By Kevin E. Noonan —

On November 19th, Junior Party the University of California, Berkeley; the University of Vienna; and Emmanuelle Charpentier (collectively, "CVC") filed its Substantive Preliminary Motion No. 3 in Interference No. 106,132 (which names Sigma-Aldrich as Senior Party), asking the Patent Trial and Appeal Board to substitute the Count of the interference pursuant to 37 C.F.R. §§ 41.121(a)(1)(iii) and 41.208(a)(1).  On February 18th, Senior Party Sigma-Aldrich filed its Opposition, and on April 7th CVC filed its Reply.

The basis for CVC's motion was to change the Count to be limited to so-called "single (RNA) molecule guide RNA (sgRNA) species."  CVC argued that substituting this Count is more symmetrical with CVC's portion of the Count and "avoids inconsistency" with the Counts in related interferences (see "CRISPR Battle Joined Again"; "The CRISPR Chronicles: Enter ToolGen"; and "Sigma-Aldrich Joins the CRISPR Interference Fray").

Sigma-Aldrich responded in its Opposition that, contrary to any nebulous (and "self-serving") "inconsistency," what CVC is actually trying to accomplish is to prevent Sigma-Aldrich from asserting its "best proofs" in the interference.  Sigma-Aldrich contended it is the only party in any of the pending interferences — CVC, ToolGen, and Broad — having proofs of reducing to practice CRISPR in eukaryotic cells having both single-molecule RNA (sgRNA) and dual-molecule ("dgRNA") RNA species.  CVC's proposed motion on its face and according to its arguments in its Motion No. 3 would change the Count to exclude dual-molecule RNA-comprising eukaryotic CRISPR.  Sigma-Aldrich argues that any concerns CVC asserted regarding "inconsistency" and "the public interest" would be served by the Board granting its own Motion No. 1 (while characterizing CVC's concerns in this regard as being "á la Chicken Little's dire predictions, . . . highly remote and purely speculative at best").  Also raising questions about CVC's "ulterior motives," Sigma-Aldrich contended that CVC's proposed Count would "not []enable CVC to better make out CVC's priority case, but instead [would] hamstring Sigma from making out Sigma's priority case" which "is not a legitimate basis to seek to change the count."  And CVC had not carried its burden in making a showing that they are entitled to the relief sought, Sigma-Aldrich argued, because they have failed to assert the conventional basis for such a motion — that it would enable CVC to proffer its best proofs in the interference but rather is a "strategic maneuver to try to prejudice Sigma's ability to proffer its proofs of invention."  Sigma-Aldrich also argued that CVC's Motion No. 3 would be moot should the Board grant Sigma-Aldrich's own motion (No. 1) to change the Count.

In its Reply, CVC argues that the Count "should reflect the common invention defining multiple pending, related interferences — single-guide CRISPR-Cas9 systems useful in eukaryotic cells."  CVC identifies Sigma-Aldrich's portion of the McKelvey Count in this interference as an outlier amongst the CVC portion of the Count (and the Counts in interference with Broad and ToolGen) because it is "not aligned with CVC's half or any other parties' halves."  CVC cites the Board's decision to challenge Sigma-Aldrich's arguments that its disclosure of dgRNA CRISPR species mandates a generic-guide Count, based on the Board's decision in the '115 Interference, citing Regents of the University of California v. The Broad Institute, Int. No. 106,115 Paper 877 (Decision on Motions) at 39:22-40:8 (P.T.A.B. Sept. 10, 2020).  Following Board rules setting out the proper structure of Reply brief in an interference (§ 41.122 and S.O. ¶122.3.2), CVC sets out it responses and rebuttals of each of Sigma-Aldrich's arguments in its Opposition.  For example, to Sigma-Aldrich's argument that CVC's Motion No. 3 will be mooted if the Board grants Sigma-Aldrich's Motion No. 1 to change the Count, CVC argues that the subject of Sigma-Aldrich's Motion No. 1 is different (being directed to "whether or not the scope of the interference is limited to cleavage plus donor integration") than the question here regarding limiting the Count to sgRNA CRISPR embodiments.

CVC also argues that whether to change the scope of the Count in this interference to be consistent with the Counts in related interferences is within the Board's sound discretion, citing Hitzeman v. Rutter, 243 F.3d 1345, 1359 (Fed. Cir. 2001), generally for the principle and In re Vivint, Inc., 14 F.4th 1342, 1351 (Fed. Cir. 2021), specifically in support of this argument.  In this regard, CVC also refutes Sigma-Aldrich's claim that it is the only party in these interferences to assert dgRNA CRISPR species, reminding the Board that Broad asserted similar "best proof" arguments in motions in the '115 interference (which the Board denied; see "PTAB Denies Broad Motion No. 2 to Substitute the Interference Count").  And CVC argues that granting its Motion No. 3 is consistent with fairness and would "limit the inherent prejudice to CVC that results from arbitrarily giving Sigma special treatment" in an interference that "Sigma requested."  CVC also argues that Sigma-Aldrich has not established that its "best proofs" are outside the scope of the CVC's proposed substitute Count, and that "substituting the Count will streamline the issues in the Interference," inter alia, by not "impact[ing]the designation of claims, priority benefit, or patentability over the [prior] art."

For all these reasons CVC asks the Board to grant its Motion No 3.

By Kevin E. Noonan —

On November 19th, Junior Party the University of California, Berkeley; the University of Vienna; and Emmanuelle Charpentier (collectively, "CVC") filed its Substantive Preliminary Motion No. 1 in Interference No. 106,132 (which names Sigma-Aldrich as Senior Party), asking the Patent Trial and Appeal Board for benefit of priority to U.S. Provisional Application No. 61/652,086, filed May 25, 2012 ("P1"), U.S. Provisional Application No. 61/716,256, filed October 19, 2012, ("P2"), and U.S. Provisional Application No. 61/757,640, filed January 28, 2013 ("P3"), pursuant to 37 C.F.R. §§ 41.121(a)(1)(ii) and 41.208(a)(3) and Standing Order ¶ 208.4.1.  On February 18th, Sigma-Aldrich filed its Opposition, and on April 7th CVC filed its Reply.

The relationships between CVC's patents and applications in the '132 interference are set forth in this chart (filed in CVC's earlier preliminary motion in Interference No. 106,115):

CVC argued it was entitled to priority because it had "invented a eukaryotic cell comprising a single-molecule guide RNA ("sgRNA") CRISPR-Cas9 system capable of cleaving or editing target DNA, as defined by the count" (an argument that may have lost most of its persuasive force after the PTAB held that inventors from the Broad Institute and colleagues were entitled to priority for this invention; see "PTAB Grants Priority for Eukaryotic CRISPR to Broad in Interference No. 106,115").  CVC further argued that developments (not the one just cited) in the '115 Interference provided additional evidence to support its motion (CVC having made a similar argument in the '127 Interference having ToolGen as Senor Party; see "The CRISPR Chronicles: Enter ToolGen").

Most of CVC's arguments will be familiar to anyone following parallel motions in the '115 and '127 interferences.  These include CVC's contention that once its breakthrough of using sgRNA-containing CRISPR embodiments had been achieved, adapting CRISPR to the eukaryotic cell environment would have been "pretty straightforward" (quoting Dr. Luciano Marraffini, who purportedly informed the Broad inventors of the sgRNA embodiment in June, 2012; see "CVC Files Motion in Opposition to Broad Priority Motion").  CVC supported this assertion with contemporaneous consistent statements from Rodolphe Barrangou, Erik Sontheimer, Samuel Sternberg, and Dana Carroll, as well as Jennifer Doudna; by the existence of "existing platforms that had already been successfully used with the two incumbent systems: zinc-finger nucleases ("ZFNs") and transcription activator-like effector nucleases ("TALENs")"; and by the successful practice of CRISPR by several groups (including Sigma-Aldrich) "[j]ust months after CVC presented this work" and the absence in the reports from any of these groups of "any 'special' adaptations or conditions needed" to achieve CRISPR gene editing in eukaryotic cells.  CVC also argued that the Board's contrary conclusion in denying CVC's motion for priority benefit to the P1 and P2 provisional applications in the '115 Interference was made "without the benefit of the now well-developed evidentiary record," specifically, that "[t]he prior decision credited assertions that have been seriously undermined by evidence presented during the priority phase of the '115 interference."  That evidence was presented in CVC's Motion, which will not be recapitulated here; subsequently, of course, the Board held that none of this new evidence was sufficiently more persuasive for the Board to arrive at CVC's conclusion.

Sigma-Aldrich's Opposition countered CVC's assertions using the same approach successfully used by Broad in persuading the Board to find priority of invention in their favor in the '115 interference (see "PTAB Holds for Broad in CRISPR Interference: The Reasoning"):  that the two provisional applications (filed on May 25, 2012 and October 19, 2012) did not disclose an operative embodiment of CRISPR that could be successfully practiced in eukaryotic cells.  (Sigma-Aldrich does not challenge CVC's motion with regard to the P3 provisional application, no doubt because inter alia its status as Senior Party in this interference would not change should the Board do so.)  Harkening back to the Board's decision on a similar CVC motion in the '115 interference, Sigma-Aldrich argued that the Board was correct in its prior determination that those applications only disclosed in vitro CRISPR methods in a "cell-free" environment.  The cornerstone of Sigma-Aldrich's motion was that neither the P1 nor P2 provisional applications disclosed any "specific instructions or conditions" required for the practice of CRISPR in eukaryotic cells and that such instructions and/or conditions were necessary in view of the several obstacles required (tracking the same distinctions between CRISPR in eukaryotic cells and under other conditions recited by Broad in the '115 interference and Interference No. 105,048; see "PTAB Decides CRISPR Interference in Favor of Broad Institute — Their Reasoning").  According to Sigma-Aldrich, nothing has changed that would have the Board render a decision different from their refusal in the '115 interference to accord CVC benefit to P1 and P2 provisional application, and the Board should come to the same conclusion.  (Sigma-Aldrich contended that most if not all the evidence CVC asserts in its brief supporting its priority benefit motion in this interference had been asserted in the corresponding brief in the '115 motion.")

CVC's Reply (filed after the Board's ruling against it in the '115 Interference, which CVC contends is not controlling here), reiterates its position that its P1 and 2 priority documents "describe[] and enable[] a eukaryotic cell comprising a sgRNA CRISPR-Cas9 system that is capable of modifying target DNA" because "[t]he level of ordinary skill in the art was high, as numerous independent groups successfully and near simultaneously demonstrated the claimed system in eukaryotes" and "[a] POSA reading P1 would have immediately understood that P1 explains how to apply the system in a fish cell (E1), human cell (E2), and fruit-fly cell (E3) using the well-known molecular biology techniques P1 described."  Moreover, CVC contends that a constructive reduction to practice does not require a working example or that CVC "dispel the hypothetical concerns that CVC's opponents have alleged."  To hold CVC to this higher standard was wrong as a matter of law by the Board and for Sigma-Aldrich to oppose CVC's Motion No. 1 on this basis, a strong statement encapsulating the burden CVC will likely need to sustain not only to prevail in this motion (which is unlikely given the Board's other decisions against CVC in other interferences) but in trying to overcome the Board's priority determination in the '115 Interference.

CVC then recites the disclosure in the P1 and P2 provisional applications in detail that would have enabled the skilled worker to achieve CRISPR cleavage in eukaryotic cells (none of which will be new to the Board and none of which has been persuasive before), asserting that "no element of Count 1 is missing from P1's description."  The brief contains several citations such as "'acknowledgment of the complexities of the science does not negate the disclosure,' where the disclosure itself does not 'fail[] to teach any essential step,' but rather describes how to obtain the subject matter by 'following the general procedure disclosed,'" citing Frazer v. Schlegel, 498 F.3d 1283, 1288-89 (Fed. Cir. 2007), supporting the principle that CVC's constructive reduction to practice in these provisional applications satisfied the factual predicate for receiving priority benefit.  CVC relies on the "new" evidence in its brief, "from six different declarants," and boldly states that "[t]he Board may not simply recycle its '115 Decision on Motions here."  These include that "[i]n vitro studies have predictive value" and "[a] POSA reading P1 would immediately envisage E1, E2, and E3."  Further, CVC argues that a reasonable expectation of success from such disclosure is not required but "even if it were, the contemporaneous evidence overwhelmingly shows that those in the field expected sgRNA CRISPR-Cas9 to function in a eukaryotic environment."  CVC also addresses Sigma-Aldrich's recitation of the various hypothetical concerns," "challenges and uncertainties" that have so far proven to be persuasive to the Board in other interferences.

In further support for its position, CVC cites interference practice principles, for example that Sigma-Aldrich did not contest any of the Material Facts in CVC's Motion No. 1, citing Zhang v. Amsel, asserting for this reason alone the Board can grant its motion.  Interference 105,550, Paper 26 at *10 (BPAI March 24, 2008).

In CVC's boldest argument (which may presage the arguments CVC makes in its appeal of the Board's decision against it in the '115 Interference), the Reply argues that the Board's Decision on Motions in the prior interference is not controlling here and that it was wrong.  CVC supports the former argument by reciting "evidence that [purportedly] was either not addressed in the '115 Interference or new evidence uncovered during the priority phase."  For its latter argument, CVC limits its contentions here to a difference in the question at issue in this Motion and the Board's decision (priority based on conception and reduction to practice versus the adequacy of the written description of the P1 and P2 applications); the Board's reliance on documents not available to a POSA on P1's filing date; the Board's refusal to consider the "viewpoint" of a POSA; and that the Board's decision in the '115 interference is not final and will be appealed (CVC asserting optimistically that "the Federal Circuit can be expected to conclude the Decision reached an incorrect legal conclusion on conception."

CVC thus asserts that the Board should accord them benefit to the P1 or P2 application filing date.