CRISPR Patents

The CRISPR-Cas9 patent dispute between the Broad Institute and UC Berkeley is one of the most consequential IP battles in biotechnology history: THE SCIENCE BACKGROUND: CRISPR-Cas9 (Clustered Regularly Interspaced Short Palindromic Repeats) is a gene editing system derived from bacterial immune defense; the system uses a guide RNA to direct the Cas9 protein to a specific DNA sequence, where Cas9 creates a double-strand break; this enables precise gene editing at specific genomic locations; THE TWO COMPETING TEAMS: UC BERKELEY TEAM: Jennifer Doudna (UC Berkeley) and Emmanuelle Charpentier (then University of Vienna, later Max Planck Institute); developed and characterized the basic biochemistry of CRISPR-Cas9 in vitro (in purified proteins, not in cells) in early 2012; published their foundational Science paper in June 2012; filed their first patent application in May 2012; BROAD INSTITUTE TEAM: Feng Zhang (Broad Institute/MIT) and colleagues; developed methods to make CRISPR-Cas9 work inside living eukaryotic cells (human and other animal cells) in late 2012; published their Cell paper in February 2013 (online January 2013); filed their first patent application in December 2012, AFTER the UC Berkeley filing; THE INTERFERENCE PROCEEDING (No. 106,048): the US patent system has a mechanism to resolve priority disputes between overlapping patent applications; USPTO declared an interference between the Broad and UC Berkeley patents; in the interference, the PTAB (Patent Trial and Appeal Board) must determine whether both parties are claiming the same invention; THE 2017 PTAB DECISION: the PTAB ruled in February 2017 that there was NO INTERFERENCE-IN-FACT; this means the Broad and UC Berkeley patents were NOT claiming the same invention; the PTAB found that the Broad's claims to CRISPR in eukaryotic cells were a non-obvious extension of UC Berkeley's work in vitro (purified components); an ordinary scientist would NOT have assumed that the in vitro CRISPR system would work in the complex environment inside eukaryotic cells; THE FEDERAL CIRCUIT AFFIRMANCE (2018): the Federal Circuit affirmed the PTAB decision in 2018 (Regents of the University of California v. Broad Institute); the court confirmed that the interference threshold (whether both parties are claiming the same patentable invention) was not met; OUTCOME: Broad Institute owns patents on CRISPR in eukaryotic cells (most therapeutically relevant use); UC Berkeley owns patents on broader CRISPR applications (in vitro and potentially prokaryotic); both portfolios remain valid and commercially important.

The CRISPR patent landscape has expanded significantly since the original dispute and now involves thousands of patent families across multiple gene editing modalities: THE BROAD INSTITUTE PATENT POSITION: Broad's key advantage: CRISPR in eukaryotic cells (including human cells) is the dominant therapeutic application; Broad has licensed patents to: Editas Medicine (exclusive license for human therapeutics); MilliporeSigma/Merck KGaA (non-exclusive for research tools); numerous other companies for specific applications; THE UC BERKELEY PATENT POSITION: UC Berkeley's foundational in vitro CRISPR patents cover the core biochemistry of the Cas9-guide RNA complex; multiple companies have licensed UC Berkeley patents including: CRISPR Therapeutics (founded by Charpentier); Intellia Therapeutics (licensed Cas9 IP); Caribou Biosciences (Doudna co-founded); the UC Berkeley patents remain commercially important even though Broad dominates the therapeutic cell editing space; SECOND-GENERATION CRISPR TOOLS (major new patent families): (1) BASE EDITING: developed by David Liu (Broad/Harvard); cytosine base editors (CBE) convert C to T without double-strand breaks; adenine base editors (ABE) convert A to G; highly specific, reduced off-target effects; strong patent position at Broad; licensed to Beam Therapeutics; (2) PRIME EDITING: also David Liu lab; uses a modified Cas9 nickase + reverse transcriptase + prime editing guide RNA; can make all 12 types of point mutations + small insertions/deletions; Prime Medicine licensed these patents; (3) CAS12A (CPFI) SYSTEMS: Jennifer Doudna and Feng Zhang both filed patents on Cas12a; different PAM sequence (TTTV vs. Cas9's NGG); cuts with staggered ends; licensed for diagnostic applications (SHERLOCK; DETECTR); (4) CAS13 SYSTEMS: RNA-targeting CRISPR; developed by Zhang lab; HEPN domain; used in RNA knockdown and diagnostics; Broad holds key patents; PATENT GEOGRAPHY: the US dispute focused on US patents; parallel EP, JP, and other national patents have their own prosecution histories and priority disputes; the European Patent Office has seen CRISPR oppositions; UC Berkeley has been more successful in some foreign jurisdictions; GLOBAL PATENT COUNT: as of 2026, over 10,000 patent families related to CRISPR technologies have been filed worldwide, covering the core tools, delivery systems, therapeutic applications, and diagnostic uses.

CRISPR and gene editing patents face multiple patent eligibility challenges under § 101 and the post-Myriad/Mayo/Alice framework: THE CORE ELIGIBILITY CHALLENGE: CRISPR-Cas9 is a system derived from naturally occurring bacterial immune defense; the Cas9 protein and its interaction with guide RNA sequences exist in nature (in Streptococcus pyogenes and other bacteria); guide RNA sequences can be designed to be complementary to any target DNA sequence; questions arise about whether claims to CRISPR systems are directed to products of nature or natural phenomena; COMPOSITION OF MATTER CLAIMS: WILD-TYPE Cas9 PROTEIN: a naturally occurring protein — NOT patentable as a composition of matter under Myriad; isolated Cas9 from bacteria without modification has the same amino acid sequence as natural Cas9; ENGINEERED Cas9 VARIANTS: specifically mutated Cas9 (e.g., dCas9 with nuclease-inactivating mutations D10A/H840A); Cas9 with enhanced nuclear localization sequences; Cas9 fused to other functional domains (activation domains; base editors; prime editors); these are NOT products of nature and ARE patentable; GUIDE RNA: naturally occurring CRISPR RNA (crRNA) and tracrRNA exist in bacteria; SYNTHETIC sgRNA (single guide RNA): the sgRNA used in CRISPR applications is a synthetic fusion of crRNA and tracrRNA; the sgRNA format does not exist naturally — it was invented by the Doudna lab; synthetic sgRNA with specific sequences for human gene targets: the COMBINATION of: (a) specific sgRNA sequence + (b) delivery into a eukaryotic cell + (c) use to edit a specific gene — is sufficiently non-natural to be patent eligible; BEST CLAIM STRATEGIES FOR ELIGIBILITY: (1) FOCUS ON MODIFIED PROTEINS: claim specifically engineered Cas9 variants (not wild-type); describe specific structural modifications and their functional advantages; (2) SYNTHETIC GUIDE SEQUENCES: claim specific sgRNA sequences designed for human gene targets (novel design choices not found in nature); (3) DELIVERY SYSTEMS: claim specific LNP formulations or AAV-CRISPR combinations as novel engineering compositions; (4) CELL TYPE CONTEXT: the Broad Institute's success in the interference shows that eukaryotic cell context can be a patentably distinct invention; (5) MULTI-COMPONENT COMPLEXES: ribonucleoprotein (RNP) complexes with specific component ratios and delivery characteristics are novel non-natural compositions; WRITTEN DESCRIPTION AND ENABLEMENT: CRISPR patents for broad genus claims face the Amgen v. Sanofi challenge; genus claims covering 'any guide RNA targeting any disease gene' must be enabled across the full scope; specification should include: multiple examples of different guide RNA designs; validated target loci; off-target analysis; functional characterization (editing efficiency; specificity).

The commercial CRISPR therapeutics landscape is shaped by several major company patent positions and complex licensing structures: THE BIG THREE THERAPEUTIC CRISPR COMPANIES (founded 2013-2014): (1) EDITAS MEDICINE: founded in 2013 with licenses from Broad Institute; first to bring CRISPR therapeutics to clinical trials (EDIT-101 for Leber congenital amaurosis type 10 via AAV delivery to retinal cells); exclusive therapeutic license from Broad for CRISPR-Cas9 in human therapeutics (with field-of-use limitations); also has licenses on certain Cas12a IP; (2) CRISPR THERAPEUTICS: founded by Emmanuelle Charpentier; licensed IP from Charpentier's academic patents; partnership with Vertex Pharmaceuticals on CTX001 (now exa-cel, Casgevy) — first approved CRISPR therapeutic (FDA approved December 2023 for sickle cell disease/beta-thalassemia); ex vivo approach (edit cells outside the body, infuse back); (3) INTELLIA THERAPEUTICS: licensed IP from UC Berkeley/Caribou Biosciences; in vivo CRISPR delivery via LNPs; focused on liver diseases; NEWER COMPANIES WITH DISTINCT PLATFORMS: BEAM THERAPEUTICS: base editing technology; exclusive license to David Liu lab's base editing patents from Broad; precision editing without DSBs; PRIME MEDICINE: prime editing technology; exclusive license to David Liu lab's prime editing patents; GRAPHITE BIO/METAGENOMI/OTHERS: using novel Cas orthologs and compact CRISPR systems to navigate around Broad/UC Berkeley IP; LICENSE STRUCTURE OVERVIEW: RESEARCH USE: relatively broad access through MilliporeSigma non-exclusive licenses; most academic and commercial research laboratories can obtain licenses; THERAPEUTIC USE: bilateral licensing required; Editas has therapeutic exclusivity in certain fields; other companies negotiate field-of-use licenses; PATENT POOLS AND PATENT PLEDGES: some parties have pledged not to assert patents against academic research; humanitarian use licenses for developing world access; CRISPR-Cas9 does not have a comprehensive patent pool like certain standards-essential patent fields; THE DELIVERY PROBLEM: even if a company has all necessary CRISPR editing IP, it also needs delivery technology; AAV delivery patents (AveXis/Novartis; Voyager Therapeutics; Spark Therapeutics) create additional licensing layers; LNP delivery patents (Alnylam; Arbutus Biopharma) add further complexity; the full freedom-to-operate analysis for a CRISPR therapeutic requires clearance for: editing tool IP (Cas protein; guide RNA); target gene application IP (disease-specific method of treatment); delivery system IP (AAV serotype; LNP formulation).