On March 23rd, Senior Party The Broad Institute, Harvard University, and the Massachusetts Institute of Technology (collectively, "Broad") filed its Reply to Junior Party the University of California/Berkeley, the University of Vienna, and Emmanuelle Charpentier (collectively, "CVC") Motion No. 3 in Opposition to Broad's Substantive Motion No. 3 to de-designate claims as not corresponding to Count 1.

In its Motion No. 3, the Broad reiterated the arguments made in Motion No. 2, that there are two embodiments of CRISPR, one involving single-molecule RNA guide RNA (which the Broad argues here is not recited in the claims it wants the Board to designate as not corresponding to the Count) and further that certain of the Broad's claims directed to "SaCas9" systems that require two or more NLSs do not correspond to the Count.

The brief parsed the Broad's claims into three categories of claims that do not correspond to the Count, depending on how the Board rules on Substantive Motions Nos. 1 and 2:

• USP 8,865,406 – Claims 1-30 (all); 8,871,445 – Claims 1-30 (all); USP 8,889,356 – Claims 1-30 (all); USP 8,932,814 – Claims 1-30 (all); USP 8,945,839 – Claims 1-28 (all); USP 8,993,233 – Claims 1-43 (all); USP 8,999,641 – Claims 1-28 (all); USP 8,697,359 – Claims 1-3, 5-10, 12-17, and 19-20; USP 8,771,945 – Claims 1-4 and 6-29; USP 8,895,308 – Claims 1-9 and 11-28; USP 8,906,616 – Claims 1, 3-4, 6-30; USP 9,840,713 – Claims 1-7, 10-15, 17-26, and 28-41; and U.S. Patent Application No. 14/704,551: in the event that the Board denies both Motions No. 1 and 2

• USP 8,865,406 – Claims 1-30 (all) and USP 8,895,308 – Claims 1-30 (all): in any event, claims reciting Ca9 from Staphylococcus aureus

• USP 8,871,445 – Claims 1-30 (all); USP 8,932,814 – Claims 1-30 (all); USP 8,993,233 – Claim 7; USSN 14/704,551 – Claims 9-11: clams reciting two or mote nuclear localization signal

And what would remain, should the Board grant this motion:

• U.S. Patent No. 8,697,359, claims 4, 11, and 18; U.S. Patent No. 8,795,965, claims 1-30 (all); U.S. Patent No. 8,771,945, claim 5; U.S. Patent No. 8,906,616, claims 2 and 5; and U.S. Patent No. 9,840,713, claims 8-9, 16, and 27

Regarding the first set of claims the Broad asserted do not correspond to Count No. 1, the Broad argued that the Count of the interference as declared is directed to "single-molecule guide RNA molecule"-comprising embodiments and the claims it has asked the Board to designate as not corresponding to the Count do not encompass these embodiments.  The brief set forth the Broad's understanding that, should the Board deny the Broad's Substantive Motions Nos. 1 and 2, then the interference will involve priority to such single-molecule guide RNA embodiments as a separate, patentable invention over claims that encompass both single-molecule and dual molecule embodiments.  Under PTAB Rule 207(b), the Board provides relief to an inventor of a generic claim facing a specific count to move, as the Broad has done here, for their generic claims to be designated as not corresponding to the Count.  Thus, the Broad argued that its claims limited to dual-molecule embodiments do not correspond to the Count and the Board should so designate.

The Broad also argued that its claims to SaCas9 embodiments and to claims requiring two or more nuclear localization sequences (NLS's) do not correspond to Count 1.  The Broad argued that these embodiments were not disclosed in the prior art and "provide[] a surprising combination of benefits not taught or suggested by the art" for both types of embodiments.

In its Opposition, CVC argued that the Board should decide the issue under Rule 207(b)(2):

A claim corresponds to a count if the subject matter of the count, treated as prior art to the claim, would have anticipated or rendered obvious the subject matter of the claim.  37 C.F.R. §41.207(b)(2).

CVC argued that this Rule gave the Board ample reason to deny Broad's Motion No. 3; in addition CVC argued that Broad had not satisfied the burden set forth in 37 C.F.R. §§ 41.121(b) and 41.208(b) that it was entitled to the relief requested.  And CVC argued that the Broad will not be able to meet this burden because a claim to a species (single-molecule guide RNA CRISPR embodiments) anticipates a claim to a genus (generic-guide RNA CRISPR embodiments), citing In re Gostelli, 872 F.2d 1008 (Fed. Cir. 1989).

CVC also argued that Broad could not rely on its experts' testimony because these experts did not review documentary evidence supporting the Broad's assertions that the Broad inventors practiced generic-guide RNA CRISPR in 2011 (prior to CVC's earliest priority date), as the Broad alleges in its motion.

And with regard to the Broad's arguments concerning S. aureus Cas9 claims and claims reciting multiple nuclear localization signal (NLS), that the Broad argued should be de-designated as not corresponding to Count 1, CVC made its case that these proteins were known in the art and their smaller size and capacity to be introduced using adeno-associated virus (AAV) vectors would have motivated a person of ordinary skill in the art to use them for eukaryotic CRISPR and further that there would be a reasonable expectation of success in doing so.  CVC also made a detailed case with regard to why the SaCas9 species are not patentably distinct, as well as similar arguments regarding CRISPR embodiments comprising multiple NLS species.

Broad in its Reply argues that CVC did not address the "unfairness" of maintaining designation of certain of its claims as identified in its Motion No. 3 as corresponding to Count 1.  Broad argues that designating generic claims to what it maintains is a "single-molecule" guide RNA-reciting Count is unfair and Broad should not be made to present a full priority showing. Broad argues that "CVC seeks to prevent the PTAB from making any priority determination as 3 to who invented the generic RNA eukaryotic CRISPR invention first" while at the same time opposing Broad Motion No. 3, which inter alia seeks to remove Broad's generic guide RNA claims from the Interference.  Broad argues that the Board denying Broad's Motion Nos. 2 and 3 "would be unjust, unfair, and illogical" and that "CVC's arguments to the contrary fail in every respect."  As a consequence, according to Broad, the Board could award priority for generic guide RNA claims to the party (in Broad's opinion, CVC) that was not (in Broad's opinion) the first to invent uses of CRISPR in eukaryotic cells.

The brief further argues that whether Broad performed dual-molecule guide RNA experiments before CVC (which it asserts its inventors did) is not relevant to the fairness question.  The brief characterizes CVC's Opposition to require Broad to make a "full priority showing" to prevail in its Motion No. 3, which Broad argues is not the proper place and that, "if the Interference proceeds with Count 1 only, Broad will never be permitted to make such a showing during the priority phase as to the generic invention."  "Broad should not be at risk of losing those generic claims if it is not allowed to show priority as to the generic invention," according to the Reply brief.

Procedurally, Broad argues that CVC did not address the contingent nature of Broad' Motion No. 3, which the Board will only consider if it determines that the generic guide RNA and single-molecule guide RNA embodiments are separately patentable.  And, reiterating its unfairness theme, the brief asserts that "[i]f there is no patentable distinction, but the interference still proceeds with Count 1, Broad would be precluded from relying on its dual-molecule proofs that fall within the scope of the single invention at issue."

As it has done in other Replies, Broad asks the Board to reject what it terms "attorney argument" made by CVC regarding Broad's early single molecule work.  This includes CVC's argument (as Broad interprets it) that the early experiments performed by Broad inventors used single-molecule guide RNA, which Broad disputes based on Inventor Zhang's declaration and the factual allegations contained therein (as it did in its Reply to CVC's Opposition to Motion No. 2, the brief contains this illustration from Dr. Zhang's declaration, which Broad argues shows that its inventors' earliest experiments applying CRISPR to eukaryotic cells employed dual-molecule guide RNAs:

Addressing the contingencies regarding the Board's consideration of Broad's Motion No. 2 to substitute the Count, by arguing that in any event Broad's generic guide molecule claims identified in its Motion should not correspond to either Count.

Regarding CVC's invocation of Rule 207(b)(2), Broad argues that the Rule is not inflexible but raises a presumption (by the plain language of the Rule) that can be and has been rebutted in this case.  The brief disputes CVC's "rigid" interpretation of the Rule, rejects application of Executive Orders cited by CVC in its opposition, and accuses CVC of itself relying on the rebutability of the Rule 207 presumption on its own behalf.  The brief challenges CVC's assertions in this regard that CVC's own prior statements were made in the context of a two-count interference and that Broad's claims are all limited to single-molecule CRISPR systems.

Finally, Broad argues that neither SaCas9 nor claims reciting two or more NLSs are obvious over the prior art.