1DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on September 25, 2026 has been entered.
Applicants’ previously canceled claims 1-57, and now cancel claims 62 and 68. Applicants amend claims 58, 61, 63-64, 67, 69-70, and 77, and add new claims 78-79. Claims 58-61, 63-67, and 69-79 are pending in this application and are under examination.
Any objection or rejection of record in the previous Office Action, mailed March 25, 2026, which is not addressed in this action has been withdrawn in light of Applicants’ amendments and/or arguments.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 58-61, 63-67, 69, and 78-79 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-11 of U.S. Patent No. 11,180,793. This rejection is modified as necessitated by Applicants’ amendments.
Although the claims at issue are not identical, they are not patentably distinct from each other because both the ‘793 patent and the instant application claim methods of screening for and determining the stability of Cas9/gRNA complexes using melting point determinations and comparisons with reference Cas9/gRNA complexes. Both the ‘793 patent and the instant application claim methods of determining the stability of such complexes using thermal assays, including differential scanning fluorimetry, differential scanning calorimetry, or isothermal titration calorimetry. Both the ‘793 patent and the instant application claim that Cas9/gRNAs can be screened/selected/stability determined by comparing the Tm values of a Cas9/gRNA complex and a Cas9 molecule in the absence of a gRNA. Both the ’793 patent and the instant application claim evaluation of guide RNAs that are different, which is interpreted as differing in length, sequence, and/or modifications. Because the claims for the ’793 patent and the instant application claim the same methods having the same steps, the claims are not deemed to be patentably distinct.
Claims 70-77 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-11 of U.S. Patent No. 11,180,793 in view of Wu et al. (32(7) Nature Biotechnology 670-676. Online Methods (2014), and cited in the Information Disclosure Statement filed April 21, 2022). This rejection is modified as necessitated by Applicants’ amendments.
The ‘793 patent claims methods of screening for and determining the stability of Cas9/gRNA complexes, as discussed above.
The ‘793 patent does not claim methods of determining binding activity of the Cas9/gRNA complex.
Regarding claim 70, Wu discloses that inactive Cas9 can be loaded with guide RNAs in mouse embryonic stem cells (abstract). Wu discloses a two-stage model of Cas9 binding and cleavage (abstract).
Regarding claim 71, Wu discloses that the ability of a Cas9/gRNA complex to target sites can be measured, which is interpreted as including measuring the binding of the complex components (paragraph bridging pages 670 and 671 and Figure 1).
Regarding claim 72, Wu discloses the use of libraries as control samples, which is interpreted as being able to determine a relative binding value of a Cas9/gRNA Page 671, column 1, second full paragraph to column 2, second full paragraph).
Regarding, claims 73-74, Wu discloses testing the binding ability of the Cas9/gRNA complex by use of in vitro gel shift assays (a kinetic assay to determine binding activity (page 671, column 2, first full paragraph, Figure 2, and Online Methods, Gel Shift Assy).
It would have been obvious to one with ordinary skill in the art before the effective filing date of the claimed invention to use Wu’s gel shift assay to determine the binding ability of the Cas9/gRNA complex in order to determine the stability of the complex according to the ‘793 patent. One of ordinary skill in the art would have had a predictable and reasonable expectation of success in using Wu’s assay, in conjunction with the thermal stability assay of the ‘793 patent because by measuring the binding ability of a Cas9/gRNA complex can provide information as to the ability of the complex to act on a target sequence, whether inducing cleavage, insertions, or deletions of sequences.
Response to Amendments and Arguments
Regarding the rejections under 35 U.S.C. § 103, Applicants’ amendments and arguments have been fully considered and are deemed to be persuasive. Because none of the cited prior art disclose or suggest methods of screening for a cas9/gRNA complex by detection of melting points, where the selection is based upon the change/difference in melting temperatures between a Cas9/gRNA complex and a Cas9 molecule in the absence of a gRNA.
Regarding the non-statutory double patenting rejections over U.S. Patent No. 11,180,793, Applicants request that these rejections be held in abeyance until the claims are otherwise indicated as allowable. Therefore, these rejections are maintained.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to NANCY J LEITH whose telephone number is (313)446-4874. The examiner can normally be reached Monday - Thursday 8:00 AM - 6:30 PM.
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NANCY J. LEITH
Primary Examiner
Art Unit 1636
/NANCY J LEITH/Primary Examiner, Art Unit 1636
