Inequitable Conduct by Senior Party Broad Alleged in Interference No. 106,115 (and PTAB May Finally Hear Evidence About It)

By Kevin E. Noonan --

An enduring and persistent (albeit until now unresolved) issue in the patent interferences involving the Broad Institute, Harvard University, and MIT (collectively, "Broad") as Senior Party and the University of California/Berkeley, the University of Vienna, and Emmanuelle Charpentier (collectively, "CVC") as Junior Party has been the question of whether Broad had committed inequitable conduct in prosecuting its patents- and applications-in-interference.  CVC raised the issue in its proposed motions in Interference No. 105,048 (see "CRISPR Interference Motions Set" and "PTAB Redeclares CRISPR Interference and Grants Leave for Some (But Not All) of Parties' Proposed Motions") and in this '115 Interference (see "CRISPR Interference Parties Propose Motions").  In both interferences, the Board denied CVC authorization to file its motions grounded in inequitable conduct as being premature but granted leave for CVC to file a motion for authorization to file their inequitable conduct motion at the end of the priority phase.

That day never came in the '048 Interference, because the Board granted Broad's motion that there was no interference-in-fact and the Broad prevailed (see "PTAB Decides CRISPR Interference -- No interference-in-fact").  In this '115 Interference, CVC made much the same allegations made in the earlier interference (see "CRISPR Interference Parties Propose Motions").  According to CVC, "Broad made at least one affirmative material misstatement during prosecution of each of Broad's involved patents, applications, or parent applications to which they claim priority" -- specifically, in a declaration by named inventor Zhang regarding actual reduction to practice of CRISPR-Cas9 in eukaryotic cells prior to May 2012.  CVC asserted that these statements were untruthful because the CRISPR system did not comprise tracrRNA, which is necessary for CRISPR to be functional.  CVC asserted that it was undisputed that tracrRNA is necessary for CRISPR function, using disclosure from U.S. Provisional Patent Application No. 61/736,527 as well as in the Broad's involved patents and independent prior art.  CVC also asserted that Dr. Zhang's "conception" arose only after reading a Berkeley prior art disclosure.  The proposal for this motion extensively analyzed purported evidence for actual reduction to practice to show the Broad's asserted failure, alleging that the Broad "cherry-picked data" that "intentionally omitted the context that shows his claims of successful DNA cleavage to be false."  This motion applied to all the Broad's patents- and applications-in-interference because the alleged untruthful statements were submitted in all applications.

CVC also made similar allegations for another declaration submitted by a different inventor, which they contend evinced "a larger pattern of deception."  These allegations were supported by an e-mail from a Zhang lab member and named inventor on the Broad's provisional application (albeit in a context where there seems to exist an axe to grind against Dr. Zhang):

The 15-page declaration of [Feng Zhang] and Le Cong's luciferase data is mis- and overstated to change the examiner's decision, which seems to be a joke. . . .

After seeing your in virto [sic, in vitro] paper, Feng Zhang and Le Cong quickly jumped to the project without letting me know.  My lab notebooks, emails and other files like dropbox or gel pictures recorded every step of the lab's failure process.  I am willing to give more details and records if you are interested or whoever is interested to clear the truth. . . .

We did not work it out before seeing your paper, it's really a pity.

It appears, however, that CVC's time may have come.  On June 25th, CVC by e-mail requested leave to file its inequitable conduct motion which included an assertion that "there are new justifications for [the] requested motion" (which Broad opposed).  The Board denied this request by Order under 37 C.F.R. § 41.104(a) on July 8th.  However, on November 12th, the Board entered an Order under 37 C.F.R. § 41.104(a) granting CVC leave to file a paper of no more than five pages that listed its "additional justifications" for filing its inequitable conduce motion.  On November 18th, in a Paper entitled "CVC's Additional Justifications Supporting Authorizing a Motion for Unpatentability due to Inequitable Conduct," CVC filed its list pursuant to the Board's November 12th Order.  In that Paper, the CVC provided the following allegations:

1.  That Dr. Zhang testified in the '115 Interference that "demonstrate[ed] that his 2014 Declaration [in the '048 Interference] knowingly mischaracterized his March 2011 experiments.

2.  That "the record in this ['115] interference shows that Zhang's 2015 Declaration misrepresents his alleged possession of 'a single molecule' guide RNA."

Regarding the first allegation, CVC argues that statements made by Dr. Zhang in a Declaration dated January 30, 2014 were "knowingly false."  The statement in question reads as follows:

Exhibit 7 [i.e., experiments conducted in March 2011, as first revealed in this interference] shows that prior to May 2012, I conceived and reduced to practice . . . [a]n engineered, programmable, non-naturally occurring Type II CRISPR-Cas system . . . . [Ex. 3424]

The bases for CVC's allegation of knowing falsehood include 1) that Dr. Zhang had "since conceded that those experiments did not include any tracrRNA, which he knew was a necessary component when he signed his 2014 Declaration"; (2) that Dr. Zhang in two instances (during cross-examination and in a 2020 inventor declaration) "admitted . . . , that he did not begin introducing any form of tracrRNA into his experiments until April of 2011," supported by his further admission that "he learned about the existence of tracrRNA only after reading Deltcheva et al. (Ex. 3214), which first published in Nature on March 30, 2011" made during his deposition and that he began adding "the native tracrRNA" on April 5, 2011.  From this CVC drew the conclusion that because this was after the March 2011 experiments, Dr. Zhang had made a materially false statement in this regard in his earlier declaration.  CVC then argues that this timeline and truthful testimony (after the fact) was consistent with the deposition testimony CVC elicited from Dr. Marraffini (see "CVC Files Motion in Opposition to Broad Priority Motion") regarding CVC's contention that "[Dr.] Zhang did not know that tracrRNA was part of the DNA-cleavage complex until June 26, 2012."  Because "[b]y the time [Dr.] Zhang signed his 2014 Declaration, however, he did know that tracrRNA was a necessary part of the Type II CRISPR-Cas9 system" and "[Dr.] Zhang knew that his March 2011 experiments did not include any form of tracrRNA," CVC contends that "[i]t was therefore knowingly false to declare that these experiments 'describe and enable' and 'reduced to practice' the claimed Type II CRISPR-Cas9 system," which was Dr. Zhang's testimony in his 2014 declaration.

Accordingly, should the Board agree that Dr. Zhang's testimony amounts to a knowingly false statement, CVC argues that under Therasense, Inc. v. Becton, Dickinson & Co., 649 F.3d 1276, 1292 (Fed. Cir. 2011) (en banc), these statements would be material to patentability per se.  Because Dr. Zhang's averments in his declaration were "for the purpose of removing prior art to obtain allowance of claims" (and indeed "the examiner expressly relied on Zhang's 2014 Declaration in her reasons for allowance in each of Broad's 13 involved patents and involved '551 application), CVC argues that an intent to deceive was an appropriate inference for the Board to draw (supported by Dr. Zhang's statement in his declaration that "I understand that . . . if I can show conception and actual reduction to practice prior to the filing dates of the [art] . . . then I have removed the [art] from being prior art . . . ." (emphasis added in CVC's brief).

Regarding the second allegation, CVC raises Dr. Zhang's 2015 declaration wherein "[Dr.] Zhang attests that Figure 4B in a 2012 grant proposal to the National Institutes of Health ("the NIH grant") showed that "a single RNA can be used as a guide in the CRISPR-Cas9 system."  Ex. 3424.  This testimony is inconsistent with Dr. Zhang's testimony (and Broad's arguments) in this interference, wherein "[Dr.] Zhang and Broad have represented in this proceeding that the same Figure 4B of the NIH grant shows a dual-molecule guide system and not a single-molecule guide system" (emphasis added).  CVC adds Dr. Zhang's further assertions from his 2015 declaration:

Having generated the figure of part B in the above illustration from the January 12, 2012 R01 NIH grant application, prior to January 12, 2012, I appreciated the mammalian expression system illustrated could be constructed, and when introduced into a mammalian cell could express products and function in vivo for cleavage and genome editing, as illustrated above, and as actually done prior to November 30, 2011, with appreciation that a single RNA can be used as a guide in the CRISPR-Cas system, including as shown by . . . the illustration of the NIH R01 grant application . . . . [Ex. 3424]

CVC then cited the phrase "used as a guide" in this passage of Dr. Zhang's deposition testimony in contrast with Dr. Zhang's deposition testimony in this interference to refer to "RNA that's guiding Cas9 to the target" and consequently that "[Dr.] Zhang declared to the Office that Figure 4B 'show[ed]' that he appreciated that 'a single RNA can be used as a guide in the CRISPR-Cas system.'"  Once again, CVC argues that this statement is "knowingly false" because here "[Dr.] Zhang has admitted in this proceeding [i.e., in his 2020 inventor declaration in this interference] that Figure 4B in fact shows a dual-molecule guide system."  CVC also notes that Broad has taken this position (that Figure 4B shows a dual-molecule embodiment of CRISPR) in this interference, inter alia, "[i]n support of its motions to change the count and de-designate claims corresponding to the count (both of which the Board denied), citing several arguments in Broad's motions and replies to CVC's oppositions to these motions.  Further, CVC argues that a proper interpretation of Figure 4B as not showing a single-molecule RNA-comprising embodiment of CRISPR is consistent with Dr. Maraffini's testimony "that he first conveyed such a system to Zhang on June 26, 2012, by showing him CVC's work" (neatly wrapping in CVC's arguments that if Df. Zhang had achieved a single-molecule RNA-comprising embodiment of CRISPR in eukaryotic cells he had done so by deriving the invention from CVC's inventors).  Once again, CVC argues that Dr. Zhang's statements in this instance are "unmistakably false and thus per se material" and that the examiner relied upon these statements in allowing the '551 application.  And, CVC argues, the Board can infer an intent to deceive in view of Dr. Zhang's participation inter alia in an examiner interview "that involved discussion of 'whether there need be consideration of interference [sic] as to [CVC] applications.'"

CVC further asserts that the Board should hear its motion before Final Judgment, based on circumstances where "the factual record is complete, no discovery is required, and resolution is in the public interest," citing  McDonald v. Miyazaki, Interference No. 104,544, Paper 149.  There, where "an inventor submitted a declaration during prosecution that misrepresented certain experiments and activities in an effort to antedate prior art," the Board entered judgment cancelling all involved claims on inequitable conduct grounds saying these circumstances were "the sort of over-reaching and truth-shaving that Rule 56 was enacted to prevent."  According to CVC, Dr. Zhang's and Broad's inequitable conduct here has been "[e]ven more egregious and pervasive."

Under these circumstances, CVC asserts in support of its demand that the Board hears (and presumably decides this motion before Final Hearing) that "the PTAB has a duty to protect the public from inequitably procured patents and to enforce Rule 56 to prevent abuse of declaration practice, as the examining corps is not equipped to police such misconduct."

Comments

[Paul F Morgan]

Keven, even if inequitable conduct is found in an application in interference, that still leaves the historical messy question of what can or should be its consequences for the interference? Or, what is the appropriate extent or type of the sanction in the interference itself? The IC party's ultimate patents may be unenforceable for IC, but the PTAB does not have jurisdiction to make that decision. It has been argued that IC alone does not logically justify interference judgements effectively awarding patent claims to other parties who would not have won on a priority contest?

[Kevin E Noonan]

Paul: the case the PTAB cited, Miyazaki, seems to indicate that the Board thought it had the authority to do so, and you could make the argument that a showing of inequitable conduct should make the claims unenforceable (which could be appealed in due course). But this doesn't answer the priority question. I suspect a decision rendering the claims unenforceable might motivate the parties to settle the interference in CVC's favor with Broad getting some sort of (non-exclusive) license and perhaps some small portion of CVC's royalties for licensing their patents.

I looked for the Miyazaki interference decision and could not find it; the case was appealed to the Federal Circuit in 2004 (Docket No. 04-1245) but haven't found a decision on the CAFC website.

I'll let you know if I find anything else. Thanks for the comment.

[kotodama]

I found a copy of the McDonald case at the BPAI. (According to a docket sheet I also found, the CAFC appeal was dismissed by mutual agreement before any briefs were filed.) Here is the Casetext link.

https://casetext.com/admin-law/ex-parte-mcdonald-39

The IC discussion begins at paragraph [61]. As one can see, that paragraph also states that a finding of IC empowers the Board to hold claims unenforceable during an interference—but only the involved claims.

-kd

[david.k]

Too many crispr interference.. about Sigma, CVC, Broad, how is it going?

[Kevin E Noonan]

Thanks, kd - greatly appreciated.

[Kevin E Noonan]

david - if you put CRISPR in the PatentDocs search box you will get an up-to-date description of where we are. Short answer: in the '115 (CVC v Broad) interference, the only thing remaining is the Oral Hearing on priority, and this inequitable conduct motion.

For both the '126 (Broad v. ToolGen) and '127 (CVC v. ToolGen) they have their Oral Hearing on the Preliminary Motions. It is unlikely that the Board will change the Count or dedesignate claims (what Broad wants) and if they don't then whether they grant "inside" priorities to ToolGen becomes less significant.

Of course, should the Board find IC as asserted by CVC in the '115 interference then a similar outcome could arise in the '126 Interference.

I think (unless I've missed it) that Sigma hasn't had an interference declared yet.

Thanks for reading

[david.k]

Thank you for your comments.

But I think you need to check below website.

https://acts.uspto.gov/ifiling/PublicView.jsp?identifier=106132&identifier2=null&tabSel=1&action=filewrapper&replyTo=PublicView.jsp

https://acts.uspto.gov/ifiling/PublicView.jsp?identifier=106133&identifier2=null&tabSel=1&action=filewrapper&replyTo=PublicView.jsp

[Kevin E. Noonan]

Thanks very much!

[Kevin E Noonan]

david k: any idea if Sigma is provoking an interference with ToolGen?