On May 28th, Junior Party the Broad Institute, Harvard University, and MIT (collectively, “Broad”) filed its Substantive Preliminary Motion No. 3 in CRISPR Interference No. 106,126 (where ToolGen is the Senior Party). This motion, pursuant to 37 C.F.R. §§ 41.121(a)(1)(iii) and 41.208(a)(1) requests that the Board de-designate Broad claims in these five categories as not corresponding to either Count 1 or proposed Count 2 (A-E) or Count 1 (F):
• Category A: use of vectors for RNA expression;
• Category B: Staphylococcus aureus Cas9 protein (“SaCas9”);
• Category C: Cas9 chimeric CRISPR enzyme;
• Category D: Cas9 with two or more nuclear localization signals (“NLSs”);
• Category E: Cas9 fused to specified protein domains; and
• Category F: Claims not limited to single-molecule RNA.
The brief asserts that, should the Board grant this motion and deny Broad Substantive Motion No. 1 (see “Broad Files Substantive Preliminary Motion No. 1 in CRISPR Interference“) these of the Broad claims would correspond to Count 1:
claim 18 of U.S. Patent No. 8,697,359, claims 26-30 of U.S. Patent No. 8,795,965, claims 2 and 5 of U.S. Patent No. 8,906,616,and claim 16 and 27 of U.S. Patent No. 9,840,713 [exhibit references omitted]
while should the Board grant both this motion and Broad’s Motion No. 1, these of Broad’s claims would remain in the interference as corresponding to Proposed Count 2:
claims 15-20 of the ‘359 patent, claims 26-29 of U.S. Patent No. 8,771,945, claims 26-30 of the ‘965 patent, claims 24-30 of U.S. Patent No. 8,889,356, all claims of the ‘616 patent, claims 21-28 of U.S. Patent No. 8,945,839, and claims 15-17, 20-24, 26-28, 31-35, and 38-39 of the ‘713 patent, as well as allowable claims 1, 40, and 41 of Application 15/160,710 and allowable claims 74, 94, and 95 of Application 15/430,260 should the Board also grant Broad’s Contingent Substantive Motion No. 2 [see “Broad Files Contingent Preliminary Motion No. 2 in CRISPR Interference“; exhibit references omitted]
(the exercise nicely illustrating the strategic considerations involved in Preliminary Motion interference practice).
These five categories comprise claims drawn to “patentably distinct” inventions from the inventions within the scope of either Count 1 or Count 2. Broad argues that these distinctions are neither disclosed nor obvious in view of the Counts as they would be understood by those having ordinary skill in the art. Moreover, and consistent with Broad’s arguments in this interference and in Interference No. 106,115 Broad contends that dual-molecule and single molecule guide RNA embodiments of CRISPR are also patentably distinct and claim not limited to single-molecule embodiments should be de-designated as not corresponding to Count 1. And as Broad argued with regard to Substantive Motion No. 1 in this interference, ToolGen’s disclosure and claims are not to the contrary.
The brief then sets forth its arguments why claims from each of these categories do not correspond to the Count:
• Category A (use of vectors for RNA expression): neither of the Counts recite limitations regarding use of a vector for delivering RNA species to eukaryotic cells (for example, microinjection is an alternative). In the absence thereof Broad argues there is no anticipation, and there is also any reasoned basis for choosing a vector (and, consistent with Broad’s arguments against CVC’s reduction to practice, no reasonable basis for success in introducing these specie using a vector into eukaryotic cells) and thus these embodiments would not have been obvious. Broad relies on expert testimony adduced in the ‘115 Interference (and Interference No. 106,048 before that), as well as ToolGen’s evidence in this interference, to argue that practicing CRISPR in eukaryotic cells would face terrible obstacle and would not have been routine, obvious, or subject to reasonable expectations of success. Stating that “[t]he prior art does not teach or suggest the use of, or providing reasons to select from that list, a vector for delivery of the RNA,” Broad argues that “[w]here, as here, the prior art provides a number of choices, without any reason to make a particular selection, the selection is not obvious,” citing Ortho-McNeil Pharm., Inc. v. Mylan Labs., Inc., 520 F. 3d 1358, 1364 (Fed. Cir. 2008). Broad also asserts unexpected results and commercial success in support of the non-obviousness of using a vector to express RNA species in eukaryotic embodiments of CRISPR.
• Category B (Staphylococcus aureus Cas9 protein): Broad argues that neither Count contains a limitation for using Cas9 from aureus (and thus does not anticipate) and that there is no basis either for choosing this species of Cas9 nor would it have been obvious to do so. Citing the “more than 600 bacterial Cas9 analogues” known in the art, Broad asserts that “[w]here, as here, the prior art choices are vast, the prior art must provide some reason to make the selection in order to find obviousness,” citing Ortho-McNeil Pharm., Inc. v. Mylan Labs., Inc., 520 F.3d 1358, at 1364 (Fed. Cir. 2008).” In arguing that S. aureus Cas9 CRISPR embodiments would not have been obvious. There is no significant sequence similarity between S. aureus Cas9 and Staphylococcus pyogenes Cas9 known in the art, and the smaller size of the S. aureus Cas9 ortholog was not recognized as being preferred at the time the parties conceived of eukaryotic CRISPR embodiments. As with Category A, Broad argues unexpected results and commercial success for S. pyogenes Cas9 embodiments in support of its non-obviousness contentions.
• Category C (Cas9 chimeric CRISPR enzyme): citing embodiments claimed in Broad’s U.S. Patent No. 8,889,418, Broad argues that there is no disclosure in the art relating to Cas9 enzymes chimeric in comprising fragments from two different Cas9 proteins. Broad cites disclosure from the ‘418 patent regarding the benefits of chimeric Cas9 unknown in the prior art and not recited in the Counts in support of these contentions.
• Category D (Cas9 with two or more NLS): NLS-comprising Cas9 species are not recited in either Count and hence claims reciting these alternatives are not anticipated by the Counts. With regard to obviousness, Broad argues that there was no teaching nor suggestion regarding Cas9 proteins modified with any NLS, much less to of them. In addition to arguing no reasonable expectation of success (based on purported folding and other protein changes grafting NLS-encoding amino acid sequence onto Cas9) Broad argues that its inventors showed unexpectedly improved in vivo eukaryotic CRISPR results using Cas9 enzymes having more than one NLS.
• Category E (Cas9 fused to specified protein domains): Broad makes similar arguments as it does for Categories C and D with regard to this category, for much of the same reasons.
• Category F (Claims not limited to single-molecule RNA): while limiting this category to claims corresponding to Count 1 (and not Count 2), Broad provides in brief arguments made in the ‘115 Interference and with regard to its Substantive Motion No. 1 in this interference. The brief specifically explicates Broad’s arguments for involved claims in its ‘713, ‘418, ‘308, and ‘616 patents, including claim differentiation arguments with regard to construction of the term “guide RNA,” which the Board limited to sgRNA species in the ‘115 Interference (a decision Broad continues to dispute).
Finally, Broad takes its opportunity to again argue that its involved claims encompassing both dual-molecule and single-molecule RNA species should not correspond to Count 1, for reasons set forth in its Substantive Motion No. 1 in this interference and in the’115 Interference.