Merck Sharp & Dohme LLC v. Johns Hopkins University

1. Case Identification

• Case #: IPR2024-00622
• Patent #: 10,934,356
• Filed: March 4, 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 microsatellite instability
• Brief Description: The ’356 patent claims methods for treating cancer by administering the PD-1 inhibitor drug pembrolizumab to patients identified as having tumors with high microsatellite instability (MSI-H) or mismatch repair (dMMR) deficiency.

3. Grounds for Unpatentability

Ground 1: Anticipation over MSI-H Study Record - Claims 1, 6-11, 13-20, 22-24, and 26-28 are anticipated under 35 U.S.C. §102 by the MSI-H Study Record.

• 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 clinical trial protocol published more than a year before the patent’s earliest possible priority date, discloses every limitation of the challenged claims. The protocol describes a method of treating cancer by administering a specific dose of pembrolizumab (10 mg/kg every 14 days) to patients with MSI-H colorectal and non-colorectal cancer. Petitioner asserted that limitations related to improved outcomes (e.g., objective response rate) are inherently disclosed, as they are the necessary and inevitable result of practicing the disclosed method, even if the clinical results themselves were not part of the initial protocol publication.
  • Key Aspects: The core of this ground relies on the legal doctrine of inherent anticipation, arguing that the Examiner erred during prosecution by requiring an explicit disclosure of the treatment's efficacy, which Federal Circuit precedent holds is not required when the result is inherent to practicing the disclosed method.

Ground 2: Obviousness over MSI-H Study Record, Pernot, and Benson - Claims 1, 6-11, 13-20, 22-24, and 26-27 are obvious over the MSI-H Study Record in view of Pernot and Benson.

• Prior Art Relied Upon: MSI-H Study Record (NCT01876511), Pernot (a 2014 journal article on colorectal cancer and immunity), and Benson (a 2014 clinical practice guideline for colon cancer).
• Core Argument for this Ground:
  • Prior Art Mapping: Petitioner argued that, even if the MSI-H Study Record does not anticipate, its teachings render the claims obvious. The MSI-H Study Record discloses the core method of treating MSI-H patients with pembrolizumab. Pernot explicitly taught that MSI-H cancers are "good candidates for immunotherapy" with PD-1 inhibitors like pembrolizumab. Benson disclosed the standard of care for clinical trials involving colorectal cancer, teaching that the patient population would typically have metastatic and progressive disease that had failed prior therapies.
  • Motivation to Combine: A person of ordinary skill in the art (POSITA) would combine the MSI-H Study Record with Pernot because Pernot provided the scientific rationale for why the study was likely to succeed, thus motivating a POSITA to carry out the protocol. A POSITA would have looked to Benson to understand the standard patient characteristics for such a clinical trial, making it obvious to include patients with metastatic and treatment-refractory cancer, as recited in several dependent claims.
  • Expectation of Success: A POSITA would have had a reasonable expectation of success because the prior art taught that MSI-H tumors possessed the very characteristics (e.g., high mutational load, infiltration by immune cells) known to make tumors susceptible to PD-1 inhibitor therapy.

Ground 3: Obviousness over MSI-H Study Record, Brown, Duval, and Benson - Claims 1, 6-11, 13-20, 22-24, 26-28 are obvious over the MSI-H Study Record in view of Brown, Duval, and Benson.

• Prior Art Relied Upon: MSI-H Study Record (NCT01876511), Brown (a 2014 journal article on neo-antigens), Duval (a 2004 journal article on the mutator pathway), and Benson (the 2014 clinical guideline).

• Core Argument for this Ground:

  • Prior Art Mapping: This ground presented an alternative obviousness argument with a deeper scientific rationale for the expectation of success. The MSI-H Study Record and Benson provided the same foundational disclosures as in Ground 2. Brown and Duval together taught the underlying mechanism for why MSI-H tumors respond well to immunotherapy: they have cancer cells that are easy for immune cells to recognize.
  • Motivation to Combine: A POSITA would combine these references to gain a complete picture of the proposed therapy. The MSI-H Study Record proposed the "what" (the clinical trial), Brown and Duval explained the "why" (the biological basis for efficacy), and Benson provided the "who" (the standard patient population). This combination would have rendered the claimed invention obvious.
  • Expectation of Success: The teachings of Brown and Duval, explaining that MSI-H cancers are inherently easy for the immune system to recognize and attack, would have provided a strong expectation that a PD-1 inhibitor like pembrolizumab, which "releases the brakes" on the immune system, would be effective.

• Additional Grounds: Petitioner asserted additional obviousness challenges, including combinations incorporating Chapelle (a 2010 article teaching standard methods for MSI-H testing) and Hamid (a 2013 article confirming intravenous administration for pembrolizumab), to address specific dependent claim limitations related to diagnostic methods and drug administration.

4. Arguments Regarding Discretionary Denial

• Petitioner argued that discretionary denial under Fintiv is inappropriate because the parallel district court case is in a very early stage, a stay will be sought upon institution, and a final written decision would issue long before any potential trial date.
• Petitioner further argued that discretionary denial under §325(d) is inappropriate because, although the Examiner considered the MSI-H Study Record, the Examiner committed a clear legal error by failing to apply the controlling Federal Circuit precedent on inherent anticipation. Petitioner contended this error presents a compelling reason for the Board to reconsider the prior art.

5. Relief Requested

• Petitioner requests institution of an inter partes review (IPR) and cancellation of claims 1-28 of the ’356 patent as unpatentable.