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For journalists: Statement and background on the CRISPR patent process

by Broad Communications
Updated April 5, 2019
communications@broadinstitute.org

 

The ability to precisely edit the genome of a living cell holds enormous potential to accelerate life science research, improve biotechnology, and diagnose and treat human disease. CRISPR research is a large, highly collaborative field that involves contributions from many talented scientists around the world.

It is time for all institutions to move beyond litigation and instead work together to ensure wide, open access to this transformative technology.

The best thing, for the entire field, is for the parties to reach a resolution. This is why, for seven years, we have made many attempts to engage University of California-Berkeley, directly and through their exclusive licensee and through patent pools. These efforts began before UCB licensed its IP exclusively and entirely to commercial entities, and we will continue to pursue a path towards resolution.

THE IP LANDSCAPE

Broad’s issued patents are for genome editing and uses in eukaryotic cells -- including cells from animals, humans, and plants. (Broad manages a patent portfolio on behalf of several collaborating institutions, including Broad, MIT, and Harvard.)

UCB’s issued patents are not specific to uses in eukaryotic cells. The UCB estate is built on initial applications drawn only from work in test tubes -- not in cells -- that do not support claims to genome editing or use in eukaryotic cells.

As federal courts have made clear, the UCB patents do not affect the Broad CRISPR patent estate in any way, because Broad’s claims are patentably distinct.

In September, 2018, the United States Court of Appeals for the Federal Circuit upheld earlier rulings that the Broad patents granted by USPTO concerning CRISPR editing of eukaryotic genomes do not interfere with patent claims filed by UCB. The Patent Trial and Appeal Board described the important differences between Broad’s work and UCB’s:

"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 a eukaryotic environment. This evidence shows that the parties' claims do not interfere."

Because the patent estates cover different methods, a commercial entity seeking to use CRISPR might require a license from both Broad/MIT/Harvard and UCB.

This is a complex patent and licensing landscape that threatens innovation. Broad continues to call on UCB to join discussions for a patent pool or another coordinated licensing approach, such as the joint licensing framework Broad developed for CRISPR in agriculture.

QUESTIONS AND ANSWERS ABOUT CRISPR PATENTS

Q: What’s the difference between the Broad patents and the UCB patents?

In the United States, Broad’s issued patents are for genome editing and uses in eukaryotic cells -- including cells from animals, humans, and plants.

UCB’s issued patents are based on studies in cell-free systems and include methods and systems for modifying a target DNA molecule without limitation to uses in eukaryotic cells.

Q: Why did Broad receive a CRISPR patent before UCB, even though UCB applied first?

The Broad patent estate and the UCB patent estate concern different inventions, so the order of issuance (or application dates) does not matter.

In December, 2012, Broad requested “accelerated examination” of its application and paid the standard $70 fee. This meant the USPTO considered the application more quickly and the Broad agreed to respond more quickly to questions raised by the USPTO. The Broad 8,697,359 patent was issued in April, 2014.

(Accelerated examination does not change the level of scrutiny applied to the application — the same process of comparing the application to all other potentially-related patents takes place.)

UCB did not request accelerated examination when it applied for a patent in May, 2012. This, and UCB’s decision in 2015 to request that the USPTO declare an interference -- especially the unnecessary three-year process that followed that UCB request -- delayed their patent application from being considered until late 2018.

(To visualize the various patent applications and connected publications, see this timeline.)

Q: What was at issue in the interference process?

In 2015, UCB asked the USPTO to declare an “interference” between the claims of its ‘859 application and the Broad 8,697,359 patent, which had recently been issued. Under the "first to invent" patent system in place at the time, when two different sets of inventors claimed overlapping inventions, a key question was: Which set of inventors was the "first to invent" by "reducing the concept to practice.”

UCB argued that Broad’s inventions, for editing genes in eukaryotic cells, were obvious extensions of their work on cutting purified DNA in test-tube environments -- and therefore should not be patented.

The Patent, Trial and Appeal Board ruled in 2017 that the claims in Broad’s patents and in UCB’s applications concerned different inventions, and that Broad’s inventions in eukaryotic cells were not drawn from nor obvious over UCB’s work, particularly the experiments in test tubes as in Jinek 2012, and without work in eukaryotic cells. UCB appealed to the United States Court of Appeals for the Federal Circuit, which ruled in Broad’s favor in 2018. (A summary of the key motions in the PTAB proceedings is available here and the CAFC ruling is available here.)

Q: Can CRISPR be patented?

No. CRISPR itself cannot be patented. Cas9, for example, 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 methods, engineered components and compositions specifically altered from their naturally-occurring form to be useful for editing the genomes of living mammalian cells.

Q: What is the key issue with respect to the CRISPR-Cas9 patents?

The patent applications filed by Broad were not the first applications related to CRISPR, but they were the first that described the complete invention of mammalian genome editing — that is, actual experimental data constituting a reduction to practice.

Various patent applications with speculation about the potential utility of CRISPR for genome editing have been filed over the years. This includes applications by:

  • Northwestern University in September 2008 (Erik Sontheimer and Luciano Marraffini, US Patent Application No. 61/099,317);

  • Vilnius University in March 2012 (Virginijus Siksnys and others, US Patent Application No. 61/613,373);

  • UC Berkeley in May 2012 (Jennifer Doudna and others, US Patent Application No. 61/652,086); and

  • ToolGen in October 2012 (Jin Soo Kim and others, US Patent Application No. 61/717,324).

In April, 2014, the USPTO granted US Patent No. 8,697,359 to Broad, 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 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.

Q: Do patents limit the ability to share CRISPR widely?

This depends on the choices made by the institution or company that is licensing an invention. Broad believes CRISPR technology should 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.

Q: How does Broad share CRISPR?

Broad has worked for more than six years to ensure that CRISPR tools are made widely available to maximize public benefit.

  • We make CRISPR tools, knowledge, methods and other IP for genome editing freely available to the academic and non-profit community.

  • We license CRISPR IP non-exclusively to companies to use in their own commercial research.

  • In 2014, we developed the Inclusive Innovation Model -- which allows a primary licensee to devote sufficient investment to develop CRISPR-based genome editing technology to treat human diseases, while supporting broad development of medicines to reach many patients.

  • In 2017, we joined discussions to create a non-exclusive joint licensing pool coordinated by MPEG LA. These discussions are well underway.

  • In 2017, we reached an agreement that removed a major roadblock to the use of CRISPR-Cas9 genome editing in agriculture. This agreement included IP from private companies as well as from academic institutions -- including IP that DuPont-Pioneer had licensed from University of California, although UC itself was not part of the discussions.

Q: How many CRISPR patents are there?

CRISPR research is a large field that involves contributions from many talented scientists around the world. The US Patent and Trademark Office has issued more than 80 patents with claims to CRISPR and/or Cas9 to more than 300 inventors from nearly 60 applicant organizations. The European Patent Office (EPO) has issued more than 20 such patents to approximately 30 inventors from about ten applicant institutions. In addition, there are more than 1,500 applications filed (but not yet granted) around the world.

Broad holds 29 key CRISPR-Cas9 patents in the United States and Europe.

Over the next several years, there will be many more patents issued in the CRISPR field, to many inventors from many institutions, in recognition of each individual's contribution to advancing CRISPR technology.

Q: Why is the patent landscape different around the world?

CRISPR research is a large field that involves contributions from many talented scientists around the world. Countries issue patents in different ways under different laws and with different timing. In addition, the process for challenging patents is different depending on the jurisdiction. The US Patent and Trademark Office has issued more than 80 patents with claims to CRISPR and/or Cas9 to more than 300 inventors from nearly 60 applicant organizations. The European Patent Office (EPO) has issued more than 20 such patents to approximately 30 inventors from about ten applicant institutions. In addition, there are more than 1,500 applications filed (but not yet granted) around the world.

In the United States, Broad has been granted 13 patents for CRISPR-Cas9, as well as one CRISPR-Cpf1 patent. The USPTO has issued three patents directed to CRISPR-Cas9 to UC Berkeley (UCB), University of Vienna and Emmanuelle Charpentier.

In Europe, Broad has been issued 10 fundamental CRISPR patents since 2015. UCB was issued a CRISPR patent in 2017. For one of the Broad patents, a panel of the European Patent Office (EPO) denied the Broad’s reliance on its U.S. priority provisional application in Europe based on a technical formality. The decision does not involve the actual scientific merits of the CRISPR patent application, but concerns the current interpretation of rules that dictate what happens when the names of inventors differ across international applications. This interpretation affects many other European patents that rely on U.S. provisional patent applications, and is inconsistent with treaties designed to harmonize the international patent process, including that of the United States and Europe. Broad has appealed and is confident that the EPO will harmonize the EPO procedures to be consistent with international treaties -- and recognize the same priority dates for the inventions as those the USPTO has repeatedly affirmed for the Broad’s U.S. applications.

In China, the State Intellectual Property Office has issued a patent to UCB. It is currently considering Broad patent applications, which we expect will issue. In China, patents are subject to invalidation proceedings after they are issued.

Broad and collaborators have been issued three CRISPR patents in Australia and one in Japan. Other applications are in process.