Narrower Patent Means CRISPR Victory for Broad Institute

By: Smitha Gundavajhala

On February 28, 2022, the US Patent and Trademark Office (USPTO) handed down a ruling in one of the most bitterly fought patent turf wars in biotechnology: the battle over the use of CRISPR-Cas9 in humans. The two major groups that were vying for recognition were the Broad Institute, consisting of researchers from Harvard, and MIT and CVC, consisting of researchers from UC Berkeley, the University of Vienna, and Emmanuelle Charpentier. 

CRISPR-Cas9 is a revolutionary gene editing tool that has implications for healthcare, agriculture, and more. CRISPRs are DNA sequences with proteins that act like scissors. Originally derived from bacterial genomes, CRISPR technology has since been extended to apply to eukaryotes, which are multicellular organisms. Examples of eukaryotes include plants, animals, and humans. As one might imagine, the latest evolution in CRISPR technology is immensely lucrative. The technology could be used to prevent viral infections and chronic conditions in humans, as well as to genetically modify produce to carry more nutrients.  Both Broad Institute and CVC stood to lose a great deal in their hard-fought dispute about the CRISPR-Cas 9 patent.

The dispute between these parties was complicated by timelines, the change in US patent law, and the contradictory decisions of different jurisdictions across the world. Jennifer Doudna of UC Berkeley was the first to file a patent application in 2012, a few months before Feng Zhang and the Broad Institute filed their patent application. However, prior to 2013, the USPTO’s rules were different: the agency awarded patents to the entity that was the “first to invent,” rather than the entity that was “first to file.” 

Thus, when Doudna asked USPTO to declare an “interference” between the two patents in 2015, the office had to consider which group was the first to invent by “reducing the concept to practice.” CVC argued that Broad Institute’s patent for gene editing in eukaryotes was a mere extension of CVC’s seminal work on CRISPR-Cas9. In 2017, the Patent Trial and Appeal Board (PTAB) ruled that Broad Institute’s patents were not derived from CVC’s patents. In 2019, PTAB again declined to declare an interference regarding claims to CRISPR-Cas9 technology used in eukaryotes, and confirmed that the Broad Institute’s patents were properly issued.

Ultimately, Doudna’s patent application did not explicitly address CRISPR-Cas9 applications for eukaryotes, and Zhang’s patent application did. Thus, Zhang and the Broad Institute were determined to be the “first to invent” CRISPR-Cas9 gene editing for humans. This year’s USPTO decision represents potential losses of billions in licensing revenue for UC Berkeley and priority of invention for Broad Institute.

However, this turf war is far from over and recognition of the Broad Institute’s and CVC’s patents varies across jurisdictions. Currently, CVC maintains fundamental CRISPR-Cas9 patents in over 80 jurisdictions, including China, Japan, and the European Union. CVC and the Broad Institute also face challenges in other countries: South Korea’s ToolGen and Germany’s Sigma Aldrich still have open interference motions with the Broad Institute. From the looks of it, the international fight for CRISPR-Cas9 patent recognition won’t be over any time soon, even while the dust has seemingly settled in the United States.

Why Don’t We Have a Free Bluebook App?

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by Christine Minhee

Imagine a monastery for luddites. Outside: brain implants reverse paralysis, gene therapies cure inherited diseases, and self-driving trucks deliver personal quantum computers purchased using payments authorized by face-scanning technologies. Inside: bunioned academics with chips on their shoulders pore over their worn copies of a legal citation manual, lovingly, reverently thumbing through its 560 pages in order to confirm truths like the italicization afforded to “construed in” but not to “construing” (Rule 1.6(c)).

Their holy text is called The Bluebook, and it promises not salvation, but merely, “A Uniform System of Citation.”

The Bluebook has been skewered so many times that it should have its own shish kabob. Above the Law features posts like: Want To Work In-House? Burn Your Bluebook, It’s Sad When The Bluebook Is An Important Part Of Your Day, and Yaw Law Students Support The End Of The Bluebook. UW Law’s own write pieces entitled The Dreaded Bluebook and The Worst System of Citation Except for All the Others. And UW’s Gallagher Library has this to say:

“Think Bluebooking is challenging? So do a lot of other people! There are many different tools out there to help you create Bluebook-formatting citations. But beware–none of these tools are a perfect solution for all of your Bluebook troubles. You will need to double-check your citations to make sure they’re correct even after using one of these tools.”

(Bolded, underlined emphasis is theirs, not mine.) While some students would even call Bluebooking a form of “academic hazing,” the uniform hatred of citation is less intriguing to this author than the Harvard Law Review Association’s stubborn, litigious unwillingness to grant access to the resource in a way that is neither analog nor expensive.

A one-year, digital subscription of The Bluebook is available online for $36. A search for “Bluebook” in the App Store will yield an infuriating swarm of car-buying apps, but a quick Google search reveals The Bluebook’s availability as an iOS-only, $39.99 in-app purchase in an app called Rulebook.

And the only “free,” unaffiliated “Bluebook”—The Indigo Book—was virtually the product of happenstance. When an earlier version of The [real] Bluebook happened to fall into the public domain, an NYU law professor fought to democratize the resource in open-source format, despite The Harvard Law Review Association engaging white-shoe firm Ropes & Gray LLP to fend off the attempt. (Interestingly, the founder of the site that publishes The Indigo Book was also sued for posting the Official Code of Georgia Annotated on his website—an act the State of Georgia described as “terrorism” in its complaint.)

So, why doesn’t the Harvard Law Review publish a free web app and bring The Bluebook outside of the walled, hegemonic garden of academic publishing and into the digital age? Much has been written about copyright claims over The Bluebook, the gist being that Section 102(b) of the Copyright Act states that systems—like a uniform system of citation—cannot be protected by copyright. And according to the Harvard Law Record, a “brief glance at the history of the Internet suggests that in a world where prestige matters, where students and practitioners alike begun their practice with the Bluebook, it is certainly possible to compete with free.”

Reasonably Expecting to Change the World: The CRISPR-Cas9 Patent Battle

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By Michael Rebagliati

In addition to the cited sources, the author would like to thank a family member with far more scientific knowledge, Michael R. Rebagliati, Ph.D., for his essential scientific edits, commentary and analysis.

Right now, a new gene-editing technology called CRISPR-Cas9 is spreading throughout the scientific and business communities and into the public consciousness. The scientific implications are vast because CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) is not just one scientific invention with one purpose. Rather, it is a natural process that has been harnessed and redirected into a gene-editing technique that is (relatively) easy to use. Moreover, its high efficiency means that scientists can use it to edit the genetic code of any gene in many kinds of organisms. Think Industrial Revolution for genetic engineering. Continue reading