On December 3rd, Junior Party the Broad Institute, Harvard University, and MIT (collectively, Broad) filed its Contingent Preliminary Motion No. 3 in Interference No. 106,133 (which names Sigma-Aldrich as Senior Party), asking the Patent Trial and Appeal Board to designate certain claims deemed in the Declaration as corresponding to the Interference Count as not having such correspondence, under 37 C.F.R. 4 §§ 41.121(a)(1)(i) and 41.207(b)(2).  These claims fall into five discrete categories:

Category A:      Staphylococcus aureus Cas9 protein ("SaCas9");
Category B:      Cas9 chimeric CRISPR enzyme;
Category C:      Cas9 with two or more nuclear localization signals ("NLSs");
Category D:      Cas9 fused to specified protein domains; and
Category E:      Claims that are generic as to RNA and also do not specify integration of a donor polynucleotide sequence ("Donor Template Integration" claims), i.e., the only claims that should remain designated as corresponding to Count 1 are those that are either (i) limited to single molecule RNA ("sgRNA"), or (ii) require Donor Template Integration and are not otherwise separately patentable.

Broad sets forth the claims they ask be de-designated for each example, but perhaps more telling is the recitation of the claims remaining as corresponding to the Count should the motion be granted:  "claims 4, 11 and 18 of U.S. Patent No. 8,697,359 . . . , claim 5 of U.S. Patent No. 8,771,945 . . . , all claims (1-18, 30) of U.S. Patent No. 8,795,965 . . . , claims 2, 5 and 30 of U.S. Patent No. 8,906,616 . . . , claims 8-9, 14, 16 and 27 of U.S. Patent No. 9,840,713 . . . , and claims 14-16 of Application No. 14/704,551 . . ." (references to exhibits and abbreviations omitted).

The brief sets forth the relevant characteristics of the "McKelvey" Count comprising a claim from a Broad-involved patent (claim 18, U.S Patent No. 8,697,359) or claim 31 of Sigma-Aldrich's U.S. Application No. 15/456,204.  Broad makes as a basis for its motion the distinction that the Broad portion of the Count is directed to CRISPR-mediated cleavage in a eukaryotic cell (that "cover[s] many different inventions that are separately patentable from Count 1") while Sigma-Aldrich's portion of the Count recites CRISPR-mediated cleavage coupled with integration of a heterologous DNA molecule, termed "Donor Template Integration," should be de-designated as not corresponding to Count 1 of the '133 Interference (while being "generic" for the structure of the RNA CRISPR component, i.e., single- or dual-molecule embodiments).  The distinctions Broad draws in its argument track the categories of claims set forth above, and Broad argues that "[n]one of the claims directed to those improvements and selections are anticipated by, or obvious in view of Count 1 if considered as prior art alone or in proper combination with the prior art."  The brief reminds the Board that in related Interference No. 106,132, Sigma-Aldrich itself argued that these CRISPR embodiments were not obvious in view of what was known in the art in December, 2012  (see "Sigma-Aldrich Files Substantive Preliminary Motion 1 to Change the Count in Interference No. 106,132").  Broad also argues that "Proposed Count 2 in the 132 Interference and Count 1 (as well as Proposed Count 3) here are materially the same with respect to the relevant Cas9 and NLS related limitations" in support of its Motion.

Getting to the point, the brief argues that Broad's claims "that are both generic as to RNA and not limited to Donor Template Integration" should be de-designated as not corresponding to Count 1 of the '133 Interference as declared (in addition to the categories of claims set forth above).  "The only claims that should correspond to Count 1 are those that either are limited to use of sgRNA (and so correspond to the Broad half of Count 1) or recite Donor Template Integration (and so correspond to the Sigma half of Count 1)," Broad argues.  In addition, Broad argues that its generic claims "that do not limit the RNA configuration to sgRNA are currently designated as corresponding to Count 1," even though the Count is limited to single-molecule guide RNA (sgRNA) and thus should not correspond to the Count (while conceding that the term "guide RNA" was limited to sgRNA by the Board in related Interference No. 106,115).  Broad supports its argument by noting that neither Sigma-Aldrich in this interference or the related '132 Interference, nor ToolGen in related Interference No. 106,126 limit the term "guide RNA" to the sgRNA species.  And under the "plain meaning" rubric of claim construction, Broad argues, the term "guide RNA' should not be limited to the sgRNA species.  Thus, according to Broad, the Board has basis to de-designate many of its claims are not corresponding to the "Broad" portion of McKelvey Count 1 of this interference.

Moreover, Broad argues that many of its claims are not limited to eukaryotic CRISPR embodiments reciting the limitation for Donor Template Integration as recited in the Sigma-Aldrich portion of the McKelvey Count in this interference as declared.  Broad argues the patentable distinction between the invention(s) encompassed by this portion of the Count and Broad's claims is supported by Sigma-Aldrich's consistent arguments, during prosecution of its '204 application-in-interference.  Thus, Broad argues such claims do not correspond to the Count and the Board should accordingly de-designate them from this interference.

The brief then sets forth in detail how its claims limited to each of the categories set forth above are neither anticipated not rendered obvious by the Count as declared and thus are independently patentable from the subject matter defined by the Count.  These claims are identified in the brief as follows:

Category A:      All of the Involved claims of U.S. Patent No. 8,865,406, U.S. Patent No. 8,895,308 and Application No. 15/330,876, because these claims are limited to using Staphylococcus aureus Cas9 protein ("SaCas9") and, at the relevant times (2012) "there were more than 600 bacterial Cas9 orthologs that had been identified" but no suggestion of using SaCas9 in eukaryotic CRISPR embodiments; moreover, SaCas9 and SpCas9 (from Streptococcus pyogenes) shared only 17% amino acid sequence identity.  Regarding the obviousness question Broad also asserts several of the objective indicia of non-obviousness, including unexpected results and commercial success.

Category B:      All of the involved claims of Broad's U.S. Patent No. 8,889,418 ("418 patent") reciting Cas9 chimeric CRISPR enzymes, because these claims are not anticipated by the Count nor would these claims be obvious, a position Broad asserts Sigma-Aldrich itself advanced during prosecution of its '204 application in interference and in the related '132 Interference (supported by expert testimony).

Category C:      All of the claims of U.S. Patent No. 8,871,445, U.S. Patent No. 8,932,814, claim 7 of U.S. Patent No. 8,993,233, claims 9-11 of U.S. Patent Application No. 14/704,551, and claim 34 of U.S. Patent Application No. 15/330,876, which recite Cas9 with two or more nuclear localization signals ("NLSs").  Broad argues that the Broad portion of the Count is limited to Cas9 species bearing a single NLS (and hence does not anticipate) and regarding obviousness that "a POSA would have understood that adding amino acids to a protein such as Cas9 could alter its folding affecting its structure and function in ways that were not predictable."  This position, Broad argues, is one Sigma-Aldrich also took during ex parte prosecution of the '204 application-in-interference and in the related '132 Interference.  Finally, Broad argues unexpected results in the disclosure set forth in U.S. Application No. 61/736,527, filed December 12, 2012.

Category D:      All of the claims (1-43) of Broad's U.S. Patent No. 8,993,233, all claims (1-28) of U.S. Patent No. 8,999,641, claims 18, 19, 25, 29-30, and 36 of U.S. Patent No. 9,840,713, and claim 21 of U.S. Patent Application No. 15/330,876, having claims reciting Cas9 fused to specified protein domains.  Broad argues that the Count recites no such limitation and thus does not anticipate and, as for obviousness, "there is no teaching or suggestion in Count 1 or the prior art directing a POSA to modify the naturally occurring Cas9 protein sequences as set forth in these claims" and the unexpected results set forth in the specifications of these Broad patents and applications supports a conclusion of non-obviousness.  Also, Broad here as elsewhere notes that Sigma-Aldrich has taken a like position the related '132 Interference (albeit directed to NLS-modified Cas9 species).

Category E:      Claims Broad argues do not correspond to the Count as declared in this category "fall into one of three groups:"

1) "claims that do not require an RNA component at all";

2) "claims that are generic as to the RNA component and do not use the term 'guide RNA'"; and

3) "claims that use the term 'guide RNA' but are still generic as to the RNA component under the proper construction of 'guide RNA.'"

These claims include claims 15, 17-26, and 28-41 of U.S. Patent No. 9,840,713; claims 1-24 of U.S. Patent No. 8,889,418; claim 13 of U.S. Patent No. 8,871,445; claims 1, 2, 5, and 30 of U.S. Patent No. 8,906,616; claims 1, 8, 9, and 14 of U.S. Patent No. 9,840,713; claims 1, 4, 8, 11, 15, and 18 of U.S. Patent No. 8,697,359; claims 1 and 5 of U.S. Patent No. 8,771,945; claims 1, 6, 10, 25, 29, and 30 of U.S. Patent No. 8,895,308.

Broad argues that these claims inter alia recite the RNA component of the CRISPR-Cas9 complex as generic with regard to single- and dual-molecule embodiments.  Thus these claims do not correspond to the Broad portion of the Count (although they are within its scope to the extent that they read on sgRNA CRISPR embodiments).  Broad addresses the fact that the Board disagreed with this argument in denying its Preliminary Motion No. 3 in the '115 Interference (see "PTAB Decides Parties' Motions in CRISPR Interference") but asserts that "evidence provided herewith shows that the BRI of "guide RNA" in Broad's claims is not so limited" (although it is unclear how the evidence set forth herein is substantially different).  Nevertheless Broad argues that the plain meaning under the "broadest reasonable interpretation" (BRI) standard supports its arguments, citing Bamberger v. Cheruvu, 55 U.S.P.Q.2d 1523, at *2 (B.P.A.I. 1998), and that their interpretation is further supported by how the term "guide RNA" was used in the art in 2012, in the Sigma-Aldrich application-in-interference here, and by ToolGen in the related '126 Interference.  Broad also argues the intrinsic evidence, specifically the disclosures in the specifications of its patents and applications-in-interference show a pattern of disclosing (and claiming) generically followed by narrowing disclosures and claims to particular RNA species.  Broad invokes the doctrine of claim differentiation in this regard, and recites what it characterizes as "the hierarchy of claim construction as counseling against interpreting claims "in a way that renders them void, meaningless, or superfluous," citing Wasica Fin. GmbH v. Cont'l Auto. Sys., Inc., 853 F.3d 1272, 1288 n.10 (Fed. Cir. 2017), and reciting specific instances as U.S. Patent Nos. 8,895,308 and 8,909,616.  To the extent generic "guide RNA" is disclosed, Broad further argues that interpreting these claims to fall within the scope of a Count directed to sgRNA embodiments would exclude these (preferred) embodiments from the claims, which is "rarely if ever correct," citing Ex Parte Andrew Graham, Ando Feyh, & Bernhard Gehl, Appeal No. 2017-009616, 2018 WL 4356999, at *3 (P.T.A.B. Aug. 23, 2018), and MBO Labs., Inc. v. Becton, Dickinson & Co., 474 F.3d 1323, 1333 (Fed. Cir. 2007).  Finally, Broad recites extrinsic evidence in support of its arguments, including Jinek 2012 (A programmable dual-RNA-guided DNA endonuclease in adaptive bacterial immunity, Science 337: 816-821), Sigma-Aldrich's disclosure, the disclosure in ToolGen's application-in-interference at issue in the '126 Interference.

With regard to the Sigma-Aldrich portion of the McKelvey claim Count, the Board's failure to de-designate these claims would "work an unfairness to Broad and unfairly reward Sigma for limiting its claims in prosecution" because Sigma itself had represented to the USPTO, in both ex parte examination and in the related '132 Interference that such claims were patentably distinct from claims falling within the scope of the Broad portion of the Count (i.e., directed to "cleavage-only" aspects of CRISPR practiced in Broad's claims).

Finally, Broad recites arguments raised in other interferences regarding its "best proofs" related to dual-molecule RNA embodiments of CRISPR and to the Board's decision (affirmed by the Federal Circuit) in Eli Lilly & Co. v. Bd. of Regents of Univ. of Wash., 334 F. 3d 1264, 1268 (Fed. Cir. 2003), directing that the one-way test for determining interference-in-fact would be "over-inclusive" because a "'genus [that] was invented before' a species is 'separately patentable from, the species' for the purposes of determining an interference-in-fact."

The brief is supplemented with Appendices including, inter alia, a Summary Chart of Grounds and Claims (Appendix C) and a Claim Differentiation Chart (Appendix D).