The Broad Institute, Inc. v. the Regents of the University of California

CourtCourt of Appeals for the Federal Circuit
DecidedMay 12, 2025
Docket22-1653
StatusPublished

This text of The Broad Institute, Inc. v. the Regents of the University of California (The Broad Institute, Inc. v. the Regents of the University of California) is published on Counsel Stack Legal Research, covering Court of Appeals for the Federal Circuit primary law. Counsel Stack provides free access to over 12 million legal documents including statutes, case law, regulations, and constitutions.

Bluebook
The Broad Institute, Inc. v. the Regents of the University of California, (Fed. Cir. 2025).

Opinion

Case: 22-1653 Document: 4 Page: 1 Filed: 05/12/2025

United States Court of Appeals for the Federal Circuit ______________________

THE REGENTS OF THE UNIVERSITY OF CALIFORNIA, UNIVERSITY OF VIENNA, EMMANUELLE CHARPENTIER, Appellants

v.

THE BROAD INSTITUTE, INC., MASSACHUSETTS INSTITUTE OF TECHNOLOGY, PRESIDENT AND FELLOWS OF HARVARD COLLEGE, Cross-Appellants ______________________

2022-1594, 2022-1653 ______________________

Appeals from the United States Patent and Trademark Office, Patent Trial and Appeal Board in No. 106,115. ______________________

Decided: May 12, 2025 ______________________

JEFFREY A. LAMKEN, MoloLamken LLP, Washington, DC, argued for appellants. Also represented by LOIS AHN, KENNETH E. NOTTER, III; ELIZABETH KATHLEEN CLARKE, Chicago, IL, SARA MARGOLIS, New York, NY.

RAYMOND NIMROD, Quinn Emanuel Urquhart & Sulli- van, LLP, New York, NY, argued for cross-appellants. Also represented by MATTHEW D. ROBSON; HUGH S. BALSAM, Case: 22-1653 Document: 4 Page: 2 Filed: 05/12/2025

STEVEN R. TRYBUS, Troutman Pepper Locke LLP, Chicago, IL. ______________________

Before REYNA, HUGHES, and CUNNINGHAM, Circuit Judges. REYNA, Circuit Judge. The Regents of the University of California, the Uni- versity of Vienna, and Emmanuelle Charpentier (collec- tively “Regents”) appeal from the Patent Trial and Appeal Board’s determinations in a patent interference proceed- ing. The Broad Institute, Massachusetts Institute of Tech- nology, and the President and Fellows of Harvard College (collectively “Broad”) conditionally cross-appeal. After re- solving preliminary motions, the Board issued a final deci- sion concluding that Broad has priority over Regents with respect to a CRISPR-Cas9 system that contains a “single- guide” RNA that edits or cleaves DNA in eukaryotic cells. We affirm-in-part, vacate-in-part, and remand as to the main appeal and dismiss as to the cross-appeal. BACKGROUND This appeal involves an invention relating to the adap- tation of “CRISPR”1 systems to edit eukaryotic DNA. Ap- pellant Br. 1; Cross-Appellant Br. 20. Scientists at Regents claim they invented this technology. Appellant Br. 1–2, 8–22. Scientists at Broad argue they are the true inventors. Cross-Appellant Br. 1–2, 14–22. As such, this

1 CRISPR (“clustered regularly interspaced short palindromic repeats”) comprises a family of DNA loci. J.A. 3051 (U.S. Patent No. 8,697,359, at 15:58–61). A “CRISPR system” “refers collectively to transcripts and other elements involved in the expression of or directing the activity of CRISPR-associated (‘Cas’) genes[.]” Id. at 16:32–34. Case: 22-1653 Document: 4 Page: 3 Filed: 05/12/2025

REGENTS OF THE UNIVERSITY OF CALIFORNIA v. 3 BROAD INSTITUTE, INC.

dispute centers on one of the oldest doctrines in U.S. patent law, conception. I. A. Early Research CRISPR systems are immune defense systems in pro- karyotic cells that naturally edit DNA. 2 One of the “sim- plest” types of CRISPR systems, a “Type II CRISPR system,” uses an RNA sequence, “crRNA,” to guide a pro- tein to a particular DNA sequence as part of the process of editing the DNA. J.A. 64098. Scientists sought to use the natural editing capabilities of CRISPR systems to edit DNA in eukaryotic cells. Broad’s and Regents’ scientists claim that, by 2011 or early 2012, they knew CRISPR Type II systems edit DNA using three components: mature tracrRNA, mature crRNA, and a protein called “Cas9.” J.A. 74998–99; J.A. 5597–641 (Martin Jinek et al., A Programmable Dual-RNA-Guided DNA Endonuclease in Adaptive Bacterial Immunity, 337 SCIENCE 816 (2012)) (“Jinek 2012”). According to Regents, its scientists believed this biological triptych—called a “CRISPR-Cas9 complex” or “CRISPR-Cas9 system”—could be used to edit eukaryotic DNA without having to design a new protein for every new target DNA sequence, as was necessary when using prior gene-editing tools. Appellant Br. 4–5. Regents’ scientists claim that they further simplified CRISPR-based gene editing in 2012 by linking two RNA

2 Every living organism is one of two types: prokary- otic or eukaryotic. Prokaryotes are single-celled organisms lacking a nucleus, such as bacteria, while eukaryotes are more complex organisms, such as animals and plants, whose cells possess a nucleus. Appellant Br. 4; Cross-Ap- pellant Br. 10. Case: 22-1653 Document: 4 Page: 4 Filed: 05/12/2025

sequences in the CRISPR-Cas9 system into a single-mole- cule “chimeric” RNA, called a “single-guide” RNA (“sgRNA”). J.A. 57592, 67247–48. They claim that they made a CRISPR-Cas9 system from a sgRNA they designed, called “chimera A,” and Cas9. Jinek 2012; J.A. 67260–61. They claim to have used this system to successfully target and edit DNA in a cell-free in vitro environment. J.A. 67260–61, 67286–87. As Regents puts it, this system “simpl[ified]” gene editing by allowing the system to be “re- programmed by changing the crRNA.” Appellant Br. 7. Starting in March 2012, Regents’ scientists, directed by Charpentier, Jennifer Doudna, and Martin Jinek, planned experiments to show the single RNA CRISPR-Cas9 system could be used to edit eukaryotic DNA. On March 1, 2012, Jinek wrote a notebook entry and exchanged emails with Doudna in which they described the system and experi- ments using it in mammalian cells, to test if the system could successfully edit eukaryotic DNA. J.A. 69007–09; see Regents of the Univ. of Cal. v. Broad Inst., Inc., No. 106,115, 2022 WL 1664028, at *16 (P.T.A.B. Feb. 28, 2022) (“Final Decision”). On April 11, 2012, Jinek emailed Doudna an invention disclosure form describing various techniques for editing eukaryotic DNA using one of two methods, “mi- croinjection” or expression “vectors,” in various types of eu- karyotic cells. J.A. 65628–31, 65643–51. After these initial plans, Regents filed its first provisional patent application, “P1” (U.S. Patent App. No. 61/652,086), on May 25, 2012. Regents’ scientists then planned two specific experi- ments. First, leading up to May 28, 2012, Jinek wrote note- book entries describing a plan to test the system’s ability to edit eukaryotic DNA, using expression vector techniques with human cells. J.A. 69071–77, 67284–85 (Jinek testify- ing that he “started” these notebook entries “before May 28, 2012”). Second, on June 28, 2012, Charpentier and Krzysztof Chylinski, another Regents scientist, ex- changed emails with two scientists from another labora- tory, Florian Raible and Kristin Tessmar, describing a Case: 22-1653 Document: 4 Page: 5 Filed: 05/12/2025

REGENTS OF THE UNIVERSITY OF CALIFORNIA v. 5 BROAD INSTITUTE, INC.

second plan to test the system using microinjection tech- niques in “two well-established fish systems”: zebrafish and medaka fish. J.A. 66308, 66311–13. B. Testing the System 1. Tests by Other Scientists Around the time Regents’ scientists drew up their plans, Regents’ scientists made public announcements in June 2012, describing the single RNA CRISPR-Cas9 sys- tem in a conference presentation at the University of Cali- fornia, Berkeley (“2012 Berkeley Conference Presentation”) and an article in Science. J.A. 65907, 65915, 65929–34 (Krzysztof Chylinski & Martin Jinek, “A programmable dual RNA-guided DNA endonuclease in a Type II CRISPR system,” Presentation at the University of California, Berkeley, June 2012); Jinek 2012. Over the remainder of 2012, scientists from laborato- ries outside of Regents, including scientists at Broad, at- tempted to use the system to edit DNA in eukaryotic cells. Of these laboratories outside Regents, five reported success from July to December 2012, using expression vector or mi- croinjection techniques. J.A. 53203–06, 15794–807, 79043–44, 47104–27, 75072–95, 75935–58, 76553–56. Re- gents claims these other scientists learned of the single RNA CRISPR-Cas9 system from Regents’ scientists’ June 2012 presentation or article. Appellant Br. 15–18.

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