Enthusiasm about the therapeutic potential of CRISP-Cas9 seems to be matched only by the bitterness of the fight over intellectual property rights to the technology.
In one corner stands the University of California (UC), the University of Vienna and microbiologist Emmanuelle Charpentier, co-author along with molecular biologist Jennifer Doudna of a 2012 scientific paper on the gene editing technique and subsequent patent application. In the other, a team led by Feng Zhang at the Broad Institute of MIT and Harvard University in Cambridge, Massachusetts, which filed a patent application the following year.
Last year, the U.S. Patent and Trademark Office (USPTO) started an investigation into whose claim for the patent on using CRISPR-Cas9 to edit genes is stronger—and so determine who profits from CRISPR in the coming years. That culminated in a win for Broad in February, with the USPTO ruling that the inventions claimed by the Broad and the University of California are distinct.
Now, UC and its compatriots have launched an appeal seeking to overturn that earlier decision, saying that the USPTO's Patent Trial and Appeal Board "failed to properly apply controlling U.S. Supreme Court and Federal Circuit precedents."
The patent dispute boils down to whether Broad's patents relating to the use of CRISPR-Cas9 in the cells of humans and other eukaryotes infringe on UC et al's earlier patent, which focused on using CRISP-Cas9 to edit DNA in a test tube. UC argued that use in eukaryotes was an obvious extrapolation of its work. Broad—and the PTAB—disagreed, and that decision will now be put on trial.
The appeal claims that the PTAB "applied a narrow and restrictive approach that ignored certain key evidence, including the steps actually employed by those of skill in the art at the time, and also effectively required a 'guarantee' that UC's CRISPR-Cas9 invention would work in eukaryotic cells, when well-established case law requires only a 'reasonable expectation of success.'"
It also maintains that six different laboratories successfully applied UC 's invention in eukaryotic cells using conventional techniques in months after it disclosed the technique—some of them prior to Broad's patent filing.
The fortunes of two scientific camps are mirrored by the CRISPR-focused drug developers who have licensed their IP. Shares in Broad partner Editas rocketed on news of the USPTO ruling but were largely unaffected by news of the latest appeal. Similarly, shares of CRISPR Therapeutics, Intellia Therapeutics, Caribou Biosciences and ERS Genomics—which all license the UC group's IP—largely stayed put, with investors recognizing that this dispute could take some time to play out.
In fact, it's likely that regardless of the outcome of the interference lawsuit, the impact on the companies developing CRISP-Cas9-based therapeutics will be minimized, since the parties involved opting for licensing deals to avoid disrupting the flow of potentially valuable new drugs through the pipeline.
Meanwhile, the patent situation in Europe is no less messy than in the U.S., with several parties objecting to patents awarded on the technology and lawyers predicting that it could take years for the situation to be resolved. And the patents continue to flood in. Just this week, Cellectis was awarded an EU patent for the invention of using RNA-guided endonucleases, such as Cas9 or Cpf1 for the genetic engineering of T-cells.