Type of information: Patent infringement lawsuit
Product name: CRISPR’s in-licensed gene editing technology
Compound: CRISPR/Cas9 single-guide gene editing system
Therapeutic area: Technology - Services
Action mechanism: genome editing product
Company: Crispr Therapeutics (Switzerland - UK)
- • On June 19, 2017, CRISPR Therapeutics announced that China’s State Intellectual Property Office (“SIPO”) has granted a patent broadly covering CRISPR’s in-licensed gene editing technology. The claims are directed to CRISPR/Cas9 single-guide gene editing methods for modifying target DNA in both non-cellular and cellular settings, including in cells from vertebrate animals such as human or mammalian cells – as well as composition of matter and system claims for use in any setting, including claims for use in producing medicines for treating disease.
- The European Patent Office and the United Kingdom’s Intellectual Property Office have previously issued patents from the underlying international patent application. This application is based on the same U.S. priority application that has been involved in an interference proceeding with the Broad et al., which priority application (USSN 61/652086) was filed on May 25, 2012, on behalf of CRISPR’s co-founder Dr. Emmanuelle Charpentier (currently a director at the Max-Planck Institute in Berlin) along with the Regents of the University of California (the assignee of Jennifer Doudna and colleagues) and the University of Vienna (the assignee of Krzysztof Chylinski).
- • On April 26, 2017, Intellia Therapeutics and CRISPR Therapeutics announced that the United States Patent and Trademarks Office is expected to issue a CRISPR/Cas9 genome editing patent to Vilnius University (“Vilnius”). Intellia and CRISPR are nonexclusive sublicensees for a defined field of human therapeutic, prophylactic, and palliative uses (including companion diagnostics), excluding anti-fungal and anti-microbial applications.
- The Vilnius patent claims are directed to CRISPR/Cas9 complexes assembled in vitro and used for site-specific modification of target DNA sequences. CRISPR/Cas9 complexes, referred to as CRISPR ribonucleoproteins or “RNPs,” are contemplated for use in a number of ex vivo applications in which cells, such as blood cells, may be corrected or edited outside of the body before being returned to a patient as a potential therapeutic. The patent is expected to issue on May 2, 2017 as U.S. Patent No. 9,637,739.
- This new patent, together with the companies’ respective rights to foundational CRISPR/Cas9 intellectual property co-owned by The Regents of the University of California, University of Vienna and Dr. Emmanuelle Charpentier, provide CRISPR and Intellia with complementary rights to inventions claimed by the earliest developers in the discovery and application of CRISPR/Cas9 technology.
• On March 28, 2017, Crispr Therapeutics reported that the European Patent Office (EPO) has announced its intention to grant a patent broadly covering CRISPR’s in-licensed gene editing technology. The claims are directed to the CRISPR/Cas9 single-guide gene editing system for uses in both non-cellular and cellular settings, including in cells from vertebrate animals such as human or mammalian cells – as well as composition claims for use in any setting, including claims for use in a method of therapeutic treatment of a patient.
- The European patent application (No. 13793997) was the subject of numerous third-party observations or ‘TPOs’ filed by the Broad Institute and others attempting to prevent or delay its grant. Following review of those submissions, the EPO determined that the technical evidence and associated legal arguments did not alter patentability of the inventions by the applicants, and accordingly announced its intention to advance the case to grant in Europe. The full EPO case files, TPOs, and claims intended for grant are available on-line via the EPO’s official website.
- The underlying international patent application is based on the same U.S. priority application that has been involved in an interference proceeding with the Broad et al., which priority application (USSN 61/652086) was filed on May 25, 2012, on behalf of Crispr’s co-founder Dr. Emmanuelle Charpentier (currently a director at the Max-Planck Institute in Berlin) along with the Regents of the University of California and University of Vienna.
- The United Kingdom’s Intellectual Property Office (UKIPO) has also examined the related applications, and likewise considered technical evidence and arguments submitted by third parties, before ultimately reaching similar conclusions to those of the EPO. The UKIPO granted a first UK Patent to the CRISPR/Cas9 single-guide gene editing system for uses in both non-cellular and cellular settings (No. 2518764), and a second UK Patent to ‘chimeric’ CRISPR/Cas9 systems in which the Cas9 protein is modified to provide alternative DNA-modulating activities (No. 2537000).
Submission of marketing authorization application USA :
Submission of marketing authorization application UE:
Withdrawal of marketing authorization application USA:
Withdrawal of marketing authorization application UE:
Favourable opinion UE:
Favourable opinion USA:
Orphan status USA:
Orphan status UE:
Pediatric exclusivit _USA:
Pediatric exclusivity UE:
- • On July 25, 2017, CRISPR Therapeutics, Intellia Therapeutics, Caribou Biosciences and ERS Genomics announced that The Regents of the University of California, the University of Vienna, and Dr. Emmanuelle Charpentier, co-owners of foundational intellectual property relating to CRISPR/Cas9 genome engineering, submitted an appellate brief to the U.S. Court of Appeals for the Federal Circuit seeking reversal of a decision by the U.S. Patent and Trademark Office’s Patent Trial and Appeal Board in an interference proceeding relating to CRISPR/Cas9 gene editing technology. In the appeal, they requests reversal of the PTAB’s decision terminating the interference between certain CRISPR/Cas9 patent claims owned by UC and claims of the Broad Institute, Harvard University and the Massachusetts Institute of Technology.
- In its brief to the Federal Circuit (Case No. 17-1907), UC asserts that the PTAB’s February 15, 2017 determination that the UC patent claims did not make the Broad’s patent claims obvious is based on a misapplication of controlling legal standards established by U.S. Supreme Court and Federal Circuit precedent. In its decision, the PTAB had concluded that UC’s claims covering CRISPR/Cas9 single guide gene editing technology and its application in any cellular or non-cellular setting did not make obvious Broad’s claims covering application of the same technology limited to use in eukaryotic cellular settings. In its brief, UC sets forth multiple errors in the PTAB’s holding that the use of CRISPR/Cas9 in eukaryotes is separately patentable as alleged by Broad, including the following:
- With respect to the obviousness of applying the technology to eukaryotic cells, U.S. Supreme Court and Federal Circuit precedents clearly mandate that obviousness determinations be based on an “expansive and flexible approach” including consideration of “the inferences and creative steps that a person of ordinary skill in the art would employ.” In contrast, the PTAB applied a narrow and restrictive approach that ignored certain key evidence, including the steps actually employed by those of skill in the art at the time, and also effectively required a “guarantee” that UC’s CRISPR/Cas9 invention would work in eukaryotic cells, when well-established case law requires only a “reasonable expectation of success.”
- With respect to the reasonable expectation of success standard that establishes obviousness, the PTAB effectively ignored U.S. Supreme Court and Federal Circuit case law, which emphasize that an invention can be obvious if it is “obvious to try,” even if success is not guaranteed, “[w]hen there is a design need or market pressure to solve a problem,” “there are a finite number of identified, predictable solutions,” and experimentation leads to “the anticipated success.”The PTAB ignored U.S. Supreme Court and Federal Circuit precedent highlighting that the occurrence of what appear to be simultaneous “inventions” arising close together in time is itself strong evidence of their obviousness, and accordingly requiring that such evidence be considered in any obviousness analysis. In contrast, in terminating the interference, the PTAB essentially dismissed as “irrelevant” the evidence that six different laboratories successfully applied UC’s claimed CRISPR/Cas9 invention in eukaryotic cells using conventional techniques within months after UC publicly disclosed the invention - some of them prior to Broad’s first filing.
The PTAB effectively ignored that Broad’s own eukaryotic application of UC’s CRISPR/Cas9 invention had simply utilized conventional prior art techniques. As a consequence, it failed to consider that Broad’s alleged invention did not reflect any significant innovation on Broad’s part, an important issue under applicable precedent.
The PTAB failed to hold Broad to its burden of proving, among other things, the effective priority date for its patent claims, as required by the PTAB’s own rules and Federal Circuit precedent. By not requiring the Broad to meet its burden of proof, and by merely assuming that all of the Broad’s claims were entitled to their earliest possible filing date despite Broad’s failure of proof, the PTAB improperly ignored relevant intervening art that made the Broad’s claims obvious.
- As explained in UC’s brief, application of the correct legal standards to the case is believed to require reversal of the PTAB’s decision. For these reasons, UC requests that the Federal Circuit instruct the PTAB to reinstate the interference proceeding so that it can properly determine priority of inventorship, as previously requested by UC. The PTAB’s failures to consider pertinent evidence and apply appropriate legal standards should at the very least require the matter to be remanded so that the PTAB can properly consider the evidence related to obviousness and Broad’s no-interference-in-fact motion using appropriate legal standards.
- In the PTAB’s February decision terminating the interference proceeding prematurely, it had not yet considered the teachings of UC’s own prior-filed patent application with respect to using CRISPR/Cas9 in eukaryotic cells. Instead, the PTAB only addressed the threshold question of whether use in eukaryotic cells can be separately patentable from use in all settings as covered by UC’s claims. However, determinations on the underlying substantive matters have recently been made in parallel prosecution before the U.S. Patent & Trademark Office. The USPTO has rejected a series of patent applications filed by Broad that are directed to uses of CRISPR/Cas9 technology in eukaryotic cells as being non-novel in view of UC’s prior-filed patent application, which the USPTO examiners considered to have effectively taught use of the CRISPR/Cas9 technology in eukaryotic cells. In addition, patent applications filed by Sigma-Aldrich and Toolgen that similarly claim use of CRISPR/Cas9 in eukaryotic cells (both of which filed applications before Broad’s application) have likewise recently been rejected as being either non-novel or obvious in view of the prior-filed UC patent application with specific respect to its teachings regarding application of the invention to use in eukaryotic cells.
Consistent with the substantive determinations reached by the USPTO regarding the broad teachings of the UC patent application, UC’s corresponding cases covering use of CRISPR/Cas9 in all settings, including in eukaryotic cells, have been advanced to grant or decisions to grant in numerous jurisdictions worldwide, including in the United Kingdom, the nearly 40 other countries that are members of the European Patent Convention, and more recently in other jurisdictions such as Australia, New Zealand, Singapore and China.
- • On April 13, 2017, CRISPR Therapeutics, Intellia Therapeutics, Caribou Biosciences and ERS Genomics announced that The Regents of the University of California, the University of Vienna, and Dr. Emmanuelle Charpentier (collectively “UC”), co-owners of foundational intellectual property relating to CRISPR/Cas9 genome engineering, have appealed to the U.S. Court of Appeals for the Federal Circuit the decision by the Patent Trial and Appeal Board to terminate the interference between certain CRISPR/Cas9 patent claims owned by UC and patents and patent applications owned by the Broad Institute, Harvard University and the Massachusetts Institute of Technology.
- In the appeal, UC is seeking review and reversal of the PTAB’s February 15, 2017 decision, which terminated the interference without determining which inventors actually invented the use of the CRISPR/Cas9 genome editing technology in eukaryotic cells. In its decision, the PTAB concluded that, although the claims overlap, the respective scope of UC and Broad’s claim sets as presented did not define the same patentable invention and, accordingly, terminated the interference without deciding which party first invented the use of the CRISPR/Cas9 technology in eukaryotic cells. UC is asking the Federal Circuit to review and reverse the PTAB’s decision.
- In parallel with the appeal, UC is pursuing applications in the U.S. and other jurisdictions worldwide to obtain patents claiming the CRISPR/Cas9 technology and its use in non-cellular and cellular settings, including eukaryotic cells. Corresponding patents have already been granted in the United Kingdom, and the European Patent Office is also granting a patent to UC, which will issue on May 10, 2017. UC’s earliest patent application describing the CRISPR/Cas9 genome editing technology and its use was filed on May 25, 2012, while the Broad’s earliest patent application was filed more than six months later, on December 12, 2012.
- The law firm of Munger, Tolles & Olson LLP will be handling the appeal, with Don Verrilli, former Solicitor General of the United States, as lead counsel.