McDonnell Boehnen Hulbert & Berghoff LLP

In the Patent Trial and Appeal Board's decision on motions issued September 10th in Interference No. 106,115 (see "PTAB Decides Parties' Motions in CRISPR Interference") between Senior Party The Broad Institute, Harvard University, and the Massachusetts Institute of Technology (collectively, "Broad") and Junior Party the University of California/Berkeley, the University of Vienna, and Emmanuelle Charpentier (collectively, "CVC") the Board denied Broad's Motion No. 2 to substitute the Count.

To recap, the Count in the '115 interference as declared recited in the alternative either claim 18 of the Broad's U.S. Patent No. 8,697,359 (dependent on claim 15), which taken together recites the following invention:

An engineered, programmable, non-naturally occurring Type II CRISPR-Cas system comprising a Cas9 protein and at least one guide RNA that targets and hybridizes to a target sequence of a DNA molecule in a eukaryotic cell, wherein the DNA molecule encodes and the eukaryotic cell expresses at least one gene product and the Cas9 protein cleaves the DNA molecules, whereby expression of the at least one gene product is altered; and, wherein the Cas9 protein and the guide RNA do not naturally occur togetherwherein the guide RNAs comprise a guide sequence fused to a tracr sequence.

(where the underlined portion recites the relevant language from claim 18), or Claim 156 of Berkeley's U.S. Patent Application No. 15/981,807:

A eukaryotic cell comprising a target DNA molecule and an engineered and/or non-naturally occurring Type II Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-— CRISPR associated (Cas) (CRISPR-Cas) system comprising
    a) a Cas9 protein, or a nucleic acid comprising a nucleotide sequence encoding said Cas9 protein; and
    b) a single molecule DNA-targeting RNA, or a nucleic acid comprising a nucleotide sequence encoding said single molecule DNA-targeting RNA; wherein the single molecule DNA-targeting RNA comprises:
        i) a targeter-RNA that is capable of hybridizing with a target sequence in the target DNA molecule, and
        ii) an activator-RNA that is capable of hybridizing with the targeter-RNA to form a double-stranded RNA duplex of a protein- binding segment,
    wherein the activator-RNA and the targeter-RNA are covalently linked to one another with intervening nucleotides; and
    wherein the single molecule DNA-targeting RNA is capable of forming a complex with the Cas9 protein, thereby targeting the Cas9 protein to the target DNA molecule, whereby said system is capable of cleaving or editing the target DNA molecule or modulating transcription of at least one gene encoded by the target DNA molecule.

Broad's Motion No. 2 requested that the Board substitute proposed Count 2:

A method, in a eukaryotic cell, of cleaving or editing a target DNA molecule or modulating transcription of at least one gene encoded by the target DNA molecule, the method comprising:
    contacting, in a eukaryotic cell, a target DNA molecule having a target sequence with an engineered and/or non-naturally-occurring Type II Clustered Regularly lnterspaced Short Palindromic Repeats (CRISPR)-CRISPR associated Cas) (CRISPR-Cas) system comprising:
        a) a Cas9 protein, and
        b) RNA comprising
            i) a targeter-RNA that is capable of hybridizing with the target sequence of the DNA molecule or a first RNA comprising (A) a first sequence capable of hybridizing with the target sequence of the DNA molecule and (B) a second sequence; and
            ii) an activator-RNA that is capable of hybridizing to the targeter-RNA to form an RNA duplex in the eukaryotic cell or a second RNA comprising a tracr sequence that is capable of hybridizing to the second sequence to form an RNA duplex in the eukaryotic cell,
    wherein, in the eukaryotic cell, the targeter-RNA or the first sequence directs the Cas9 protein to the target sequence and the DNA molecule is cleaved or edited or at least one product of the DNA molecule is altered.

The distinction Broad made was between embodiments of CRISPR methods that are limited to "single-molecule guide RNA" (aka "fused" or "covalently linked" species), versus embodiments that encompass single-molecule and "dual molecule" species (wherein in the latter versions, the "targeter-RNA" and "activator-RNA" as recited in the proposed Count are not covalently linked).  Broad argued that its Proposed Count 2 should be adopted by the Board because it "properly describes the full scope of the interfering subject matter between the parties because both parties have involved claims that are generic, non-limited RNA claims."  The brief also argued that Proposed Count 2 "sets the correct scope of admissible proofs [i.e., their own] for the breakthrough invention described by the generic claims at issue in these proceedings—the successful adaption of CRISPR-Cas9 systems for use in eukaryotic environments," which Broad contended current Court 1 (in either alternative) does not.

The Board denied this motion for the simple reason that, in its opinion, "Broad fails to provide a sufficient reason why the count should be changed."  Citing Louis v. Okada, 59 U.S.P.Q.2d 1073, 1076 (BPAI 2001) (relied upon in opposition by CVC), the Board notes that it will only change the Count when reasons for doing so are "compelling."  Broad's motion argued that their claims (and CVC's) were directed to eukaryotic embodiments of CRISPR that were not limited to either single- or dual-molecule RNA species, but that the phrase "guide RNA" was generic.  Based on the claim construction, the Board rejected this construction, limiting the claims to single-molecule RNA embodiments.

The Decision also states that "Broad's argument for broadening the scope of the count to be generic as to RNA configuration is unpersuasive."  According to the Decision, CVC convinced the Board that there were other differences between Count 1 (as declared in the interference) and Broad's proposed Count 2.  These include that Count 2 is directed to a method whereas Count 1 recites system or eukaryotic cell.  This is enough, the Board states, for the PTAB to deny Broad's Motion No. 2 simply on these grounds.  The Board also was persuaded by CVC's argument that all of the Broad's claims are directed to "guide RNA" or "chimeric RNA" and thus to single-RNA molecule eukaryotic CRISPR embodiments.  Further, the Board faulted the Broad for not specifically identifying all the claims it contends recite generic eukaryotic CRISPR embodiments with regard to its RNA components.  Continuing, the Decision asserts that Broad also failed to convince the Board that the few claims that expressly recited "fused" RNA embodiments were sufficient under the doctrine of claim differentiation to construe the independent claims as encompassing both single- and dual-RNA molecule eukaryotic CRISPR embodiments.

As is its wont, the Board identified formal deficiencies in some Broad arguments that were sufficient to deny the relief requested under the rubric set forth in 37 C.F.R. § 41.121(b) that "the party filing the motion has the burden of proof to establish that it is entitled to the requested relief."  These include instances where the Broad's brief cited a footnote that does not stand for the cited proposition, and hence that "CVC did not have notice of arguments regarding claim 15 or of any other claim Broad asserts is directed to a generic RNA configuration without using the term 'guide RNA'".  Accordingly, the Board concluded that "[b]ecause Broad did not provide arguments about the interpretation of specific claims in its Motion 2 we are not persuaded by its argument that the scope of the 'vast majority' of its claims requires a broader count."

The Board's Decision also turns on its head the Broad's argument (recited throughout its briefing) that this interference is unfair to Broad due to "CVC's strategic decisions" in earlier Interference No. 105,048 between the parties.  The Board notes that the outcome in that interference, that there was no interference-in-fact, "achiev[ed] Broad's desired remedy–ending the interference."  "Had Broad wished to remain in a priority contest with CVC under the count in that interference, it could have chosen not to file the motion for no interference-in-fact," according to the decision, and thus the Board saw "no unfairness in Broad not having had a chance to present its best proofs in a priority contest with CVC in the '048 interference under these circumstances."

This portion of the decision concludes by denying Broad's alternative remedy of redeclaring the interference with both Counts, the Board stating its reasoning that "Broad fails to explain why this would be an appropriate remedy, given that we are not persuaded that a majority, or even a significant number, of its claims are drawn to a generic RNA configuration."

The remainder of the Board's Decision will be discussed in future posts.