The Patent Trial and Appeal Board issued a decision on February 28 awarding priority of invention of foundational CRISPR gene editing patents to the Broad Institute, Massachusetts Institute of Technology, and Harvard University. Pending an expected appeal, the decision ends a long-running dispute between the institutions and competing claims to the technology by UC Berkeley, the University of Vienna, and Emmanuelle Charpentier.
As a consequence of the decision, Broad Institute, Massachusetts Institute of Technology, and Harvard University (collectively, Broad)[1] control foundation patents claiming applications of CRISPR in eukaryotes (contingent on ongoing interference proceedings over the same patents involving Toolgen Inc. and Sigma).
The dispute between UC Berkeley, the University of Vienna, and Emmanuelle Charpentier (collectively, CVC) and Broad originated in an earlier interference, No. 106,048 (’048 interference or Broad/CVC I), which involved claims from CVC’s first non-provisional application directed to the CRISPR technology, and 12 issued patents and one pending application owned by Broad.[2] The CVC patent had an earlier filing date (March 15, 2013) and claimed priority to an earlier filed provisional application (May 25, 2012) than Broad’s patents and application (filed October 15, 2013, claiming earliest priority to December 12, 2012). However, because Broad filed requests for accelerated examination, the Broad patents issued while the CVC application was still undergoing examination.
During the preliminary motions phase of the ’048 interference, Broad filed a threshold motion requesting that the Patent Trial and Appeal Board (PTAB) declare no interference-in-fact between the involved claims.[3] Briefly, Broad argued that CVC’s claims—which did not recite a specific cellular environment—did not anticipate or render obvious the claims of Broad’s patents and application, which expressly require eukaryotic cells. In a Decision on Motions issued on February 15, 2017, the PTAB agreed with Broad, finding that there was no reasonable expectation of successfully practicing the claims of the CVC application in eukaryotic cells.[4] In reaching this holding, the PTAB relied heavily on contemporaneous statements by the CVC inventors—and its own experts in the interference—expressing uncertainty about the viability of the CRISPR technology in eukaryotes, and in particular its therapeutic promise in humans.[5] The PTAB determination of no interference-in-fact was subsequently upheld on appeal to the Federal Circuit.[6]
However, despite this early setback for CVC, the PTAB’s holding in Broad/CVC I was only narrowly applicable to the claims at issue in that proceeding. In particular, the PTAB did not opine on whether the CVC applications described and enabled claims to use of CRISPR in eukaryotes, nor did the interference reach a priority phase to evaluate evidence of conception, diligence, and reduction to practice of such a claim.
Between April 2018 and February 2019, following the ruling in the ’048 interference, CVC filed a series of 14 continuation applications with claims that expressly recited eukaryotic applications of CRISPR technology. Those applications claimed priority to both the original non-provisional filing at issue in Broad/CVC I, and the series of provisional applications dating back to May 25, 2012. The USPTO declared a new interference, No. 106,115 (the ’115 interference, or Broad/CVC II) between these newly filed CVC applications, and the same set of Broad patents and application at issue in Broad/CVC I (with one additional Broad patent).[7]
Preliminary Motions Practice
A variety of motions were briefed and considered by the PTAB during the preliminary motions phase of Broad/CVC II. In contrast to Broad/CVC I, Broad did not dispute the existence of an interference-in-fact between the involved claims during the preliminary motions phase of Broad/CVC II. Broad instead argued (unsuccessfully) that estoppel precluded a new interference with the same claims—and therefore the same subject matter—at issue in Broad/CVC I. The PTAB disagreed, finding, among other things, that whether the claims at issue in Broad/CVC II recited different subject matter than those in Broad/CVC I was one of the very questions in dispute.[8]
One other notable finding from the preliminary motions phase of Broad/CVC II relates to the priority benefit accorded the involved CVC applications. CVC filed a preliminary motion requesting that the PTAB award priority of its involved claims to the first provisional, filed on May 25, 2012, and pointing to in vitro experimental results reported in that application—and descriptions of eukaryotic target cells in the specification—to show possession and enablement of the involved claims.[9]
In its Decision on Motions, the PTAB refused to award priority to the first application, invoking the Supreme Court and Federal Circuit admonition that “[p]atents are not awarded for academic theories, no matter how groundbreaking or necessary to the later patentable invention of others . . . .”[10] Relying heavily on expert testimony presented by Broad, the PTAB held that “absent results of a successful working example” and/or other description of the requirements for CRISPR function in eukaryotes, the first filed provisional failed to show possession of an embodiment of the count.[11] Thus, the PTAB awarded priority benefit to CVC’s third provisional, filed January 28, 2013, where an example using CRISPR in human cells was presented. Notably, CVC’s third provisional was filed after Broad’s first provisional filing date of December 12, 2012, meaning that Broad retained the status of Senior Party in the interference and the accompanying presumption of priority. Further, this ruling precluded CVC’s reliance on the May 28, 2012, filing date as its first constructive reduction to practice of an embodiment corresponding to the count.
Priority Phase
Because there was no dispute regarding an interference-in-fact and Broad’s estoppel motion was denied, the ’115 interference moved into the priority phase to resolve the ultimate question of inventorship. The parties extensively briefed and presented evidence of their respective conception and reduction to practice of an embodiment corresponding to the count.
CVC asserted a conception date of March 1, 2012, and actual reduction to practice on August 9, 2012, both falling before Broad’s accorded benefit to its December 12, 2012, provisional filing.[12] Broad countered with its own evidence of conception and reduction to practice as early as June 26, 2012, and various subsequent dates of asserted actual reduction to practice, including on October 5, 2012, the date the PTAB focused on in its decision on priority.[13]
In awarding Broad priority of invention, the PTAB found that CVC’s evidence of conception and reduction to practice showed uncertainty on the part of the inventors about the meaning or significance of the experimental results they obtained.[14] That evidence consists of experiments spanning March to August of 2012, and more significantly correspondence regarding those experiments, that the PTAB concluded show insufficient certainty about the interpretation of the experimental results.
In view of this uncertainty, the PTAB further found that CVC’s ongoing efforts to understand and refine its experiments undermined the requisite definite and permanent idea required for their asserted conception in March of that year.[15] Notably, the PTAB emphasized that it was not basing its decision on lack of a reasonable expectation of success, but rather on what it considered “multiple experimental failures before [CVC] recognized any success, even as late as mid-October 2012” amounting to evidence showing that CVC “did not have a definite and permanent idea of how to achieve [the desired] result . . . because of their perception of these multiple failures.” [16]
In contrast, the PTAB concluded that Broad established actual reduction to practice as of at least October 12, 2012.[17] In particular, the PTAB credited Broad’s evidence of reduction to practice consisting of a completed manuscript submitted on that date—before any evidence that the PTAB considered showed the required certainty to support conception or actual reduction to practice by CVC—reporting work done as early as July 2012. The PTAB concluded that the manuscript showed that the inventors recognized their completed reduction to practice, and that reviewer comments on the manuscript corroborated that recognition, by at least that date.
Pending an appeal, the PTAB decision in Broad/CVC II awards substantial control over the CRISPR patent landscape to Broad. Further, it ends prosecution of the involved CVC patents, and forecloses CVC’s pursuit of patentably indistinct claims to eukaryotic applications of the technology.
Notably, CVC holds patents issuing from its earliest application at issue in Broad/CVC I, and subsequently filed applications claiming priority to the same provisional that were not at issue in either proceeding. Those patents do not require any specific context (eukaryotic, prokaryotic, in vitro) or application of the CRISPR technology.[18]
More significantly, both Toolgen Inc. (Interference No. 106,126) and Sigma-Aldrich (Interference No. 106,133) have pending claims that the USPTO has declared interfere with the same Broad patents and application at issue in Broad/CVC II. Further, each of Toolgen and Sigma-Aldrich are senior parties in their respective interferences, though their earliest provisional filing dates post-date the actual reduction to practice recognized by the PTAB in Broad/CVC II. Accordingly, Morgan Lewis will closely watch how the parties to those proceedings react in view of the February 28 PTAB ruling.
If you have any questions or would like more information on the issues discussed in this LawFlash, please contact the authors, Christopher J. Betti, Ph.D. and Sara Sims, Ph.D., or any of the following lawyers from Morgan Lewis’s IP life sciences practice and post-grant proceedings team:
Boston
Stephen L. Altieri, Ph.D.
Joshua M. Dalton
Mark L. Hayman, Ph.D.
Century City
Olga Berson, Ph.D.
Andrew V. Devkar
Chicago
Michael J. Abernathy
Wan-Shon Lo
Krista Vink Venegas, Ph.D.
Jason C. White
Amanda S. Williamson
Houston
C. Erik Hawes
Rick L. Rambo
Orange County
M. Todd Hales
Nathan S. Smith
Philadelphia
Louis W. Beardell, Jr.
Eric Kraeutler
San Francisco
Brent A. Hawkins
Brett A. Lovejoy, Ph.D.
Christina A. MacDougall, Ph.D.
Jeffry S. Mann, Ph.D.
Silicon Valley
Dion M. Bregman
Andrew J. Gray IV
Ahren C. Hsu-Hoffman
Michael J. Lyons
Washington, DC
Jeffrey G. Killian, Ph.D.
Janice H. Logan, Ph.D.
Robert Smyth, Ph.D.
[1] Interference No. 106,115, paper 2863, Decision on Priority under 37 CFR 41.125(a); paper 2864, Judgment under 37 CFR 41.127.
[2] See, e.g., Interference No. 106,048, paper 1, Declaration under 37 C.F.R. 41.203(b).
[3] Interference No. 106,048, paper 77, Broad et al. Substantive Motion 2 (for judgment of no interference-in-fact).
[4] Interference No. 106,048, paper 893, Decision on Motions under 37 CFR 41.125(a), at p. 22.
[5] Id.
[6] Regents of Univ. of California v. Broad Inst., Inc., 903 F.3d 1286 (Fed. Cir. 2018).
[7] Interference No. 106,115, paper 1, Declaration under 37 C.F.R. 41.203(b).
[8] Interference No. 106,115, paper 877, Decision on Motions under 37 CFR 41.125(a), at p. 5.
[9] See, e.g., Interference No. 106,115, paper 212, CVC Substantive Motion 1.
[10] Interference No. 106,115, paper 877, Decision on Motions under 37 CFR 41.125(a), at p. 90 (citing University of Rochester v. G.D. Searle & Co., Inc., 358 F.3d 930, n.10 (Fed. Cir. 2004), quoting Brenner v. Manson, 383 U.S. 519, 536, (1966).
[11] Id. at p. 102.
[12] See, e.g., Interference No. 106,115, paper 1579, CVC Substantive Motion 2, pp. 7, 22.
[13] See, Interference No. 106,115, paper 2118, Broad Motion 5, pp. 12, 20.
[14] Interference No. 106,115, paper 2863, Decision on Priority, at pp. 42, 49.
[15] Id. at p. 46
[16] Id.
[17] Id., p. 64.
[18] See, e.g., U.S. Patent Nos. 10,266,850 (method of cleaving a nucleic acid); 10,301,651 (method of modulating transcription from a target DNA molecule), and. 10,113,167 (non-naturally occurring DNA-targeting RNA, or a nucleic acid encoding the non-naturally occurring DNA-targeting RNA).