NEW YORK (GenomeWeb) – The Broad Institute has denied claims made in an email that surfaced earlier this week alleging that vanguard CRISPR researcher Feng Zhang obtained patents on the technology by piggybacking on the research of Emmanuelle Charpentier and Jennifer Doudna and misleading the US Patent and Trademark Office.
The email, sent in 2015 by a Chinese scientist who temporarily worked in Zhang's lab and who is listed as a co-inventor on at least one Broad-held CRISPR patent, is an exhibit in the patent interference between parties led by the Broad and the University of California.
The Broad Institute, where Zhang is a core faculty member, issued a statement on its website refuting the claims. It also called into question the reliability of the email's author.
"Abundant evidence already shows that the student's claims are false," the Broad Institute wrote on its website addressing developments in the CRISPR interference proceedings.
As reported by MIT Technology Review, in early 2015 Shuailiang Lin, a visiting student from China who has worked at several Broad-affiliated labs, sent Doudna, a professor at UC Berkeley, an email suggesting he had evidence that Zhang did not deserve patents on CRISPR/Cas9 gene editing technology. Lin also asked Doudna for employment (he is now a postdoc at the University of California, San Francisco School of Medicine).
It's one of several eye-opening revelations in recent weeks related to the interference.
In its recently released second quarter financial results, Editas Medicine said it has spent $8.7 million on legal fees related to patent protection so far in Fiscal Year 2016. And the Broad has also raised a possible conflict of interest in the case, due to the involvement of Fenwick & West in retaining expert witnesses for UC. Several years ago, the firm advised the Broad on patent protection for transcription activator-like effector nucleases (TALENs), another genome-engineering technology Zhang developed in his lab.
"Based on the careful inspection of the Patent Application Information Retrieval of Broad's patent files, I found Feng [Zhang] is not only unfair to me, but also to the science history," Lin wrote. "The 15-page declaration of his and Le Cong's luciferase data is mis- and overstated to change the [patent] examiner's decision, which seems to be a joke."
Lin also said he could supply his own laboratory notebooks as evidence that Zhang's success in CRISPR editing came after a pivotal 2012 publication authored by Charpentier and Doudna.
"The whole lab except me focused on TALEN projects," Lin wrote. Lin said he worked on CRISPR from the time he joined the lab in October 2011 until he went back to China in June 2012 for personal reasons. Two months later, Doudna and Charpentier published a study showing the ability to program CRISPR/Cas9 to cut DNA in vitro. Lin added that Zhang and another scientist in the lab, upon seeing the paper, "quickly jumped to the project without letting me know."
In addition to the email to Doudna, an email exchange between Lin and Zhang from January 2012 discussing CRISPR experiments has been released in the interference.
The Broad Institute said that there was ample evidence that disputed Lin's version of events, including the January 2012 email exchange between him and Zhang. The Broad said the emails showed that Zhang was actively guiding Lin's research and possessed crucial knowledge on how CRISPR systems worked at that time. A grant application to the National Institutes of Health from early 2012 shows that Zhang was at least interested in finding the "minimal set of genes and RNA elements that will effectively reconstitute a functional CRISPR system in mammalian cells."
The University of California pointed to Lin's 2015 email in a filing opposing the Broad Institute's early move to shut down the interference. Broad is claiming its patents covering the use of CRISPR in eukaryotic cells is something separately patentable; UC is trying to prove they were derived from Charpentier and Doudna's work.
"Although the rotation student's email makes several claims, the Opposition Document does not include any evidence to support them," the Broad Institute said.
"There are numerous other examples that make clear that beginning in 2011, Zhang and other members of his lab were actively and successfully engineering a unique CRISPR/Cas9 eukaryotic genome-editing system prior to and independent of what was later published [by Charpentier and Doudna]," the Broad said. "Indeed, contrary to [Lin's] own current claim that there was no invention prior to [the August 2012 Science publication], the individual has previously asserted — in legal documents — that he had made contributions to an invention prior to June 2012. This is inconsistent with his current claim."
But the email re-raises an allegation, initially put forth by UC's lawyers, that Zhang and the Broad Institute were able to obtain a patent because they misrepresented evidence in a document accompanying a patent application.
Early in the interference proceeding, UC asked the USPTO for the opportunity to make this case; however, the panel of judges said such an argument would be premature. Both UC and Lin have referenced the so-called "Zhang Declaration," a document filed along with a patent application. The Zhang Declaration has not yet surfaced, but allegedly contains data on CRISPR/Cas9's ability to modify luciferase expression.
The Broad Institute said the allegation of misrepresenting data to the USPTO was also false. While it did not provide a copy of the Zhang Declaration or instructions on how to find it among the patent interference filings, it said the document was publicly available.