CRISPR patent battle heats up as new email disputes Zhang’s claims

The ongoing patent battle over just who owns the rights to the cutting-edge CRISPR-Cas9 technology has heated up this week with a new email from a junior scientist putting more confusion over who invented the gene-editing process first. 

Let’s go back to the beginning: Biochemist Dr. Jennifer Doudna, from the University of California, Berkeley, submitted her patent application for the core CRISPR technology back in May 2012 after creating the tech along with Emmanuelle Charpentier.

But then biologist Feng Zhang from the Broad Institute of Harvard and MIT submitted a similar patent application in 2013--but he requested a fast-track process and received the official patent in April 2014. Zhang has since been awarded additional patents on the technology.

The two both claim to have invented the tech, leading to a legal “interference” claim in January of this year between the two scientists’ patent apps to settle just who is right.

This battle has been simmering in 2016 but boiled over this week when an email from Shuailiang Lin, a junior scientist formerly at the Broad Institute, to Doudna has come to light disputing MIT-Harvard institution’s claims to CRISPR, and accusing the org of misleading the patent office.

The email was originally sent in February of last year, but has now been made public by the U.S. Patent Office. Hundreds of millions of dollars have already been invested into this tech and the companies working in it, including Zhang’s Editas ($EDIT), as well as CRISPR Therapeutics, Caribou Biosciences, Intellia ($NTLA) and Novartis ($NVS).

Lin’s account is made the more interesting given that he worked at Zhang’s lab at the time the patents were filed, and because he is listed as an inventor on Broad’s earliest patent filing, from December 2012, and says in the email that he was working in late 2011 on CRISPR on his own in Zhang’s lab.

He went back to China in 2012, but when Doudna’s paper on the tech was published that year, Lin alleges that Zhang and others “quickly jumped to the project without letting me know.” He says he has lists of files and documents that prove the failures coming out of his CRISPR work in those days and can show them to “whoever is interested in the truth.”

The email was in fact designed as a job application to Doudna, where he says: “I think revolutionary technology like this should not be mis-patented. We did not work it out [how to use CRISPR effectively] before seeing your paper.” Lin now works as a postdoctoral researcher at the University of California, San Francisco, but is not commenting on the email.

In a statement Lee McGuire, chief communications officer at the Broad Institute of MIT and Harvard, said that Lin was just a “rotation student, who visited the Broad for a brief period from a Peking University/Tsinghua University joint program.” They confirmed that he worked for Feng Zhang at the Broad on CRISPR projects from October 2011 to June 2012.

But he added that Lin could not be offered a position to return to the Broad Institute.

“Although the rotation student’s email makes several claims, the Opposition Document [in the ongoing patent case which is using the email] does not include any evidence to support them,” the statement says.

McGuire goes to claim that: “Abundant evidence already shows that the student’s claims are false. Examples include email exchanges between the student and Zhang:

  • August 2011: Zhang introduces Cas9 for genome editing to the student.
  • October 2011: Zhang explains to the student the necessary role of tracrRNA in the duplex with crRNA to load onto the Cas9, writing, “I don’t think transfecting crRNA alone will work. It is loaded onto csn-1 as duplex with the tracrRNA. You should read the tracrRNA Nature paper again…”
  • November 2011: The student recognizes that some of his experiments were not successful because he did not follow the guidance he had received from Zhang and other lab members. In addition the student indicates Zhang has been overseeing and guiding his work, writing “When Feng wrote on the notebook, I knew what I should do.”

Why is this important? Well, because the battle is predominately around money: Whoever owns the rights owns much of the money that will come out of meds approved in the future using this tech. It’s all still at a preclinical stage, but trials could start in the U.S. and China this year in cancer targets, with more slated to start from 2017 as a slew of different companies, academic centers and organizations seek to be the first to get into the clinic and eventually gain approval.

Each group is using CRISPR in slightly different ways, but the fundamental aspect sees the tech used to edit genes by leveraging an RNA guide molecule to enter in specific cells.

A protein called Cas9 then attaches to the DNA and essentially cuts it, all of which either gets rid of, completely removes or replaces a gene with a better strand of DNA. It could be used in a host of diseases, but oncology appears to be the favored early target.

- check out Lin’s email (PDF)
- read Broad’s statement
 -read the MIT Technology Review story here

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