CRISPR, which stands for Clustered Regularly Interspaced Short Palindromic Repeats, has been heralded as the most promising molecular tool for gene editing, one that is pushing the boundaries in many industries.
Among the signs of its enormous significance: first, two of the scientists who pioneered this technology, Drs. Emmanuelle Charpentier and Jennifer Doudna, were honored with the 2020 Nobel Prize in Chemistry; and second, The Wall Street Journal reported that in 2021 alone venture capitalists invested $1.08 billion in CRISPR startups.
The CRISPR patent landscape is vast. One estimate suggests there are already more than 11,000 families of patents on CRISPR-related technology.
CRISPR technology is being evaluated for a broad range of applications: everything from modifying human genes to eliminating certain hereditary diseases, to creating plants that can withstand climate change or contain higher concentrations of nutrients, to altering microbes that will generate biofuels. For example, CRISPR has the potential to be wholly transformative in the treatment of disease. In 2020, a person suffering from Leber congenital amaurosis, a genetic condition that causes eventual blindness, became the first human to receive a directly administered CRISPR-Cas9 gene therapy (rather than the gene editing being carried out in vitro and infused back into the patient). ClinicalTrials.gov currently lists 32 studies involving CRISPR-Cas9 to treat sickle cell disease, solid cancers, blood cancers, and diabetes, among many other ailments.
CRISPR is based on an ancient function of prokaryotes (single cell organisms, such as bacteria and archaea) – essentially, a basic adaptive immune system. Bacteria deploy a specialized CRISPR-associated molecule – Cas – to cut and destroy the DNA of invading viruses called bacteriophages. This CRISPR-Cas system has now been engineered to work in eukaryotes, like animals and plants. Its ability to make precise, targeted cuts in DNA sequences allows scientists to insert, delete, and modify DNA sequences of a wide variety of cells.
Various Cas proteins have been identified – the best known is CRISPR-Cas9, which has become an instrumental tool in genome editing.
Who owns CRISPR-Cas9?
The CRISPR patent landscape is vast. One estimate suggests that there are already more than 11,000 families of patents on CRISPR-related technology.
It should be no surprise that disputes have arisen over the ownership of IP related to this fundamentally transformative technology. Most famously, two groups have claimed rights to the use of CRISPR-Cas9 for eukaryotic gene editing: the University of California, Berkeley, University of Vienna, and Dr. Charpentier (CVC) on one side and the Harvard-MIT Broad Institute on the other side. This dispute has resulted in a complex and lengthy dispute at the US Patent office and the courts that is still ongoing.
Drs. Doudna and Charpentier, associated with UC Berkeley and the University of Vienna, respectively, first published research on CRISPR-Cas9 in prokaryotes in June 2012 and filed for a patent. Seven months later, Dr. Feng Zhang at the Harvard-MIT Broad Institute published a paper describing the use of CRISPR-Cas9 in eukaryotes (such as animals and plants) and applied for a patent. What makes this procedural history interesting from a patent perspective is that while Drs. Doudna and Charpentier filed for a patent in 2012– months before the Broad Institute did – both patent applications were filed before the US implemented a first-to-file system in 2013.
The Broad Institute’s patent issued in April 2014. In response, the CVC group requested that the USPTO institute an interference. When that was unsuccessful, they appealed to the Federal Circuit, which upheld the USPTO’s decision, awarding the rights to use CRISPR-Cas9 in animals and plants to the Broad Institute.
The CVC team tried again, requesting an interference between the Broad patent and a different patent application. While the USPTO did grant an interference, it ultimately ruled that the Broad Institute has priority for use in eukaryotic cells.
In February 2022, the USPTO named the Broad Institute the first to invent the use of CRISPR-Cas9 in eukaryotic cells. The CVC group appealed this decision in April 2022. The appeal is pending.
To complicate matters, at least two other companies have asserted that they were the first to invent the CRISPR-Cas9 technology, and additional interferences are pending at the USPTO. And the patent war between over this technology has spread to Europe with multiple opposition proceedings ongoing.
These disputes between the CVC group and the Broad Institute only cover CRISPR-Cas9. And while this patent war plays out, scientists are developing, patenting, and commercializing other Cas variations, among them whole families of CRISPR complexes. At the start of this section, we described the CRISPR patent landscape as vast – it is that, and it is still growing.
Action steps for companies
As you seek to protect the IP you are developing around CRISPR technologies, here are some issues to keep in mind:
- Companies seeking to harness the power of this technology must grapple with some uncertainties about the boundaries of the patent landscape and any freedom to operate.
- The CRISPR landscape features expansive patent estates owned by many different entities. This means taking care to ensure that you appropriately in-license any rights.
- Ensuring appropriate licensing may be a challenging task given that, depending on how the CRISPR-Cas system will be used, the rights must be obtained from different sources. Multiple licenses may be needed, and the appropriate licensing entities may vary depending on whether your company is seeking to develop a human therapeutic, genetically modified plant, or some other application. And these entities may be different in different countries.
- For instance, CRISPR-Cas9 patent-owning institutions such as UC Berkeley, the University of Vienna, and the Broad Institute have all exclusively licensed their IP to spinout companies, which in turn may grant sub-licenses for different fields of use.
- Your company may wish to sidestep the entire Cas9 issue and look at other CRISPR enzymes, such as CasX, CasY, Cas12, Cas13, and Cas14. However, clashes are already arising about the ownership of the Cas12 and Cas13 enzymes.
The complexity of the IP and licensing landscape has resulted in some calling for the creation of a patent pool to simplify licensing from multiple entities. It remains to be seen if there is any appetite for this approach.