On February 15, 2017, the Patent Trial and Appeal Board declared that the patents granted by USPTO to the Broad Institute, MIT and Harvard concerning CRISPR editing of eukaryotic genomes do not interfere with patent claims filed by UC Berkeley and the University of Vienna.
Broad Institute statement regarding PTAB decision
We agree with the decision by the patent office, which confirms that the patents and applications of Broad Institute and UC Berkeley are about different subjects and do not interfere with each other.
Broad Institute and collaborators were issued patents for methods for genome editing in eukaryotic (including human) cells, while UC Berkeley and collaborators applied for patents concerning CRISPR methods based on studies in cell-free systems that did not involve genome editing in eukaryotic cells.
CRISPR research is a very large field that involves contributions from talented scientists around the world. We have deep respect for all of these scientific contributions, including the work from Emmanuelle Charpentier, Jennifer Doudna, and their teams, as well as all of those who continue to advance the field and educate the public about this important technology.
Over the next few years there will be many patents issued in the CRISPR field to many institutions. As of February, 2017 the USPTO has issued 50 patents with claims to CRISPR and/or Cas9, including a robust portfolio of 14 CRISPR patents to the Broad Institute, MIT and affiliated groups for inventions from Dr. Feng Zhang and the Zhang lab.
We believe CRISPR should continue to be available to the global scientific community to advance our understanding of the biology and treatment of human disease, and to help lay the groundwork for a new generation of therapies. Consistent with our founding principle to propel the understanding and treatment of disease, Broad Institute and our partner organizations will continue to work to disseminate and share CRISPR genome editing tools to maximize public benefit, especially by continuing to make this transformative technology freely available to the worldwide academic community and for commercial and human therapeutic research through our inclusive innovation model.
Summary of the judgment
“Broad has persuaded us that the parties claim patentably distinct subject matter, rebutting the presumption created by declaration of this interference. Broad provided sufficient evidence to show that its claims, which are all limited to CRISPR-Cas9 systems in a eukaryotic environment, are not drawn to the same invention as UC’s claims, which are all directed to CRISPR-Cas9 systems not restricted to any environment. Specifically, the evidence shows that the invention of such systems in eukaryotic cells would not have been obvious over the invention of CRISPR-Cas9 systems in any environment, including in prokaryotic cells or in vitro, because one of ordinary skill in the art would not have reasonably expected a CRISPR-Cas9 system to be successful in an eukaryotic environment. This evidence shows that the parties’ claims do not interfere. Accordingly, we terminate the interference.”
About the hearing
This hearing reinforced the fact that the Broad Institute, MIT and Harvard were first to invent the subject matter in patent applications with regard to CRISPR genome editing in eukaryotic cells. The underlying facts have not changed and we are confident the patent office will continue to recognize the leadership of the Broad, MIT and Harvard in developing this transformative technology.
This hearing came at the request of both parties, and offered an opportunity for the respective legal teams to argue why particular motions should be granted. A summary of the key motions in the proceedings since January is available here.
The discussion focused on:
• No interference in fact: Broad has argued that the claims of its involved patents do not interfere with the involved claims of the UCB application, and thus that this interference process should not continue.
• The count: In any patent interference the judges set "the count," which is the definition of what the invention in question is. In this case, the judges have set the count as the use of CRISPR in a method in an eukaryotic cell. UCB is arguing that this decision should be revisited.
The judges have not set a timeline for a decision on these matters, although a decision is likely within a month or two after the hearing. These decisions will set the stage for the next phase of the interference process, which would likely extend through 2017 and potentially beyond.
What CRISPR-Cas9 patents have been issued to Broad Institute and MIT?
As of November 2016 the USPTO has issued 42 patents with claims to CRISPR and/or Cas9, including a robust portfolio of 13 CRISPR patents to the Broad Institute, MIT and affiliated groups for inventions from Dr. Feng Zhang and the Zhang lab. The claims of these patents are directed to mammalian genome editing methods and other distinct inventions optimizing the CRISPR-Cas9 components and system for delivery and function in such cells and organisms.
The USPTO has further issued ten additional CRISPR patents to Harvard University relating to inventions of Broad Senior Associate member George Church and the Church lab and also of Broad Institute core member David Liu and the Liu lab; three CRISPR patents to DuPont; one to Agilent Technologies; one to University of Georgia Research Foundation and one to Institut Pasteur, and one to Caribou Biosciences.
Zhang is a core member of the Broad Institute and an investigator at the McGovern Institute for Brain Research at MIT and an associate professor at MIT with a joint appointment in the Departments of Brain and Cognitive Sciences and Biological Engineering. As such, his CRISPR patents are assigned jointly to Broad Institute and MIT. For convenience they are often referred to as the "Broad patents," but Broad Institute is acting on behalf of both institutions in managing this IP portfolio.
In addition the European Patent Office (EPO) has granted six of Broad's patent applications as of February 2016.
Can CRISPR be patented?
No. CRISPR itself cannot be patented. Cas9 is a naturally occurring protein and part of a naturally-occurring bacterial process, but this process, on its own, does not work in mammalian cells. What Broad has patented are engineered components and compositions specifically altered from their naturally-occurring form to be useful in methods for editing the genomes of living mammalian cells.
What is the key issue with respect to the CRISPR-Cas9 patents?
The patent applications filed by Broad and MIT were not the first applications related to CRISPR, but they were the first that described complete invention of mammalian genome editing -- that is, actual experimental data constituting a reduction to practice.
Various patent applications speculating about the potential utility of CRISPR for genome editing have been filed over the years. They include applications by:
• Northwestern University in September 2008 (Erik Sontheimer and Luciano Marraffini, 61/099,317);
• Vilnius University in March 2012 (Virginijus Siksnys and others, 61/613,373);
• UC Berkeley in May 2012 (Jennifer Doudna and others, 61/652,086); and
• ToolGen in October 2012 (Jin Soo Kim and others, 61/717,324).
The status, elements, and outcomes of these applications have varied:
• The USPTO rejected the Sontheimer application as to failing to describe invention; the Sontheimer application was eventually abandoned.
• The applications filed in 2012 by the Vilnius team and the Berkeley team each showed only that purified Cas9 protein and a certain purified RNA could cut a short piece of DNA in a solution in a test tube. In both cases, the applications in 2012 contained no cells, no genomes, and no editing.
• The USPTO rejected the Vilnius application as not having significantly more than a study of the natural system and failing to describe invention.
• The USPTO continues to consider the Berkeley application, which describes similar results in 2012 as the Vilnius application.
• The USPTO has rejected the ToolGen application as failing to describe invention.
In April, 2014, the USPTO granted Patent No. 8,697,359 to Broad Institute, MIT and Dr. Feng Zhang. This Patent (which draws priority from a provisional patent application filed in December 2012) contained successful experiments. It was based on original work that began at the Broad Institute and MIT in early 2011, was further reflected in a January 2012 federal grant application to the National Institutes of Health and culminated in the manuscript submitted on October 5, 2012 that was published in Science on January 3, 2013 as Cong et al. It marked the world's first engineering of CRISPR-Cas9 to be delivered and used to achieve mammalian genome editing. Zhang was the first to file a patent application, on December 12, 2012, that described and enabled such a method. These components and methods have since become the leading standard for genome editing worldwide.
In awarding this patent to Broad, MIT and Dr. Zhang, the USPTO was fully aware of and fully considered the claims and materials in the other patent applications.