The parties in Interference No. 106,133, namely Senior Party Sigma-Aldrich and Junior Party the Broad Institute, Harvard University, and MIT (collectively, "Broad"), filed their respective lists of proposed preliminary motions four days prior to their August 3rd teleconference with the Board to present their arguments for the Board to grant leave to file any of them.

Junior Party Broad proposed Substantive Preliminary Motion No. 1, to change the Count under 37 C.F.R. §§ 41.121(a)(1)(i) and 41.208(a)(2).*  The justification here as in earlier interferences (Nos. 106,115 and 106,126) is to provide "a count broad enough to cover Broad's best proofs, which are directed to CRISPR-Cas9 systems using dual-molecule RNA but not including a donor polynucleotide sequence."  Proposed substitute Count 2 is:

A CRISPR-Cas9 system, for use in a eukaryotic cell, comprising:
    a) a Cas9 or a nucleic acid encoding the Cas9 and
    b) an RNA or a nucleic acid encoding the RNA, wherein the RNA is a dual RNA comprising a CRISPR RNA (crRNA) and a trans activating crRNA (tracrRNA) or wherein the RNA is a chimeric RNA comprising a crRNA fused to a tracrRNA,
wherein the crRNA directs the Cas9 to a target sequence in a eukaryotic cell, whereby a site-specific, double-strand break is introduced, or the target sequence is edited.

Once again, Broad's argument involves the purported "fairness" that this Count provides compared with the Count as declared, which Broad asserts "does not appropriately capture the common subject matter," i.e., "use of CRISPR-Cas9 systems in eukaryotic cells."  Broad's "best proofs," they argue, "include dual-molecule RNA systems without a donor polynucleotide" (this latter feature recited in Sigma-Aldrich's alternative to Count 1).  In addition, Broad argues that Sigma-Aldrich's invention is likewise not limited to single-molecule RNA embodiments of CRISPR (for clarity, these embodiments comprise a fusion of the crRNA species, specific for the target, and tracrRNA which interacts with Cas9 in forming the CRISPR complex).  Moreover, Broad cites portions of Sigma-Aldrich's prosecution history to support its motion, reminding the Board that Sigma-Aldrich asserted to the Examiner that the party "reserves the right to file patentably distinct CRISPR cleavage-only claims at a later date in one or more continuing applications."  According to Broad, Sigma-Aldrich sought to provoke an interference directed to "methods of integrating a donor polynucleotide sequence into the chromosomal sequence of a eukaryotic cell," and understandably reminds the Board that the only CRISPR interference that has reached a conclusion, No. 106,048 (which Broad "won" by having the Board find no interference-in-fact), had a scope that encompassed both single molecule and dual molecule RNA CRISPR embodiments.  And the "best proofs" Broad refers to are its achievement (disputed by Junior Party CVC in Interference No. 106,115) of dual molecule CRISPR embodiments in eukaryotic cells in 2011.

Broad also proposes an alternative Count 3 under 37 C.F.R. §§ 41.121(a)(1)(i) and 41.208(a)(2), intended to limit the scope of the interference to the extent that would support a motion by Broad to declare most of its claims to not correspond to the substituted Count.  Proposed Count 3 recites in the alternative claim 52 of Broad involved application 16/177,403:

A method comprising: introducing into, or expressing in, a eukaryotic cell having a DNA molecule,
    (I)    a Cas9 protein or one or more nucleotide sequences encoding the Cas9 protein;
    (II)   an RNA or one or more nucleotide sequences encoding the RNA, the RNA comprising: (a) a first RNA comprising a first ribonucleotide sequence and a second ribonucleotide sequence, and (b) a second RNA; and
    (III) a template polynucleotide;
wherein the second RNA forms an RNA duplex with the second ribonucleotide sequence, and wherein, in the eukaryotic cell, the first ribonucleotide sequence directs the Cas9 protein to a target sequence of the DNA molecule, whereby the Cas9 cleaves both strands of the DNA molecule and the cleavage is repaired by integration of the template polynucleotide into the DNA molecule in the eukaryotic cell.

Or, as in this interference as declared, claim 31 of U.S. Application No 15/456,204.  Broad justifies this Proposed Count 3 by asserting that:

Sigma limited its claims to only those requiring use of a donor polynucleotide, arguing that this specific limitation rendered its claims non-obvious over Jinek 2012 and Kim P1.  Having so limited its claims to only those requiring a donor polynucleotide in order to secure allowance, Sigma should not now be permitted to attempt to claim for itself broader subject matter ([i.e.,]use of CRISPR-Cas9 in eukaryotic cells more generally without a template, the subject matter of Broad's half of Count 1).

Broad helpfully recites the claims in Broad's involved application and patents that would remain in the interference should the Board substitute Proposed Count 3 in this interference:  "U. S. Patent No. 8,871,445, claim 13; U.S. Patent No. 8,932,814, claims 2, and 14-15; U.S. Patent No. 8,889,356, claims 2 and 14; U.S. Patent No. 9,840,713, claim 14; and application 14/704,551, claims 14-15" (as well as claims 52-56 of U.S. Application No. 16/177,403 should the Board grant a series of contingent motions, vide infra).

Again, pursuant to 37 C.F.R. §§ 41.121(a)(1)(i) and 41.208(a)(2), Broad proposes a series of Contingent Preliminary Motions dependent upon the Board granting its Substantive Motion No. 1 for either of the Proposed Substitute Counts.  Under circumstances where the Board grants Broad's Motion No. 1 to substitute Proposed Count 2, Broad asks the Board to grant leave to add to the interference claims 1 and 40-41 of Application No. 15/160,710; and claims 74 and 94-95 of U.S. Application No. 15/430,260.  Under circumstances where the Board grants Broad's Motion No. 1 to substitute Proposed Count 3, Broad asks the Board to grant leave to add to the interference claims 52-56 of U.S Application No. 16/177,403.

In a second Contingent Preliminary Motion Broad asks the Board for leave to designate claims as not corresponding to the substituted Count under 37 C.F.R. §§ 41.121(a)(1)(iii) and 41.208(a)(2), based on such claims reciting a Staphylococcus aureus Cas9 species not disclosed in Sigma-Aldrich's application, including all involved claims of Broad U.S. Patent Nos. 8,865,406 and 8,895,308, as well as claims 1, 16-21, and 30-40 of U.S. Application No. 15/330,876.  Under the same Rules, Broad asks the Board to de-designate all involved claims of its U.S. Patent No. 8,889,418 based on limitations in those claims that the Cas9 comprising the claimed CRISPR complex is chimeric, i.e., comprised of first and second protein fragments from different Cas9 proteins.  Also contained in this proposed Contingent Preliminary Motion is Broad's request that the Board de-designate all involved claims of its U.S. Patent Nos 8,871,445 and 8,932,814, as well as claim 7 of U.S. Patent No. 8,993,233 and claims 9-11 of U.S. Application No. 14/704,551 and claim 34 of U.S. Application No. 15/330,876.  The basis for this request is that these claims recite Cas9 species with improved nuclear localization by incorporation of more than one nuclear localization signal.  Broad further asks the Board for leave to file a Contingent Preliminary Motion to de-designate all involved claims of U.S. Patent Nos. 8,993,233 and 8,999,641 and claims 18-19, 25, 29-30 and 36 of U.S. Patent No. 9,840,713 and claim 21 of U.S. Application No. 15/330,876 on the basis that these claims do not recite Cas9 species fused to "specified protein domains or [that] includes one or more heterologous domains or includes a functional domain."  Finally, Broad asks the Board for leave to file a Contingent Preliminary Motion to de-designate all involved claims of U.S. Patent Nos 8,865,406; 8,889,356; 8,889,418; 8,932,814; 8,945,839; 8,993,233; and 8,999,641, as well as claims 1-3, 5-20, 12-17, and 19-20 of U.S. Patent No. 8,697,359; claims 1-4 and 6-19 of U.S. Patent No. 8,771,945; claims 1-12 and 14-30 of U.S. Patent No. 8,871,445; claims 1-9, 11-14, 16-25, and 27-28 of U.S. Patent No. 8,895,308; claims 1, 3-4 and 6-30 of U.S. Patent No. 8,906,616; claims 1-7, 10-13, 15, 17-26, and 28-41 of U.S. Patent No. 9,840,713, and claims 2, 4-13, and 16-18 of U.S. Application No. 14/704,551.  As Broad summed up, if the Board granted these motions:

[C]laims 4, 11, and 18 of U.S. Patent No. 8,697,359; claim 5 of U.S. Patent No. 8,771,945; claims 1-20 (all involved claims) of U.S. Patent No. 8,795,965; claim 13 of U.S. Patent No. 8,871,445; claims 10, 15 and 26 of U.S. Patent No. 8,895,308; claims 2 and 5 of U.S. Patent No. 8,906,616; claims 8-9, 14, 16, and 27 of U.S. Patent No. 9,840,713, claims 14 and 15 of application 14/704,551 and claims 1, 16-21, and 30-40 (all involved claims) of application 15/330,876 would remain designated as corresponding to Count 1 (although some of those claims are subject to other grounds for being designated as not corresponding to the Count) as those are the only involved claims that require chimeric RNA where the RNA components are fused or covalently linked through intervening nucleotides in the CRISPR-Cas9 complex and/or inclusion of a donor polynucleotide for HDR after DSB [i.e., these would be the only Broad claims involved in this Interference].

Broad also asked the Board for leave to file two additional substantive motions.  Broad Substantive Preliminary Motion No. 2 seeks judgment of unpatentability under 37 C.F.R. §§ 41.121(a)(1)(iii) on the basis that Sigma-Aldrich's involved application (Application No. 15/456,204) is not entitled to priority benefit to its first provisional application, U.S. Application No. 61/734,256, for failing to provide an adequate written description and for failing to provide a constructive reduction to practice of the claimed subject matter.  In addition, Broad argues that without such benefit prior art including Broad's Cong et al. paper (Science 339: 819-23, January 3, 2013), Mali et al., Science 339: 823-26, January 3, 2013, and U.S. Publication No. 2014/0342457, claiming priority to U.S. Application No. 61/738,355, filed December 17, 2012, are invalidating prior are under § 102 and/or § 103.

Broad's final proposed Substantive Preliminary Motion No. 3 is brought under 37 C.F.R. § 41.121(a)(3) and asks the Board to enter an Order requiring Sigma-Aldrich to keep Broad and the Board abreast of any issuance or notice of allowance for any related, pending applications.

And of course, Broad filed a motion under 37 C.F.R. § 41.208(a)(4) seeking judgment based on priority.

For its part, Sigma-Aldrich filed its list of three proposed Substantive Preliminary Motions.  In proposed Substantive Preliminary Motion No. 1, under 37 C.F.R. § 41.121(a)(1), Sigma-Aldrich asks the Board to deny Broad standing in this interference, based on failing to satisfy the requirements under the Leahy-Smith America Invents Act to fall under prior "first to invent" regime under the 1952 Patent Act.  Sigma-Aldrich asks the Board to consider this a threshold motion under 37 C.F.R. § 41.201.  Sigma-Aldrich contends that "[e]ach of Broad's involved patents and applications is subject to the first inventor-to-file ("FITF") law, regulations, rules, and procedures, as enacted and promulgated as a consequence of the AIA" because "each of Broad's involved patents and applications contains claims to subject matter that (a) contains (or at one time contained) a claim to a claimed invention having an effective filing date after March 16, 2013; and/or (b) claims (or at one time claimed) the benefit of an earlier filing date based upon an earlier application that contained such a claim," citing M.P.E.P. § 2159.02.  (CVC asked the Board for leave to file a similar Preliminary Motion in Interference No. 106,048).  Rather than burdening the text of the motion, Sigma-Aldrich provides its detailed support for this Motion in an appendix, providing in its argument a list of five claim limitations it contends were not supported by pre-AIA disclosures.  Sigma-Aldrich contends that "while an applicant is permitted to rely upon the filing date of an earlier-filed patent application, an applicant is not permitted to submit evidence of earlier invention, e.g., evidence of earlier conception and reduction to practice" under the AIA, and thus Broad lacks standing to submit any evidence of invention earlier than its first priority date, December 12, 2012, for U.S. Application No. 61/736,527 (also known as "Broad P1" in this and related CRISPR interferences).

Sigma-Aldrich's Substantive Preliminary Motion No. 2 under 37 C.F.R. § 41.121(a)(1) asks the Board to deny Broad benefit of priority to seven provisional applications in addition to P1 filed between December 12, 2012 and March 15, 2013 (P2: Application No. 61/748,427, filed Jan. 2, 2013; P3: Application No. 61/758,468, filed January 30, 2013; P4: Application No. 61/768,595, filed February 25, 2013; P5: Application No. 61/769,046, filed February 25, 2013; P6: Application No. 61/791,409, filed March 15, 2013; and P7: Application No. 61/802,174, filed March 15, 2013).  (Sigma-Aldrich notes in a footnote that these provisional applications were all filed before the effective date of the AIA, and that while Broad has 14 other related provisional applications, the complexities of their interrelatedness preclude considering the deficiencies in their disclosures in this single Motion.)  The basis for this Motion is that in these applications Broad did not demonstrate a constructive reduction to practice of an invention according to the Count, wherein is recited "a method of using CRISPR-Cas9 in a eukaryotic cell to successfully cleave a target DNA and thereafter to successfully either integrate a donor DNA sequence into that cleaved target DNA, or alter the expression of the gene product of that cleaved target DNA."

Sigma-Aldrich's Substantive Preliminary Motion No. 3 under 37 C.F.R. § 41.121(a)(3) seeks to remove Broad's allowed Application No. 15/330,876 from the interference, because "[a]ll of the claims in the '876 application are directed solely to, inter alia, a composition of CRISPR-Cas9 in a eukaryotic cell to simply cleave a target DNA molecule" and "[n]one of the claims in the '876 application recite further that the composition subsequently integrates a donor DNA sequence into the target DNA molecule, nor do they recite further that the composition alters the expression of the gene product of the cleaved target DNA molecule."  Accordingly, because "none of Broad's claims in the '876 application is substantially the same as (i.e., patentably indistinct from) Sigma's claims in the present interference . . . none of the claims in the '876 application interferes with any of the claims of Sigma's involved Application 15/456,204."

Sigma-Aldrich also seeks a Protective Order such as the one entered in other CRISPR interferences, and finally filed a motion under 37 C.F.R. § 41.208(a)(4) seeking judgment based on priority.

In addition, Sigma-Aldrich asks the Board to address some "miscellaneous administrative issues" such as deadlines for filing and service in this interference and asks the Board to waive the requirement for a separate Statement of Material Fact or not have these pages be included in the page limit.

Future posts will discuss the parties arguments at the August 3rd teleconference and the Board's determinations regarding which Preliminary Motions the parties will be permitted to file.

* Readers familiar with the other CRISPR interference will recognize this motion.