Background
CRISPR-Cas9 gene editing — a revolutionary technology for precisely cutting and modifying DNA sequences — was simultaneously developed by two competing research teams: Jennifer Doudna and Emmanuelle Charpentier (working with the University of California, Berkeley, the University of Vienna, and other institutions, collectively the “CVC” group) and Feng Zhang (working with the Broad Institute of MIT and Harvard). The CVC group filed patent applications first (in May 2012), claiming CRISPR gene editing generally. The Broad Institute filed applications shortly thereafter, specifically claiming CRISPR in eukaryotic cells (cells with a nucleus, including human cells) — the application most relevant to human therapeutics and gene therapy.
Under the patent interference procedure applicable to applications filed before the AIA’s first-inventor-to-file transition date, both groups’ claims were subject to a priority contest at the PTAB. The PTAB found that Broad’s claims to eukaryotic CRISPR were separate and distinct from CVC’s claims to CRISPR generally, because Broad independently conceived and reduced to practice the eukaryotic application — and CVC had not established conception of eukaryotic CRISPR sufficiently early to predate Broad’s priority. The PTAB awarded Broad the eukaryotic claims. CVC appealed.
The Court’s Holding
The Federal Circuit affirmed. The court held that the PTAB had correctly found that the CVC group’s earlier reduction to practice of CRISPR in prokaryotic (bacterial) cells did not establish a continuous conception and reduction to practice through to eukaryotic cells — a fundamentally more complex environment in which CRISPR’s success was neither predictable nor certain. The court applied the interference doctrine: CVC bore the burden of demonstrating prior invention (conception and reduction to practice) of the specifically claimed eukaryotic CRISPR system, not just CRISPR generally.
The court found substantial evidence supporting the PTAB’s conclusion that skilled researchers in 2012 did not believe it was reasonably certain that CRISPR would work in eukaryotic cells — the genomic environment, delivery mechanisms, and protein-DNA interactions in eukaryotes are substantially more complex than in prokaryotes. Broad’s team independently succeeded in demonstrating eukaryotic CRISPR function, and that independent success supported Broad’s priority claim to the eukaryotic applications. CVC’s earlier prokaryotic work did not predate Broad’s eukaryotic conception and reduction to practice for interference purposes.
Key Takeaways
- Under the patent interference doctrine, the party challenging the first-to-file’s priority must prove its own earlier conception and diligent reduction to practice of the specifically claimed invention — conception in a related but distinct technology environment (prokaryotic) does not establish priority for claims directed to a more complex environment (eukaryotic).
- When scientific success in one context does not predict success in another due to significantly different biological or technical environments, each context may constitute a distinct invention requiring separate proof of conception and reduction to practice.
- The CRISPR patent dispute illustrates how foundational platform technology patents can generate intense priority contests with enormous commercial and therapeutic significance — the ability to patent human therapeutic applications of CRISPR was estimated to be worth billions of dollars in future licensing revenue.
- The AIA’s first-inventor-to-file system (applicable to applications filed after March 2013) eliminated most interference proceedings, replacing them with derivation proceedings — the CRISPR interference was one of the last major battles under the old priority system.
Why It Matters
The UC/Broad CRISPR patent dispute was one of the most consequential intellectual property battles in the history of biotechnology, involving Nobel Prize-winning science, billions of dollars in potential licensing revenue, and the future of gene therapy and genome medicine. The Federal Circuit’s 2022 affirmance of Broad’s patent rights to CRISPR in eukaryotic cells — the most therapeutically relevant application — gave the Broad Institute a dominant position in the human therapeutic CRISPR patent landscape.
The case also highlighted the limitations of the first-to-file reform in resolving disputes about foundational technologies: because both groups filed before the AIA transition date, the dispute was governed by the old first-to-invent interference system. The extensive, expensive proceedings — multiple PTAB interference proceedings, Federal Circuit appeals, and parallel European Patent Office proceedings — illustrate the complexity and high stakes of university research institution patent priority contests involving transformative technologies. The CRISPR patent landscape continues to evolve as sublicensing arrangements, new patent filings, and commercial partnerships shape access to this fundamental platform technology.