By Kevin E. Noonan —

On May 20th, Junior Party the University of California, Berkeley; the University of Vienna; and Emmanuelle Charpentier (collectively, "CVC") filed their Substantive Preliminary Motion No. 2 in Interference No. 106,127 (which names ToolGen as Senior Party), asking the Patent Trial and Appeal Board to deny ToolGen benefit of priority to U.S. Provisional Application No. 16/717,324, filed October 23, 2012 ("P1"), pursuant to 37 C.F.R. §§ 41.121(a)(1)(ii) and 41.208(a)(3) and Standing Order ¶ 208.4.1.  The significance of the Board granting this motion would be that CVC would be Senior Party, with all the presumptions benefiting from Senior Party status.  On July 5th, ToolGen filed is Opposition to this Motion.  On August 27th, CVC filed its Reply.

In its Motion No. 2, CVC argued that the Board should deny ToolGen priority benefit to the '324 application because this application does not disclose an operative embodiment falling within the scope of the interference Count, based on party admissions.  Specifically, CVC argued that in the prosecution of the '324 patent application leading to allowance (and declaration of this interference), ToolGen had argued to the Patent Examiner (and PTAB) that "a codon-optimized Cas9 nucleic acid is required for CRISPR-Cas9 to function in eukaryotic cells" and that "a skilled artisan would have no idea what the outcome may be if one were to codon optimize a Cas9 nucleic acid."  This position was consistent with the prokaryotic source of Cas9, and the Board and Examiner relied upon these arguments to find allowable claims in the '324 application (now claims designated as corresponding to the Count in this interference) according to CVC.  All such claims require use of a Cas9-encoding nucleic acid that is codon-optimized for expression in eukaryotic cells, and CVC asserted that ToolGen added this limitation to the claims to overcome anticipation and obviousness rejections based on the prior art.

But, CVC argued, ToolGen's '324 application does not disclose a codon-optimized Cas9 nucleic acid, nor (by ToolGen's own argument according to CVC) would the skilled worker be able to discern such a nucleic acid with any reasonable basis for expecting such an embodiment could be produced using the disclosure in the '324 application.  Accordingly, CVC argued in its motion, ToolGen cannot in this interference renounce these arguments and rely on the priority date of the '324 patent to constitute a constructive reduction to practice for eukaryotic CRISPR-Cas9 embodiments falling within the scope of the interference Count.  Thus, according to CVC, the Board should deny ToolGen priority benefit to the '324 application (and redeclare the interference naming CVC as Senior Party).  The brief contained examples from the '324 prosecution history and at oral argument before the Board in support of its allegations.

ToolGen, characterizing CVC's arguments (as did CVC, citing Zedner v. United States, 547 U.S. 489 (2006), and Springs Window Fashions LP v. Novo Industries, L.P., 323 F.3d 989, 995 (Fed. Cir. 2003)) as sounding in judicial estoppel, argued this is a "misrepresentation of the prosecution history" and that the '324 application provides a constructive reduction to practice of eukaryotic CRISPR as defined under CVC's portion of the Count in this interference (and that CVC does not effectively challenge this disclosure) but not ToolGen's portion of the Count. ToolGen affirmatively argued that the '324 application "describes a successful experiment using a codon-optimized nucleic acid encoding Cas9 to yield a Cas9 protein complex that functions in eukaryotes to cleave DNA" in support of this assertion.  But more fundamentally, ToolGen argued, Count 1 in the interference does not require codon-optimized Cas9 as part of a eukaryotic CRISPR complex and thus CVC's argument (and Motion) should fail.  The Opposition then addressed the issues raised by CVC, most tellingly setting forth what it contended was a proper explication of the colloquies with the Board during ex parte prosecution that did not support CVC's estoppel arguments.

In it Reply, CVC reiterates its argument that P1 does not disclose a codon-optimized Cas9 species and that their allowed claims depend on arguments made in ex parte prosecution that eukaryotic CRISPR was dependent on such species and that codon-optimization was unpredictable.  Thus, CVC continues to contend, failure to describe a codon-optimized Cas9 protein is fatal to ToolGen's priority claim.  And, according to CVC, ToolGen did not rebut these arguments in its Opposition and thus the Board should grant CVC's motion and deny ToolGen priority benefit to its P1 provisional application.

The brief recaps the legal and evidentiary bases for its arguments, done in the explicatory pattern the interference rules require, selecting quotes from ToolGen's prosecution history that support its arguments and rhetorical flourishes seeming intended to impugn (regarding a ToolGen argument as "an attempt to sow confusion"; "attempts to sidestep the issue").  Of note is CVC's argument that purports to resolve (in its favor) the differing provenance of the "secret sauce" issue with regard to codon-optimized Cas9 ("it is undisputed that during this exchange ToolGen distinguished its claimed invention from the prior art based on codon optimization being required").  The core of CVC's argument, repeated in various incarnations throughout its Reply, is that:

Even if a POSA understood, as ToolGen argues, "reconstituting a nucleic acid sequence using a codon usage table to be codon optimization" or that codon optimization was a routine technique, P1 would at most teach that a Cas9 nucleic acid could be codon optimized.  . . .  But, in view of ToolGen's unpredictability assertions, a POSA would still be in the dark as to the identity of which codon-optimized nucleic acid sequence of the myriad different sequences would express a functional Cas9.  Thus, to be accorded benefit, P1 must describe the specific codon-optimized nucleic acid sequence(s) that would express a functional Cas9.  . . .  P1 fails to do that [citations to the record omitted].

Finally, even the existence of working examples of CRISPR in a eukaryotic cell is not enough, according to CVC, who state "ToolGen's second argument that its P1 describes a codon-optimized Cas9 because it includes working examples is wrong as a matter of law.  . . .  'Proof of a reduction to practice' does not salvage an application that does not otherwise 'describe or identify the invention,'" citing In re Alonso, 545 F.3d 1015, 1021 (Fed. Cir. 2008), according to CVC.

By Kevin E. Noonan —

On May 28th, Junior Party the Broad Institute, Harvard University and MIT (collectively, "Broad") filed its Preliminary Motion No. 2 in CRISPR Interference No. 106,126 (where ToolGen is the Senior Party), contingent on the Board's grant of Broad's Substantive Preliminary Motion No. 1 to substitute (in part) a new Count No. 2 in place of Count 1 in the '126 Interference as instituted (see "Broad Files Substantive Preliminary Motion No. 1 in CRISPR Interference").  In its Motion No. 2, Broad asked the Board to add their U.S. Application Nos. 15/160,710 (having allowable claims 1, 40, and 41) and 15/430,260 (allowable claims 74, 94, and 95) to the Interference and designate the allowable claims as corresponding to Proposed Count 2.  In the alternative (i.e., should the Board deny Broad's Substantive Preliminary Motion No. 1), Broad in its Motion No. 2 asked the Board to designate claim 1 of the '710 application and claim 95 of the '260 application as corresponding to current Count 1.  On August 6th, ToolGen filed its Opposition to Broad's Contingent Preliminary Motion No. 2, and on September 24th Broad filed its Reply.

In its Opposition, ToolGen asserted several bases for the Board to deny Broad's Motion No. 2.  ToolGen argued that had shown (in its Opposition to Broad Preliminary Motion No. 1) that Broad's motion to substitute the Count should be denied (in which case this motion would become moot).  ToolGen further contended that "Broad has neither demonstrated that the claims should be added, nor that alternative remedies are unavailable."  ToolGen also argued that Broad has not borne its burden under 37 C.F.R. § 41.208(b) and SO ¶ 203.2 showing why these claims should be added to this Interference and why alternative remedies are unavailing or inadequate.  With regard to such alternative remedies, ToolGen argued that Broad has not explained why any such remedies would be inadequate, despite the existence of such remedies (for example, asking the Board to declare another interference which could be combined with the current one between the parties).  ToollGen further argued that Broad's Motion No. 2 was unnecessary, because either Broad would prevail under Proposed Count 2 and the claims at issue in this motion would grant, or Broad will not prevail and Broad will be estopped from pursuing them under the principles of interference estoppel.  Finally, ToolGen argued that the motion was unauthorized and exceeded the scope of the Motions List submitted to the Board in this interference.

Broad's Reply begins by disputing ToolGen's contention that SO ¶ 203.2 requires them to show a "compelling reason" why these claims should be added to the Interference should the Board grant Broad's Preliminary Motion No. 1.  All that the Rule requires, according to Broad, is that the claims correspond to the Count, which they do (being directed to "generic" species of CRISPR comprising either dual- or single-molecule guide RNA.  Nevertheless, Broad argues they have provided compelling reasons (including remedying the "unjust structure" of the Interference) and these amount to reasons not "irrelevant" as ToolGen argued in its Opposition according to Broad.  The Reply sets out in detail how Broad's Motion No. 1 addresses the requirements of SO ¶ 203.2, including the basis for their contention that no alternative remedy would suffice to bring Broad "justice" in this interference.

Broad also argues that its Motion was authorized by the Board, including that certain of the claims corresponding to the Count are directed to single-molecule guide RNA (sgRNA) species and others are generic according to Broad's nomenclature, making its case that it was not attempting to mislead the Board (while at the same time making its case that ToolGen had tried to do so in its Opposition).  Broad provides a quotation from the hearing on motions to illustrate the consistency of "its position that the broader eukaryotic invention [encompassing generic guide RNA species] is the proper subject matter of this Interference":

. . . there are claims that Broad has that do not use the terminology 'guide RNA,' and also gets into our second motion, which we have been informed that we have other allowable claims that we—that we could potentially move to be brought in as part of the count being broaden[ed] to encompass those best proofs, because the subject matter on our side includes both the dual molecule and the single molecule . . . [emphasis in brief].

Moreover, Broad asserts that the Board was not unaware or confused about their arguments and the consistency or strategic aim of their motions request.

Finally, Broad dismisses ToolGen's argument that Broad had requested relief from the Board to designate these claims as corresponding to Count 1, saying that while they have not requested this relief they are "unaware of any authority preventing the PTAB at this stage of the Interference from adding allowable claims from applications not currently involved in the Interference if those claims correspond to Count 1; the claims limited to sgRNA configurations can be designated as corresponding to Count 1, if the PTAB believes such a designation is appropriate."

By Kevin E. Noonan —

On May 20th, Senior Party ToolGen filed its Substantive Motion No. 1 for benefit of priority to U.S. Provisional Application No. 61/837,481, filed June 20, 2013 ("P3" or "ToolGen 5 P3"), or alternatively, International Application No. PCT/KR2013/009488, filed October 23, 2013 ("PCT").  Junior Party the Broad Institute, Harvard University, and the Massachusetts Institute of Technology (collectively, "Broad") filed its Opposition to this motion, and on September 24th ToolGen filed its Reply.

As set forth in ToolGen's motion, the Board had granted ToolGen the benefit of its U.S. Provisional Application No. 61/717,324, filed October 23, 2012 ("P1"), resulting in ToolGen having an earlier priority date than Broad.  ToolGen submitted this motion to be accorded benefit of priority to two later-filed, related applications:  U.S. Provisional Application No. 61/837,481, filed June 20, 2013 ("P3" or "ToolGen 5 P3"), or alternatively, International Application No. PCT/KR2013/009488, filed October 23, 2013 ("PCT").  In its motion, ToolGen explains that it is submitting this motion contingent on the Board granting CVC's Substantive Motion No. 2, which attacks ToolGen's entitlement to priority to the P1 priority document in Interference No. 106,127.  The brief sets out graphically the relationship of these priority documents:

The brief then set out the basis for ToolGen's claim of priority, specifically its arguments for satisfaction of the written description and enablement requirements under 35 U.S.C. § 112(a) regarding two embodiments falling within the scope of the Interference Count.

In its Opposition, Broad asked the Board to defer consideration of ToolGen's Motion, properly pointing out that Broad (unlike CVC in the '127 Interference) has not challenged ToolGen's benefit of priority to its P1 provisional application.  Accordingly, Broad asserted that ToolGen's motion is premature and "completely irrelevant" at this time.  Broad further asserted that this motion may "potentially" become relevant "only if multiple contingencies in this and other proceedings—that may or may not ever come to pass—do actually arise."  These include that:

1) the PTAB finds ToolGen is not entitled to the benefit of its P1 application in the co-pending 127 Interference,

2) Broad requests and is granted permission to file a motion here challenging ToolGen's benefit to P1 based on estoppel from that determination in the 127 Interference, and

3) the PTAB grants Broad's motion, depriving ToolGen here of benefit of its P1.

Broad's justification included that the Board considering this motion under these circumstances would be "waste of judicial resources" as well as improperly constituting an advisory opinion.  The interference rules provide that the Board has discretion to defer consideration of motions under 37 C.F.R. § 41.125 as applied in Berman v. Housey, 291 F.3d 1345, 1352 (Fed. Cir. 2002).  Broad urged the Board to exercise that discretion regarding ToolGen's Preliminary Motion No. 1.  Broad's brief explicated in further detail the contingent nature of the circumstances needing to arise for ToolGen's motion to be timely, in support of its opposition and request for the Board to defer consideration thereof.

Broad argued that priority to either of ToolGen's U.S. Provisional Application No. 61/837,481, filed June 20, 2013 ("P3" or "ToolGen P3"), or alternatively, International Application No. PCT/KR2013/009488, filed October 23, 2013 ("PCT"), would never be relevant because "ToolGen will be unable to beat Broad's dates of [conception and reduction to practice]" if Broad is granted priority in the '115 Interference.  This argument also sounds in representations made by ToolGen during prosecution regarding what was needed to provide a skilled worker with a reasonable expectation of success:

Rather, the only thing that would have alleviated the unpredictability in the art and allayed the concerns of one of ordinary skill at this time would have been the actual demonstration of a Type II Cas9 system successfully introducing site-specific double-stranded breaks in a target nucleic acid sequence within a eukaryotic, e.g., mammalian, cell . . . [emphasis in brief].

Here, Broad resurrects an argument made in Interference No. 106,115, that eukaryotic CRISPR is an invention for which conception can only be shown by successful reduction to practice (under a theory of "simultaneous conception and reduction to practice" first enunciated thirty years ago regarding conception of a nucleic acid encoding a particular protein; see Amgen v. Chugai, Fed. Cir. 1990).

In its Reply, ToolGen boldly asks the Board to dismiss rather than defer its Preliminary Motion No. 1 should the Board deny CVC's Preliminary Motion No. 1 in co-pending Interference No. 106,126 to deny ToolGen priority benefit to its U.S. Provisional Application No. 61/717,324, filed October 23, 2012 ("P1").  In addition, ToolGen raises the procedural requirement that decisions on Motions must be decided prior to initiation of the Priority Phase.  And finally, ToolGen argues that should the contingency arise and the Board grant CVC's motion and deny ToolGen priority benefit to its P1 provisional application the Board should grant its Preliminary Motion No. 1 because Broad's opposition was procedural in nature and not on the merits.

Regarding the many contingencies Broad identifies in its Opposition, ToolGen argues that Broad has not brought a motion or advanced an argument to deny ToolGen the benefit of priority to its P1 application.  And at this point Broad should not be permitted to benefit from the Board deferring the priority benefit issue until after the priority phase has begun because that would be procedurally improper according to ToolGen, relying on 37 C.F.R. § 41.121(a)(1), the Standing Order at 6:22-24 and Hum. Genome Scis., Inc. v. Genentech, Inc., 589 F. Supp. 2d 512, 514 (D. Del. 2008), dismissed 368 F. App'x 116 (Fed. Cir. 2009).  And to the extent any contingency resulting in ToolGen's loss of priority benefit to the P1 application should arise, ToolGen argues, its Preliminary Motion No. 1 was not addressed on the merits in Broad's Opposition and thus its Motion No. 1 is unopposed.