In a closely watched battle over the origins of one of the most transformative technologies in modern biology, the Federal Circuit has partially reversed a PTAB ruling in Regents of the University of California v. Broad Institute, Inc., No. 22-1653 (Fed. Cir. May 12, 2025). The dispute centers on who first invented the use of CRISPR-Cas9 systems with single-guide RNA (sgRNA) to edit DNA in eukaryotic cells—a breakthrough that has revolutionized gene editing and spurred enormous commercial and scientific interest.
The Federal Circuit vacated the PTAB’s finding that the Broad Institute had priority over the University of California, University of Vienna, and Emmanuelle Charpentier (collectively, the “Regents”), holding that the Board applied the wrong legal standard for conception. While affirming the PTAB’s determination that the Regents’ provisional applications lacked adequate written description, the Court remanded for further proceedings on conception.
Background: A Decade-Long Dispute Over CRISPR Dominance
This interference proceeding is the latest chapter in a long and contentious legal saga between two groups of academic researchers. The Regents’ team, scientists, directed by Emmanuelle Charpentier, Jennifer Doudna, and Martin Jinek, published a seminal 2012 paper demonstrating that a CRISPR-Cas9 system could be programmed using a chimeric sgRNA to cut DNA in a test tube. The Broad team, led by Feng Zhang at MIT and the Broad Institute, was the first to obtain patents for using CRISPR-Cas9 in eukaryotic cells, including human cells, after submitting expedited applications to the USPTO.
The potential commercial implications of these patents are immense. CRISPR technologies are foundational in developing gene therapies, agricultural tools, and synthetic biology applications. The 2020 Nobel Prize in Chemistry was awarded to Doudna and Charpentier for their discovery, but the patent rights remained under dispute. This case, involving Interference No. 106,115, marks the second interference declared between the parties and focuses specifically on claims involving the use of a single-guide CRISPR-Cas9 system in eukaryotic cells.
Federal Circuit: PTAB Misapplied the Legal Standard for Conception
The Federal Circuit found that the PTAB improperly required the Regents’ scientists to know their invention would work in eukaryotic cells in order to establish conception. This, the Court held, conflated the distinct legal standards for conception and reduction to practice.
Citing Burroughs Wellcome Co. v. Barr Labs, Inc., 40 F.3d 1223 (Fed. Cir. 1994), the panel emphasized that an inventor need only have a “definite and permanent idea” of the complete invention. Certainty of success or experimental proof is not required at the conception stage.
The Court also held that:
- The PTAB placed undue weight on contemporaneous expressions of doubt by the Regents’ scientists, without analyzing whether these doubts led to substantive changes in their design;
- The Board erred by failing to consider whether others—using the Regents’ published design and routine methods—were able to achieve successful editing in eukaryotic cells, which would support the argument that the invention required only ordinary skill to reduce to practice;
- The PTAB wrongly disregarded the use of “routine techniques” in the field as a key factor in assessing whether conception had been achieved.
The Court remanded the case for further findings under the proper legal framework, which will allow the Regents to reargue their priority claim based on their early 2012 planning and public disclosures.
Written Description: Affirmed Due to Unpredictability in the Field
The Court affirmed the PTAB’s determination that the Regents’ first (P1) and second (P2) provisional applications lacked adequate written description under 35 U.S.C. § 112. The claims at issue involved an sgRNA-guided CRISPR-Cas9 system functioning in a eukaryotic cell.
Given the acknowledged unpredictability in adapting prokaryotic systems to eukaryotes, the Court agreed with the PTAB that the P1 application did not sufficiently convey possession of an operative embodiment. The Board reasonably found that the application lacked specific instructions or empirical evidence demonstrating success or feasibility, particularly in light of the complexity of the technology.
Although the Court reaffirmed that a working example is not required, it found the Regents’ disclosure wanting because it failed to bridge the gap between concept and implementation in eukaryotic systems.
Broad’s Cross-Appeal: Dismissed as Moot
Broad’s cross-appeal challenged the PTAB’s construction of “guide RNA” as being limited to a single-molecule configuration. However, the Court dismissed the appeal as moot because the Board had denied Broad’s related motions on independent procedural grounds that Broad did not challenge on appeal. Thus, even if the claim construction were reversed, it would not alter the outcome of those rulings.
Takeaways
This decision breathes new life into the Regents’ claims of priority in the eukaryotic CRISPR space and signals the Federal Circuit’s continued insistence on correctly distinguishing between conception and reduction to practice. Some key takeaways:
- The Court reaffirmed that certainty of success is not required for conception. Inventors need only have a definite and permanent idea of the invention that a person of ordinary skill can reduce to practice.
- In unpredictable arts like biotechnology, written description demands more. Disclosure must demonstrate possession, not just hypothesis, particularly when transitioning between biological systems.
- Experimental success by third parties using routine methods is relevant to whether an invention was complete at the time of conception.
- Procedural missteps can be fatal. Broad’s failure to adequately support its claim construction-based motions before the PTAB rendered its cross-appeal ineffectual.
As this high-stakes dispute continues to unfold, the next round at the PTAB may prove decisive in determining who truly owns the foundational CRISPR patent rights in eukaryotic systems.
By Charles Gideon Korrell