Merck Sharp & Dohme LLC v. Johns Hopkins University

1. Case Identification

• Case #: IPR2024-00624
• Patent #: 11,325,975
• Filed: March 4, 2024
• Petitioner(s): Merck Sharp & Dohme LLC
• Patent Owner(s): The Johns Hopkins University
• Challenged Claims: 1-4, 6-10, and 12-15

2. Patent Overview

• Title: Method of Treating Cancer
• Brief Description: The ’975 patent claims methods for treating cancer by administering an anti-PD-1 antibody to patients whose tumors have been determined to exhibit high microsatellite instability (MSI-H) or mismatch repair deficiency (dMMR).

3. Grounds for Unpatentability

Ground 1: Anticipation by Clinical Study Protocol - Claims 1-3, 6-10, and 13-15 are anticipated by the MSI-H Study Record under 35 U.S.C. §102.

• Prior Art Relied Upon: MSI-H Study Record (a clinical trial protocol, 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 protocol for a clinical trial, disclosed every element of the challenged claims more than one year before the patent’s effective filing date. The protocol explicitly described a method of treating cancer in patients determined to have MSI-positive tumors by administering a specific dosage of pembrolizumab, a known anti-PD-1 antibody. Petitioner contended that claimed limitations—such as an "improved outcome" compared to a reference patient—were the inherent result of practicing the disclosed method. Similarly, limitations requiring patients to have received prior cancer therapy or have metastatic cancer were argued to be inherent characteristics of the patient population for a Phase II oncology study as described in the protocol.
  • Key Aspects: The core of this ground rested on the legal principle of inherent anticipation. Petitioner argued that a published clinical trial protocol anticipates a later method claim if the claimed efficacy is a necessary and inherent result of performing the disclosed method, even if the clinical results were not yet published. Petitioner asserted that the Examiner in a related prosecution committed legal error by requiring express disclosure of these inherent results, a position contrary to Federal Circuit precedent.

Ground 2: Obviousness over Study Protocol and Scientific Literature - Claims 1-3, 6-10, and 13-15 are obvious over the MSI-H Study Record in view of Pernot and Benson under 35 U.S.C. §103.

• Prior Art Relied Upon: MSI-H Study Record, Pernot (a 2014 journal article on colorectal cancer and immunity), and Benson (a 2014 set of clinical practice guidelines).
• Core Argument for this Ground:
  • Prior Art Mapping: As an alternative to anticipation, Petitioner argued for obviousness. The MSI-H Study Record provided the foundational method of treating MSI-H patients with pembrolizumab. The additional references provided the rationale and context that allegedly made performing the study and achieving the claimed results obvious. Pernot taught that MSI-H tumors are "good candidates for immunotherapy," providing a clear scientific rationale for the treatment. Benson described the standard patient population for such clinical studies, establishing that participants would predictably have metastatic cancer that had progressed after prior drug therapies.
  • Motivation to Combine: A person of ordinary skill in the art (POSITA) would combine the MSI-H Study Record with the teachings of Pernot because Pernot’s general teaching directly applied to the specific cancer subtype and treatment modality outlined in the study protocol. A POSITA would have looked to a standard guideline like Benson to understand the patient population for the study, confirming that the claimed patient characteristics (metastatic, prior therapies) were standard for such a trial.
  • Expectation of Success: Petitioner argued a POSITA would have a reasonable expectation of success. This was based on the known immunogenic properties of MSI-H tumors and the established mechanism of action for anti-PD-1 inhibitors, which was further supported by explicit statements in references like Pernot.

Ground 3: Obviousness of Specific Testing Methods - Claims 4 and 12 are obvious over the MSI-H Study Record (and Pernot/Benson) in view of Chapelle.

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

• Core Argument for this Ground:

  • Prior Art Mapping: This ground specifically addressed dependent claims 4 and 12, which recite methods for determining a patient’s MSI-H status using specific microsatellite markers (e.g., BAT-25, BAT-26). While the primary references established the obviousness of treating the MSI-H population, Chapelle was introduced to show that the specific diagnostic methods recited in the claims were themselves well-known and routine in the art.
  • Motivation to Combine: A POSITA seeking to implement the MSI-H Study protocol would need a way to identify eligible patients. Chapelle described the "standard test" panels using the exact markers recited in the claims, making it the obvious and routine choice for fulfilling the protocol’s patient selection criteria.
  • Expectation of Success: Because the testing methods in Chapelle were standard, well-known, and widely used, a POSITA would have a high expectation of success in using them to identify MSI-H patients for the study.

• Additional Grounds: Petitioner asserted additional obviousness challenges based on the MSI-H Study Record in combination with references including Brown, Duval, and Hamid, which further supported the known scientific rationale for treating MSI-H tumors with anti-PD-1 inhibitors and the standard methods of administration.

4. Arguments Regarding Discretionary Denial

• Petitioner argued that discretionary denial would be inappropriate under both 35 U.S.C. §325(d) and the Fintiv factors.
• Regarding §325(d), Petitioner asserted that the Examiner for the ’975 patent never considered the MSI-H Study Record. Further, while the reference was considered in a related case, the Examiner allegedly made a clear legal error by failing to properly apply the doctrine of inherent anticipation, an error the Petitioner seeks to correct with new arguments and reference combinations.
• Regarding Fintiv, Petitioner argued that the parallel district court litigation is in an early stage, a stay will be sought upon institution, and a Final Written Decision would likely issue before a trial would commence, thus favoring institution to promote efficiency and avoid conflicting outcomes.

5. Relief Requested

• Petitioner requests institution of inter partes review and cancellation of claims 1-4, 6-10, and 12-15 of Patent 11,325,975 as unpatentable.