When it Comes to Eukaryotic Cells, Broad Institute Has Priority to CRISPR Gene Editing Tech, Says PTAB

“Although the CVC inventors developed a system on 1 March 2012 that they hoped would work in eukaryotic cells, the preponderance of the evidence demonstrates that they did not have a definite and permanent idea of how to achieve that result.” – PTAB

https://depositphotos.com/purchased.html?backURL%5Bpage%5D=%2Fstock-photos%2Fletter.html%3Ffilter%3DallThe U.S. Patent and Trademark Office (USPTO) ruled in an interference proceeding yesterday that The Broad Institute, Inc., Massachusetts Institute of Technology, and President and Fellows of Harvard College (“Broad”) have priority over The Regents of the University of California, University of Vienna, and Emmanuelle Charpentier (“CVC”) with respect to who was first to invent the use of single-guide CRISPR-Cas9 genome engineering technology in eukaryotic cells.

CRISPR is a gene editing technology that stands for Clustered Regularly Interspaced Short Palindromic Repeats. University of California, Berkeley, Professor Jennifer Doudna and her colleague Emmanuelle Charpentier, along with their teams at their respective institutions, won the 2020 Nobel Prize in Chemistry for their groundbreaking work on the technology. CRISPR has been the subject of a heated patent debate over simultaneous inventorship for years now.

While a previous interference proceeding and subsequent appeal to the U.S. Court of Appeals for the Federal Circuit (CAFC) determined the CVC inventors were the first to invent a CRISPR-Cas9 system with a single guide RNA to cleave DNA in a generic environment, the present case involves a CRISPR-Cas9 system having a single RNA component in a eukaryotic cell environment. The present interference relates to Broad patent 8,697,359, claim 18, or CVC application 15/981,807, claim 156. CVC’s named inventors are Doudna, Charpentier, Martin Jinek, Ph.D. and Krzysztof Chylinski, Ph.D.

Ultimately, the USPTO’s Patent Trial and Appeal Board (PTAB) determined yesterday that CVC failed “to provide sufficient, persuasive evidence of an earlier reduction to practice or conception, as they are legally defined, of each and every element of [the disputed claims] before Broad’s evidence of reduction to practice.” Thus, CVC’s claims in the present case were found to be unpatentable under 35 U.S.C. § 102(g). CVC had attempted to argue that Broad’s claims were unpatentable under 35 U.S.C. § 102(f) for failure to name the correct inventors, but the PTAB was not persuaded, and also declined to take up CVC’s arguments on inequitable conduct.

CVC asserted an earliest date of actual reduction to practice of August 9, 2012, and a conception date of March 1, 2012. Broad’s accorded benefit date is December 12, 2012. CVC said the first reduction to practice occurred in August 2012 via an experiment in zebrafish embryos performed by Florian Raible, Ph.D., the research group leader at the Center of Molecular Biology at the University of Vienna in 2012. CVC provided testimony and emails attempting to show that the experiments reduced the invention to practice, but the PTAB agreed with Broad that the evidence did not “characterize any fish experiment as successful” and was unclear overall. “In general, we find that CVC over-emphasizes isolated words by its inventors to argue that they recognized and appreciated Dr. Raible’s results,” wrote the PTAB.

CVC also said that by March 1, 2012, the inventors had conceived of a CRISPR-Cas9 system in eukaryotic cells, and provided testimony, statements and emails from Doudna and Jinek to support this. The PTAB reviewed the evidence and found that it showed the CVC inventors “encountered multiple experimental failures before they recognized any success, even as late as mid-October 2012.” The decision continues:

Although the CVC inventors developed a system on 1 March 2012 that they hoped would work in eukaryotic cells, the preponderance of the evidence demonstrates that they did not have a definite and permanent idea of how to achieve that result as of that date or by the later dates CVC asserts support that date because of their perception of these multiple failures.

It was not sufficient for CVC to show that its inventors conceived of the mechanics of a CRISPR-Cas9 system having a single RNA component in a eukaryotic cell environment; instead, CVC had to prove the inventors “had a definite and permanent idea of an operative invention, that is of a system they knew would produce the effects on genes in a eukaryotic cell recited” in the technology at issue.

In contrast, the evidence and testimony provided by the Broad inventors, Feng Zhang, Ph.D., Le Cong, Ph.D., Fei Ran, Ph.D., Patrick Hsu, Ph.D., Randall Platt, Ph.D., and Neville Sanjana, Ph.D., did support a reduction to practice, said the PTAB. In particular, an October 5, 2012, manuscript submitted to Science magazine memorialized the results of specific successful experiments conducted to demonstrate this. Since CVC did not put forth arguments to counter this assertion,  the PTAB said it was persuaded that the manuscript “is sufficient evidence of an actual reduction to practice by the Broad inventors.”

The PTAB also rejected CVC’s argument that the Broad inventors derived the invention from CVC, explaining that:

Even if CVC invented a generalized sgRNA CRISPR-Cas9 system, for which they hold numerous patents undisputed in this proceeding (see CVC Opp. 5, Paper 2657, 37:4–6; see Broad Reply 5, Paper 2745, 3:18–19), and they had an intention and hope that a CRISPR-Cas9 system would work in eukaryotic cells (see CVC Opp. 5, Paper 2657, 10:1–18:17), we are not persuaded that the determination of technical features necessary to achieve success is irrelevant. Instead, determination of those features indicated that the Broad inventors had a definite and permanent idea of a system in eukaryotic cells, which lead them to an actual reduction to practice earlier than the CVC inventors.

Finally, CVC alleged that Broad’s patents are invalid under 35 U.S.C. § 102(f) for failure to name all of the correct inventors, based on a sworn declaration by Broad’s former prosecuting patent attorney that CVC claimed conflicted with the involved patents and application. But the PTAB concluded that “[w]ithout an actual analysis of Broad’s involved claims and the alleged contributions of each asserted co-inventor, CVC’s argument is completely unpersuasive.”

The decision will necessitate renegotiation of licenses to the technology; IPWatchdog will provide further analysis in the coming days.

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