CRISPR, an acronym for “Clustered Regularly Interspaced Short Palidromic Repeats,” holds much promise as a gene therapy for agriculture and human health, and might be the most significant bio-technology of the last century. (CRISPR was named a Science Magazine “Breakthrough of the Year” in 2015, and was awarded the Gruber Genetics Prize and the Japan Prize.) CRISPR/Cas9 would allow the use of the enzyme “Cas9” to re-write DNA sequences by disabling, replacing, or otherwise changing genes. In other words, CRISPR/Cas 9 is a simple and versatile bio-technology, genetic scissors, which would enable scientists to edit genes. Very promising. I am particularly eager for CRISPR’s therapeutic application because I myself have a rare neurological disorder called HSP (Hereditary Spastic Paraplegia). In my case, HSP was “adult onset”. I was only diagnosed with HSP less than 5 years ago. CRISPR/Cas 9 bio-technology is far from therapeutic application for my or many other diseases; nevertheless, CRISPR/Cas 9 bio-technology is exciting. However, lawyers and the legal system are delaying research and the eventual application of CRISPR bio-technology. A patent dispute has delayed and could affect the cost of CRISPR/Cas 9 bio-technology.
Here is a summary of the patent dispute. As a preliminary matter, the following is a description of the parties. The two parties are the UC-Berkeley team and the Broad Institute/Zhang team. The UC-Berkeley team consists of a team of biologists at the University of California-Berkeley headed by Dr. Jennifer Doudna and Dr. Emmanuella Charpentier. Dr. Doudna is still at UC-Berkeley, and was recently elected to the National Academy of Sciences and the Institute for Medicine. In 2015, Dr. Doudna gave a TED talk about the bioethics of CRISPR. Dr. Charpentier became a member of the Max Planck Institute in Germany, leader of research at the MIMS (Molecular Infection Medicine – Sweden), a professor at Umea University in Sweden, and a visiting professor at UCMR (Umea Centre for Microbial Research). The Broad Institute/Zhang team is led by Feng Zhang of the Broad Institute (MIT and Harvard) and the McGovern Institute for Brain Research at MIT. In March of 2013, the UC-Berkeley team applied to the USPTO (United States Patent and Trademark Office) for a patent for CRISPR/Cas 9 bio-technology. The UC-Berkeley team submitted its application THE DAY BEFORE the USPTO first-to-file rule went into effect. About six months AFTER the UC-Berkeley team applied for a patent, in October of 2013, the Broad Institute/Zhang team applied for a patent relating to CRISPR/Cas9 technology for use in eukaryote cells (cells with a nucleus, including human cells). The Broad Institute/Zhang team also filed an Accelerated Examination Request. The second patent application, the Broad Institute/Zhang application, was approved BEFORE the UC-Berkeley patent application. The Broad Institute/Zhang patent at issue in the interference proceedings is Patent No. 8,697, 359 (359 patent).The first patent application, by the UC-Berkeley team remains “under review” by the USPTO. The UC-Berkeley team initiated “interference” proceedings, arguing that the 359 patent issued to the Broad Institute/Zhang team interfered with any patent that will eventually be issued to the UC-Berkeley team by the USPTO.
There might be light at the end of the tunnel…, or not. On February 15, 2017, the PTAB (Patent Trial and Appeals Board) ruled that the 359 patent issued to the Broad Institute/Zhang team does not interfere with a patent application by the UC-Berkeley team. The PTAB decision of February 15, 2017, was significant, but it might not end the CRISPR/Cas9 legal imbroglio. Professor Jason Sherkow described the PTAB decision as “one battle in a larger war, but it’s a very big, important battle.” The PTAB decision could be appealed to the U.S. Court of Appeals for the Federal Circuit. There are 60 days to file such an appeal. 37 CFR §41.54. As of this time, the time for such an appeal had not yet expired. There are also some procedural alternatives – like requesting a rehearing (37 CFR §41.54) or commencing a civil action (37 CFR §90.3). On the other hand, it might just be the end of formal legal proceedings. The patent dispute might be resolved informally, by settlement agreement.
In the meantime, because the Broad Institute/Zhang team prevailed in the interference proceeding before the PTAB, it now has the power to require that any use of the CRISPR/Cas 9 technology in eukaryotic cells, even for research, be licensed.
The UC-Berkeley team has put a positive spin on its loss before the PTAB, suggesting that the recent PTAB decision clears the way for its patent to be issued by the USPTO. Dr. Doudna said that she was “delighted” with the PTAB decision, and that the UC-Berkeley team’s patent would be like a patent for all tennis balls, and the Broad Institute/Zhang patent is like a patent just for green tennis balls.
Unfortunately, I fear that license fees might render the promise of CRISPR/Cas 9 bio-technology very high. The legal fees alone exceed $20 million. There is another reason I am braced for large cost in connection with CRISPR/Cas 9 research and therapy. Many start-ups have business plans that are CRISPR-based. Editas Medicine licenses Broad Institute/Zhang patents. Editas’ stock rose almost 30% after the recent PTAB decision was announced. Assuming the UC-Berkeley team is ultimately granted a patent, businesses that might apply CRISPR/Cas 9 bio-technology for therapies, including therapies for HSP and PLS, will be required to secure patents from BOTH the Broad Institute/Zhang team AND the UC-Berkeley team, driving up the cost.
On March 24, 2017, the EPO (European Patent Office) announced its intention to issue a patent to the UC-Berkeley team, like the patent the UC-Berkeley team has pending before the USPTO. The EPO patent to the UC-Berkeley team is expected to be issued on May 10, 2017. Although this is big news, it has no impact on the application for a patent still pending before the USPTO.