CRISPR is a breakthrough tool in the field of genetic engineering. Scientists have known about CRISPR—clustered regularly interspaced short palindromic repeats—in DNA for decades. It wasn’t until 2011, however, that researchers affiliated with the University of California were able to harness that knowledge to successfully edit DNA using CRISPR along with its associated enzyme known as Cas9. CRISPR’s uses grow daily, with new applications being discovered at breakneck pace.
Nevertheless, it is sometimes easy to get distracted by new technology at the expense of incurring excess enterprise risk. This is especially true with CRISPR because of the ever-changing patent landscape.
The value of the global gene-editing market could easily double in the next few years, topping $10 billion by 2025, according to various estimates. Dozens of clinical trials are underway for CRISPR-based therapies aimed at treating a wide range of disorders, including multiple types of cancer, Parkinson’s disease, heart disease, and hemophilia. CRISPR technology is already widely used in the field of disease diagnostics and agriculture, and some have even touted its potential in the fight against climate change. All of these developments will spark a new round of patent litigation in the US and around the world as more products made by or embodying CRISPR are commercialized.
The global patent landscape on CRISPR is constantly in flux. After a years-long battle between the Regents of the University of California and the Broad Institute, the initial division of the CRISPR patent landscape has largely settled, and there are essentially two major CRISPR licenses in the US. Licensees generally select one or the other, based on what kind of cells they need to manipulate.
Inventors from various institutions and companies have rapidly built upon the work done by both UC and Broad. This has re-muddied the waters that these two institutes spent years and millions of dollars clearing. A recent search of USPTO (US Patent and Trademark Office) patents showed that more than 600 patents with CRISPR in the claim have been issued, and more than 2,500 patent applications that reference CRISPR have been filed—just in the US. Aside from the many variations that exist on the CRISPR-Cas9 enzyme, scientists have discovered other enzymes such as Cas12, Cas14, CasX, and CasY, and have begun patenting methods for using them in gene editing as well. And, as they discover, they file for patents.
This presents new enterprise risk for companies that use CRISPR in their research and development. Depending on the type of work they are doing, researchers tend to prefer one type of CRISPR over another. Further complicating the issue is that sometimes researchers within the same company differ on which CRISPR tool they should use. Obtaining all the necessary licensing rights to these multiple CRISPRs can be prohibitively expensive, especially in fields where the success rates for commercialization are low—such as pharmaceuticals and biologics. Many of these patent licenses require large upfront licensing fees and annual maintenance fees, which are incurred years prior to commercialization. This represents a large sunk cost at even the earliest stages of research.
This risk is further magnified when viewed on the global scale. In Europe, for example, both UC and Broad continue to face significant challenges to securing CRISPR-Cas9 patent protection. In China, where extensive CRISPR research is also taking place, the vast majority of CRISPR patents has been awarded to Chinese inventors.
Before your company commits to using CRISPR, invest time in considering the following questions:
Do you really need to use CRISPR specifically? Yes, CRISPR is an amazing tool in gene editing, but if CRISPR is being used to merely simplify making something that needs initial modification and then will be used for something else, it may not be the right tool. This is especially true for cell lines that a company will use for many years, for commercial purposes, or across many products. Scientists have been making cell lines for decades before the advent of CRISPR. Choosing the older, off-patent technology could save tens, if not hundreds, of millions of dollars over the life of any CRISPR license.
Can the company consolidate the types of CRISPR systems? If CRISPR is the chosen path, then limiting which CRISPRs to license can streamline the licensing process and minimize the risk of infringement. As patents continue to issue across various types and uses of CRISPRs, limiting a company’s footprint will help avoid the need to take numerous licenses or to be sued for patent infringement.
Can the company use CRISPRs with more favorable licensing terms? The variation in licensing terms between different CRISPR patent holders is vast. Some require a large, upfront fee and annual maintenance fees, while others are willing to defray costs until a product is commercialized. Still others are more interested in granting only research licenses so that once a product gets commercial approval from FDA, companies have no choice to pay whatever the licensor wishes. Choosing the right CRISPR that comes from the right licensing partner can help alleviate initial costs and downstream risks.
Answering these questions will require input from often disparate portions of any given company—research scientists, in-house counsel, licensing professionals, intellectual property counsel, and business leaders. But, as with many things, this upfront, thoughtful effort could mitigate substantial downstream risk and financial losses later.
Anne Elise Herold Li, partner in Crowell & Moring's Life Sciences Litigation, Intellectual Property, and Trade Secrets groups in New York