By Kevin E. Noonan —

Senior Party Toolgen and Junior Parties The Broad Institute, Massachusetts Institute of Technology, and Harvard University (collectively, "Broad") in Interference No. 106,126 and University of California/Berkeley, the University of Vienna, and Emmanuelle Charpentier (collectively, "CVC") in Interference No. 106,127, each filed Lists of Proposed Motions that the Board considered last week and responsive thereto will issue its rulings shortly (see "The CRISPR Chronicles: Enter Toolgen").  The Toolgen lists have sufficient similarities that they will be the subject of this post, with the individual Junior Parties' lists being the subject of later posts.

As a reminder, an interference proceeds in two stages.  The first stage involves the parties presenting motions that can modify the count, have certain claims declared outside the scope of the count (or vice versa), seek to establish an earlier priority date, and ask for a finding that their opponents' claims are invalid under any of the provisions of the patent statute.  If these motions are not decided in a way that would disqualify one or both parties, then the interference will move to a second stage, where in each Interference the Junior Party (Broad, in the '126 Interference and CVC in the '127 Interference) will present its proofs of conception and reduction to practice and the Senior Party Toolgen will be permitted to oppose and/or present its own priority evidence.  The Senior Party is under no obligation to present proofs earlier than its earliest filing date unless the Junior Party evinces evidence of (at least) earlier conception.  In practice, the parties can both be expected to submit their priority evidence.

As might be expected, there are several similarities in Toolgen's lists for each Interference.  Toolgen's Motion No. 1 is the same on each list.  It requests the Board's permission to file an expedited miscellaneous motion under 37 C.F.R. §1.645(d)* asking the Board to stay the '126 Interference (as well as the '127 Interference) until the Federal Circuit rules on any appeal of the Board's Final Judgment in Interference No. 106,115 now pending between Broad as Senior Party and CVC as Junior Party.  In the alternative, Toolgen asks for the stay to extend until after Final Board Decision if there is no appeal.  The basis is that such a stay will "promote efficient and fair resolution of the pending interferences," upon which grounds it is within the Board's discretion to grant.  In addition, the Board's decision in the '115 Interference may result in "cancellation of all of Broad's or CVC's claims, or a combination," which would "narrow the issues for this and the '127 Interference."  This argument is based on the Board having declared this interference (and the '127 Interference) having as a Count the same Claim 18 of Broad's U.S. Patent No. 8,697,359 as in the '115 Interference Count, and having each claim involved in this (and the'127) interference also being involved in the '115 Interference.  Toolgen also notes that "in both interferences, parties are challenging Broad's involved claims under Section 102(f) for improper inventorship, for which briefing already is underway in the 115 Interference" and "the briefing, discovery and priority proofs in the 115 Interference will clarify the priority dispute in this proceeding."  That earlier Interference should be concluded well in advance of this one, providing further basis for granting the motion.  Toolgen asks the Board to set a briefing schedule for a total of five weeks, and to set Time Period No. 1 (when all other motions briefs are due) for no less than six weeks after this motion is decided.

Toolgen's Motion No. 2 under 37 C.F.R. §§ 41.121(a)(1)(ii) and 41.208(a)(3) is also the same on each list, and Toolgen seeks to be granted the priority benefit of U.S. Provisional Application Publication No. 61/837,481, filed June 20, 2013; and PCT Application KR2013/009488, filed October 23, 2013.  These are "interior" priorities arising after the earliest filed provisional application and before the pending application upon which this Interference (and the '127 Interference) was declared.

Toolgen's Motion No. 3 under 37 C.F.R. §§ 41.121(a)(1)(ii) and 41.208(a)(3) is a motion to attack accorded benefit.  In the '126 Interference against Junior Party Broad, the motion is directed to benefit of Provisional Application No. 61/736,527, filed on December 12, 2012.  In the '127 Interference against Junior Party CVC, the motion is directed to Provisional Application No. 61/757,640, filed on January 28, 2013.

Toolgen's Motion No. 4 under 37 C.F.R. § 41.121(a)(1)(iii) is for judgment that the involved patents or applications of each Junior Party are unpatentable for failure to satisfy the written description and enablement requirements of 35 U.S.C. § 112(a).  The basis in each case is that the patents and applications "do not enable one of ordinary skill in the art to practice the use of CRISPR-Cas technology in all types of eukaryotic cells without undue experimentation."

Toolgen's Motion No. 5 in the '127 Interference and Motion No. 7 in the '126 Interference under 37 C.F.R. § 41.121(a)(1)(iii) is for judgment that the involved patents or applications are unpatentable under 35 U.S.C. § 102 or § 103.  In the '126 Interference, the grounds for this motion are that CVC's involved claims in all the patents or application in interference are anticipated or obvious over U.S. Application Publication No. 2016/0298138 assigned to Sigma-Aldrich Co. LLC, and/or U.S. Application Publication No. 2015/0322457 assigned to ToolGen, as well as additional references set forth in an Appendix to this paper.  In Motion No. 5 in the '126 Interference, Toolgen contends that Broad's involved claims in all the patents or applications in interference are anticipated or obvious over Cong et al., "Multiplex Genome Engineering Using CRISPR/Cas Systems," Science 339: 819-23 (February 2013; published online January 2013), and/or Mali et al., "RNA-Guided Human Genome Engineering Via Cas9," Science 339: 823-26 (February 2013; published online January 2013), as well as additional references set forth in an Appendix.  In both motions, Toolgen asks the Board to relax the 25-page limit to permit them to explain how each of the involved claims recited in the motion are unpatentable.

The lists then vary considerably between the Interferences.  In the '126 Interference, Motion No. 5 under 37 C.F.R. § 41.121(a)(1)(iii) is for judgment that Broad's patent and applications in interference are unpatentable for improper inventorship under 35 U.S.C. § 102(f) (pre-AIA) or 35 U.S.C. § 115(a) (post-AIA).  The basis for this motion is the record of proceedings involving Broad's European Patent No. EP 2771468, which include a declaration from Broad's attorney Thomas Kowalski, who testified as to inventorship in that application.  According to Toolgen, "[a] number of the alleged inventive contributions detailed in the Kowalski Declaration are applicable not only to the PCT Applications**, but also to the Broad claims involved in this interference."  Accordingly, Toolgen requests leave to file a motion of unpatentability due to these alleged deficiencies.

Toolgen's Motion No. 6 in the '126 Interference under 37 C.F.R. 41.150(c) is for additional discovery, specifically with regard to Dr. Luciano Marraffini.  The Board has granted a similar motion to CVC in the '115 Interference (see "PTAB Grants CVC Motion for Marraffini Deposition").  "Because Dr. Marraffini's testimony is equally as pertinent to the present interference as it is to the 115 Interference," Toolgen argues, "additional discovery concerning Dr. Marraffini is warranted here, as well."  Toolgen asks as part of this motion for "copies of documents from Dr. Marraffini produced in the 115 Interference and to participate in, including by examination or cross-examination, any deposition examination or cross-examination of Dr. Marraffini in the 115 Interference," as well as leave to serve its own subpoenas for documents or further deposition.

Toolgen's Motion No. 8 in the '126 Interference is for judgment under 37 C.F.R. § 41.121(a)(1) that all Broad's patents and applications are unenforceable for inequitable conduct.  The basis for this motion asserted by Toolgen is purported irregularities in how certain applications were designated first as having post-AIA and then pre-AIA status, as well as statements that "Zhang's lab had reduced to practice a working CRISPR-Cas9 cleavage system in a eukaryotic cell prior to May 2012," which Toolgen asserts was untrue.

Toolgen's Motion No. 9 in the '126 Interference and Motion No. 6 in the '127 Interference are for a protective order under 37 C.F.R. § 42.54 to allow Toolgen to file its priority statement under seal.  The basis for this motion is to protect "sensitive and confidential information" from disclosure to "third-party competitors, such as Sigma-Aldrich."  (It should be remembered that CVC asked for a similar protective order in the '115 Interference, which the Board denied; see "Board Denies CVC Motion to Seal Priority Statement".)

Toolgen's Motion No. 10 in the '126 Interference and Motion No. 7 in the '127 Interference is a miscellaneous motion under 37 C.F.R. § 41.104(a) for the Board to order the '126 and '127 Interferences to proceed on the same schedule.

Finally, Toolgen's Motion No. 11 in the '126 Interference and Motion No. 8 in the '127 Interference are each motions under 37 C.F.R. § 41.208(a)(4) for judgment based on priority of invention.

The Board having set February 4th as the date for a teleconference with each set of  parties jointly, the Board's Order notifying the parties as to which motions they are authorized to file and which have been deferred or denied is expected within the week.  During the call, the parties were able to inform the Board more specifically of the bases for their motions, provide a proffer if the Board needs additional evidence or information, and provide opposing parties the opportunity to give the Board their views.  With the Order on which motions are permitted, the Board will also set a briefing schedule.  All these events will be the subject of future posts.

* The Interference Rules were revised several years ago and collected with all post-grant proceedings in Chapter 41 of the C.F.R.  Nevertheless, the current rules have provisions for such stays which it can be expected the Board will consider when it decides whether to grant leave for Toolgen to file a brief in support of this motion.

** These include PCT/US2013/074611; PCT/US2013/074667; PCT/US2013/074691; PCT/US2013/074736; PCT/US2013/074743; PCT/US2013/074790; PCT/US2013/074800; PCT/US2013/074812; PCT/US2013/074819; and PCT/US2013/074825.

By Kevin E. Noonan —

Senior Party Toolgen and Junior Parties The Broad Institute, Massachusetts Institute of Technology, and Harvard University (collectively, "Broad") in Interference No. 106,126 and University of California/Berkeley, the University of Vienna, and Emmanuelle Charpentier (collectively, "CVC") in Interference No. 106,127 each filed Lists of Proposed Motions that the Board considered today and responsive thereto will issue its rulings shortly (see "The CRISPR Chronicles: Enter Toolgen").  The CVC list will be the subject of this post.

CVC's list contains six proposed motions and in some respects mirrors the motions filed in on-going Interference No. 106,115 against Broad (see "CRISPR Interference Parties Propose Motions").  CVC Motion No. 1 under 37 C.F.R. §§ 41.121(a)(1)(ii) and 41.208(a)(3) seeks to be awarded priority to their first-filed priority applications (specifically, in the alternative either the P1 or P2 applications), as set forth in this diagram:

As shown in the diagram, all of CVC's applications having allowable claims that have formed the jurisdictional basis for this interference depend on the four provisional applications designated P1 through P4, and have an earliest priority date of May 25, 2012.  Given their status as the discoverers of CRISPR (for which Jennifer Doudna and Emmanuelle Charpentier received the 2020 Nobel Prize in Chemistry), it is unsurprising that CVC has the earliest priority date.  Whether this is enough to constitute a constructive reduction to practice is the issue in the 106,048 Interference; CVC is careful to argue that "no estoppel or prior decision of the PTAB weighs against authorizing this motion" and "[t]he PTAB's Decision on Motions in Interference No. 106,115 is not final, as it is still subject to review by the Federal Circuit," citing Vardon Golf Co. v. Karsten Manufacturing Corp., 294 F.3d 1330 (Fed. Cir. 2002).  In addition, CVC notes that the Count in this interference is not the same as the Count in the '048 Interference.  CVC also requests that the Board increase the page limits for its brief to 55 pages, and exclude claim charts from that limit, "[d]ue to the complexity of the issues and extensive evidentiary record implicated by this Motion."

CVC Motion No. 2 seeks to have the Board deny the benefit of Toolgen's priority application, U.S. Provisional Application No. 61/717,324, filed October 12, 2012.  This proposed motion is devoid of any further asserted bases for the Board to grant leave to file this motion, stating merely that "CVC should be given the opportunity to develop its arguments in full."

CVC Motion No. 3 under 37 C.F.R. § 41.121(a)(3) and Standing Order, ¶ 203.2, seeks to have the Board add Toolgen's U.S. Patent No. 10,851,380 to this interference.  The grounds for this motion is that the '380 patent contains at least one claim within the scope of the Count, specifically that recites "methods of introducing a site-specific, double-stranded break at a target nucleic acid sequence in a eukaryotic cell, the method comprising introducing a chimeric guide RNA (i.e., a single guide RNA) and Cas9 into the eukaryotic cell."  In the alternative, CVC asks the Board to add the '380 patent to this interference sua sponte.

CVC's Motion No. 4 under 37 C.F.R. § 41.121(a)(1) is for judgment that Toolgen's involved claims corresponding to the Count are unpatentable.  CVC contends that Toolgen's involved claims are invalid under 35 U.S.C. § 102 over CVC's U.S. Patent Application Publication No. 2014/0068797, which claims the benefit of priority to the P1 provisional application illustrated above.  Specifically, CVC notes that "ToolGen added a codon-optimization limitation to overcome an anticipation rejection over the '797 publication" and CVC's P1 and P2 priority applications disclose codon optimization.  Presciently addressing the expected response to this argument, that as Broad has contended in the '048 and '115 Interferences that CVC's P1 and P2 provisional applications do not disclose eukaryotic CRISPR embodiments, CVC's brief notes that "[an] anticipatory reference need not demonstrate utility," citing Rasmusson v. SmithKline Beecham Corp., 413 F.3d 1318, 1326 (Fed. Cir. 2005).  And CVC argues that "[b]ecause the requirements for an anticipatory reference differ from the written description requirement to support a constructive reduction of practice of a count, the Board's Decision on Motions in the '115 interference between CVC and the Broad Institute does not control here."  Finally, CVC argues that the Board authorizing its Motion No. 4 would be consistent with 37 C.F.R. § 41.1(b) "to secure the just, speedy, and inexpensive resolution of every proceeding before the Board" and inter alia that "ToolGen aggressively sought this interference via petition and ex parte prosecution, which included inaccurate characterizations of what CVC's P1 and P2 disclose, including incorrect statements regarding the necessity of codon optimization and NLSs for functionality in eukaryotes."  As with Motion No. 3, CVC asks the Board to increase the page limit to 40 pages and to exclude claim charts from this number.

CVC's Motion No. 5 (contingent) is for judgment that Toolgen's claims are unpatentable under 35 U.S.C. §§ 102 or 103 over Sigma's U.S. Application Publication No. 2016/0298138, which claims priority to its first provisional application filed October 23, 2012, should the Board grant CVC's Motion No. 2 that Toolgen's application in interference is not to be entitled to priority its U.S. Provisional Application No. 61/717,324, filed October 12, 2012.

Finally, CVC's Motion No. 6 under 37 C.F.R. § 41.208(a)(4) seeks judgment based on priority.

The Board having set February 4th as the date for a teleconference with each set of parties jointly, the Board's Order notifying the parties as to which motions they are authorized to file and which have been deferred or denied is expected within the week.  During the call, the parties were able to inform the Board more specifically of the bases for their motions, provide a proffer if the Board needs additional evidence or information, and provide opposing parties the opportunity to give the Board their views.  With the Order on which motions are permitted the Board will also set a briefing schedule.  All these events will be the subject of future posts.

* As a reminder, an interference proceeds in two stages.  The first stage involves the parties presenting motions that can modify the count, have certain claims declared outside the scope of the count (or vice versa), seek to establish an earlier priority date, and ask for a finding that their opponents' claims are invalid under any of the provisions of the patent statute.  If these motions are not decided in a way that would disqualify one or both parties, then the interference will move to a second stage, where in each Interference the Junior Party (CVC, in the '126 Interference and CVC in the '127 Interference) will present its proofs of conception and reduction to practice and the Senior Party Toolgen will be permitted to oppose and/or present its own priority evidence.  The Senior Party is under no obligation to present proofs earlier than its earliest filing date unless the Junior Party evinces evidence of (at least) earlier conception.  In practice, the parties can both be expected to submit their priority evidence.

By Kevin E. Noonan —

The U.S. Patent and Trademark Office Patent Trial and Appeal Board has declared interferences individually between Toolgen as Senior Party and as Junior Party the parties in the pending interference, Broad Institute, Harvard University, and the Massachusetts Institute of Technology (collectively, "Broad") and The University of California/Berkeley, the University of Vienna, and Emmanuelle Charpentier (collectively, "CVC") (see "Separate Interferences Declared between Toolgen and Broad and CVC over CRISPR Priority Question)".  This raises questions about the strength and priority position of Toolgen's claims, which suggests a review of the prosecution might reap benefits in relevant comprehension.

Toolgen filed its earliest priority applications as U.S. Provisional Application Nos. 61/717,324, filed October 23, 2012; 61/803,599, filed March 20, 2013; 61/837,481, filed June 20, 2013; and International Application No. PCT/KR2013/009488, filed in the Korean Patent Office on October 23, 2013.  Thus, its earliest priority date, October 23, 2012, is two months prior to Broad's earliest priority date of December 12, 2012 for U.S. Provisional Application No. 61/736,527 (see "PTAB Decides Parties' Motions in CRISPR Interference").  Upon entering U.S. national phase as a continuation, U.S. Application No. 14/685,510, on April 13, 2015, Applicant Toolgen filed a preliminary amendment, having claims directed to provoking an interference with Broad and its colleagues and CVC.

Seven months later, on November 17, 2015, the USPTO issued an Office Action from Primary Examiner Catherine S. Hibbert, rejecting the claims under 35 U.S.C. §§ 101, 103, and 112.  The §§ 101 and 112 rejections were quickly dispatched by amendment, but rejections under § 103 persisted until the Patent Trial and Appeal Board reversed the Examiner in a decision handed down June 22, 2020.  The basis for the obviousness rejection was, as a primary reference, the first Doudna et al. U.S. Application Publication No. US2014/0068797, claiming priority to provisional applications filed in May and September 2012, combined with references teaching nuclear localization signal modifications to target the Cas9 protein to the eukaryotic nucleus, and a reference for codon optimization for enhanced expression in human cells) or the Jinek 2012 Science paper (Jinek et al., 2012, "A Programmable Dual-RNA–Guided DNA Endonuclease in Adaptive Bacterial Immunity," Science 337: 816-21) combined with these secondary references.  Toolgen responded by asserting that the skilled artisan would not have had a reasonable expectation to expect that CRISPR exemplified in bacterial cells would be operable in eukaryotic cells (a very similar argument to the one The Broad and colleagues used to prevail in the first Broad/CVC interference (see "PTAB Decides CRISPR Interference in Favor of Broad Institute — Their Reasoning" and "Regents of the University of California v. Broad Institute, Inc. (Fed. Cir. 2018): Federal Circuit Affirms PTAB in Appeal of CRISPR Interference").

This argument did not persuade the Examiner, who maintained the rejection substantially unfazed through a Final Rejection, a Non-Final Rejection after Toolgen filed a Request for Continued Examination, followed by another Final Rejection, this last in the face of expert testimony from Dr. Bryan R. Cullen, and through several Examiner interviews.  These later rejections were maintained even after the PTAB's decision in the earlier Broad/CVC interference, on the rationale that "the fact pattern for each of the application records for the Broad/UC Interference were different than the fact pattern for the instant application and the Board's decision in the Broad/US Interference was not precedential" (perhaps and certainly true, respectively, but frustratingly missing the point).  Further, the same rationale was proffered by the Office when Toolgen argued that "the fact that different patent applications include difference fact patterns and evidence does not give the Patent Office latitude to characterize the same prior art disclosure completely differently across different patent applications," Toolgen arguing that doing so is "arbitrary and capricious."  The Office took a similar stance in rejecting Toolgen's arguments for unexpected results by citing the Doudna and Jinek prior art as teaching that CRISPR cleavage was not unexpected because those references taught such cleavage.  Of course, this rationale ignored the argument Toolgen was making that the achievement of CRISPR cleavage in a eukaryotic cell was surprising and unexpected for all the reasons previously persuasive to the Board and Federal Circuit in the first Broad/CVC interference.

Finally, Toolgen appealed (successfully) but in the interim the PTAB declared Interference No. 106,115 (see "New CRISPR Interference: The Details"), and like Sigma-Aldrich had done previously (see "Sigma-Aldrich Wants Its Piece of CRISPR Pie"), petitioned the Director under 37 C.F.R. §§ 1.181 and 1.1.83 and the Chief Administrative Patent Judge under 37 C.F.R. §§ 41.3 and 41.103 on September 29, 2019 to declare an interference.  (This petition was dismissed on procedural grounds on April 6, 2020.)

Shortly thereafter the PTAB reversed the § 103 rejection.  In its opinion, the Board wrote:

Although the Examiner extensively discussed the disclosures of the Doudna '086 provisional and the Doudna '256 provisional and explained why she determined they disclosed the claimed subject matter, the Examiner did not establish that Doudna, which incorporates these provisionals by reference . . . is prior art.  The Examiner never compared any claim of Doudna to the disclosures of the Doudna '086 provisional or the Doudna '256 provisional.  . . .  It was the Examiner's initial burden to do so but, even were it not, it became the Examiner's obligation to do so once Appellant argued that Doudna was not prior art . . . .

The Board also noted that it was persuaded by Toolgen's argument that the cited art did not support a skilled worker having had a reasonable expectation of success in practicing CRISPR in a eukaryotic cell, at least in part due to Dr. Cullen's expert testimony as well as evidence of record of Dr. Doudna's contemporary statements regarding her uncertainty about the unpredictability of eukaryotic cell embodiments of CRISPR (some of the same evidence The Broad successfully asserted in the first Broad/CVC Interference).  The Board summarized its decision as follows:

To conclude, on the present record, the Examiner has not demonstrated that all references in the cited combination qualify as prior art.  However, even had the Examiner done so, we determine that the Examiner has not established a prima facie case of obviousness.  Although the Examiner accounted for each claim element in the cited prior art combination, "[o]bviousness requires more than a mere showing that the prior art includes separate references covering each separate limitation in a claim under examination."  UnigeneLabs.,Inc. v. Apotex, Inc., 655 F.3d 1352, 1360 (Fed. Cir. 2011).  Proof of obviousness requires a showing of at least a reasonable expectation of success from the perspective of a person of ordinary skill in the art.  In re Vaeck, 947 F.2d488, 493 (Fed. Cir. 1991) . . . .  Here the balance of evidence of record supports that the relevant field was highly unpredictable, which diminishes any reasonable expectation of success in achieving the claimed invention.  Considering the evidence of record, on balance it supports Appellant's positions. We therefore reverse the Examiner's rejection over Doudna, Gustafsson, and Chen.

And the Board came to a similar conclusion regarding the obviousness rejection asserted using Jinek as the primary reference.

This prosecution history presages Toolgen's likely arguments in each of the current interferences.  Like Broad, Toolgen will likely argue that CVC's earlier priority dates were inoperable in eukaryotic cells and thus its October 2012 date (and any earlier dates of conception followed by actual reduction to practice) should entitle it to priority.  The path forward against Broad is less clear, however, particularly in view of the evidence presented in Broad's priority motion (see "Broad Files Priority Motion in CRISPR Interference*"), including this timeline:

Toolgen has no priority application filed earlier than Broad's asserted July 20, 2012 date of actual reduction to practice, and should the Board (and Federal Circuit) be persuaded by Broad's "simultaneous conception and reduction to practice" standard for awarding priority, Toolgen may be no more successful than CVC in having priority awarded to its patent application (depending, of course, on its first successful demonstration of practicing CRISPR in eukaryotic cells).

But that remains in the future.  Both sets of interference parties have proposed Preliminary Motions, which the Board will consider tomorrow.  These motions, and the Board's decision on which motions it will entertain, will be the subject of future posts.