We answer some of the most commonly asked questions about the CRISPR-Cas9 intellectual property situation globally.
We answer some of the most commonly asked questions about the CRISPR-Cas9 intellectual property situation globally.
The USPTO has not yet determined who was first to invent CRISPR-Cas9 gene editing in eukaryotic cells. What we do know is that the Broad was the fourth team to file a patent application for use of CRISPR-Cas9 gene editing in eukaryotic cells:
We also know that in addition to the Broad, four other teams published articles describing experiments in eukaryotic cells in January 2013:
The appearance of all these publications within weeks of each other reflects the importance of the Jinek 2012 paper — published nearly seven months earlier by the Doudna-Charpentier team — and the incredible ease of applying this technology in multiple contexts. Within seven months, each research team was able to plan experiments, order materials, complete and replicate multiple experiments, draft its manuscript, undergo peer-review, revise its manuscript and publish.
No, it was not difficult. No additional special instructions or inventions were needed beyond what was presented in the Jinek 2012 paper and known already by scientists in the field. Many different types of routine techniques were easily and quickly used by numerous groups to apply the CRISPR-Cas9 system to many different types of eukaryotic cells.
All of the techniques used to transfer the CRISPR-Cas9 system to eukaryotic cells had already been used and known for decades. The USPTO acknowledged this, stating: “We credit Drs. Greider’s and Carroll’s testimony regarding some of the strategies that were known in the art, including direct injection, codon optimization, and targeting of proteins and RNA to the cell nucleus. According to their testimony, these techniques were routine and known to be useful in achieving activity of prokaryotic proteins in eukaryotic cells.” (PTAB decision, page 35, lines 3-7.)
Within a year after the Jinek 2012 paper, at least ten different groups were able to plan experiments, order materials, complete and replicate multiple experiments, draft manuscripts, undergo peer-review, revise their manuscripts and publish. These groups used a variety of different common techniques – some injected the CRISPR-Cas9 complex directly into eukaryotic cells, some introduced the RNA guides directly and produced the Cas9 through expression vectors, and some produced both the RNA guides and the Cas9 through expression vectors. Some groups added extra features to increase targeting to the cell nucleus, but some did not. All achieved success, enabled by the information in the Jinek 2012 paper.
There are always hypothetical reasons why a scientific experiment might not work, but none of the successful teams reported that they needed to take special steps to account for potential obstacles.
It was apparent from the quick, simultaneous implementation that there were no substantial technical challenges or obstacles; the promise of the CRISPR-Cas9 system was immediately recognized and immediately applied by many groups at the same time.
Under U.S. patent law, an invention must be new, useful and nonobvious. As such, a scientist is not entitled to a patent simply because he or she performed an experiment that has not yet been done by someone else. A claimed invention must be a concept that is not an obvious variation or use of techniques or components already known to the public.
After publication of the Jinek 2012 paper, no inventive steps were needed to use the CRISPR-Cas9 system in eukaryotic cells. No additional special instructions were needed beyond what was presented in the Jinek 2012 paper. Many different types of routine techniques were easily and quickly used by numerous groups to apply the CRISPR-Cas9 system to many different types of eukaryotic cells. Thus, using the CRISPR-Cas9 system in eukaryotic cells was not a separately patentable invention when compared to the Doudna-Charpentier team’s work.
This rapid success of so many different groups using so many different well-known techniques illustrates how easy and obvious it was to apply the CRISPR-Cas9 system in eukaryotic cells.
Five research teams filed patent applications in the U.S. within a period of seven months for certain applications of CRISPR-Cas9 genome editing technology in eukaryotic cells. Of these teams, the Broad was the fourth to file its patent application. Although it was the fourth filer, the Broad paid a fee to the USPTO for expedited review of its patent application, which allowed it to be the first to present arguments to the USPTO; because of this, the Broad received the first patent granted on CRISPR-Cas9 genome editing in eukaryotic cells.
It is important to note that the USPTO has not, in fact, determined who was first to invent the use of the CRISPR-Cas9 system in eukaryotic cells. Although CVC asked the PTAB to declare an interference to decide who first invented CRISPR-Cas9 genome editing, the Broad asked to terminate the interference without deciding the question of who invented first, and the PTAB granted the Broad’s request. The decision by the CAFC, like that of the PTAB, did not decide whether CVC or the Broad was first to invent the CRISPR-Cas9 genome editing technology in eukaryotic cells, or any other environment.
Thus, to date, there has been no determination by and decision from the USPTO that the Broad is the first to invent any aspect of the CRISPR-Cas9 genome editing technology.
Before March 16, 2013, the U.S. patent system operated on a “first to invent” basis, which awarded patents to the first person to invent the invention. Effective March 16, 2013, the U.S. adopted a “first to file” system, which awards patents to the first inventor to file a patent application on an invention.
Under the “first to invent” system, an interference is a USPTO proceeding designed to determine who was first to invent an invention. A three-judge panel of administrative patent judges receives arguments and evidence regarding what is overlapping subject matter and the relative invention dates of the involved parties; the panel decides who was the first to invent the overlapping subject matter. There are two stages to an interference: a motions phase and a priority phase.
CVC requested an interference, which was granted in January 2016.
The Broad filed a request (a motion) with the PTAB asking it to terminate the interference without deciding the question of who invented first. The PTAB granted the Broad’s motion and terminated the interference after the motions phase. Thus, the priority phase did not occur, and the PTAB did not decide who was first to invent gene editing using CRISPR-Cas9.
In legal terms, the PTAB decided that “the parties’ claims do not interfere” because they are of different scope; CVC’s claims are not restricted to any environment, while the Broad’s claims are all limited to use of CRISPR-Cas9 systems in a eukaryotic cell environment. Thus, the PTAB’s decision said that the PTAB would “terminate the proceeding without entering judgment against either party’s claims.”
No. The PTAB terminated the ‘048 Interference without deciding who was the first to invent. CVC had requested that the PTAB proceed to review the parties’ laboratory notebooks and other evidence to determine which party actually invented first. The Broad, however, asked the PTAB to end the proceeding without reviewing any evidence or making a decision regarding dates of invention. Because CVC’s patent application claims cover the CRISPR-Cas9 genome editing and its use in any cellular or non-cellular setting, the Broad argued that using the system specifically in eukaryotic cells was sufficiently different so that the PTAB should not proceed with a determination of who was first to invent. The PTAB concluded that, even though CVC’s claims were broader than the Broad’s, there was still enough of a difference that the interference should not proceed. Accordingly, the PTAB refused to use this particular set of claims from CVC to determine which party was the first to invent the application of CRISPR-Cas9 to eukaryotic cells.
CVC appealed to the CAFC to reverse or remand the February 2017 PTAB decision, finding no interference in fact between issued patents of the Broad on CRISPR-Cas9 genome editing in eukaryotic cells and a patent application filed earlier by CVC for genome editing in all environments, both cellular and non-cellular. The arguments on appeal focused on the fact that the PTAB used incorrect standards in assessing whether CRISPR-Cas9 genome editing in eukaryotic cells was an obvious extension of its core invention and the Jinek 2012 Science paper describing it. Specifically, CVC argued that previous court decisions, including by the U.S. Supreme Court, established that the correct standard is whether, given the teaching of the CVC patent claims, the Jinek 2012 paper and standard laboratory techniques known and available to those skilled in the art, researchers would have had a “reasonable expectation of success” in achieving CRISPR-Cas9 genome editing in eukaryotic cells. CVC pointed out that six different labs quickly achieved eukaryotic editing using the information provided in the Jinek 2012 paper, including CVC itself, in work conducted before the Broad filed its patent application
The CAFC issued its opinion on September 10, 2018 and indicated that because it would “not reweigh the evidence,” due to the deferential nature of appellate review, the PTAB had sufficient basis to discontinue the interference “given the mixture of evidence in the record.” The CAFC, like the PTAB, did not decide whether CVC or the Broad first invented the CRISPR-Cas9 genome editing technology.
CVC has ten U.S. patents covering various aspects of the CRISPR-Cas9 genome editing technology, including the use of single guide RNA formats in various environments, including eukaryotic cells and human therapeutics, as well as a number of allowed and pending patent applications covering aspects of the foundational CRISPR-Cas9 genome editing technology.
When the same research team successfully argues for a patent on a specific technology, the USPTO often will allow a second or subsequent patent to the same research team for overlapping or related aspects of the technology. Having multiple patents does not make it more likely that you were first to invent. Whether you have one patent or many, any number of patents can be brought into a single interference, at which time the PTAB will decide which group was first to invent.
The CAFC issued its opinion on September 10, 2018 (Case No. 17-1907) and indicated that because it would “not reweigh the evidence,” due to the deferential nature of appellate review, the PTAB had sufficient basis to discontinue the interference “given the mixture of evidence in the record.” The CAFC, like the PTAB, did not decide whether CVC or the Broad first invented the CRISPR-Cas9 genome editing technology. The CAFC opinion also does not preclude other proceedings, either at the USPTO or in the courts, to determine which research group is the actual inventor and, thus, the proper owner of the CRISPR-Cas9 genome editing technology. The court expressly indicated that its decision was limited to “the scope of two sets of applied-for claims, and whether those claims are patentably distinct.” The CAFC also emphasized that its decision was “not a ruling on the validity of either set of claims.”
Consistent with the consensus of the scientific community, the CRISPR Collective firmly believes in the strength, breadth, and scope of the foundational IP covering the CRISPR-Cas9 genome editing technology developed by Drs. Emmanuelle Charpentier and Jennifer Doudna, and their colleagues. The CRISPR Collective expects that the USPTO will continue to issue patents to CVC covering the foundational CRISPR-Cas9 genome editing technology, including its use in any environment, and that CVC believes it will prevail in the event a second interference is declared relating to who invented the use of the technology in eukaryotic cells.