CRISPR‑Cas9 in Europe: the Current Situation and What Comes Next

The discovery of CRISPR/Cas9, a groundbreaking biotechnology platform enabling precise DNA modification, ignited one of the most complex patent battles in recent memory. Multiple groups filed patents relating to CRISPR in 2012–2013, leading to overlapping claims and years of legal wrangling over patent rights covering the technology. Two camps emerged as the principal rivals:

• University of California, University of Vienna, & Emmanuelle Charpentier (collectively abbreviated “CVC”) – led by Jennifer Doudna and Emmanuelle Charpentier who together won the Nobel Prize for the discovery of CRISPR/Cas9.

• Broad Institute/Massachusetts Institute of Technology/Harvard College/Rockefeller University (collectively abbreviated “Broad”) – led by Feng Zhang and colleagues.
  

Both sought patent protection alongside other players like ToolGen, Sigma-Aldrich, and Vilnius University. The result is a complex and evolving landscape of patent rights demanding careful navigation for companies seeking to use the technology.

Below, we present an up-to-date overview of the status of the foundational EP patent families (the platform families filed in 2012–2013). In the US there are ongoing interference proceedings due to the filing dates of the patents preceding the America Invents Act (AIA). This means the issues at play in the US are very different from those at the EPO, and are beyond the scope of this article. Also beyond the scope of this article are the multitude of follow-on patents and applications directed to variants and modifications of the core CRISPR technology.

We focus on the EP portfolios of CVC and Broad, touch on other contenders (ToolGen, Sigma-Aldrich, Vilnius University), explain how recent events before the EPO Opposition Division and Boards of Appeal have impacted the landscape, and look ahead to upcoming developments.

Summary of current opponent challenges facing each EP portfolio and the next key decisions

CVC’s EP Portfolio: Early success, and the impact of the opponents’ PAM objection 

Key background dates:

• 25 May 2012 - Doudna, Charpentier, Martin Jinek of UC Berkeley, and Krzystof Chylinski of the University of Vienna file first US patent application for CRISPR-Cas9 gene editing (P1).

• 28 June 2012 - The Doudna-Charpentier team publishes the first scientific article detailing their discovery (Jinek et al. in Science).

CVC secured granted patents EP2800811 (EP’811) and EP3401400 (EP’400) in 2017 and 2019, respectively. These patents, claiming priority to the May 25, 2012 US application (P1), covered methods and compositions for RNA-guided DNA cleavage (the core function of CRISPR/Cas9), and were seen as the cornerstone CRISPR patents for CVC.

Shortly after grant, multiple parties filed oppositions against these cornerstone patents. CVC secured significant victories before the EPO’s Opposition Division, with both EP’811 and EP’400 being upheld in 2020 and 2022, respectively.

However, the story took a dramatic turn in 2024. Opponents had appealed the Opposition Division’s decisions, sending the cases to the EPO’s Boards of Appeal. In mid-2024, the Board of Appeal handling CVC’s cases issued a preliminary opinion indicating that it considered the patents to be invalid. Specifically, the preliminary opinion signalled that because CVC’s earliest priority filing (P1) didn’t mention the protospacer-adjacent motif (PAM) used to help Cas9 recognize DNA targets, CVC’s claims could not validly claim priority back to P1. (Note that a preliminary opinion of a Board of Appeal is often written by just one member of the three-member Board, in advance of the hearing, and is not its actual decision.) The preliminary opinion said that the role of PAMs was not common general knowledge at the priority date. Thus, the claimed invention was preliminarily opined to be not disclosed in P1 in an enabling manner such that the famous June 2012 Science paper by Jinek et al. (co-authored by Doudna and Charpentier) was citable prior art for patentability. The preliminary opinion considered that if P1 was not enabling then the invention would lack novelty over Jinek et al..

This preliminary opinion meant that after prevailing at first instance, CVC now faced the possibility of losing both patents before the Boards of Appeal. CVC’s attorneys filed letters stating they “no longer approve the text” of EP’811 and EP’400. In this situation the EPO issues a decision to revoke the patent in question, without commenting on the merits of the case. CVC’s letters included a detailed explanation of the rationale for their action, setting out reasons for their disagreement with the preliminary opinion. The attorney letters also aired concerns about the strictness of Boards of Appeal in (not) admitting new evidence in response to their preliminary opinions.

CVC already had other pending divisional applications which it continued to pursue following the revocation of EP’811 and EP’400. In February 2025, the EPO granted a divisional patent, EP4289948 (EP’948), which contains claims covering CRISPR–Cas9 systems using single-guide RNAs (sgRNA). Further, the claims specify that the Cas9 enzyme is a naturally-occurring Cas9 endonuclease.

Multiple parties filed oppositions against CVC’s EP’948 in late 2025, and those opposition proceedings are currently ongoing, with CVC expected to file their response to the oppositions in June 2026. One point the EPO Opposition Division will consider is the opponents’ priority entitlement objection raised on the earlier cases (dubbed “the PAM objection”).

Meanwhile, another patent in the CVC family, EP3597749, was revoked by an Opposition Division in November 2025. Interestingly, the preliminary opinion issued by the Opposition Division in March 2025 explicitly noted CVC’s disapproval of the text on EP’811 and EP’400, and stated that “Regardless of what the OD will decide with respect to enablement of PAM, its decision will in all likelihood be appealed and the BoA will take a final decision. Therefore, as concerns consistency and procedural efficiency it appears appropriate for the OD to adopt the BoA's preliminary opinion on this issue, unless facts and evidence have changed which, as discussed herein above, does not appear to be the case."

Following the issuance of this preliminary opinion, CVC had filed new evidence, including expert declarations in support of its position on the common general knowledge on PAMs at the priority date, and made claim amendments to simplify proceedings down to just the PAM objection. However, EP3597749 was subsequently revoked. CVC recently filed its grounds of appeal against this decision, arguing that the OD had erred in its decision on the PAM objection firstly by not considering all of the evidence presented to it, and secondly by not applying the “balance of probabilities” standard for evidence of the common general knowledge. Interestingly, CVC’s arguments on these points draw on Enlarged Board of Appeal decision G1/23 (about novelty of commercially available products, which issued after the Board’s preliminary opinions on EP’811 and EP’400). The appeal proceedings will be watched with interest as CVC argues against the PAM objection. A decision on this case is not expected until 2028 at the earliest.

CVC also has a further pending application EPA 25159662.3 with claims directed to DNA-targeting RNAs that interact with naturally-occurring Cas9 endonucleases. This application received a positive search report in September 2025. Anonymous third-party observations have since been filed raising clarity objections, but the examiner’s reaction to these observations remains to be seen. CVC recently filed an adapted description and included comments on the TPOs.

In summary, the CVC portfolio in Europe has been impacted by the opponents’ PAM objection. The initial cornerstone patents have been revoked, but CVC is appealing the decision to revoke EP3597749, and has since secured a further patent (EP4289948) with claims to CRISPR’s core components.

Broad’s EP portfolio: Rebounding on priority, but facing opponent challenge on inventive step

Key background dates:

• 12 December 2012 - Earliest US provisional application filed by the Broad, listing Luciano Marraffini of Rockefeller University as an applicant.

• 3 January 2013 - Zhang and his team publish their first scientific article detailing the engineering of two different Cas9 orthologs (from S. thermophilus and S. pyogenes) and targeted genome cleavage in human and mouse cells (Cong et al., 2013 in Science).

• 12 December 2013 - PCT application filed, Luciano Marraffini is not listed as an applicant.

The Broad was quicker than CVC to obtain a granted EP CRISPR patent with EP2771468 granted on 11 February 2015 and covering an engineered CRISPR-Cas9 system in a eukaryotic cell. But in January 2018 it was revoked by the EPO’s Opposition Division due to an invalid priority claim caused by a mismatch between the applicants listed on the provisional and PCT applications.

Whereas the earliest US provisional application listed Luciano Marraffini of Rockefeller University as an applicant alongside the Broad Institute, MIT, and Harvard, Marraffini did not appear as an applicant on the PCT application forming the basis of EP2771468. There was also no evidence that Marraffini had assigned his rights to The Broad Institute before the filing date of the PCT application. Under the EPO’s approach at that time, this mismatch meant the Broad lost entitlement to claim priority to its earlier application, exposing the patent to intervening prior art that invalidated Broad’s claims. The landmark appeal case T 844/18 issued in 2020 confirmed the Broad’s loss.

However, later developments have reversed Broad’s fortunes on priority entitlement in Europe. The Enlarged Board of Appeal issued its decision in G 1/22 (consolidated with G 2/22), which significantly relaxed the EPO’s approach to ‘same applicant’ priority. Under the old approach, a priority claim was deemed invalid if a proprietor was unable to show, when challenged, that the applicants for the subsequent application included all of the applicants for the priority application or their successor(s) in title at the time the subsequent application was filed. Under the new approach, the Enlarged Board held that there is a strong, rebuttable presumption that the priority applicants approve of the subsequent applicants’ entitlement to priority, regardless of any difference in names.

In March 2024, an EPO Board of Appeal, following this new guidance from decisions G 1/22 and G 2/22, held that Broad is entitled to claim priority from its US provisional, thereby restoring the priority and filing date for certain key patents.

With priority now resolved in Broad’s favour, EP2764103, EP2784162, EP2896697, and EP2931897 were remitted back to the EPO Opposition Division for consideration of other grounds, shifting the battleground primarily to inventive step.

Oral proceedings are scheduled for 8 July 2026 on EP2784162, and the OD issued a preliminary opinion in October 2025 indicating their view that the claims add matter and that they lack inventive step in view of Jinek et al..

This position has already been adopted by the EPO in other cases: in October 2025, the Opposition Division revoked Broad’s EP3252160, citing Jinek et al. as making the Broad’s claimed eukaryotic CRISPR implementation obvious:

“The fact that the authors of D1 [Jinek et al.] started experiments in eukaryotic cells in Spring 2012 and that a number of other groups of scientists started experiments and achieved cleavage in eukaryotic cells very shortly after publication of D1, is in the OD's opinion evidence that the skilled person, in view of D1, had a reasonable expectation of success and therefore started experiments. Moreover, it would have been clear to the skilled person that a setup encoding the CRISPR-Cas9 system from D1 with vector systems and regulatory elements could be tested in eukaryotic cells using routine means only (i.e. within acceptable time limits). Moreover since only hypothetical obstacles exist, the skilled person would have a reasonable expectation of success from the tests using routinely employed means only.”

Notably, the OD also referenced an earlier Sigma-Aldrich case T 1080/22 (discussed below) as precedent that there was a reasonable expectation of success in introducing the CRISPR-Cas9 system into eukaryotic cells in view of Jinek et al..

Broad has recently filed its grounds of appeal against the EP3252160 revocation, which sets out Broad’s position that the suggestion in D1 [Jinek et al.] to use the CRISPR system in eukaryotic cells “would have been understood by the skilled person as speculative - a hopeful suggestion for future work. It would not have changed the analysis of the skilled person that the system was unlikely to function in eukaryotic cells” (point 46). The opponent’s replies to the grounds of appeal are due in August 2026, while a decision on this case is not expected until 2028 at the earliest.

Broad also has some granted patents in Europe that are unchallenged and in force: EP2840140 and EP2848690. These cover CRISPR-Cas9 in methods of selecting prokaryotic cells – a domain less contested by other parties, possibly due to lower commercial interest.

In summary, G1/22 and G2/22 led to a reversal of Broad’s fortunes with regard to priority entitlement, but the Broad’s claimed eukaryotic CRISPR implementation still faces inventive step objections from opponents.

Other Contenders: ToolGen, Sigma-Aldrich, and Vilnius University

Beyond the CVC and Broad portfolios, other organizations have sought EP patents directed to the CRISPR platform – notably ToolGen, Sigma-Aldrich, and Vilnius University.

ToolGen

ToolGen has focused their efforts around protecting the delivery of Cas9 as a ribonucleoprotein (RNP) complex.

ToolGen’s patent EP3346003, which claims a method of using polyethylene glycol (PEG) to introduce a pre-formed Cas9–sgRNA RNP into plant cells (protoplasts), was upheld by the EPO Opposition Division in November 2025, but it remains to be seen whether the opponents will appeal.

Of more relevance to therapeutic applications, ToolGen obtained a further granted patent EP4357457 in 2024, which contains claims to compositions of Streptococcus pyogenes Cas9 protein and sgRNA in specific molar ratios, with no limitation on cell type. EP4357457 was swiftly opposed by multiple parties as soon as it was granted, and those opposition proceedings are underway, with a hearing scheduled for 29 May 2026. ToolGen faces an uphill battle, with the OD’s preliminary opinion that the main request adds subject matter and lacks inventive step.

ToolGen has also secured further patents (e.g. EP4342987, EP4397760) with claims broadly covering ex vivo or in vitro delivery of Cas9 RNPs into eukaryotic cells. Both were granted in January 2026 and multiple notices of opposition have already been filed against both patents.

Notably, ToolGen has been assertive in enforcing its rights: in April 2025, ToolGen filed an infringement suit in the UK against Vertex, claiming that the recently approved CRISPR-based therapy Casgevy (for sickle cell disease) infringes EP4357457.

Sigma-Aldrich

Sigma-Aldrich obtained patents such as EP3138911 and EP3360964 directed to CRISPR-Cas9 in eukaryotic cells, including technical details like use of Pol III promoters for guide RNA expression and nuclear localization signals (NLS) on Cas9. However, the EPO Opposition Division revoked these patents for lack of inventive step, and Sigma-Aldrich eventually withdrew its appeal on both cases (T 1080/22 and T 2228/22).

At the heart of the appeal proceedings was the question of whether applying the CRISPR system in eukaryotic cells by adding NLS for nuclear import or Pol III promoters was inventive in view of prior art such as Jinek et al.. The withdrawal means there will be no written reasoning, but these cases may provide an indication of how the EPO is likely to consider inventive step of other patents relying on the application to eukaryotic cells for patentability (e.g. the Broad cases discussed above).

Sigma-Aldrich have two pending applications: EPA19201769.7 and EPA19189913.7, both of which face objections from the Examining Division in line with the earlier decisions in this family.

Vilnius University 

Vilnius University (the team of Prof. Virginijus Šikšnys) filed a patent application in March 2012 which slightly preceded CVC’s filing date. EP2828386 granted in 2019, claiming priority to the March 2012 filing. The Vilnius patent’s claims specified a two-molecule crRNA–tracrRNA guide complex with Cas9 for cutting DNA in vitro. However, Vilnius University’s priority claim was found to be invalid, with the Opposition Division deciding that the priority documents did not disclose the crRNA–tracrRNA guide complex with Cas9. The claims were therefore deemed to be anticipated by Jinek et al.. Vilnius withdrew their appeal to the decision in March 2025 but has a pending divisional application EPA19179124.3 with claims to “an in vitro method of assembling a catalytically active Cas9-crRNA complex from three components, wherein said Cas9-crRNA complex is competent for site-specific DNA cleavage”.

Summary and Future Outlook

In summary, of the foundational families filed around 2012-2013, if we consider the granted European patents relevant for eukaryotic and therapeutic uses then none have yet emerged from the EPO’s opposition-appeals process: they have all either been revoked or still have an opposition or appeal pending. 

The next significant development in these families is likely to be the Opposition Division’s decision on ToolGen’s EP4357457 at the hearing scheduled for 29 May 2026. The appeal proceedings relating to CVC’s EP3597749 and Broad’s EP3252160 will also continue to be watched with great interest, with decisions in those cases not expected until 2028 at the earliest.

Whether helping clients draft, prosecute, defend, oppose, and litigate patents concerning innovations in the gene editing and advanced therapeutics spaces before the EPO and UPC, or advising on FTO and licensing questions relating to CRISPR/Cas9, our considerable experience and technical prowess in this area means we are well placed to assist.

The information provided herein reflects the personal views and considerations of the author. They do not represent legal counsel and should not be attributed to Mewburn Ellis LLP or to any of its clients.