ToolGen sues Vertex over alleged unlicensed use of CRISPR tech in gene therapy

ToolGen is taking its decade-long IP fight commercial. The Korean biotech said Tuesday that it filed a patent infringement lawsuit against Vertex Pharmaceuticals in a U.K. court, accusing the drugmaker and its contract manufacturing partners, Lonza and RoslinCT, of using its proprietary CRISPR RNP (ribonucleoprotein complex) delivery technology without a license in the production of Casgevy, a gene-editing therapy for sickle cell disease and beta-thalassemia—two inherited blood disorders that affect hemoglobin.

The suit, filed in Casgevy’s first approved market after “reviewing various circumstances globally,” according to a ToolGen's spokesperson, alleges that Vertex’s delivery mechanism for Cas9 -- a DNA-cutting enzyme central to CRISPR-based editing -- relies on a method ToolGen patented in Europe and Japan in October 2024.

ToolGen says the delivery approach enables Cas9 to enter cells in protein form without degradation, avoiding the cytotoxicity and genomic integration risks seen with DNA or mRNA delivery while also minimizing off-target edits. 

“We believe that Casgevy clearly used our RNP method -- at least, that’s our current assessment,” a ToolGen spokesperson told Korea Biomedical Review Tuesday, while declining to discuss how the technology was applied.

But Vertex, for its part, pushed back on the claims. A spokesperson told Korea Biomedical Review in a written statement that the company had challenged ToolGen’s European patent after it was granted, arguing it was “invalid on multiple grounds.” The spokesperson also noted that an anonymous third party filed a formal notice of opposition with the European Patent Office on the same day, signaling that concerns about the patent’s validity aren’t limited to Vertex.

When asked whether Casgevy’s manufacturing process relies on ToolGen’s patented RNP-based delivery method, Vertex did not address the technical specifics. Instead, the company said it remains “very confident in our global intellectual property that provides protection for many future years,” adding that its existing portfolio “has no impact on our own and licensed intellectual property.”

The lawsuit marks a turning point for ToolGen, which has long operated on the periphery of the foundational CRISPR patent battle. While the company holds patents in Korea and 10 other countries, its U.S. claims remain tied up in interference proceedings against both the Broad Institute and the University of California–Vienna–Charpentier (CVC) group. The RNP patent, however, is distinct and is being pursued as a standalone case.

“This patent is essential because it forms the foundation of our first business model,” the spokesperson said. “Without U.S. approval, licensing and royalty-based revenues remain in limbo.”

Casgevy, co-developed by Vertex and CRISPR Therapeutics, was approved in the U.K. in November 2023 and by the U.S. FDA just weeks later. At $2.2 million per dose and with a potential patient population in the tens of thousands globally, the therapy is on track for blockbuster status.

Vertex originally partnered with CRISPR Therapeutics, a CVC-aligned company, to bring Casgevy to market. But in December 2023, Vertex also signed a non-exclusive license with Editas Medicine, which licensed its CRISPR-Cas9 technology from the Broad Institute, paying $57 million upfront for access to ex vivo CRISPR-Cas9 technology targeting the BCL11A gene. ToolGen said none of these agreements cover its proprietary RNP delivery system.

“Vertex’s Casgevy was born from ToolGen's proprietary CRISPR RNP technology,” ToolGen CEO Ryu Jong-sang said in a statement. “As the company behind the world’s first CRISPR-Cas9-based gene therapy, we believe Vertex should recognize ToolGen’s contribution through appropriate licensing.”

ToolGen emphasized that the suit is not aimed at limiting patient access to Casgevy. “It seeks to ensure ToolGen is properly acknowledged and rewarded through a fair licensing agreement,” Ryu said.