Merck Sharp & Dohme LLC v. Johns Hopkins University

1. Case Identification

• Case #: IPR2024-00649
• Patent #: 11,629,187
• Filed: March 13, 2024
• Petitioner(s): Merck Sharp & Dohme LLC
• Patent Owner(s): The Johns Hopkins University
• Challenged Claims: 1-28

2. Patent Overview

• Title: Methods of Treating Cancer with Mismatch Repair Deficiency
• Brief Description: The ’187 patent claims methods for treating cancer by administering the PD-1 inhibitor drug pembrolizumab to patients whose solid tumors have been identified as having high microsatellite instability (MSI-H) or being DNA mismatch repair deficient (dMMR).

3. Grounds for Unpatentability

Ground 1: Anticipation of Claims 1-2, 4-7, 9-12, 14-17, 19-28 under §102

• Prior Art Relied Upon: MSI-H Study Record (ClinicalTrials.gov record 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 a year before the patent’s priority date, discloses every element of the challenged claims. The protocol described a clinical study treating patients having MSI-H non-colorectal cancer with 10 mg/kg of pembrolizumab every 14 days. Petitioner contended that the protocol expressly or inherently taught treating patients with specific solid tumors (claim 1), that those patients would have had metastatic cancer that progressed after prior treatment, and that the treatment would be therapeutically effective. The protocol required patient selection based on MSI status, which necessarily involved prior testing of a biological sample (e.g., tumor tissue).
  • Key Aspects: Petitioner’s core legal argument rested on the principle of inherency. It argued that even though the study record did not contain the results of the clinical trial, it anticipated the claims because it described a method where the claimed efficacy was an inherent result of performing the disclosed steps. Petitioner asserted that under Federal Circuit precedent, a prior art reference need only enable the claimed method, and any inherent results (like efficacy) do not need to be expressly disclosed to anticipate.

Ground 2: Obviousness of Claims 1-2, 4-7, 9-12, 14-17, 19-28 under §103

• Prior Art Relied Upon: MSI-H Study Record in view of Brown (a 2014 journal article on PD-1 inhibitors), Duval (a 2004 journal article on MSI-H cancers), 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 every limitation (such as an improved outcome, specific cancer types, or prior treatment progression), these features would have been obvious to a Person of Ordinary Skill in the Art (POSA). The MSI-H Study Record provided the foundational method of treating MSI-H patients with pembrolizumab.
  • Motivation to Combine: Petitioner argued a POSA would have been motivated to carry out the clinical trial described in the MSI-H Study Record and would have had a high expectation of success. Brown taught that PD-1 inhibitors were more effective against tumors with many mutations (a known characteristic of MSI-H tumors), and Duval taught that MSI-H cancers are highly immunogenic, making them good candidates for immunotherapy. Benson provided the standard of care for clinical trials, teaching that participants in such studies typically have metastatic or progressive disease that has failed at least one prior therapy. Therefore, a POSA would have been motivated to apply the teachings of Benson to the patient population of the MSI-H study.
  • Expectation of Success: Petitioner asserted a high expectation of success based on the known biological mechanisms. The art taught that MSI-H tumors possessed the two key characteristics that predicted success with PD-1 inhibitors: they are highly mutated (making them easy for immune cells to recognize) and are often heavily infiltrated by immune cells. Furthermore, since pembrolizumab was already approved for another cancer, the probability of success for a second indication was known to be significantly higher.

• Additional Grounds: Petitioner asserted additional obviousness challenges based on the core combination of the MSI-H Study Record, Brown, Duval, and Benson, augmented with single references to teach specific dependent claim limitations. These included adding Koh (clinical guidelines for uterine neoplasms) to address claims covering endometrial cancer; Chapelle (a 2010 article on MSI testing) to teach the use of specific MSI markers from tumor tissue; Steinert (a 2014 article) to teach testing for MSI-H in body fluids; and Hamid (a 2013 article) to explicitly teach intravenous administration of pembrolizumab.

4. Arguments Regarding Discretionary Denial

• Discretionary Denial under Fintiv: Petitioner argued against discretionary denial, stating that the parallel district court litigation is in a very early stage, with a trial date not expected until mid-2026, well after a Final Written Decision (FWD) would issue. Petitioner represented it would seek a stay of the district court case upon institution, minimizing any overlap of resources. It also argued that the merits of the petition are exceptionally strong, weighing against denial.
• Discretionary Denial under §325(d): Petitioner argued denial under §325(d) is inappropriate because the Examiner made a legal error during prosecution of a related patent by failing to properly apply the doctrine of inherent anticipation to the MSI-H Study Record. Further, the Examiner for the ’187 patent did not consider the MSI-H Study Record at all, and none of the Examiners in the patent family considered the specific obviousness combinations presented in the petition.

5. Relief Requested

• Petitioner requests institution of an inter partes review and cancellation of claims 1-28 of the ’187 patent as unpatentable.