CRISPR Patent Wars: Ownership, Licensing, and Expiration

CRISPR patent ownership and licensing centers on two dominant estates: the Broad Institute of MIT and Harvard, which controls the use of CRISPR-Cas9 in cells with a nucleus, and the CVC group led by the University of California, Berkeley, which controls the underlying biochemistry of the CRISPR-Cas9 system. A company developing a human or agricultural CRISPR product almost always needs rights from both. Three smaller holders — MilliporeSigma, ToolGen, and Vilnius University — control narrower claims that can also come into play depending on the application.

The Five Institutions That Own CRISPR-Cas9

The CVC group is a three-party collaboration: UC Berkeley, the University of Vienna, and researcher Emmanuelle Charpentier. Its foundational work showed that CRISPR-Cas9 could be programmed to cut DNA at a chosen target in a test tube. CVC filed early, and its patents reach the basic system itself.

The Broad Institute holds patents specifically covering the use of CRISPR-Cas9 in eukaryotic cells — the cells found in humans, animals, and plants. The Broad has been granted 31 U.S. CRISPR patents, including 26 for CRISPR-Cas9 and 3 for the related CRISPR-Cas12 system.¹

MilliporeSigma, a subsidiary of Merck KGaA, holds patents on using CRISPR to integrate external DNA sequences into eukaryotic cell genomes.² ToolGen, a South Korean biotechnology company, and Vilnius University in Lithuania round out the group. ToolGen has actively enforced its European patents, filing infringement suits against companies commercializing CRISPR therapies, though the European Patent Office has challenged some of those patents on the grounds that certain technical steps lacked an inventive step over earlier gene-editing methods.

Why There Are Two Estates: The Eukaryotic Cell Fight

The reason a licensee usually needs deals with both CVC and the Broad traces to a decade of litigation over one question: who invented the use of CRISPR-Cas9 inside cells with a nucleus? The test-tube chemistry is valuable, but nearly every commercial application — medicine, agriculture, livestock — requires the system to work inside eukaryotic cells.

CVC filed first for the general system. The Broad filed later but used expedited review to secure its eukaryotic-specific patents sooner. In 2017, the Patent Trial and Appeal Board ruled that the Broad’s eukaryotic inventions were patentably distinct from CVC’s test-tube work and not obvious from CVC’s earlier filings.¹ That split the field into two separate patent estates.

CVC challenged again, arguing its researchers conceived the eukaryotic application first. The PTAB sided with the Broad in 2022. The Federal Circuit vacated that decision in 2025, finding that the Board had conflated the legal standards for conception and reduction to practice, and had ignored whether a skilled scientist could have carried out CVC’s concept using routine methods.³ On remand, on March 26, 2026, the PTAB again ruled for the Broad, finding that CVC had not shown by a preponderance of the evidence that its inventors conceived a working eukaryotic system before the Broad’s team reduced one to practice.¹

CVC may still appeal. But as of now, the Broad’s priority for eukaryotic applications has survived three rounds of administrative review and one federal appeal. Both novelty under 35 U.S.C. § 102 and non-obviousness under 35 U.S.C. § 103 must be satisfied for a patent to stand, and the PTAB’s repeated non-obviousness finding is what keeps the Broad’s patents intact.⁴ For a company entering the space, the practical takeaway is simple: plan on licensing from both estates.

What the Patents Actually Cover

CRISPR patents don’t just protect the concept of gene editing. They cover the specific molecular components and the engineered modifications that make the system work, which is why licensing negotiations get granular.

The Cas9 Protein

The Cas9 enzyme is the cutting engine. Patents cover the specific amino acid sequences that make it effective and stable inside a cell. Commercial use of Cas9 in its engineered form requires authorization from the relevant patent holder.

Guide RNA

The guide RNA directs Cas9 to the correct spot on the DNA strand. In nature, this targeting involves two separate RNA molecules; researchers engineered a single fused guide that’s easier to work with. Patents cover the chemical modifications that improve stability and binding accuracy, plus specific nucleotide sequences used for targeting. Because the guide RNA is where much of the custom engineering happens for each new therapeutic, these patents reach deep into downstream products.

Alternative Nucleases and Newer Systems

The landscape extends beyond Cas9. The Broad holds patents on Cas12a (also called Cpf1), which cuts DNA differently and is preferred for certain applications. Pioneer Hi-Bred International, a Corteva Agriscience subsidiary, holds a separate Cas12a patent covering systems that use a DNA guide or a DNA-RNA hybrid, originally assigned from Caribou Biosciences.⁵

Base editing and prime editing modify individual DNA letters without fully cutting the double strand. The foundational patents trace back to David Liu’s lab at the Broad and Harvard. Their patent landscape is emerging, increasingly fragmented, and adds another layer of licensing complexity for companies building on these newer tools.

How Commercial Licensing Actually Works

The academic institutions that own foundational patents don’t develop drugs themselves. They grant exclusive licenses to commercial partners that handle clinical development, and those partners in turn sublicense to others.

The Surrogate Company Structure

Each major patent holder has at least one commercial partner. The Broad granted Editas Medicine an exclusive, worldwide, royalty-bearing license to its CRISPR-Cas9 patents for human gene therapy, with the right to sublicense.⁶ On the CVC side, Caribou Biosciences holds an exclusive license to the foundational UC Berkeley and University of Vienna patents and co-founded Intellia Therapeutics with an exclusive sublicense for human gene and cell therapies.⁷ Charpentier licenses her rights globally through ERS Genomics, which manages access for both CVC’s claims and Charpentier’s individual intellectual property. CRISPR Therapeutics is a key licensee on that side of the divide.

Exclusive arrangements are typically carved by therapeutic area. One company might hold rights for blood disorders while another controls ophthalmology. The Editas license, for example, explicitly excludes agriculture, livestock, and small-molecule drug discovery.⁶ If a license transfers essentially all rights in a patent, courts may recharacterize it as a full assignment regardless of the label, which changes who has standing to enforce.

What Licensing Costs

The numbers get large fast. Vertex Pharmaceuticals paid CRISPR Therapeutics $100 million upfront for a non-exclusive license to develop hypoimmune cell therapies for type 1 diabetes, with up to $230 million more in milestone payments tied to research and commercial progress, plus royalties in the low-to-mid single digits on product sales.⁸ That covered one indication from one patent holder. A company developing a human CRISPR therapy typically needs rights from both the Broad and CVC estates, potentially doubling the cost.

Freedom-to-Operate Before You Negotiate

Before licensing talks begin, most biotechnology companies run a freedom-to-operate analysis to identify which active patents a planned product might infringe. This work should start at the earliest stage of development. Discovering a blocking patent after years of clinical investment can be catastrophic. Clearance searches in a field this complex can run tens of thousands of dollars, which is minor compared to the cost of litigation.

Why a Single Pool Hasn’t Emerged

MPEG LA has attempted to build a consolidated CRISPR-Cas9 patent pool that would let companies obtain access through a single point of contact. The Broad submitted patents to the platform.⁹ Competing commercial interests among the major holders have kept the pool from achieving the broad adoption needed to simplify industry licensing.

Academic Use Sits Outside the Commercial Fight

Researchers at universities and nonprofits face a much lower barrier. CRISPR tools are widely distributed through repositories like Addgene under the Uniform Biological Material Transfer Agreement, which restricts use to teaching and academic research and provides materials at no cost or a nominal fee.¹⁰ Eligible recipients include universities, 501(c)(3) organizations, and government agencies.

The boundary is commercial use. A university lab can work with CRISPR-Cas9 freely for research, but the moment that work heads toward a product, a commercial license becomes necessary. Many academic spinoffs first encounter the patent thicket at this point, sometimes after significant research investment.

What Happens If You Skip the License

Using patented CRISPR technology without a license exposes a company to serious liability. Federal law requires courts to award damages sufficient to compensate for the infringement, with a floor of a reasonable royalty. For willful infringement, courts can treble damages, meaning up to three times the amount initially assessed.¹¹

A patent holder can also seek a permanent injunction forcing the infringer to stop making, using, or selling the product. In biotechnology, where a therapy in clinical trials might benefit patients with no alternative treatment, the public interest factor complicates the analysis, and a court might permit continued use in exchange for ongoing royalty payments rather than shutting down a promising therapy. High-stakes biotechnology patent litigation routinely costs millions through trial, which is part of why licensing, even at eye-watering prices, usually wins out.

When These Patents Start Expiring

Standard U.S. patents last 20 years from the earliest domestic filing date. The Broad’s first CRISPR-Cas9 patents rest on applications filed in late 2012 and 2013, meaning the earliest foundational patents will begin expiring in the early-to-mid 2030s. CVC’s timeline is similar. As these patents expire, the underlying technology enters the public domain.

CRISPR therapies requiring FDA approval may qualify for patent term extensions under 35 U.S.C. § 156, which lets a patent holder recapture some of the patent life lost during regulatory review. The extension cannot exceed five years, and the total remaining patent term after extension cannot exceed 14 years from FDA approval. Only one patent per approved product can receive an extension, and the application must be filed within 60 days of marketing approval.¹²

The first CRISPR therapy to reach market was Casgevy, approved by the FDA on December 8, 2023, for sickle cell disease, developed by Vertex Pharmaceuticals and CRISPR Therapeutics.¹³ With commercial products now on the market during the foundational patent term, extension provisions have become practically significant.

A U.S. License Doesn’t Cross Borders

Patent rights are territorial. A U.S. CRISPR license offers no protection in Europe, Asia, or anywhere else. Both the Broad and CVC have pursued parallel filings worldwide, and outcomes have not always matched the American results. The Broad holds 33 European CRISPR patents, including 29 related to Cas9 and 4 related to Cas12; CVC also holds European CRISPR patents.¹ Most patents on both sides have been challenged through European Patent Office opposition proceedings.

One notable European development: the EPO denied the Broad’s reliance on its U.S. provisional application for one patent (EP 2771468B) based on a technical formality about mismatched inventor names across international filings, not on scientific merits. The majority of the Broad’s European Cas9 patents, including key therapeutic claims, were not affected.¹ Any company that plans to manufacture, sell, or import CRISPR-based products internationally needs to clear rights in each jurisdiction separately.

1
Broad Institute. Statements and Background on the CRISPR Patent Process
2
Merck KGaA. MilliporeSigma Awarded Its First CRISPR Patent by Australian Patent Office
3
United States Court of Appeals for the Federal Circuit. Regents of the University of California v. Broad Institute, Inc.
4
Office of the Law Revision Counsel. 35 U.S. Code 103 – Conditions for Patentability; Non-obvious Subject Matter
5
Broad Institute. Information About CRISPR-Cpf1 (Cas12a) Systems
6
U.S. Securities and Exchange Commission. Editas Medicine, Inc. – Amended and Restated Cas9-I License Agreement
7
Caribou Biosciences. Caribou Biosciences Announces Co-Founding of Intellia Therapeutics
8
Vertex Pharmaceuticals. Vertex and CRISPR Therapeutics Announce Licensing Agreement to Accelerate Development of Vertex’s Hypoimmune Cell Therapies for the Treatment of Type 1 Diabetes
9
MPEG LA. The Broad Institute of MIT and Harvard Among Those Participating
10
Addgene. UBMTA
11
Office of the Law Revision Counsel. 35 U.S. Code 284 – Damages
12
Office of the Law Revision Counsel. 35 U.S. Code 156 – Extension of Patent Term
13
U.S. Food and Drug Administration. FDA Approves First Gene Therapies to Treat Patients With Sickle Cell Disease