“The PTAB decision means that a number of U.C.’s patents that are directed to using the CRISPR-Cas9 system in eukaryotic cells, could be rendered invalid…. In the event [they are found] invalid, U.C. could potentially lose significant licensing revenue.”
As previously reported here, on February 28, 2022, in Interference 106,115, the Patent Trial and Appeal Board (PTAB) issued a decision in which it awarded inventive priority to the Broad Institute (Broad) over the University of California (U.C.) on an invention covering applications of the CRISPR-Cas9 gene editing system in eukaryotic cells. This decision purports to award substantial control of the CRISPR-Cas9 patent landscape to Broad.
This article provides additional background on CRISPR-Cas9 technology, outlines the critical findings in Interference 106,115 that resulted in the PTAB awarding priority to Broad, and describes the impact of the PTAB’s decision for Broad, U.C., and other companies involved in the development of CRISPR-Cas9 technology.
The CRISPR-Cas9 system is a revolutionary technology that is capable of genomic editing through precise cutting of the genome. This cutting allows for removal or alteration of genes within the genome, as well as additions of genetic material to the genome. Essentially, the CRISPR-Cas9 system permits specific and controlled rewriting of the genetic code. The therapeutic implications of this technology are vast; the CRISPR-Cas9 system could be used to treat genetic disorders, infectious diseases, and cancer, amongst many others.
The development of CRISPR-Cas9 technology as a method of modifying the genome began in the early 2010s. Around 2012, Jennifer A. Doudna (a professor at the University of California, Berkeley), and her collaborator Emmanuelle Charpentier (the director of the Max Planck Unit for the Science of Pathogens), discovered how CRISPR-Cas9 could be used to cut and edit genomic DNA. In 2020, Doudna and Charpentier were awarded the Nobel Prize in Chemistry for their discovery. Roughly concurrently with Doudna’s and Charpentier’s discovery, Feng Zhang (a professor of the Broad Institute of the Massachusetts Institute of Technology and Harvard University), was developing the use of the CRISPR-Cas9 system in eukaryotic cells (cells of higher organisms such as humans). In 2013, Zhang published a paper in the scientific journal, Science, which demonstrated the functionality of CRISPR-Cas9 system in eukaryotic cells.
Both U.C. and Broad filed patent applications related to the discoveries by Doudna/Charpentier and Zhang, respectively. Notably, in some of these filings, U.C. and Broad claimed the use of the CRISPR-Cas9 system in eukaryotic cells. As a result, both U.C. and Broad currently hold patents that claim applications of the CRISPR-Cas9 system with a eukaryotic cell limitation. Many of these patents were the patents in suit in Interference 106,115.
At issue in Interference 106,115 was which party, U.C. or Broad, was the first to conceive and reduce to practice using CRISPR-Cas9 in eukaryotic cells. Based on their patent filings, U.C. was accorded a filing date of January 28, 2013 and Broad was accorded a filing date of December 12, 2012. However, both parties filed motions arguing for dates of conception and reduction to practice that were earlier than their accorded filing dates.
Broad asserted that one of its dates of reduction to practice was October 5, 2012. In support of this assertion, the PTAB found evidence of experiments that were allegedly performed in July of 2012 in which Zhang and his collaborators successfully targeted and edited a specific gene in mice (an organism comprised of eukaryotic cells). The results of these experiments were reported in a manuscript that was submitted to the scientific journal, Science, on October 5, 2012.
Broad argued that the decision to submit the manuscript, thereby subjecting its findings to peer review, indicated that Zhang understood and appreciated that the results successfully showed the ability of the CRISPR-Cas9 system to edit genes in eukaryotic cells. Further, Broad pointed to the comments by the reviewers of the manuscript as evidence that use of the CRISPR-Cas9 system in eukaryotic cells had been successfully reduced to practice. The reviewers stated that “The authors report…the milestone implementation of a bacterial CRISPR system in human cells, and show it can be used for…cleavage and genome engineering.” Relying heavily on the reviewers’ comments, the PTAB found that Broad had reduced to practice using CRISPR-Cas9 in eukaryotic cells at least as early as October 5, 2012.
U.C. alleged that its reduction to practice occurred prior to October 5, 2012. In particular, U.C. argued that experiments performed by Doudna/Charpentier and their collaborators on August 9, 2012, demonstrated editing of the zebrafish genome (an organism comprised of eukaryotic cells) using the CRISPR-Cas9 system. Notably, U.C. relied on lab notes and emails that allegedly memorialized these experiments.
In dispute of U.C.’s position, the PTAB found evidence that the U.C. inventors encountered numerous experimental failures in trying to apply the CRISPR-Cas9 system in eukaryotic cells. Specifically, the PTAB stated that “the CVC [U.C.] inventors’ experimental failures reveal uncertainty undermining a definite and permanent idea of an sgRNA CRISPR-Cas9 system that edits or cleaves DNA.” These experimental failures, according to the PTAB, persisted at least to mid-October 2012. Thus, by October 5, 2012, the date Zhang submitted his manuscript to Science, the PTAB found that U.C. had not reduced to practice genetically modifying eukaryotic cells using the CRISPR-Cas9 system.
Accordingly, the PTAB granted priority to Broad the invention of modifying the genome of eukaryotic cells using the CRISPR-Cas9 system.
Impact of the PTAB’s Decision
The PTAB’s decision in Interference 106,115 is appealable by U.C. However, pending the outcome of any appeal, this decision results in Broad having ownership over applications of CRISPR-Cas9 technology in eukaryotic cells. This provides Broad with substantial control over the CRISPR-Cas9 patent landscape because it provides ownership to Broad of using the CRISPR-Cas9 system to edit the genomes of higher organisms.
Moreover, this decision means that a number of U.C.’s patents that are directed to using the CRISPR-Cas9 system in eukaryotic cells, could be rendered invalid. Many of these patents are the subject of licensing agreements between U.C. and third parties. In the event these patents are invalid, U.C. could potentially lose significant licensing revenue.
In addition, the PTAB’s decision in Interference 106,115 may impact other pending interference proceedings. Currently, the companies ToolGen and Sigma-Aldrich are involved in pending interference proceedings (Interference 106,126 and 106,133, respectively) in which the USPTO has judged that these companies have pending claims that interfere with the same Broad patents that were in suit in Interference 106,115. Thus, the outcome of these proceedings may further impact ownership of the CRISPR-Cas9 technology.
The PTAB’s decision in Interference 106,115 has significantly impacted the CRISPR-Cas9 patent landscape by awarding significant control of the CRISPR-Cas9 technology to Broad. The outcome of a potential appeal by U.C., and the outcome of the pending interference proceedings with ToolGen and Sigma-Aldrich, will have an impact on whether Broad retains this control.
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