Regents of the University of California v. Broad Institute, Inc. (Fed. Cir. 2025)

By Kevin E. Noonan --

Only a few days after the one-year anniversary of hearing oral argument, the Federal Circuit handed down its decision in Regents of the University of California v. Broad Institute, Inc. on Monday.  The opinion reviewed the Patent Trial and Appeal Board's decision in Interference No. 106,115 between Senior Party the Broad Institute, Harvard University, and MIT (collectively, "Broad") and against Junior Party the University of California/Berkeley, the University of Vienna, and Emmanuelle Charpentier (collectively "CVC" before the PTAB, here, "Regents") over CRISPR (clustered regularly interspaced short palindromic repeats) technology for gene editing.

To briefly recap, the '115 interference was the second interference between these parties after Interference No. 106,048 was dismissed for there being no interference-in-fact; see "PTAB Decides CRISPR Interference in Favor of Broad Institute -- Their Reasoning" and affirmed by the Federal Circuit in Regents of the Univ. of Cal. v. Broad Inst., Inc., 903 F.3d 1286 (Fed. Cir. 2018).  The '115 interference was provoked by Regents to overcome the basis for the decision in the '048 Interference; specifically Regents filed additional continuation applications reciting eukaryotic embodiments of CRISPR technology, reading directly on eukaryotic CRISPR claims in Broad's granted patents.  The PTAB awarded priority to Broad in this interference based, inter alia, on Broad convincing the Board that putative failures by Regents in reducing to practice their conception indicated that Regents' conception was incomplete or defective and Broad's conception thus occurred before Regents'.  The specifics of this reasoning is set forth in the Board's decision (see "PTAB Grants Priority for Eukaryotic CRISPR to Broad in Interference No. 106,115") and the parties arguments and grounds for appeal set forth in their briefs (see "CVC Files Appeal Brief in Interference No. 106,115"; "CVC Files Response and Reply Brief in Interference No. 106,115 Appeal"; "Broad Files Reply Brief in Interference No. 106,115 Cross-Appeal").

The Federal Circuit's opinion recites much of the factual and procedural background contained in these briefs and the history of the '115 interference (including the Board's decisions on the parties' Preliminary Motions; see "PTAB Decides Parties' Motions in CRISPR Interference"), but the opinion is significant for its decision that the Board erred as a matter of law on the priority question.  It is interesting to note that the panel is careful to describe in their explication what each party claims to be the case regarding their conception and reduction to practice of the claimed eukaryotic CRISPR embodiments.

The opinion, by Judge Reyna joined by Judges Hughes and Cunningham, affirmed in part, vacated in part, and remanded, in consideration of these grounds of appeal.  Regents based its appeal on the Board's priority determination and that its earliest provisional applications (P1, filed May 2012 and P2, filed October 2012) failed to satisfy the written description requirement and thus Broad was designated Senior Party.  For Broad, its appeal was based on the Board's claim construction regarding the scope of the term "guide RNA" as being limited to single guide RNA species wherein the crRNA and tracerRNA components of the CRISPR-Cas9 complex were covalently linked, usually by a short spacer nucleic acid (a species of which, termed Chimera A, was the basis for Regents' earliest date of conception).

The opinion begins with Regents' disputed date of conception and the completeness thereof.  The panel held that the basis for the Board's determination that Regents' conception was defective was legal error, because it "require[ed] Regents' scientists to know that their invention would work."  This amounted to a conflation of the "distinct legal standards for conception and reduction to practice."  Reciting established law, the opinion asserts "[t]here are three stages to the inventive process: (1) conception, (2) reasonable diligence, and (3) reduction to practice," citing Mahurkar v. C.R. Bard, Inc., 79 F.3d 1572, 1577 (Fed. Cir. 1996).  Under Burroughs Wellcome Co. v. Barr Lab'ys, Inc., 40 F.3d 1223, 1228 (Fed. Cir. 1994), the panel states that "an inventor need not know that his invention will work for conception to be complete" because, inter alia, "[k]nowledge that the invention will work, 'necessarily, can rest only on an actual reduction to practice,'" citing Applegate v. Scherer, 332 F.2d 571, 573 (CCPA 1964), and Univ. of Pittsburgh of Commonwealth Sys. of Higher Educ. v. Hedrick, 573 F.3d 1290, 1299 (Fed. Cir. 2009).  Based on this precedent, the Board having denied Regents the benefit of its earliest conception date based on uncertainty on its operability was error according to the Federal Circuit.  The panel further noted that the evidentiary basis for the Board's decision was "almost exclusively . . . Regents' scientists' statements expressing uncertainty about whether the experiments had succeeded and suggesting modifications to their CRISPR-Cas9 system" and thus to conclude that they did not have a "definite and permanent idea" on this basis was error.  The Board improperly applied the Burroughs standard, which defined "[f]actual uncertainty [which] is when '[the subsequent course of experimentation, especially experimental failures, reveal uncertainty that so undermines the specificity of the inventor's idea that it is not yet a definite and permanent reflection of the complete invention as it will be used in practice.'"  The Board's error was in depending on the Regents' scientists statements rather than determining whether those statements were accompanied by "modifications in their experiments that substantively changed their original idea."

Another basis for Board error was the failure to determine whether Regents' conception (i.e., the "plan" for performing CRISPR gene editing in eukaryotic cells) was used successfully by Regents scientists themselves or any other groups, using only routine skill and routine techniques.  Put another way, the opinion asserts that the proper analysis is to determine "whether [Regents' scientists] had formed the idea of [the invention's] use for [its intended] purpose in sufficiently final form that only the exercise of ordinary skill remained to reduce it to practice" "without extensive research or experimentation" under Burroughs.  The experiences of third parties is relevant both for their failures (citing Amgen, Inc. v. Chugai Pharm. Co., 927 F.2d 1200, 1207 (Fed. Cir. 1991)) and successes (citing Brand v. Thomas, 96 F.2d 301, 303 (CCPA 1938)).  Also relevant, according to the opinion was the course of conduct of the "alleged inventor" with regard to whether she "contemplated the use of routine skill or methods at an asserted conception date, or used such routine skill or methods during subsequent, successful experimentation conducted by [her]."  The Board's failure to consider routine methods or skill in reducing the invention to practice, and instead "focusing almost entirely on Regents' scientists' statements about perceived experimental difficulties and doubts about success" was another source of Board error.  This error was illustrated by the Board deciding that it was not enough that the Regents' inventors had "conceived of the mechanics" of the invention but instead must have had an "operative invention" to have conceived.  In doing so, the panel found that the Board had misapplied the Court's Hitzeman v. Rutter precedent, which concerned an instance where there was a "bare hope" for a result that had "never before [been] achieved," 243 F.3d 1345, 1358–59 (Fed. Cir. 2001).  The proper distinction in this case was that the claim limitations were not directed to a result but rather to whether CRISPR functions in a eukaryotic cell, according to the opinion.  Failing (refusing, according to the panel) to consider "whether a person of ordinary skill could have achieved the function of editing eukaryotic DNA" was error by the Board.  The proper standard is there being "more than a 'general hope,' but less than knowing with certainty that the invention would work" according to the opinion.

The Court also held that the Board erred by failing to consider Regents' evidence of the success of others in using their conception to successfully reduce eukaryotic CRISPR to practice.  By focusing on the purported difficulties encountered by Regents' scientists in reducing the invention to practice the Board legally erred in not considering whether Regents' scientists "described routine methods or skill at the asserted conception dates and used those methods or that skill to achieve purported successes during subsequent experimentation."  The Board erred by assuming that the purported difficulties in reduction to practice indicated that the invention required undue experimentation to be carried out, according to the opinion.

The opinion sets out its conclusions as to the scope and extent of the Board's error in its priority determination:

In sum, the Board erred by failing to consider routine methods or skill, focusing almost entirely on Regents' scientists' perceived experimental difficulties and related statements of doubt.  We thus vacate the Board's decision on conception and remand for the Board to decide on conception under the proper application of the legal framework.  On remand, the later party to reduce to practice will have the opportunity to show, under a conception date established by the correct standard, either (1) it was "the first to conceive of the invention and that it exercised reasonable diligence in later reducing that invention to practice," Cooper v. Goldfarb, 154 F.3d 1321, 1327 (Fed. Cir. 1998), or (2) it had "prior conception of the claimed subject matter and communication of the conception to the adverse claimant."  Price v. Symsek, 988 F.2d 1187, 1190 (Fed. Cir. 1993).

The opinion then turned to Regents' appeal of the Board's decision in Preliminary Motions that Regents' earlier priority documents did not satisfy the written description requirement for determination of which party was entitled to be designated as the Senior Party.  The panel determined that the Board properly applied the rubrics regarding whether the P1 or P2 disclosures satisfied the requirement based on the complexity and unpredictability of the invention as understood by one having ordinary skill in the art. While acknowledging that working examples or description of an actual reduction to practice are not required under Ariad Pharms., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1351 (Fed. Cir. 2010) (en banc), the panel also asserted that the determination depends on how the ordinarily skilled worker would understand what was described within "the four corners of the specification."  The Board here "properly tailored its analysis to the specific facts of this case, rather than applying a one-size-fits-all approach."  The Federal Circuit also rejected Regents' argument that the Board's decision violated the provisions of the Administrative Procedures Act for failing to consider disclosure that would have supported possession of the invention.  The Court saw no indication that the Board had improperly relied upon or only considered evidence of one route of practicing the invention (using expression vectors) and not others (microinjection) and thus upheld the Board's written description determination.

Turning to Broad's appeal on claim construction grounds regarding the term "guide RNA," the panel held that the appeal is moot, because the Board made its determinations in denying Broad's Preliminary Motions on "independently sufficient grounds . . . unrelated to claim construction."  Under these circumstances, "the relief sought would not have an impact on the legal interests of the parties" and thus the appeal is moot.

The decision was entirely in Regents' favor with regard to priority and amounts to almost a mandate in Regents' favor on remand.  The opinion criticized, found legal error, and vacated every basis upon which the PTAB panel awarded priority to Broad.  Of course, as a consequence the question of what group of inventors were the first to invent and thus are entitled to patents on eukaryotic versions of CRISPR remains undecided, with all the investment and licensing uncertainty that these circumstances create.  And it is unlikely that investors, licensees, or the public will have a definitive answer on this issue any earlier than one or two years from now.

Regents of the University of California v. Broad Institute, Inc. (Fed. Cir. 2025)
Panel: Circuit Judges Reyna, Hughes, and Cunningham
Opinion By Circuit Judge Reyna

Comments

[Paul Morgan]

Before this blog was published I had asked these questions on the Patent-Os blog:
"This long-awaited CRISPER interference CAFC appeal decision took a long time. And it is not even over yet, given the CAFC remand. Has any expert yet predicted the final result?*
Is this long dragged out invention priority dispute [in perhaps the most important 21st century invention so far?] still that important or disruptive commercially? More specifically, will all the claims in the eventually-winning patents be limited to the Cas9 version of CRISPR and not cover other subsequently developed versions?
*The statement here that "The decision was entirely in Regents' favor with regard to priority and amounts to almost a mandate in Regents' favor on remand" is as close to a prediction that I have seen to that first question.

[Kevin E Noonan]

Dear Paul:

Being fully cognizant of the risks of prediction in a case as complex as this one (evinced by how long it took for the Court to come to a decision), it seems that the decision to vacate rather than reverse has to do with the fact-specific nature of the issues and the Dickenson v Zurko deference the Court must give to the PTAB. However the Court decided the issue as a matter of law, loosening the panel from this restriction, and thus was able to give the instruction to apply conception and the effects on reduction to practice between the parties as set forth in the opinion.

There is a "common sense" aspect to the decision, provided that it is accepted that it was the use of sgRNA that permitted scientists to overcome the relatively higher complexity of eukaryotic cells (relied upon by Broad in having the PTAB and CAFC to decide there was no interference-in-fact in the earlier Interference No. 106,048 between the parties) in achieving CRISPR DNA cleavage in eukaryotic cells. If THAT was the relevant conception then CVC clearly had conception prior to anyone else.

While your question about Cas9 is important, perhaps what is more important is that the earliest foundational patents for both parties will expire in about 6 years once priority is finally determined.

And don't forget that there are two other interferences that will proceed once this one is finally decided.

Thanks for the comment