In its appeal from an adverse decision on priority by the Patent Trial and Appeal Board (PTAB) in Interference No. 106,115 (directed to CRISPR-mediated gene editing), Junior Party the University of California/Berkeley, the University of Vienna, and Emmanuelle Charpentier (collectively, "CVC") filed on May 19th its Response and Reply Brief to earlier briefing by Senior party Broad Institute, Harvard University, and MIT (collectively, "Broad").

CVC's approach has always been directed to the apparent equities -- that its inventors conceived first and were diligent in efforts to reduce their invention to practice while Broad obtained the seminal sgRNA embodiment from their (perhaps improvident, in retrospect) disclosure, while Broad has taken the approach of applying interference law to these facts and using the improvident statements of CVC's inventors in support of their argument that CVC was not entitled to the claimed invention because their conception was not complete.  CVC follows their basic approach in its Reply brief, avoiding arguments that could be countered by the "substantial evidence" deference the Board's factual determinations are given in favor of "legal standards" (which are reviewed de novo).

In the Reply portion of the brief, CVC argues that "Broad's brief speaks most loudly through omission" insofar as CVC argues the brief does not identify anything Broad's inventors contributed to the Count (meaning conception, presumably, because it cannot be denied that the Broad inventors achieved successful reduction to practice before CVC).  The reason for Broad's "admission" and the basis for the Board's putative error according to CVC is that "[Broad inventor] Zhang learned of every feature of the count—CVC's discovery of the necessary and sufficient components for CRISPR-Cas9 gene editing, CVC's then still-unpublished single-guide RNA sequence, and their use for eukaryotic gene editing—when Zhang's collaborator, Marraffini, gave them to Zhang" (emphasis in brief).  And CVC points out the curious circumstance of the Board citing (and relying on) as evidence of Broad's conception an e-mail from Dr. Marraffini to the Broad inventor describing what he had learned from CVC.  Thereafter, CVC contends, all Broad did was what several other labs were able to do -- efficiently practice sgRNA-comprising embodiments of CRISPR for gene editing in eukaryotic cells.  (The difference, of course, is that none of these other labs filed patent applications or obtained patents on claimed CRISPR embodiments that interfered with CVC's applications.)  Under Applegate v. Scherer, 332 F.2d 571, 573-74 & n.1 (C.C.P.A. 1964), CVC contends, the Board's determination that Broad was the first to invent under these circumstances contradicts the principal that the patent should be awarded to the inventor "'who had the thought,' not the mechanic who 'merely made the test' to prove it worked."  Voicing a direct challenge to Broad's (understandable) reliance on the Board's factual determinations and the substantial evidence deference due thereto, CVC argues the question before the Court is one of law, that their conception -- the completeness vel non thereof being the basis for the Board's decision -- was complete when a skilled artisan can reduce it to practice "regardless of whether the inventor succeeds" (emphasis in brief).

CVC argues that "conception is complete when the invention is ready for hand-off to skilled artisans for reduction to practice," which is the situation in this interference in their telling of the tale.  CVC argues that the Board failed to apply this "governing" law, under which the facts establish that CVC had conceived of the invention before Broad.  In this regard, CVC cites Sewall v. Walters, 21 F.3d 411, 415 (Fed. Cir. 1994)(that conception is complete when an inventor's idea is sufficiently "definite and permanent" that "one of ordinary skill in the art could construct the apparatus without unduly extensive research or experimentation"); Cameron & Everett v. Brick, 1871 C.D. 89, 90 (Comm'r Pat.), and Dolbear v. American Bell Telephone Co., 126 U.S. 1 (1888) (the telephone interferences, wherein Bell prevailed despite not being first to reduce to practice).  The Board erred, CVC contends, by improperly relying on Burroughs Wellcome Co. v. Barr Laboratories, Inc., 40 F.3d 1223 (Fed. Cir. 1994), for the principle that a need for "extensive research or experimentation" can indicate incomplete conception.  CVC arrays copious precedent to the contrary, including Mergenthaler v. Scudder, 11 App. D.C. 264, 279 (1897), and In re Tansel, 253 F.2d 241, 244 (C.C.P.A. 1958), to the extent that, in their view, all these cases "say the same thing": that "[c]onception is complete when 'the work of the inventor ceases and the work of the mechanic begins'" and that additional work that was not "inventive" does not rebut conception, citing Acromed Corp. v. Sofamor Danek Group, Inc., 253 F.3d 1371 (Fed. Cir. 2001).  CVC accuses Broad of "changing the subject" by convincing the Board to focus on CVC's purported "difficulties" in reducing the invention to practice rather than recognizing CVC's exclusive conception of sgRNA-comprising CRISPR-mediated gene editing in eukaryotic cells, citing the conventionality of how the invention was reduced to practice by several other groups once CVC's conception of the invention was shared with the scientific community.  And the brief characterizes as "new rationales" Broad's assertions that two of the other groups that reduced the invention to practice were not "independent" of CVC, noting that these groups reduced the invention to practice using "different (prior art) techniques" than those proposed and used by CVC (emphasis in brief).  Repeating in this context its fundamental argument regarding conception versus reduction to practice, CVC posits that taking Broad's and the Board's position would result in "award[ing] the invention of the century to the lab that was quickest to reduce to practice" which "cannot be correct," citing Edison v. Foote, 1871 C.D. 80, 81 (Comm'r Pat.) ("Invention is not the work of the hands, but of the brain,"), and Sinclair & Carroll Co. v. Interchemical Corp., 325 U.S. 327, 330 (1945) ("patent law rewards 'innovation,' not 'the work of a mechanic'").

The brief then attacks the basis for the Board's priority decision, CVC's difficulties in reducing its invention to practice.  CVC here relies on Sewall and Rey-Bellet v. Engelhardt, 493 F.2d 1380, 1387 (C.C.P.A. 1974), in arguing that even "extensive testing" itself does not disprove conception, and Cameron that an inventor can have complete conception even where "much patience and mechanical skill, and perhaps a long series of experiments" turn out to be necessary to reduce an invention to practice.  The proper interpretation of the history of its efforts to reduce their invention to practice, CVC argues, is that they "planned to reduce its invention to practice with prior-art techniques; that [their] plan never changed; and that [they] succeeded with the same design it started with."  Instead, and erroneously CVC argues, the Board imposed a standard of "certainty of success" that the history of CVC's efforts did not satisfy (but should not have been required to do so) that even Broad concedes.  But while Broad emphasizes that the Board recited the proper legal standard (that did not require certainty) CVC argues that this was not the standard the Board applied (that did so require).  CVC supports this argument with citations to the record where the Board stated as much, defining conception for example as "a definite and permanent idea . . . of a system [CVC} knew would" work, and that their research plan was required to "achieve a functional . . . system" (emphasis in brief).

Finally in this regard the brief recites arguments made by Broad that are consistent with this misapplication of the legal standards CVC argues support its claim to priority for this invention, most of which involve CVC's experimental difficulties (wherein the proper standard is "whether a skilled artisan could succeed with ordinary skill, not whether the inventor did") (emphasis in brief).  CVC also repeats its argument that the students initially tasked to reduce to practice sgRNA-comprising CRISPR-mediated gene editing in eukaryotic cells were of less than ordinary skill in the art (which while true does not impress as their strongest argument).

CVC also attacks Broad's arguments in its brief by invoking seven "failed" attempts by CVC inventors, 5 of which that were not considered by the Board and the other two having been successful:

And could be further distinguished either by not having been begun by October 2012 or that were later successful:

And Broad's arguments are further flawed, CVC argues, because they simply repeat the Board's errors of law regarding incomplete conception.  Rather than being supported by the Burroughs Wellcome precedent (misapplied, according to CVC), the Board's and Broad's arguments on incomplete conception are contrary to interference rubrics that conception is evaluated at the alleged conception date whether "subsequent testing succeeded or failed, or even took place" which is not by itself dispositive, citing In re Jolley, 308 F.3d 1317, 1325 (Fed. Cir. 2002) ("[w]hether the inventor's experiments 'succeeded or failed, or even took place, does not determine whether conception was complete'").  And the consistency of the elements of the invention, i.e., "(1) a single-guide CRISPR-Cas9 complex; (2) comprising crRNA, tracrRNA, and Cas9; (3) in a 'eukaryotic cell'; (4) 'capable of cleaving' 'target DNA'" which was used by CVC, Broad, and the other labs was further evidence of conception.  Broad's arguments (erroneous, according to the brief) that CVC was "reconsidering" other elements (such as codon optimization) are "irrelevant" and wrong, inter alia, as not being recited in the Count.

CVC turns from arguing about the bases and grounds of the Board's decision to recite its fundamental argument that "awarding the invention to a copyist flouts the originality requirement."  Most of the arguments in this section of the brief reiterate CVC's argument that Broad obtained every element of the invention from CVC's disclosure ("Zhang contributed nothing") and reduced the invention to practice using "routine techniques."  CVC cites Burroughs Wellcome (somewhat ironically) for its holding wherein priority was awarded to the party that conceived of treating AIDS with AZT, not the party that had "confirmed [its] operability"; the outcome in Barba v. Brizzolara, 104 F.2d 198 (C.C.P.A. 1939), that "awarded the patent to Brizzolara, who 'had the idea' of mounting an air conditioner above the train car headroom, not Barba, who worked out 'particular means' to mount it 'without the exercise of invention'"; and the outcome in Applegate where the patent was awarded to the party that "'had the thought' of using the particular chemical on lampreys—not Applegate, 'who merely made the test' to prove efficacy."  Yet another Board error, according to CVC, is to "equat[e] reduction to practice with invention where originality is at issue," under circumstances where "Zhang spent a year trying to solve a puzzle with the wrong pieces before jettisoning his experiments, and claiming conception, the same day Marraffini slipped him the right pieces—every feature of the count—from CVC" (emphasis in brief).  And CVC dismisses Broad's assertions that their inventors had reduced dual-guide CRISPR embodiments by late 2011 as being "flatly contradicted by the record" and barred under SEC v. Chenery Corp., 318 U.S. 80, 93-94 (1943), as not being raised below.  Additionally, CVC reminds the Court that in 2011 there was no recognition in the art that the tracrRNA molecule was needed for CRISPR activity until CVC's inventors disclosed that "mature tracrRNA was critical to the final DNA-cleavage complex" (emphasis in brief).  There is no evidence according to CVC that the Broad inventors either told anyone they appreciated the importance of the tracrRNA nor performed any experiments to confirm this activity, while on the contrary there was evidence (records from a Broad lab meeting and an NIH grant proposal) indicating that the Broad inventors had no understanding of the role of the tracrRNA in CRISPR-mediated gene editing.  And all that changed, according to CVC, when Dr. Marraffini disclosed CVC's sgRNA CRISPR embodiment, illustrated by this graphic:

The brief is succinct:  "Zhang invented nothing before June 26."

CVC completes this portion of the brief by frankly accusing Broad of misrepresenting the facts on several occasions ("reflect[ing] an unfortunate pattern"): in 2014 during ex parte prosecution, by telling the PTO that its inventors had successfully achieved CRISPR-mediated gene editing including tracrRNA that, in this interference, was admitted to be untrue, and that a 2012 NIH grant proposal recognized sgRNA species could be used in CRISPR and in this interference admitting that sgRNA was provided by Dr. Marraffini from CVC. CVC provides this synopsis:

After a decade of patent prosecution, a prior interference, and an appeal to this Court, Broad finally revealed—halfway through this second interference—that Zhang learned of CVC's invention, including its sgRNA sequence, from Marraffini.  Broad concealed that for years.  It resisted discovery even after the Marraffini email was revealed.  . . .  Broad's assertions that Zhang invented everything cannot be credited, let alone for the first time on appeal.

The remainder of CVC's Reply brief is devoted to CVC's other grounds of appeal.  These include their arguments that the PTAB violated the requirements for Administrative Procedures Act (APA) review for being "inconsistent with the APA's promise of reasoned decisionmaking."  These arguments substantially repeat the arguments in CVC's opening brief, including that the Board held for Broad because there "must be differences" between CVC's efforts to reduce the invention to practice and the Broad inventors' efforts with no evidence other than the difference in timing of successful outcomes; that the Board "fail[ed] to consider contrary evidence" to Broad's argument that CVC's conception was incomplete, including the consistency in CVC's inventive efforts in reducing the invention to practice; disregarding the success of other groups to reduce to practice gene editing in eukaryotic cells by sgRNA-comprising CRISPR based on CVC's conception; and the Board's purportedly mistaken analysis of CVC's actually achieving success in reducing embodiments within the scope of the Count using microinjection.

The Reply also addresses CVC's argument -- and Broad's  response -- regarding the proper standard for satisfaction of the written description requirement as it was applied by the Board in denying CVC benefit to its earliest-asserted priority document, U.S. provisional application 61/654,086, filed May 25, 2012 ("P1") (the significance of which is a contrary decision would have resulted in CVC being Senior Party in the interference). CVC insists that its disclosure satisfies the statutory requirements as they have been explicated by the Court, in Evans v. Eaton, 20 U.S. (7 Wheat.) 356, 434 (1822); Alcon Rsch. Ltd. v. Barr Labs., Inc., 745 F.3d 1180, 1190 (Fed. Cir. 2014); and Crown Packaging Tech., Inc. v. Ball Metal Beverage Container Corp., 635 F.3d 1373, 1380-81 (Fed. Cir. 2011).  This allegation of misapplication is based on CVC's assertion that the PTAB required them to provide a working example to support an "expectation of success," based on the Board awarding priority to CVC's later-filed U.S. provisional application 61/757,640, filed January 28, 2013 ("P3") which differs, CVC contends, only by providing such a working example.  This is contrary to how the written description requirement has been interpreted by the Court, inter alia, in Ariad Pharms., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1352 (Fed. Cir. 2010) (en banc), and by the Supreme Court in Diamond Rubber Co. v. Consolidated Rubber Tire Co., 220 U.S. 428, 435-36 (1911).  Once again, CVC is succinct in its argument, stating that "[c]onvincing others the invention will work is not part of written description" (emphasis in brief).  The brief further characterizes Broad's argument that the Board's decision is supported by substantial evidence as a "strawman" because it supports (not surprisingly) the Board's factual determinations (and their accompanying entitlement to deference) on the written description issue.

The brief then turns to CVC's response to Broad's appeal of its contingent motion that the Board should have either expanded the Count to encompass dual-guide RNA (dgRNA) or remove certain of Broad's claims from the scope of the interference.  Part of CVC's argument is procedural: despite the Board having "multiple, independent grounds" for denying Broad's Preliminary Motions on these issues in the interference Broad challenges only one ground for each, which "dooms the cross-appeal" by "fail[ing] to show entitlement for relief," citing LSI Corp. v. Regents of Univ. of Minn., 43 F.4th 1349, 1355 (Fed. Cir. 2022), and providing illustrations of these alternative yet unchallenged grounds for each Motion.

After setting forth its counter-statement of the issues and facts on appeal (and providing the following illustration of the differences between sgRNA and dgRNA species):

CVC's brief sets forth the Board's decision on motions and CVC's contentions that the decisions were proper and correct.  The bases for CVC's argument is that the Board's construction of the term "guide RNA" (as a claim construction issue, reviewed de novo by the Federal Circuit; Intel Corp. v. Qualcomm Inc., 21 F.4th 801, 808 (Fed. Cir. 2021)), to mean sgRNA species thereof was consistent with Broad's own disclosure in the specification(s) of Broad's patents and applications in the interference.  On this basis, CVC argues the Board's claim construction was correct under the "broadest reasonable interpretation" standard applied in interferences, under Dionex Softron GmbH v. Agilent Techs., Inc., 56 F.4th 1353, 1358 (Fed. Cir. 2023).  And using that standard, CVC argues, the meaning of the term "guide RNA" is controlled by the disclosures in the specification (which are "clear and unambiguous" and "consistent" according to CVC) under Phillips v. AWH Corp., 415 F.3d 1303, 1315 (Fed. Cir. 2005) (en banc).  Nor does the doctrine of claim differentiation mandate a different construction, according to CVC, because the doctrine is "a guide" that does not provide " rigid rule," and the specification dictates a contrary construction as recognized in GPNE Corp. v. Apple Inc., 830 F.3d 1365, 1371 (Fed. Cir. 2016).  And the Board's claim construction cannot be overturned by the application of the Jinek 2012 reference (Jinek et al., 2012, "A Programmable Dual-RNA–Guided DNA Endonuclease in Adaptive Bacterial Immunity," Science 337(6096): 816-21)) because that is extrinsic evidence (which the Board and both parties recognized during the interference), and in any case the Jinek 2012 reference did not establish a plain and ordinary meaning of the term "guide RNA understood by those skilled in the art according to CVC.  Finally, CVC notes that the Board refused to consider publications asserted by Broad in its brief and in the interference that predated the Jinek 2012 reference in view of the plain meaning of the "guide RNA" term in Broad's specifications.

Broad has filed its Reply to CVC's Responsive brief (which will be the subject of a future post).  With this filing briefing in this interference is complete and the parties (and the rest of us) await scheduling of the oral hearing (which to date is not on the Federal Circuit's calendar).