In the latest clash of titans more formally known as the CRISPR patent dispute, the University of California, Berkeley, has asked the US patent office to let it subpoena Harvard Medical School’s George Church.
The visionary bioengineer will, Berkeley’s attorneys argued in a patent office filing this week, undermine key assertions made by the Broad Institute of MIT and Harvard, which was awarded several patents on the CRISPR method of genome-editing that Berkeley claims it should have been granted.
To recap for genome-editing fans just tuning in: The Broad has been awarded 13 patents on the CRISPR system based on work led by bioengineer Feng Zhang.
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The first, and key, one came in April 2014. Berkeley argues that it should have been awarded that patent, based on work by Berkeley biochemist Jennifer Doudna. She and her colleagues did pioneering experiments showing that CRISPR, which in nature is a bacterial immune system, can edit DNA in a test tube, and filed for a patent before the Broad did.
The Broad counters that Zhang went well beyond Doudna’s work, getting CRISPR to edit genomes in the living cells of mice and humans — an achievement that was far from an obvious or easily accomplished advance on Doudna’s work.
The ultimate winner at the patent office could reap millions of dollars in licensing fees and royalties and possibly have a leg up on a Nobel Prize for its scientist. The value of the fundamental CRISPR patent became clearer last month, when it was revealed that companies had spent more than $20 million and counting on legal fees for Berkeley and the Broad.
Berkeley’s request for permission to subpoena Church does not imply that he is unwilling to submit to a deposition. Instead, Church is a “non-party deponent,” said Jacob Sherkow, an expert on intellectual property law at New York Law School.
“He’s neither a listed inventor on Zhang’s patents, nor is he an employee of the Broad,” Sherkow said. “Since you can’t just haul anyone into court or a deposition conference room, you need permission from a judge or a clerk of court. That’s called a subpoena.”
A Berkeley spokesman said its attorneys “decline to comment on any aspect of the case.” Church’s office could not be immediately reached for comment.
Still, a close reading of its subpoena request suggests that Berkeley believes deposing Church can help it in at least two ways.
First, the Broad has argued that Doudna’s 2012 paper did not “trigger” the work of either Zhang or Church, whose lab independently reported developing CRISPR-based genome-editing in human cells in the same 2013 issue of Science that Zhang’s lab did.
In its filing with the patent office, Berkeley said it will “rebut that assertion by presenting testimony of Dr. Church.” Berkeley seems to expect Church to say that he was indeed inspired by Doudna’s 2012 paper. That might support Berkeley’s claim that Zhang and Church’s achievements — getting CRISPR to edit genomes in human and other animals’ cells — was an obvious extension of her work and not deserving of the patent that the Broad was awarded.
Second, the Broad has argued that the Church and Zhang labs were not completely independent, since they shared some graduate students. It would help Berkeley’s case if those labs were independent, non-cooperating, and sharing no tips. The reason is somewhat convoluted, but stick with us: If independent labs were racing to develop CRISPR, and two of them — Church’s and Zhang’s — succeeded in doing so, then it would strengthen Berkeley’s core argument that Doudna’s work provided a roadmap to CRISPR-based genome-editing that (nearly) anyone could follow. If Church confirms that his lab and Zhang’s were separate and independent, Berkeley might therefore score a point.
Of course, neither Zhang nor Church is exactly “just anyone” in biology. The fact that two of the brightest stars in the bioengineering firmament got CRISPR toward where it is today probably falls short of saying the advance could have been made by any POSITA (person of ordinary skill in the art [of genetics]), to use the legal term, as Berkeley claims.
But what if it wasn’t Church himself who made CRISPR work, but a lowly graduate student? “Remember, [Berkeley] gets to ask the questions” if it deposes Church, Sherkow said. “So they could focus, entirely, on what his graduate students were doing. If he thought it was so obvious, and simply instructed his students to do it, that’s a point in [Berkeley’s] favor. But deposing George is likely a dangerous thing. And having him say that Zhang is a genius does UC no favors.”
Berkeley has also asked the patent board for approval to depose Shuailiang Lin, a former student in Zhang’s lab who asked Doudna for a job and was subsequently hired by the UC system.
It is clear what Berkeley expects him to say: That during his time as a student in Zhang’s lab from late 20111 to early 2012, Zhang and his colleagues all failed to make CRISPR work, as Lin said in an email to Doudna asking her for a job. That would undermine the Broad’s argument that Zhang developed CRISPR-based genome-editing before, and largely unaided by, Doudna’s 2012 paper.
Broad spokesman Lee McGuire said the institute stands by its previous statements that Lin’s claims about Zhang’s failures “are false.” As for the subpoena request, “Our team is reviewing the request by UCB and will soon file a full response,” he said. “But regardless of their claims today, the underlying facts have not changed. The Broad Institute is confident the USPTO will reach the same conclusion it did initially when it awarded these patents.”
Berkeley is hoping for a quick OK from the patent judges on its request to subpoena Lin. A Chinese national now working at Berkeley on a temporary visa, he “may not be available in the United States past September 2016.”
This story has been updated to include comment from the Broad and corrected to say that Lin was hired by the University of California.