By: Bethany Butler

Gene editing technologies have the potential to greatly influence medicine and impact future therapies to treat debilitating conditions. Gene editing research seeks to “modify genes of living organisms to improve our understanding of gene function and develop ways to use it to treat genetic or acquired diseases.” One gene editing tool is the CRISPR/Cas-9 system, which allows for precision genome editing by cutting DNA in targeted locations for replacement. The first gene editing therapy utilizing CRISPR/Cas-9, called Casgevy, was approved by the Food and Drug Administration (FDA) in December of 2023. Casgevy is a treatment for patients with sickle cell disease, an inherited blood disorder that may cause painful symptoms and require lifelong interventions.

The emergence of CRISPR/Cas-9 Technology

The history of the CRISPR/Cas-9 system’s discovery and application largely involves two prominent research teams battling for its intellectual property rights. One team (“the Broad Institute”) hails from molecular biologist Feng Zhang of the Broad Institute, Harvard University, and the Massachusetts Institute of Technology; the other (“Charpentier and Doudna”) represents researcher Emmanuelle Charpentier of the Max Planck Institute for Infection Biology, Jennifer Doudna of the University of California, Berkeley, and the University of Vienna. Both teams have found success with their CRISPR/Cas-9 systems. In 2020, Emmanuelle Charpentier and Jennifer Doudna won the Nobel Prize in chemistry for the team’s 2012 discovery of the Cas-9 enzyme’s role in the CRISPR process. 

The two groups have not existed in harmony though, as patent battles between them stem from each groups’ 2012 US Patent and Trademark Office (“USPTO”) filings. Both teams filed applications to protect their respective gene editing tools, and unless the teams claimed distinct inventions regarding the use of the CRISPR/Cas-9 technology in human genomes, the USPTO would not allow patent protection to extend to both. 

Patent Protections of Gene Editing Technology

There are three types of patents that an inventor may file with the USPTO: utility, design, and plant. Gene editing technologies, like the CRISPR/Cas-9 system, often fall under the utility patent category. Utility patents are useful, new, and non-obvious. The non-obvious requirement refers to if a person of ordinary skill in the art would likely predict the invention by combining prior art references. CRISPR/Cas-9 patent rights come with limited monopolies, the potential for patent royalties, access to license the technology for future therapies in human cells, like the newly approved sickle cell therapy. 

Charpentier and Doudna’s May 2012 patent application demonstrated the use of this technology but did not go so far as to claim its use in eukaryotic cells (i.e. CRISPR/Cas-9 gene editing in human cells). Conversely, the Broad Institute demonstrated the use of this technology specifically in eukaryotic cells in their December 2012 patent application. The Broad Institute’s patent application was approved on April 15, 2014, and the team received the first patent for a method of altering eukaryotic cells using the technology. 

The CRISPR/Cas-9 Patent Fight

The Broad Institute, led by molecular biologist Feng Zhang, prevailed over Doudna and Charpentier regarding patent rights related to the CRISPR/Cas-9 technology. The main issue over these rights is which team developed the use of the CRISPR/Cas-9 gene editing in the modification of eukaryotic genomes.

Over the last 10 years, the two research teams have appealed various patent decisions, with the Patent Trials and Appeals Board (PTAB) and the Federal Circuit continually ruling in favor of the Broad Institute. For example, in a 2017 appeal, the Federal Circuit confirmed the PTAB’s finding that the Broad Institute’s claims were non-obvious regarding “the extent to which the art provided instructions for applying the CRISPRCas9 technology in a new environment”. The latest decision was on February 28, 2022, confirming the Broad Institute’s team was the first to invent the technology for modifying genomes in human cells. The decision stemmed from earlier interference claims holding that the Broad Institute’s patents claimed distinct subject matter compared to Doudna and Charpentier’s claims. Currently, the Broad Institute and Zhang’s team has prevailed in the patent space for the rights to CRISPR/Cas-9 gene editing technology in eukaryotic cells and now are able to license this technology for therapeutic applications. 

The CRISPR/Cas-9 Technology In Action Today

The Broad Institute licensed its technology to Editas Medicine in 2014. Vertex Pharmaceuticals, the pharmaceutical company that developed the sickle cell therapy, Casgevy, reached a licensing deal with Editas Medicine in December 2023. This deal pertains to the use of the CRISPR/Cas-9 technology in the Casgevy treatment and other sickle cell therapies. Individuals with sickle cell disease inherit genes that encode for abnormal hemoglobin production resulting in abnormal red blood cells. The Casgevy treatment uses the CRISPR/Cas-9 technology to edit patients’ blood stem cells to increase the production of fetal hemoglobin, which is not affected by the sickle cell mutation, thereby diluting the affected sickled blood cells. The edited cells are then infused back into the patient and have the potential to treat the disease. For the use of this technology, Vertex Pharmaceuticals agreed to pay Editas Medicine $50 million dollars upfront and licensing fees through 2034 ranging from $10 million to $40 million dollars annually. 

The far reaches of gene editing technologies have the potential to transform medicine and better the lives of many. CRISPR/Cas-9 editing technology is a vital therapeutic tool in this space and the fight for its patent rights continues. With the rollout of novel therapies, U.S. patent law is the key to lucrative licensing deals for the victors in these CRISPR/Cas-9 patent wars.