitioner argued that the Examiner in a related case erred by requiring an express disclosure of the treatment's results, contrary to established law on anticipation.

Ground 2: Obviousness of Claims 1-2, 4-7, 11-17, 19-22, and 26-38 under §103

• Prior Art Relied Upon: MSI-H Study Record in view of Brown (a May 2014 journal article on neo-antigens and patient survival), Duval (a 2004 journal article on the mutator pathway), and Benson (a July 2014 article on colon cancer clinical practice guidelines).

• Core Argument for this Ground:

  • Prior Art Mapping: As an alternative to anticipation, Petitioner argued that even if the MSI-H Study Record was not anticipatory, it rendered the claims obvious in combination with other prior art. The MSI-H Study Record served as the primary reference disclosing the core method of treating MSI-H non-colorectal cancer with pembrolizumab. Brown and Duval provided the scientific rationale for the study, teaching that MSI-H tumors are highly immunogenic and have characteristics that make them prime candidates for treatment with PD-1 inhibitors. Benson provided context on standard clinical trial practices, teaching that patients in such studies for advanced cancers would typically have metastatic, progressive disease and have failed prior therapies.
  • Motivation to Combine: A Person of Ordinary Skill in the Art (POSA) would have been motivated to execute the clinical trial described in the MSI-H Study Record. The teachings of Brown and Duval provided a strong scientific rationale, explaining that MSI-H tumors were known to be particularly susceptible to immunotherapy because they have many mutations that are easily recognized by the immune system. This knowledge would have motivated a POSA to combine the known drug (pembrolizumab) with the known patient population (MSI-H cancer patients) as outlined in the study record.
  • Expectation of Success: A POSA would have had a reasonable expectation of success. The art taught that PD-1 inhibitors like pembrolizumab were most effective in tumors that were highly mutated and infiltrated by immune cells. Brown and Duval specifically taught that MSI-H tumors possessed these exact characteristics. This strong correlation between the drug's mechanism of action and the tumor's biology would have provided a POSA with a clear expectation that the treatment proposed in the MSI-H Study Record would be effective.

• Additional Grounds: Petitioner asserted additional obviousness challenges for specific claim groups, including:

  • Claims 1-2, 4-7, 11, 13-17, 19-22, 26, and 28-38 over the MSI-H Study Record, Brown, Duval, Benson, and Koh (a 2014 article on uterine neoplasms).
  • Claims 2, 8, 17, and 23 by adding Chapelle (a 2010 article on MSI testing) to the primary combinations to teach testing tumor tissue.
  • Claims 3 and 18 by adding Steinert (a 2014 article on immune escape) to teach using body fluid as the biological sample.
  • Claims 9-10 and 24-25 by adding Salipante (a 2014 article on MSI detection) to teach using PCR or next-gen sequencing.
  • Claims 11 and 26 by adding Hamid (a 2013 article on pembrolizumab) to teach intravenous administration.

4. Arguments Regarding Discretionary Denial

• Discretionary Denial under Fintiv: Petitioner argued that denial would be inappropriate because the parallel district court litigation was in a very early stage, with significant investment still required. Petitioner stated it would seek a stay, and a final written decision from the PTAB would likely issue before a district court trial, promoting efficiency.
• Discretionary Denial under §325(d): Petitioner argued that denial would be inappropriate because the Examiner did not consider the MSI-H Study Record during prosecution of the ’491 patent. Furthermore, during prosecution of a related patent, the Examiner made a legal error by failing to apply Federal Circuit precedent on inherency when evaluating the same reference. Finally, 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 1-38 of the ’491 patent as unpatentable.