By Kevin E. Noonan --
Senior Party The Broad Institute, Harvard University, and the Massachusetts Institute of Technology (collectively, "Broad") recently filed its reply to Junior Party The University of California/Berkeley, the University of Vienna, and Emmanuelle Charpentier (collectively, "CVC") opposition to its motion for priority in Interference No. 106,115.
CVC's opposition raised two grounds for the PTAB to base a decision that CVC should prevail in the priority phase of the interference. The first is that Broad inventor Zhang derived the invention claimed in the patents-in-interference from disclosure of CVC's conception from Dr. Marraffini. Dr. Marraffini was in possession of CVC's invention because he was a confidential reviewer of the manuscript later published in Science as Jinek et al. (2012, "A Programmable Dual-RNA-Guided DNA Endonuclease in Adaptive Bacterial Immunity," Science 337: 816–21). Dr. Marraffini also attended a CRISPR conference at Berkley on June 26, 2012 where the Doudna lab disclosed its CRISPR findings. Indeed, CVC's opposition brief contained a comparison between what was disclosed at the meeting, what Dr. Marraffini disclosed to Dr. Zhang, and what Dr. Zhang communicated to his colleague Dr. Cong, first author on the paper published in the January 2013 issue of Science and containing Broad's disclosure of CRISPR practiced in eukaryotic cells:
Second, CVC argued that once its seminal finding was made public, that CRISPR could be performed using sgRNA, no fewer than five labs ("Church (Harvard), Kim (ToolGen), Joung collaboration, and Chen (Sigma-Aldrich)"), including the Zhang lab, were able to perform eukaryotic CRISPR using routine, conventional laboratory methods, as evidenced by scientific papers from these labs published in Science in January 2013. Indeed, CVC's opposition brief argued that Dr. Zhang's alleged reduction to practice in June 2012, after receiving the information regarding sgRNA from Dr. Marraffini, is itself evidence of CVC's complete conception, because the information Dr. Marraffini communicated to Dr. Zhang came from Jennifer Doudna and Emmanuelle Charpentier.
Broad raises three flavors of argument against these allegations. The first is procedural: Broad argues that CVC's derivation arguments, arising for the first time in their opposition, are untimely and improper, because they needed to be raised in a substantive motion filed with Board permission under Bd. R. 121 and 37 C.F.R. § 41.208. According to Broad, CVC was aware of these circumstances prior to deposing Dr. Marraffini and had the knowledge and opportunity to request the Board's permission to file a substantive motion at the appropriate time earlier in this interference. Accepting these arguments now, according to Broad, is unduly prejudicial (it is unlikely any CVC argument would not be somewhat prejudicial to Broad) because it has deprived Broad the opportunity to submit its own opposition to these allegations complete with declaration testimony and the opportunity to depose CVC's declarants. (This argument loses some of its rhetorical punch in view of the Board's granting Broad the opportunity to cross-examine Dr. Marraffini during CVC's deposition; see "PTAB Grants CVC Motion for Marraffini Deposition," but is certainly true for the other declarants.)
Broad's second argument is entirely substantive: Broad provides its rebuttal to CVC's allegations of derivation, relying heavily on citations to the evidentiary record (which presumably will not pose as challenging a task to evaluate as it does the casual observer); specifically, as an example, the brief provides this table showing Broad's possession of every aspect of eukaryotic CRISPR except the sgRNA embodiments prior to Dr. Marraffini's disclosure:
The focus of much of these arguments is Broad's allegation that its lead inventor, Dr. Zhang, had successfully reduced eukaryotic embodiments of CRISPR using "dual RNA molecule" (i.e., the structural tracrRNA and the sequence-specific crRNA) versions in 2011 through early 2012, and that his immediate success in reducing to practice sgRNA embodiments (the subject of this interference) after Dr. Marraffini disclosed them was the consequence of those efforts, and not because CVC's inventors had complete conception of the invention falling within the scope of the interference Count:
CVC claims Zhang surreptitiously took the entire invention from CVC through Marraffini. But the truth is simpler and in no way nefarious: Zhang included a small, single adaptation that the CVC inventors chose to put into the public domain. He was so far ahead of CVC with the work that mattered—creating a functioning eukaryotic CRISPR-Cas9 system—that he was able to reduce the chimeric RNA system to practice multiple times as memorialized in his complete, groundbreaking manuscript, all while CVC struggled and failed despite their multiple, highly experienced eukaryotic co-collaborators.
In this regard, Broad's Reply continues its litany of reasons why it contends CVC's inventors failed to reduce eukaryotic CRISPR to practice to such an extent that the Board should conclude that their conception was incomplete until actually reducing such embodiments to practice at CVC's earliest priority date in this interference, January 23, 2013. (This date is far after Broad's earliest claimed priority date, June 26, 2012, and its several actual reduction to practice dates in the month or two thereafter.) Specifically, Broad argues (again) that mere disclosure of sgRNA embodiments of CRISPR-Cas9 is not enough for conception (discounting CVC's argument that once CVC showed activity of these constructs in vitro routine microinjection methods, which CVC showed were functional in zebrafish, were enough to provide complete conception). These arguments weave a careful mixture of alleging that conception required that an inventor have a reasonable expectation of success for conception to be complete and an argument that the Board's decision that the Jinek reference (containing the experimental results that support CVC's reduction to practice) was insufficient to render Broad's invention obvious as decided by the Board in its final decision in the earlier interference between the parties (Interference No. 105,048) supports its allegations here that CVC's conception was incomplete at its earliest claimed conception date. In this regard, Broad provides some inspiring rhetoric (e.g., "CVC is trying to wish away the forest of evidence by focusing on a single, irrelevant tree"). Also in this regard, Broad apparently has abandoned its earlier reliance on the principle of simultaneous conception and reduction to practice in its attack on CVC's conception ("simultaneous conception/reduction to practice is irrelevant on the facts"), seemingly being content to rely on evidence of CVC's purported failures of actual reduction to practice or statements supporting the uncertainty in achieving functional CRISPR in eukaryotic cells by CVC's inventors.
Broad's third argument alleges that CVC's fact witnesses (Drs. Barrangou and Sontheimer) supporting their derivation arguments should be disregarded due to bias, because they are all involved with Intellia Therapeutics, a company commercializing eukaryotic CRISPR embodiments with Jennifer Doudna, one of CVC's lead inventors, and Dr. Marraffini, as well as their testimony being "inconsistent with the facts."
In addition to these arguments, Broad addresses several less critical points raised in CVC's opposition, including whether the testimony of certain of their declarants should be disregarded because it is uncorroborated inventor testimony (as well as arguing that this testimony is unnecessary to establish Broad's actual reduction to practice). Also, Broad argues that CVC's allegations that some of Broad's arguments raised in opposition to CVC's conception are "lack[ing] candor" and "a sham" involve requirements asserted by the Board in its decision that there was no interference-in-fact in the '048 Interference (Broad taking the opportunity to accuse CVC of "fabricating a story inconsistent with the state of the art in 2012 and the prior decisions of the PTAB and Federal Circuit"). And Broad argues that CVC's opposition does not refute Dr. Zhang's conception or any evidence regarding their actual reductions to practice (this being the consequence, of course, of CVC's decision to assert its derivation argument, for which the relative ease of Broad's reduction to practice CVC argues is evidence of their own complete conception as conveyed by Dr. Marraffini to Dr. Zhang). Included in these arguments are a rebuttal of CVC's argument that Dr. Zhang did not understand the need or function of tracrRNA, based on specific citations to the Broad's evidence, and Broad's assertion that far from being routine and conventional, "CVC itself identifies no less than 12 adaptations that Zhang made to his CRISPR-Cas9 system to overcome the numerous eukaryotic challenges" in achieving CRISPR functional in eukaryotic cells.
Both parties have filed Motions to Exclude evidence that involve some of the testimony relied upon by the other party with regard to their priority positions, which will be the subject of future posts.
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