Patent Board Rules Against Johns Hopkins in Pembrolizumab Patent Dispute with Merck
核心洞察
The Patent Trial and Appeals Board issued final written decisions on September 18-19, 2025, finding all claims in four Johns Hopkins pembrolizumab patents unpatentable in challenges brought by Merck.
The disputed patents cover the use of pembrolizumab (KEYTRUDA) for treating colorectal cancer (搜索) and solid tumors (搜索) in patients with microsatellite instability (搜索)-high or mismatch repair deficiency (搜索).
The decisions are part of a broader intellectual property dispute involving nine inter partes reviews filed by Merck against Johns Hopkins patents related to their research collaboration on pembrolizumab effectiveness.
The Patent Trial and Appeals Board (PTAB) delivered a significant victory to Merck Sharp & Dohme LLC in its ongoing intellectual property dispute with Johns Hopkins University, ruling that all claims in four pembrolizumab patents are unpatentable. The final written decisions, issued on September 18 and 19, 2025, mark the latest development in a complex patent battle over one of the world's most successful cancer immunotherapies.
Patent Challenge Details
The PTAB found all claims unpatentable in four inter partes review (IPR) challenges: IPR2024-00625 (U.S. Patent No. 11,339,219), IPR2024-00647 (U.S. Patent No. 11,649,287), IPR2024-00649 (U.S. Patent No. 11,629,187), and IPR2024-00650 (U.S. Patent No. 11,634,491). These patents are directed toward the use of pembrolizumab in treating and reducing the risk of progression of colorectal cancer (搜索) and various types of solid tumors (搜索) following positive diagnostic testing for microsatellite instability (搜索) high (MSI-H) or mismatch repair deficiency (搜索) (dMMR).
The Board's analysis followed similar reasoning to its June 9, 2025 final written decision in IPR2024-00240 (U.S. Patent No. 11,591,393), which found all 42 claims unpatentable. In each case, the PTAB determined that the claims were unpatentable over prior art that includes the study record of Johns Hopkins's Phase 2 clinical trial examining the effectiveness of KEYTRUDA in patients with MSI-H or dMMR cancer.
Research Collaboration Dispute
The patent dispute stems from what Merck alleges was a research collaboration between the parties to study the effectiveness of KEYTRUDA (pembrolizumab) on tumors that carry a high mutational load. However, Johns Hopkins counters that "the concept for the groundbreaking clinical study developed by Hopkins researchers was prepared before there was any agreement between Hopkins and Merck, and the contributions Merck alleges to have made to the study protocol were known, trivial and have never been claimed as inventions by the Hopkins Inventors."
The Board agreed with Merck that the main prior art reference cited, a record of a Phase 2 clinical trial completed by Johns Hopkins, teaches the efficacy requirement wherein a patient with an unresectable or metastatic MSI-H tumor administered an effective amount of pembrolizumab would have an improved outcome over a reference patient that had been also administered pembrolizumab, but whose tumor does not exhibit an MSI-H status.
Broader Legal Context
These four IPRs are part of nine total challenges filed by Merck to contest patents at issue in the district court litigation Merck Sharp & Dohme LLC v. The Johns Hopkins University, 1:22-cv-03059-JRR (D. Md.). All nine IPRs were instituted and the district litigation was stayed pending their resolution.
Four IPRs remain pending with extended deadlines. The deadline for IPR2024-00622 (U.S. Patent No. 10,934,356), IPR2024-00623 (U.S. Patent No. 11,325,974), and IPR2024-00624 (U.S. Patent No. 11,325,975), originally September 23, 2025, has been extended to November 7, 2025. The deadline for IPR2024-00648 (U.S. Patent No. 11,643,462), originally October 3, 2025, has been extended to November 18, 2025.
Commercial Significance
The stakes in this patent dispute are substantial, given pembrolizumab's commercial success. Merck reported $29.5 billion in worldwide KEYTRUDA sales in 2024, making it one of the pharmaceutical industry's most valuable assets. The drug is FDA-approved for patients with microsatellite instability (搜索)-high and dMMR colorectal cancer (搜索), among numerous other cancer indications.
The ongoing patent challenges highlight the complex intellectual property landscape surrounding breakthrough cancer immunotherapies, particularly when academic institutions and pharmaceutical companies collaborate on clinical research that leads to significant therapeutic advances.