by Broad Communications
Updated January 16, 2020
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.
January 16, 2020: Update on patent process in Europe
Today, the EPO Board of Appeal dismissed the Broad Institute’s appeal of an earlier Opposition Division decision which denied the Broad’s reliance on its U.S. priority provisional application for one patent in Europe based on a technical formality.
The decision does not involve the actual scientific merits of the patent application, but concerns the interpretation of rules that dictate what happens when the names of inventors differ across international applications. Because several other patents are connected to this application, the decision may affect nine of Broad’s 21 CRISPR-Cas9 patents in Europe if the EPO does not later harmonize these requirements.
The majority of Broad’s CRISPR-Cas9 patents in Europe are not affected by this decision. These include the fundamental claims in EP 2825654B1, as well as others covering certain key therapeutic indications -- including for previously untreatable diseases. In addition, Broad has numerous other CRISPR-Cas9 patent applications pending in Europe that are not affected by this formalities issue, as well as granted and pending patents related to CRISPR-Cas12/Cpf1, which are not affected.
We continue to urge all institutions to move beyond litigation and instead work together to ensure wide, open access to this transformative technology.
July 31, 2019: Statement on motions
Today, the parties to the 115 Interference each filed their proposed “Motions List.” The documents will be considered by the Administrative Patent Judges at the PTAB, and discussed with counsel for the Parties on August 5th. Like in the ‘048 Interference before, based on these lists, the PTAB will authorize some motions to go forward in the first phase, and defer or deny others.
The Broad Motions List seeks authorization to establish how this Interference on certain eukaryotic claims differs from the earlier 048 Interference, and attempts to establish a path forward to resolve any remaining substantive issues between these Parties.
In contrast, the Motions List of the University of California-Berkeley attempts to avoid any evaluation of who actually invented first, because all of the evidence clearly demonstrates that UC was not the first to invent any method of using CRISPR in eukaryotic cells. Instead, UC casts baseless claims [see below] at the Broad patents and inventors in the hope of avoiding having to provide any actual evidence of UC’s work in eukaryotic cells.
The Broad Institute stands behind the scientific claims and filings it has made to the Patent Office over many years.
It is deeply unfortunate, for the entire field, that the University of California-Berkeley has chosen this strategy.
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 UC licensed its IP exclusively and entirely to commercial entities, and we will continue to pursue a path towards resolution.
It is time for all institutions to move beyond litigation and instead work together to ensure wide, open access to this transformative technology.
The University of California-Berkeley repeats the same false claims that it made in the last interference. For example:
(i) UC repeats its previous false claim that the Broad inventions are based on UC’s work (Jinek et al.). It is obvious from the records and scientific papers that Broad did not rely on this work, because it used a clearly different approach. This approach, together with supporting evidence, inventors, and citations, is clearly outlined in Cong et al. and patent applications.
(ii) UC repeats its previous false claim around an email from a student with an expiring visa who emailed Dr. Doudna seeking a job and promising information. The student was hired by the UC system within days. The email was inaccurate and contrary to all records.
These claims did not succeed in the last interference; they will not succeed now.
Update on the June, 2019 interference process
On June 24, 2019, the Patent Trial and Appeal Board initiated a new interference process involving the UCB patent estate. Unlike the first interference process, which was requested by UCB, this interference was initiated by the USPTO itself and challenges the validity of UCB’s eukaryotic claims.
We welcome this action by the PTAB, which has previously ruled that the claims of the Broad patents, issued for methods for eukaryotic genome editing, were properly granted.
Importantly, in this interference, the USPTO designated Broad, MIT, and Harvard as the Senior Parties and UCB as the Junior Party, with the Count directed to uses of the CRISPR system in eukaryotic cells. (Read the order and declaration.) This further underscores the significance of Broad’s prior claims.
The Senior Party is presumed to be the “first to invent,” and the Junior Party carries the burden of proof. (In this case, the Broad, MIT, and Harvard inventions go back to 2011.)
Broad Institute looks forward to participating in the interference process.
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 seven 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 300 patents with claims to CRISPR and/or Cas9 to more than 500 inventors from nearly 100 applicant organizations. The European Patent Office (EPO) has issued more than 100 such patents to approximately 250 inventors from about 60 applicant institutions. In addition, there are more than 4,500 patent families filed (but mostly not yet granted) around the world.
Broad holds more than 40 key CRISPR patents in the United States, Europe, China, and elsewhere.
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?
In the United States, Broad has been allowed 20 patents for CRISPR-Cas9, as well as three for CRISPR-Cas12/Cpf1. The USPTO has also granted patents directed to CRISPR-Cas9 to UC Berkeley (UCB), University of Vienna and Emmanuelle Charpentier.
In Europe, Broad has been allowed or granted 22 CRISPR patents since 2015, including 21 related to CRISPR-Cas9 and one related to CRISPR-Cas12/Cpf1. UCB has also been issued CRISPR patents in Europe. Most, if not all, of the patents of both parties have been opposed by multiple parties. For one of the Broad patents, EP 2771468B, 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 did 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. The majority of Broad’s CRISPR-Cas9 patents in Europe were not affected by this decision. These include the fundamental claims in EP 2825654B1, as well as others covering certain key therapeutic indications -- including for previously untreatable diseases. In addition, Broad has numerous other CRISPR-Cas9 patent applications pending in Europe that are not affected by this formalities issue, as well as granted and pending patents related to CRISPR-Cas12/Cpf1, which are not affected.
In China, the State Intellectual Property Office has allowed three Broad patent applications, and we expect further to be granted based on pending applications. UCB also has patents in China. In China, patents are subject to invalidation proceedings after they are issued.
Broad and collaborators have been allowed and granted eight CRISPR patents in Australia, eight CRISPR patents in Japan, four CRISPR patents in South Africa, three CRISPR patents in Russia, two CRISPR patents in Israel and two CRISPR patents in Singapore. Other applications are in process.