By Kevin E. Noonan —

Junior Party University of California/Berkeley, the University of Vienna, and Emmanuelle Charpentier (hereinafter, "CVC") and Senior Party The Broad Institute, Massachusetts Institute of Technology, and Harvard University (hereinafter, "Broad") each filed Motions to Exclude Evidence and Requests for Oral Hearing in Interference No. 106,115.

CVC's motion to exclude is directed to "declarations of Benjamin Davies (Ex. 3435), Mark Kay (Ex. 3436), Alan Lambowith (Ex. 3437); Paul Simons (Exs. 3438 and 3440); Erez Lieberman Aidan (Ex. 3439), Greg Hannon (Ex. 3441 and 3442), Mark Isalan (Ex. 3443), Caixao Gao (Ex. 3446); Adam Bogdanove (Ex. 3449), Thierry VandenDriessche (Ex. 3450), Bryan Cullen (Ex. 3451), Paula Cannon (Ex. 3452), portions of the Third Declaration of Ronald Breaker (Ex. 3448)," and certain documentary exhibits.  The legal basis for the motion is that these exhibits and testimony "seeks to exclude violates the Federal Rules of Evidence, the Standing Order (Paper 2), and the Supreme Court's decision in Daubert v. Merrell Dow Pharmaceuticals, 509 U.S. 579, 593-94 (1993)."

With regard to CVC's arguments based on the Rules of Evidence, CVC objects to Broad being permitted to rely on testimony proffered in support of its motion that has not been offered for witness cross-examination by CVC.  This is prejudicial to CVC, the motion explains, because "it had no opportunity to confront and challenge these witnesses on their statements, including their purported recollections, proffered opinions, and potential biases."  This testimony is particularly relevant because Broad has relied on it to show whether a person of ordinary skill in the art would have expected CRISPR-Cas9 to work in eukaryotic cells in early 2012; this testimony thus involves "disputed facts at the heart of [Broad's] opposition" to CVC's priority position.  In addition, because "[m]any of these witness statements were submitted in foreign patent office proceedings" they were not sworn to under oath and also constitute hearsay and thus should not be entered into evidence.

In addition to CVC's objections based on the Federal Rules of Evidence, the motion asserts that this evidence is contrary to Standing Order (SO) ¶ 157.3, which provides that testimony not subject to cross-examination can be excluded.  Permitting Broad to rely on such unchallenged testimony is also contrary to relevant precedent, including Rose v. Frazer, Inf. No. 104,733 Paper 73 at 4 (B.P.A.I. Mar. 29, 2002); Praxair Distrib., Inc. v. INO Therapeutics LLC, IPR2015-00529, Paper 33 at 2 (PTAB Dec. 22, 2015); and Mexichem Amanco Holdings S.A. de C.V. v. Honeywell Int'l, Inc., Case IPR2013-00576, Paper 36 at 3 (PTAB Sept. 5, 2014), as well as 37 C.F.R. § 42.51(c).  This precedent stands against Broad's arguments that cross-examination is unnecessary because the statements contained therein are part of the "public record" according to CVC.

CVC points out for particular objection portions of Dr. Breaker's declaration as hearsay for relying on declarations of others he stated show that others in the field shared his opinions with regarding to eukaryotic CRISPR embodiments; to do so would contravene Federal Circuit precedent according to CVC, citing Wi-Lan Inc., v. Sharp Electronics Corp., 992 F.3d 1366 (Fed. Cir. 2021).  In addition to striking the specified portions of Dr. Breaker's testimony, CVC asks the Board to give no weight to citations of Dr. Breaker's opinion in Broad's priority motions, oppositions, and replies.  And because Dr. Breaker's reliance on unchallenged opinions of others is accordingly unreliable, those portions violate Daubert as well, according to CVC's brief.  To an anticipated response by Broad that an expert is entitled to rely on hearsay in forming their opinions, CVC argues that while true an expert cannot be used as a "conduit" for bringing hearsay to the factfinder for the truth of the matter asserted, citing the Federal Circuit's reliance on Marvel Characters, Inc. v. Kirby, 726 F.3d 119 (2d Cir. 2013), in its Wi-Lan Inc., v. Sharp Electronics Corp. decision.

With regard to certain exhibits, CVC objects as hearsay to recent books about CVC inventors including Walter Isaacson (The Code Breaker: Jennifer Doudna, Gene Editing, and the Future of the Human Race) and Kenneth (sic) Davies (Editing Humanity: The CRISPR Revolution and the New Era of Genome Editing) that CVC contends the Broad proffered as "purported evidence of the timing, difficulty, challenges, and the role different people played in the events leading up to the CVC inventors' fame and accolades."  Rather than providing admissible evidence, CVC contends that these books are the authors' words and interpretations of information they gathered and that the authors are without personal knowledge of the events they describe.  Nor have these authors submitted declarations under oath nor been made available for deposition.  And as "hearsay within hearsay" (as being the authors' hearsay statements regarding what others have said to them) these exhibits are inadmissible under FRE 805.  As stated by CVC in its motion, "[t]here is no hearsay exception for a published book, even a popular one."

Broad's motion to exclude is more limited, being specifically directed to testimony from Dr. Phillip Zamore regarding "how a person having ordinary skill in the art ("POSA") allegedly would have understood (1) the March 2011 Deltcheva et al. reference's disclosures regarding tracrRNA, (2) the RNAi, pre-mRNA, and DNA systems he alleges are relevant to Deltcheva et al.'s disclosures, and (3) Dr. Zhang's October 24, 2011 email regarding the role of tracrRNA in the CRISPR-Cas9 cutting complex."  According to Broad, what Dr. Zamore's declaration did not attest to was "(1) whether a 2012 POSA would have had a reasonable expectation of success of using CRISPR-Cas9 in eukaryotic cells; (2) the state of the art after the Jinek 2012 paper; or (3) relevant prokaryotic-based systems, such as Group II introns," all of which were issues upon which CVC Priority Motion.  But these issues were attested to not by Dr. Zamore in support of CVC's priority claims but by another witness, who did not opine on them.  Thus, CVC's proffer of Dr. Zamore's testimony on these matters is an attempt, in Broad's view, to "untimely seek[] to obtain expert testimony on these topics via improper re-direct testimony by Dr. Zamore" (i.e., during Broad's cross-examination of CVC's witness).  And Broad asserts that its cross-examination of Dr. Zamore was properly limited to "the actual opinions expressed in Dr. Zamore's declaration and his qualifications," and thus did not "open the door" to the testimony CVC elicited on redirect examination.

The brief recites specific portions of Dr. Zamore's redirect testimony to illustrate that Broad terms "an obviously rehearsed question and answer session that attempted to add to the record new testimony regarding reasonable expectation of success."  Broad's brief sets forth with specificity the testimony Broad asks the Board to exclude:

Broad's basis for this relief is that the Board "allowing the challenged po1tions of Dr. Zamore's testimony into evidence here would prejudice Broad" because "Broad was denied a fair opportunity to prepare a full rebuttal to Dr. Zamore on topics such as prior art systems and reasonable expectation of success given such opinions were not in Dr. Zamore's declaration and only proffered for the first time on a purported re-direct, after Broad's opposition was filed."

Both Broad and CVC request oral hearing and present a list of issues for the Board to resolve.  For Broad, these issues include Broad's Motion No. 5 for judgment of priority, as well as CVC's Opposition Motion and Broad's Reply; Broad's motion No. 9 to exclude evidence (as well as any opposition by CVC and reply by Broad); CVC's Motion No. 2 for priority judgment, as well as Broad's Opposition and CVC's Reply; CVC's Motion No. 3 for misjoinder of inventorship, Broad's Opposition, and CVC's Reply; and Broad's Contingent Motion No. 6, CVC's Opposition, and Broad's Reply for Correction of Inventorship if the Board grants CVC's Motion No. 3 on misjoinder.  Broad also lists for the Board any motions to exclude by CVC and "any other issues that the PTAB would like Senior Party to address."

For CVC the issues on which CVC asks the Board to hear oral argument include CVC's Motion No. 2 for priority judgment, as well as Broad's Opposition and CVC's Reply; CVC's Motion No. 3 for misjoinder of inventorship, Broad's Opposition, and CVC's Reply; CVC's Motion No. 7 to exclude evidence, as well as any Broad Opposition and CVC Reply; Broad's Motion No. 5 for judgment of priority, as well as CVC's Opposition Motion and Broad's Reply; and Broad's Contingent Motion No. 6, CVC's Opposition, and Broad's Reply for Correction of Inventorship if the Board grants CVC's Motion No. 3 on misjoinder.  CVC also includes any other issues "raised by Broad during oral argument or issues the PTAB would like CVC to address."

The Board in its discretion will decide whether to grant these requests for oral hearing and set a hearing date in due course.

Finally, Broad has filed an unopposed Miscellaneous Motion (No. 8) pursuant to Standing Order ¶¶ 121 and 123 to seal redacted material under the protective order contained in portions of the deposition transcripts of two CVC witnesses, Erik Joseph Sontheimer (Ex. 6214) and Rodolphe Barrangou (Ex. 6212).  This testimony relates to financial disclosures and licensing information that, if disclosed, would "compromise privacy interests and competitively sensitive information about licensing held by non-parties to this proceeding."  Broad makes the case that the redactions are "narrowly tailored" to minimize negative impact on the public, and that the redacted information is not necessary for the public to understand the context or substantive merits in the interference.

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.