UPDATED – Status “Interference — Initial memorandum” – CRISPR/Cas9 – The Biotech Patent Fight of the Century: UC, Berkeley and Broad Institute @MIT
Reporter: Aviva Lev-Ari, PhD, RN
UPDATED on 6/30/2019
Patent office renews dispute over patent rights to CRISPR-Cas9
Schematic representation of the CRISPR-Cas9 system. The Cas9 enzyme (orange) cuts the DNA (blue) in the location selected by the RNA (red). (Image courtesy of Carlos Clarivan/Science Photo Library/NTB Scanpix)
The Patent Trial and Appeal Board (PTAB) of the U.S. Patent and Trademark Office (USPTO) has declared an interference between 10 University of California patent applications and multiple previously issued Broad Institute patents.
This action is addressing the following 9/2018 determination:
In September 2018, the United States Court of Appeals issued a ruling that upheld a Patent Trial and Appeal Board (PTAB) judgment that had found no interference-in-fact between UC claims and patents already issued to Broad, stating that the claims were not directed to the same subject matter. That ruling made no specific determination regarding priority of invention of genome editing within eukaryotic cells. UC was subsequently issued six U.S. patents for CRISPR technologies in other cellular or non-cellular settings, with six additional applications set to issue in the coming weeks and holds more than 50 CRISPR patents worldwide.
Interpretation of 6/2019 declaration of an interference by The Patent Trial and Appeal Board (PTAB) of the U.S. Patent and Trademark Office (USPTO) between 10 University of California patent applications and multiple previously issued Broad Institute patents.
The action jeopardizes 13 of the Broad’s 15 CRISPR-Cas9 U.S. patents and one patent application, and signals that the USPTO will take up the issue of who first invented CRISPR-Cas9 genome editing in eukaryotic cells, that is, plant and animal cells.
The CRISPR-Cas9 DNA-targeting technology was invented by Jennifer Doudna and Martin Jinek at the University of California, Berkeley; Emmanuelle Charpentier, then of Umea University in Sweden; and Krzystof Chylinski at the University of Vienna.
Eldora L. Ellison, Ph.D., lead patent strategist on CRISPR matters for UC and a director at Sterne, Kessler, Goldstein & Fox. “We are confident that the USPTO will ultimately recognize that the Doudna and Charpentier team hold the priority of invention specific to eukaryotic cells, as well as other settings covered by previous patents.”
Edward Penhoet, special advisor to the UC Berkeley chancellor and special assistant to the president of the University of California. “We are committed to protecting the intellectual property of the groundbreaking inventions of UC faculty, like the CRISPR-Cas9 breakthrough. Today’s declaration of interference reinforces the importance of the university’s role in protecting discoveries and their pursuit.”
Today’s declaration of interference affects 13 of the Broad’s 15 U.S. patents, as well as one application — essentially all of its CRISPR patents involving eukaryotic cells. The six U.S. patents received to date by UC are not included in this interference. Based on current PTAB interference schedule, the interference is likely to be completed within two years.
In addition to six U.S. patents, UC has received four patents from the European Patent Office (representing more than 30 countries), as well as patents in the United Kingdom, China, Japan, Australia, New Zealand, Mexico and other countries.
The international scientific community has widely acknowledged the pioneering invention by the Doudna-Charpentier team on CRISPR-Cas9 genome editing through numerous awards, including the Breakthrough Prize in Life Science, Japan Prize, Gruber Prize in Genetics, BBVA Frontiers of Knowledge Award, and Kavli Prize in Nanoscience.
UC has a long-standing commitment to develop and apply its patented technologies, including CRISPR-Cas9 genome editing, for the betterment of humankind. Consistent with its open-licensing policies, UC allows nonprofit institutions, including academic institutions, to use the technology for non-commercial educational and research purposes.
UC encouraged widespread commercialization of the CRISPR-Cas9 technology through its exclusive license with Caribou Biosciences, Inc. of Berkeley, California, which has sublicensed the technology to many companies internationally, including Intellia Therapeutics, Inc. for certain human therapeutic applications. Additionally, Charpentier has licensed the technology to CRISPR Therapeutics AG and ERS Genomics Limited.
The ten UC patent applications in the proceeding are: US 15/947,680; US 15/947,700; US 15/947,718; US 15/981,807; US 15/981,808; US 15/981,809; US 16/136,159; US 16/136,165; US 16/136,168; and US 16/136,175.
The Broad patents affected include patents 8,697,359; 8,771,945; 8,795,965; 8,865,406; 8,871,445; 8,889,356; 8,895,308; 8,906,616; 8,932,814; 8,945,839; 8,993,233; 8,999,641; 9,840,713; and application 14/704,551.
RELATED INFORMATION
SOURCE
https://news.berkeley.edu/2019/06/25/patent-office-renews-dispute-over-patent-rights-to-crispr-cas9/
UPDATED on 6/25/2019
Patent office reopens major CRISPR battle between Broad Institute and Univ. of California
The U.S. patent office has declared an interference between a dozen key patents awarded to the Broad Institute on the genome-editing technology CRISPR and 10 CRISPR patent applications submitted by the University of California and its partners, according to documents posted by the U.S. Patent and Trademark Office.
The declaration of an interference means that the patent office has determined that one or more patent applications describe inventions that are substantially the same as those for which patents have already been issued. In this case, the patents awarded to the Broad, beginning in 2014, describe the use of CRISPR-Cas9 to edit the genomes of eukaryotes — organisms whose genomes are enclosed within a cell nucleus, including all plants and animals — based on the research of Broad biologist Feng Zhang. UC’s patent applications also cover the use of CRISPR in eukaryotes, based on the work of UC Berkeley biochemist Jennifer Doudna and her collaborator Emmanuelle Charpentier.
UC and the Broad already went through an interference proceeding that went all the way to federal appeals court, with the Broad prevailing.
The patent office has designated the Broad as the “senior party” in the interference and UC as the “junior party.” That means the Broad, with patents in hand since 2014, is presumed to be the rightful, first inventor. UC therefore has to prove its case to the patent office.
Unlike the last interference, which UC requested, neither party asked for this one. But that can be done “indirectly,” Noonan said.
“Now we’re having the fight over who invented CRISPR in eukaryotes,” said Eldora Ellison of Sterne Kessler Goldstein & Fox, who represents UC. The declaration of interference, she said, “means that the patent office has recognized that it has a duty to determine who invented this important invention. The fact that the Broad has patents does not resolve that question.”
The answer to that question would reverberate well beyond the potentially billion-dollar market for CRISPR therapies. Those are being developed by at least three companies, including Editas Medicine, CRISPR Therapeutics, and Intellia Therapeutics. The outcome could also affect who the science record books, to say nothing of the Nobel Prize committee, recognizes as the inventors of this revolutionary technology.
On Twitter active discussion followed STAT article on 6/25/2019, above update
UC Berkeley gets patent dispute with Broad Institute renewed. I looked at the documents: technically, appears UC is betting everything on fact that their CRISPR invention used a “single” guide RNA, whereas Broad initially used two RNAs.
PS- Here is a screen cap of Broad Institute statement. Provides a different narrative, that USPTO is challenging Berkeley claims to CRISPR in human cells. I don’t see that in the documents but might be missing it.
In summary, as far as I can gather—(and this could definitely be wrong)–Berkeley is now saying “all your single RNA patent claims belong to us.” Also, “keep your stinkin double RNA invention”. /END
[[ The “Heroes” article was notorious for providing a detailed history of CRISPR and priority claims but not mentioning the patent dispute or big financial interests of the author’s institution in the outcome. ]]
The fly in the ointment — maybe — is that the early Broad experiments involved seperate RNAs (the tracrRNA and the crRNA). Here is Eric Lander, head of the Broad Institute, saying it himself in his notorious Heroes of CRISPR piece in cell.
whereas Broad has said that in its labs, by mid-2012, it was also doing CRISPR editing (but didnt publish). That unpublished claim to have invented CRISPR first is what allowed them to get their patents in the first place.
see this
@geochurch paper from 2013 (predating dispute) in which he describes Berkeley system in much the same way.In nature, CRISPR uses two RNAs to guide the cut–a CRISPR array and a tracrRNA. But Doudna et. al showed these could be combined to one easily programmed RNA molecule. “necessary and sufficient” — all you need, and nothing you don’t. One RNA, not two.
In documents connected to the new case, Berkeley making a big deal of the fact that in 2012, in their famous Science paper, Jennifer Doudna, Emmanuel Charpentier, et al, published the “necessary and sufficient” components to program CRISPR cut DNA in a test tube.
Almost all CRISPR experiments use a single guide RNA. And pretty much any therapeutic use of gene editing in humans would as well. So it would be a big deal if Berkeley could grab that part of human editing.
CRISPR involves a cutting protein (Cas9) and a “guide RNA” molecule to tell it where to cut a genome. These guides are cheap and available from companies like Synthego. They are how you point CRISPR at a specific place.
At a technical level, I think Berkeley is saying is they want all Broad’s patent claims that rely on a “single” guide RNA. (but pls comment if you think different). I will try to explain why I think so.
But now as stat reports there is going to be a new interference, this time just about eukaryotes (i.e. human cells). In an interference, one party can take over the other’s patent claims.
The dispute previously led to an “interference” proceeding, in which USPTO decided that basic CRISPR editing and CRISPR in human cells are different inventions. And it gave CRISPR in eukaryotes to Broad Institute.
Our original scoop on the CRISPR patent dispute from 2014 still provides a good explainer of the basic situation, and the VERY hard feelings involved. https://www.technologyreview.com/s/532796/who-owns-the-biggest-biotech-discovery-of-the-century/VERY …
UPDATED on 9/14/2018
The patent battle:
- In 2012, Jennifer Doudna and Emmanuelle from UC Berkeley first filled patents on using CRISPR/Cas9 gene editing in small organisms, like bacteria.
- In 2014, two years later, while the UC Berkeley patent application was pending, Feng Zhang’s team at the Broad Institute of MIT and Harvard filled a rushed patent on using CRISPR/Cas9 gene editing in more complex cells, which was approved in 2017.
- The UC Berkeley team then filled appeals to invalidate the Broad patent.
- In 2017, the Patent Trial and Appeal Board voted that the Broad application is unique enough for its own patent.
- On 2018, Sep. 10th, the US Court of Appeals for the Federal Circuit agreed to uphold the patent filed by the Broad Institute on CRISPR/Cas9 gene editing in organisms with complex cells. Judge Kimberly Moore wrote that “The Board’s underlying factual findings are supported by substantial evidence and the Board did not err… We have considered UC’s remaining arguments and find them unpersuasive.”
- Even though UC Berkeley team can appeal this decision to the US Supreme Court, it is unclear whether the Supreme Court will accept this case.
SOURCE
UPDATED on 10/13/2016
Could Cellectis upend CRISPR patent drama?
Cellectis’ patent covers all gene-editing technologies that depend on chimeric endonucleases to alter and repair DNA, providing the DNA sequence has at least 12 base pairs, and only for in vitro applications. Cellectis CEO Andre Choulika says that this definition “covers most of the gene editing procedures done with a nuclease,” including those based on CRISPR/Cas9.
Other companies have already begun to dispute this read of Cellectis’ patent. And Jacob Sherkow, a patent specialist who works at New York Law School in New York City and has closely monitored the CRISPR landscape so far, doesn’t agree that CRISPR is covered by Cellectis’ umbrella patent. “I think Cellectis is taking an overly generous view of both the validity and scope of its new patent,” he says. “And given the state of the chimeric restriction endonuclease art prior to the patent’s 1999 date, there are some serious doubts as to its validity. We’ll see what Cellectis does with it.”
UPDATED on 10/10/2016
Dramatic twists could upend patent battle over CRISPR genome-editing method
By Jon Cohen Oct. 5, 2016 , 1:30 PM, Science
- Last week, attorneys for the Broad Institute in Cambridge, Massachusetts, one of the research organizations vying for CRISPR rights, submitted motions that could let it win even if it loses.
- On 28 September the Broad Institute asked patent office officials to separate four of its issued patents from the case.
- The Broad [Harvard+MIT] holds 13 CRISPR patents that are under fire from the University of California (UC) and two co-petitioners.
- “all or nothing affair”: Whoever was going to win would control the most important aspects of the CRISPR patent landscape. But if the Broad Institute wins its request to separate the four patents from the larger case, he says “there may be a way for both sides to walk away with a little IP
- Yesterday, a new player in the drama, a French biopharmaceutical company called Cellectis, may have made the whole fight moot, revealing it has just been issued patents that it says broadly cover genome-editing methods, including CRISPR.
- Doudna, Charpentier, and their team reported in the 28 June 2012 online issue of Sciencethat they had taken a CRISPR system used by bacteria to thwart reinfections with viruses and created an artificial version that showed the components needed to edit genes.
- Zhang’s group at MIT/Broad reported in the 15 February 2013 online issue of Sciencethat CRISPR worked in eukaryotes.
SOURCE
UPDATED on 8/24/2016
Broad Institute Refutes Claims in Leaked Email Suggesting CRISPR Patent Malfeasance
Aug 18, 2016
UPDATED on 8/19/2016
CRISPR patent battle heats up as new email disputes Zhang’s claims
by Ben Adams |
Aug 18, 2016 6:42am
– check out Lin’s email (PDF)
– read Broad’s statement
-read the MIT Technology Review story here
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Editas partners to bring CRISPR to gene therapy in inherited retinal diseases
Groundbreaking gene editing player Caribou raises $30M B round
UPDATED on 3/29/2016
In CRISPR Patent Interference, Parties Argue Over What to Argue About
On March 17, judges from the US Patent Trial and Appeal Board (PTAB) issued rulings on a number of motions put forward by lawyers for UC — the senior party in the case based on theirunawarded patent application‘s earlier filing date — and the Broad, which holds more than a dozen patents related to CRISPR, including the keystone Patent No. 8,697,359 (the ‘359 patent).
On March 17, 2016, The judges said that it would be premature to consider this argument at this time, because they had yet to establish the
- relationship between tracrRNA,
- the interfering claims, and
- proof of priority.
While Charpentier (but not Doudna) first described tracrRNA and showed its importance in a 2011 paper published in Nature, “Whether or not tracrRNA is an essential element of the interfering subject matter will likely be apparent from the priority proofs,” the judges wrote. “UC may request authorization to file its motion after the conclusion of the priority phase of the interference.”
Zhang and Broad will hope that question never comes to bear. If Broad can win the argument that there’s actually nothing to any of the interference claims, the process will be over before it truly begins.
But beyond that, it’s almost impossible to predict how the fight will turn out. Any number of permutations and combinations of arguments could wind up going forward. What the early judgments show is that it’s far too early to begin keeping score.
In the bigger picture, Sherkow stressed that the patent interference is really only suitable to address whether there is a conflict between the two parties. “It is not a referendum on the scientific priority of the dispute, it’s not a referendum on the merits of [Broad’s] patents,” he said.
“It’s not even a referendum on whether CRISPR should be patented at all,” he said.
UPDATED on 3/17/2016
67 articles in PharmaceuticalIntelligence.com
http://pharmaceuticalintelligence.com/category/crisprcas9-gene-editing/
UPDATED – Medical Interpretation of the Genomics Frontier – CRISPR – Cas9: Gene Editing Technology for New Therapeutics
Authors and Curators: Larry H Bernstein, MD, FCAP and Stephen J Williams, PhD and Curator: Aviva Lev-Ari, PhD, RN
Nine Parties had come forward: Opposition Procedure to the Broad Institute’s first European CRISPR–Cas9 Patent
Curator: Aviva Lev-Ari, PhD, RN
CRISPR: A Podcast from Nature.com on Gene Editing
Reporter: Aviva Lev-Ari, PhD, RN
http://pharmaceuticalintelligence.com/2016/03/17/crispr-a-podcast-from-nature-com-on-gene-editing/
UPDATED on 2/29/2016
Perspective
The Heroes of CRISPR
Eric S. Lander
DOI: http://dx.doi.org/10.1016/j.cell.2015.12.041
Volume 164, Issues 1-2, p18–28, 14 January 2016
http://www.cell.com/cell/abstract/S0092-8674(15)01705-5
How One Man Tried to Write Women Out of CRISPR, the Biggest Biotech Innovation in Decades
http://jezebel.com/how-one-man-tried-to-write-women-out-of-crispr-the-big-1753996281
On March 6, 2016 Court hearing on the INTERFERENCE will take place
The USPTO has awarded the Broad Institute more than a dozen CRISPR-related patents based on the work of Feng Zhang, a core faculty member at the Broad Institute and assistant professor at the Massachusetts Institute of Technology, and his colleagues — notably Fei Ann Ran, a postdoc in Zhang’s lab. The University of California submitted its patent application first, based on the work of UC-Berkeley Professor Jennifer Doudna and Emmanuelle Charpentier, then at Sweden’s Umeå University; however, the Broad application was reviewed and awarded under the USPTO’s “accelerated examination” procedures.
In a statement, the Broad Institute said that by awarding US Patent 8,697,359 to the Broad, MIT and Zhang, the USPTO “was fully aware of and fully considered the claims and materials in the other patent applications,” including UC-Berkeley’s. The University of California’s patent application claims a priority date of May 25, 2012.
Administrative Patent Judge Deborah Katz will manage the proceedings. Vedder Price will act as counsel to the Broad Institute. Buchanan, Ingersoll & Rooney and Goodwin Procter will serve as counsel for the party led by the University of California.
The parties will participate in an initial conference call on March 9.
According to the USPTO, the senior party — the University of California — is responsible for initiating settlement discussions.
SOURCE
Historic CRISPR Patent Fight Primed To Become Head-To-Head Battle
“Interference — Initial memorandum” is a higher level of adjudication, known as interference in PTO-speak, only takes place when a challenger has made a strong argument that the PTO should reconsider a granted patent.
Doudna and company, in this case, are the challengers. The patents they want re-examined belong to the Broad Institute of MIT and Harvard and the principal Broad scientist Feng Zhang. The PTO granted Zhang and Broad the first-ever CRISPR patent in April of 2014, with a dozen more to follow.
- The Doudna camp has been fighting that decision ever since, gathering evidence and testimony on who was the first to invent this new gene editing technology.
- A large part of the patent dispute hinges upon whose work first described a gene editing system that worked not just in test tubes or prokaryotic cells, such as bacteria, but also in eukaryotes—that is, more advanced life forms.
- @MIT, Zhang’s described in September a new enzyme—the molecular scissors used to snip the DNA—called Cpf1 that, they say, when used with the CRISPR editing system could get around some of the problems with the Cas9 enzyme.
If PTO will declare the interference Doudna and Zhang might have to “take the stand, or at least testify under oath in a deposition.
CRISPR patent dispute between the Doudna and Zhang camps is being fought under old PTO rules, thanks to an overhaul of American patent law in 2011. Under the old rules, the first person to prove his or her invention was rewarded with a patent.
Under the new rules, the patent goes to whoever is first to file an application. Because of the slow pace of putting laws in place, the CRISPR case will be settled under the old rules, likely making it the last great “first to invent” fight in U.S. patent history. The PTO must approve a settlement — if no settlement takes place, the outcome of the interference can be appealed up through the U.S. court system. In other words, the biotech patent fight of the century might feel like it lasted the better part of the century.
Gene Edit Summit Leaders Stop Shy Of Call To Ban Germline Changes
There is great promise, too. Several companies with licenses to the competing Doudna and Zhang patents—and with other IP in their portfolios—are racing to move CRISPR-based therapies into clinical trials to treat genetic disease. The CEO of Cambridge, MA-based Editas Medicine—which has license to the Zhang patents—said in November that her company hopes to have a treatment for a rare form of blindness in the clinic by 2017.
SOURCE
Other related articles to CRISPR/Cas9 were published in this Open Access Online Scientific Journal, 50 articles, including
http://pharmaceuticalintelligence.com/?s=CRISPR%2FCas9
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Aashir Awan, Phd
Abhisar Anand
Adina Hazan
Alan F. Kaul, PharmD., MS, MBA, FCCP
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apreconasia
aviralvatsa
David Orchard-Webb, PhD
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Demet Sag, Ph.D., CRA, GCP
Dror Nir
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Ethan Coomber
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Srinivas Sriram
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