A revolutionary biotechnology tool is the focus of an intense biotechnology patent dispute that will have far-reaching impact in coming years. The dispute is over the rights to the CRISPR-cas9 system, a versatile molecular scissors that allows precise editing of a genome. "CRISPR" stands for Clustered Regularly Interspaced Short Palindromic Repeats, and "cas" for CRISPR-associated proteins.
Who will own the patent rights and thus the profit from its commercialization? The central question is who first discovered how the system could be harnessed for genome editing, with two separate scientific teams asserting discovery. The USPTO is currently evaluating whether to declare an interference, on technology that could generate billions of dollars for its ultimate owners.
Parties to the Dispute
In April 2014, the USPTO granted a patent (US 8,697,359), with claims broadly covering the CRISPR/cas9 system for genome editing, to Dr. Feng Zhang at The Broad Institute. In negotiating for the patents with the USPTO, Dr. Zhang produced laboratory notebooks that he claims are evidence that he figured out how to use the CRISPR system first and independently.
Having been examined on a fast track, without being published first, and granted quickly, the issuance of the '359 patent was a surprise to many, not least Drs. Jennifer Doudna and Emmanuelle Charpentier, and their team from UC Berkeley. Academic and industry sources had already widely recognized their June 2012 paper in Science as the first publication showing how the naturally occurring CRISPR/cas9 system in bacteria could be adapted as a custom, "programmable" genome editing device, to make virtually any desired change in a genome. They had filed their own patent application seven months earlier than Zhang's application. Last December, they were awarded the Breakthrough Prize and $3 million each.
How Did This Happen and What are Possible Outcomes?
The Zhang patent and the application filed by Doudna/Charpentier essentially claim the same invention, and are subject to examination under the old, first-to-invent (pre-AIA) rules. Had the Zhang application not been fast-tracked, the USPTO may have recognized the conflict and declared an interference proceeding before either was allowed. Instead, with the Zhang patent granted, the University of California filed a request for the USPTO to review the Zhang patent in view of the earlier filed Doudna/Charpentier application. Thousands of pages of documents have been submitted by UC to support its contention that the UC Berkeley scientists discovered the invention first. The USPTO has not yet issued its decision about declaring an interference.
The IP situation thus is very uncertain and likely to remain so for a few years. Depending on the outcome of several decisions by the USPTO, and potentially a later court dispute, either The Broad Institute or the University of California could prevail in a winner-takes-all scenario, or both could hold some portion of ownership. Further complicating the situation is that Caribou, a CRISPR company founded by Doudna and partners to broadly develop CRIPSR applications, has an exclusive license from the owners of the Doudna/Charpentier patent.
What Options Are Available for Companies Wishing to Use the Technology Now?
Companies wishing to practice the CRISPR/cas technology now can seek a non-exclusive license from The Broad Institute for the issued Zhang patent, and optionally seek to license other CRISPR-related technology to build a portfolio. Non-exclusive licenses are available for some other important CRISPR-based patents. Risk lies in the uncertainty of whether the USPTO will disturb the Zhang patent, and how much, if at all, it may be dominated by the Doudna/Charpentier claims, if they issue at all. In any case, it will be important to keep close watch on developments with the Doudna/Charpentier patent application and interference petition.
Developing Your Own Patent Rights Strategy
Companies wishing to be well-positioned to negotiate as any license can do well by developing their own suite of patents covering specific applications of, or improvements on the CRISPR/cas system. Doing so does not obviate the need to license foundational CRISPR/cas technology from its presumptive owners, but owning patent rights covering key applications or improvements places a company in a good position for possible cross-licensing arrangements.
Summary
The patent situation for CRISPR/cas is uncertain and will likely remain so for several years. Companies wishing to use this powerful and flexible new genome editing technology may choose for now to pursue a non-exclusive license with The Broad Institute. Strategies to position well for future deal-making include development of one's own proprietary technology on applications and improvements of the CRISPR technology, and obtaining licenses to other important CRISPR-based technology.
