RN Collins (Series 3) No.14: CRISPR Cannabis: The Foundational Patent Fight and Its Implications for Freedom to Operate

RN Collins, M.S., JD Candidate https://www.linkedin.com/in/rn-collins/

I. Introduction: The Genome as IP Territory

In March 2026, the Patent Trial and Appeal Board ruled for the third time that the Broad Institute holds priority for CRISPR-Cas9 in eukaryotic cells, including plant cells.¹ That ruling could carry implications for cannabis operators who are using, considering using, or acquiring a company that uses CRISPR for cultivar development, though how far those implications extend may depend on the specific editing method and cell type involved. Cannabis increasingly resembles an agricultural biotechnology crop in the eyes of patent law, and the IP battles that have shaped corn, soybean, and cotton markets for two decades appear to be arriving in cannabis, in some respects faster than the industry may have anticipated.

The chromosome-level Cannabis sativa genome assembly, completed in 2018, provided the first complete and contiguous map of the genetic architecture encoding cannabinoid biosynthesis.² Within three years, researchers in China had applied CRISPR-Cas9 to Cannabis, demonstrating both Agrobacterium-mediated genetic transformation and targeted mutagenesis.³ These developments, taken together, sketch the outline of an emerging patent battlefield: the genome supplies the map; CRISPR supplies the editing tool; and yield enhancement through molecular breeding supplies the commercial incentive. The resulting IP landscape may go a long way toward determining who controls the genetic foundation of the cannabis industry for a generation, though it is too early to say with confidence how that landscape will finally settle.

The IP questions this landscape raises are largely transactional in character. Mergers and acquisitions in the cannabis industry frequently involve cultivar portfolios; licensing agreements often turn on freedom-to-operate; and venture investment valuations may rest, in part, on assessments of IP defensibility. A cannabis operator that has not accounted for the intersection of agricultural biotechnology patent law, plant variety protection, USDA biotechnology regulatory frameworks, and cannabis-specific compliance requirements may be making significant IP decisions without a complete picture of the terrain.

This article attempts to sketch that terrain, organized around several recurring strategic questions that appear to confront cannabis IP strategy in the current environment. Those questions are discussed in the framework set out in Part VIII and inform the analysis throughout. Part II reviews the technology. Part III analyzes the applicable IP frameworks. Part IV addresses the CRISPR foundational patent landscape and freedom-to-operate considerations. Part V covers the regulatory classification of gene-edited cannabis cultivars following the SECURE Rule vacatur. Part VI addresses the trade secret versus patent election. Part VII covers international IP considerations. Part VIII sets out a strategic framework as an analytical tool rather than a set of instructions. Part IX addresses IP due diligence in M&A. Part X covers post-grant proceedings and patent validity. Part XI concludes.

II. The Technology: Genome Assembly, Molecular Breeding, and CRISPR in Cannabis

A. The Chromosome-Level Genome Assembly

The chromosome-level genome assembly of Cannabis sativa represents a qualitative advance over earlier fragmented assemblies.⁴ A chromosome-level assembly anchors contigs to chromosomes through Hi-C chromatin conformation capture and optical mapping, providing a contiguous sequence that permits identification of gene clusters and regulatory elements that may have been inaccessible from fragmented assemblies.

For cannabinoid biosynthesis, the assembly permitted identification of the THCA synthase and CBDA synthase genes in their genomic context.⁵ The finding that cannabinoid synthase genes may be organized in a metabolic gene cluster, analogous to biosynthetic gene clusters identified in other organisms, could matter for both patent prosecution (the cluster itself may be patentable as a composition of matter) and for competitive positioning (a competitor who sequences a cultivar’s genome may be able to infer its synthase allele configuration without physical access to the originating facility, though this inference is less certain than direct disclosure would be).

B. Molecular Breeding and QTL-Based Yield Enhancement

The cannabis analog to artemisinin yield enhancement through molecular breeding appears to be the development of high-yielding, chemotype-stable cultivars with predictable and consistent cannabinoid profiles, an agronomic goal that seems central to commercial cannabis production. QTL-based molecular breeding uses molecular markers to identify plants with desired genetic combinations and to accelerate selection.⁶ It does not require genetic transformation and therefore falls outside most biotech regulatory frameworks, at least under the current understanding of those frameworks. Molecular marker IP, including the codominant THCA/CBDA synthase allele markers documented in Canter et al. 2005, may be protectable by utility patent, subject to the usual novelty and obviousness constraints.

C. CRISPR-Cas9 in Cannabis: Current State

CRISPR-Cas9 has been applied to Cannabis sativa, though the technology’s application to the plant remains at a comparatively early stage. The most comprehensive study identified, Zhang et al. 2021, demonstrated both Agrobacterium-mediated genetic transformation and CRISPR/Cas9-targeted mutagenesis in Cannabis using developmental regulator genes.⁷ Additional work has included protoplast transformation for CRISPR editing in high-THC genotypes (Matchett-Oates et al. 2021) and nanoparticle-based transformation (Ahmed et al. 2021). Stable transgenic production across a wide range of Cannabis genotypes appears to remain difficult due to recalcitrance to in vitro regeneration. The trajectory nonetheless seems reasonably clear, and IP activity in the space appears to be underway already.

III. The IP Frameworks: Plant Patent Act, Utility Patents, and Molecular Markers

A. The Plant Patent Act

The Plant Patent Act of 1930 provides patent protection for distinct and new varieties of asexually reproduced plants, which could include cannabis cultivars propagated by cuttings.⁸ PPA protection is narrow. It appears to cover the specific cultivar as asexually reproduced, not necessarily the underlying genetic traits that produce its characteristics. A competitor that independently produces a cultivar with a similar phenotype through a different genetic route may not infringe a PPA patent, though the precise contours of this limitation can turn on the specific facts.

B. Utility Patents: Broader Coverage

Utility patent protection under 35 U.S.C. § 101 is available for processes, machines, manufactures, and compositions of matter that are new, useful, and non-obvious.⁹ Since Diamond v. Chakrabarty, 447 U.S. 303 (1980), utility patents on living organisms, including plants with specific genetic modifications, have generally been available.¹⁰ Utility patent coverage for cannabis-related inventions could plausibly extend to specific gene sequences (for example, a THCA synthase allele associated with high yield), methods of using molecular markers to select Cannabis plants with desired cannabinoid profiles, CRISPR-edited Cannabis plants with specific genetic modifications, and methods of producing cannabinoids using gene-edited Cannabis, though each category would need to satisfy the ordinary requirements of novelty and non-obviousness on its own facts.

C. Molecular Marker IP

Molecular markers for Cannabis, including the RAPD, AFLP, and microsatellite markers documented in Canter et al. 2005, and the codominant alleles for THCA synthase and CBDA synthase, may be viable subject matter for utility patent protection.¹¹ An entity that sequences and characterizes a novel SSR or AFLP marker strongly associated with a commercially valuable cannabis phenotype could potentially seek utility patent protection for the marker sequence and for methods of using the marker to select plants. A freedom-to-operate analysis appears advisable before deploying molecular marker-based breeding, since existing patents on marker sequences in the cannabinoid synthase loci may already have been filed by academic institutions or agricultural biotechnology companies, though the scope of any such filings would need to be confirmed on a case-by-case basis.

IV. The CRISPR IP Landscape: Foundational Patents and Freedom-to-Operate

A. The Broad-Berkeley Patent Dispute

CRISPR-Cas9 technology is subject to extensive foundational patent claims asserted by two principal competing claimants: the Broad Institute (MIT and Harvard) and the University of California, Berkeley. As of the PTAB’s March 26, 2026 decision on remand from the Federal Circuit, the Broad Institute holds confirmed priority for CRISPR-Cas9 in eukaryotic cells, including plant cells.¹² The CVC group has indicated it is reviewing options for further challenge; the dispute does not appear fully resolved, though the Broad’s eukaryotic cell patent portfolio currently appears to be operative and enforceable pending any further appeal.

For cannabis operators considering CRISPR-based cultivar development, a practical question that may arise is which foundational CRISPR patents a freedom-to-operate analysis would need to address. The answer likely depends on the specific application: editing in protoplasts (potentially within the Berkeley portfolio’s scope), editing in transformed plant tissue culture (potentially within the Broad portfolio’s scope), and the specific guide RNA and Cas9 variant used. A freedom-to-operate opinion informed by agricultural biotechnology patent experience, rather than cannabis-generalist patent experience alone, may be useful before CRISPR work is undertaken, though the appropriate level of diligence will vary with the scale and stage of the specific program.

B. Agricultural Biotechnology CRISPR Licenses

Corteva Agriscience, BASF, and Bayer have each pursued licensing arrangements for CRISPR use in agricultural crops. Cannabis does not appear to be named in any publicly disclosed CRISPR agricultural license as of this writing. This suggests that a cannabis company seeking to use CRISPR-Cas9 for cultivar development would need to either obtain an independent license from the foundational patent holders or develop a credible non-infringement position based on a freedom-to-operate analysis. The non-infringement path does not appear foreclosed: newer CRISPR base editing systems, built by fusing a Cas9 nickase or catalytically inactive Cas9 to a separate deaminase enzyme, were developed largely through later, independent research distinct from the foundational Cas9 patents at issue in the Broad-Berkeley dispute.¹³ Licensing terms for these base-editor patents may nonetheless differ from those governing the foundational Cas9 patents, and that question should be confirmed with IP counsel before being relied upon in any specific transaction. Any freedom-to-operate analysis premised on a base-editing approach would likely need to precede rather than follow the start of an editing program.

V. Regulatory Classification of Gene-Edited Cannabis Cultivars

A. The SECURE Rule Vacatur and Current Framework

USDA APHIS regulates genetically engineered organisms under 7 C.F.R. Part 340. The SECURE Rule, published May 18, 2020 at 85 Fed. Reg. 29,790, revised the APHIS biotechnology regulatory framework to focus on plant characteristics rather than the method of genetic modification, and created exemptions for gene-edited plants whose modifications could theoretically have been produced through conventional breeding.¹⁴ The SECURE Rule was vacated by the U.S. District Court for the Northern District of California on December 2, 2024, which appears to have restored the pre-2020 regulatory framework that was in effect as of June 16, 2025.

Under the currently operative pre-2020 regulations, an operator seeking to release a gene-edited Cannabis cultivar into the environment would need to determine whether the genetic modifications constitute “regulated articles” under 7 C.F.R. Part 340 and, if so, would likely need to either obtain an APHIS permit or provide notification. Written APHIS confirmation of regulatory status for planned gene edits, sought before a program is initiated, appears to be one of the more reliable ways to establish regulatory clarity in the current environment, though the process and its timing may vary by application.

B. Regulatory Precedent: Mushrooms, Waxy Maize, High-Oleic Soybeans

The USDA’s 2016 determination that CRISPR-edited white button mushrooms developed by Yinong Yang at Penn State were not subject to APHIS regulation established a precedent that the SECURE Rule later appeared to codify.¹⁵ Similar determinations were reportedly made for CRISPR-edited waxy maize and high-oleic soybeans. The underlying logic in each case seems to have been that the modification could have been achieved by conventional mutagenesis or natural variation. Whether the same logic would apply to Cannabis applications targeting cannabinoid biosynthesis pathway genes is not clear, and the answer likely depends on the specific modification and how the pre-2020 regulatory framework’s provisions are ultimately applied to it.

C. State Cannabis Regulatory Classification

No state cannabis agency appears to have issued guidance on whether CRISPR-edited Cannabis plants require separate approval, special labeling, or additional testing beyond what is required for conventionally propagated cultivars. This regulatory silence could create both risk and opportunity. A state or an operator that engages proactively on a classification framework for gene-edited cultivars before such products reach the market may be in a more stable regulatory position than one that waits for a challenge after commercial launch, though this is a prediction rather than a settled outcome.

VI. Trade Secret vs. Patent: The Election for Cannabis IP

For proprietary cannabinoid biosynthesis pathways and breeding innovations, the choice between patent protection and trade secret protection is a strategic one with real consequences either way.¹⁶ Patent protection can provide broad, legally enforceable exclusivity for 20 years from filing and generally prevents competitors from using the claimed pathway regardless of independent discovery, but it requires full public disclosure and may allow competitors to design around the claims. Trade secret protection can last indefinitely as long as secrecy is maintained and requires no public disclosure, but it provides no protection against independent discovery or reverse engineering.

A workable approach for many cannabis operators may be to use trade secret protection for process parameters, fermentation conditions, and production yields that are difficult to reverse-engineer from the end product, and to consider patent protection for isolated pathway genes, specific genetic modifications, and marker sequences that are more susceptible to independent discovery or competitive sequencing. The two strategies are not mutually exclusive. They can potentially be layered, with trade secret protecting the process and patent protecting the composition, though the right mix will depend on the specific asset and business model involved.

VII. International IP Considerations

A. PCT and European Prosecution

Cannabis-related patent applications filed in the United States can generally be extended internationally through the PCT system.¹⁷ The European Patent Convention excludes from patent protection plant varieties and essentially biological processes for the production of plants.¹⁸ The EPO’s decision G 3/19 confirmed that this exclusion applies to plants produced by essentially biological processes even where the claims are directed to the process rather than the variety. Utility patents on specific genes, CRISPR modifications, or methods of using molecular markers may still be available in Europe, but patents on cannabis plant varieties or on processes consisting entirely of crossing and selection appear to be excluded.

B. Plant Variety Rights

The UPOV 1991 Convention provides plant variety rights protection for distinct, uniform, and stable plant varieties for terms of 20-25 years, with a breeders’ exemption allowing use of protected varieties for further breeding.¹⁹ PVR protection may be more accessible than utility patents for cannabis cultivar protection in UPOV member states, since it does not appear to require the same degree of inventive step. Gene-edited cultivars can potentially receive PVR protection where the modified variety is distinct, uniform, and stable, regardless of how the modification was achieved, though this remains subject to each jurisdiction’s specific administrative practice.

VIII. A Strategic Framework for Cannabis IP Analysis

Several recurring questions seem to organize IP strategy for cannabis businesses navigating the current environment, and addressing them roughly in sequence may help avoid compounding exposure, though the appropriate order and depth of analysis will vary by business and by transaction. The following table sets out this framework as an analytical tool rather than a set of directives to any single audience.

IX. IP Due Diligence in Cannabis M&A: The Cultivar Portfolio Problem

Cannabis mergers and acquisitions have accelerated as state markets mature and consolidation appears to be replacing the fragmented early-license era. IP due diligence in these transactions increasingly seems to center on the target’s cultivar portfolio. Acquirers not infrequently discover that what was described as a proprietary cultivar collection is, on closer review, a collection of unregistered varieties with no formal IP protection, or, in some cases, a collection that includes CRISPR-modified material for which no freedom-to-operate analysis appears to have been conducted.

The following table sets out categories that due diligence in this space might reasonably cover, along with an indication of which categories may warrant resolution before closing rather than after.

X. Post-Grant Proceedings and Patent Validity in Cannabis IP

Cannabis-related utility patents appear subject to the same post-grant validity challenge mechanisms as any other utility patent: inter partes review (IPR) under 35 U.S.C. § 311, post-grant review (PGR) under 35 U.S.C. § 321, and ex parte reexamination under 35 U.S.C. § 302.²⁰ The cannabis molecular marker and genomic IP space appears to have an extensive prior art landscape in the agricultural biotechnology and plant genomics literature. Canter et al. 2005 describes molecular markers for Cannabis that were published and publicly available before many cannabis-related utility patents were filed. RAPD, AFLP, and SSR markers applied to Cannabis are documented in a scientific literature that predates most cannabis IP filings, which suggests that a cannabis utility patent claiming molecular authentication methods without adequate differentiation from this prior art could be vulnerable to an IPR challenge on obviousness grounds, though the outcome of any such challenge would depend on the specific claims at issue.

The CRISPR foundational patents are themselves the subject of extensive post-grant proceedings. The Broad’s PTAB March 2026 confirmation does not appear to foreclose further Federal Circuit appeal by the CVC group, and the dispute may not be finally resolved for some time.²¹ Tracking the status of both the Broad and Berkeley foundational patent portfolios seems likely to remain useful as the dispute continues to evolve.

XI. Conclusion

The chromosome-level Cannabis genome assembly and the demonstrated application of CRISPR-Cas9 to Cannabis appear to mark the opening of a patent contest whose outcome cannot yet be predicted with confidence. That contest already appears to be underway in some respects: academic institutions have filed patent applications, agricultural biotechnology companies appear to be watching the space, and the cannabis operators best positioned to navigate it may be those that recognize they are operating substantially within agricultural biotechnology law, rather than within cannabis law alone.

The framework set out in Part VIII is offered as a starting point for thinking through cultivar development, M&A, and licensing questions in this space, not as a complete or final answer to them. The relevant tools, the Plant Patent Act, utility patent doctrine, APHIS regulatory frameworks, and plant variety protection systems, already exist. What remains less settled is how they will be applied together, in practice, as gene-edited cannabis cultivars move from research programs toward commercial release.

ENDNOTES

1. Patent Trial and Appeal Board, Decision on Remand (Mar. 26, 2026) (confirming Broad Institute priority for CRISPR-Cas9 in eukaryotic cells), https://www.wsgr.com/en/insights/ptab-again-rules-in-favor-of-broad-in-crispr-cas9-patent-dispute.html; Federal Circuit, No. 22-1653 (May 12, 2025), https://www.cafc.uscourts.gov/opinions-orders/22-1653.OPINION.5-12-2025_2512679.pdf.

1. Li Guo et al., Natural Products of Medicinal Plants: Biosynthesis and Bioengineering in Post-Genomic Era, 9 Horticulture Res., uhac223 (2022), https://doi.org/10.1093/hr/uhac223.

1. Xiaoyu Zhang et al., Establishment of an Agrobacterium-Mediated Genetic Transformation and CRISPR/Cas9-Mediated Targeted Mutagenesis in Hemp (Cannabis Sativa L.), 19 Plant Biotechnology Journal 1979 (2021), https://doi.org/10.1111/pbi.13611 (using CsGRF3-CsGIF1 chimeric developmental regulator to achieve 1.7-fold increase in regeneration efficiency; DMG278 strain selected as model; phytoene desaturase gene CsPDS1 edited; four albino-phenotype seedlings produced).

1. Guo et al., supra note 2.

1. Id. (noting identification of THCA synthase and CBDA synthase genes in genomic context).

1. Peter H. Canter, Howard Thomas & Edzard Ernst, Bringing Medicinal Plants into Cultivation: Opportunities and Challenges for Biotechnology, 23 Trends Biotechnology 180, 181 (2005), https://doi.org/10.1016/j.tibtech.2005.02.002 (noting that specific markers for codominant alleles thought to code for the two synthases responsible for cannabinoid biosynthesis have also been sequenced, specifically with a view to their use in breeding pharmaceutically useful lines).

1. Zhang et al., supra note 3.

1. Plant Patent Act of 1930, 35 U.S.C. § 163 (2018), https://uscode.house.gov/view.xhtml?req=granuleid:USC-prelim-title35-section163&num=0&edition=prelim.

1. 35 U.S.C. § 101 (2018), https://uscode.house.gov/view.xhtml?req=granuleid:USC-prelim-title35-section101&num=0&edition=prelim.

1. Diamond v. Chakrabarty, 447 U.S. 303 (1980), https://supreme.justia.com/cases/federal/us/447/303/.

1. Canter et al., supra note 6.

1. PTAB, supra note 1; see also Fed. Cir. No. 22-1653, supra note 1.

1. See generally agricultural biotechnology CRISPR licensing developments; adenine and cytosine base editors are built by fusing a Cas9 nickase or catalytically inactive Cas9 to a separate deaminase enzyme and were developed largely through later, independent research distinct from the foundational Cas9 interference patents (see, e.g., Addgene, CRISPR 101: Cytosine and Adenine Base Editors, https://blog.addgene.org/single-base-editing-with-crispr). Licensing terms for base-editor patents may differ from those governing the foundational Cas9 patents and should be confirmed with IP counsel before being relied upon in a specific transaction.

1. USDA APHIS, Movement of Certain Genetically Engineered Organisms (SECURE Rule), 85 Fed. Reg. 29,790 (May 18, 2020) (vacated Dec. 2, 2024; pre-2020 regulations restored June 16, 2025).

1. USDA APHIS, Response to Inquiry Regarding Genome-Edited White Button Mushroom (Apr. 14, 2016), https://www.aphis.usda.gov/library/form/pdf/15_321_01n.pdf.

1. See 18 U.S.C. §§ 1836-1839 (Defend Trade Secrets Act), https://uscode.house.gov/view.xhtml?req=granuleid:USC-prelim-title18-section1836&num=0&edition=prelim.

1. Patent Cooperation Treaty, 28 U.S.T. 7645, T.I.A.S. 8733 (1970).

1. European Patent Convention art. 53(b) (2013); EPO, Decision of the Enlarged Board of Appeal G 3/19 (May 14, 2020), https://www.epo.org/law-practice/case-law-appeals/communications/2020/20200514a.html.

1. International Convention for the Protection of New Varieties of Plants (UPOV 1991), https://www.upov.int/upovlex/en/conventions/1991/act1991.html.

1. 35 U.S.C. §§ 302, 311, 321, https://uscode.house.gov/view.xhtml?req=granuleid:USC-prelim-title35-section311&num=0&edition=prelim.

1. PTAB, supra note 1 (noting CVC group indicated it is reviewing options for further challenge).