DETAILED 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 .
Election/Restrictions
1. Applicant’s election without traverse of the invention of Group I (drawn to an SCN10A-targeting sgRNA) in the reply filed on 11/25/2025 is acknowledged.
Claim 17-20 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.
Claims 1-16 are under examination.
Claim Objections
2. Claims 1 and 14 should recite “and 23799” in the last line.
3. Claims 2 and 15 should recite “and 39795” in the last line.
4. Claims 3 and 16 should recite “and 26128” in the last line.
5. Claim 10 should recite “the Cas9” in the first line.
6. Claims 14 is objected to because of the recitation “is selected from any one of” in line 11. Correction to “is selected from” is required.
7. Claim 15 is objected to because of the recitation “is selected from any one of 22845,”. Correction to “is selected from SEQ ID NOs: 22845” is required.
8. Claim 16 is objected to because of the recitation “is selected from 22845 or 26128”. Correction to “is selected from SEQ ID NOs: 22845 and 26128” is required.
Double Patenting
9. 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 U SPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re V ogel, 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.
10. Claims 14-16 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-10 of U.S. Patent No. 11,601,313. Although the claims at issue are not identical, they are not patentably distinct from each other because both claims sets encompass the same method for editing SCN10A by using the same sgRNA targeting SEQ ID NO: 21893. The specific cells recited in the patent claims anticipate the genus recited in the instant claims. The method recited in the instant claims encompasses in vivo therapy as recited in the patent claim 2. The instant specification discloses that Cas9 could be optimized and could contain one or more NLSs, the sgRNA/Cas9 could be encoded by an AAV, the sgRNA could be precomplexed with Cas9 (see [0023]; [0028]; [0099]; [0185]; [0428]). The patent specification discloses that the sgRNA comprises a spacer extension and a tracRNA extension (see paragraph bridging columns 3 and 4).
Thus, the patent claims and the instant claims are obvious variants.
Claim Rejections - 35 USC § 103
11. In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
12. Claims 1-3 and 13-16 are rejected under 35 U.S.C. 103 as being unpatentable over Greenberg et al. (WO 17/083722), in view of both Huang et al. (J. Neurosci., 2013, 33: 14087-14097) and Zhu (Front. Biol., 2015, 10: 289-296). All references are of record in the parent application 16/315,540.
Greenberg et al. teach a method for treating pain in a subject (such as a human subject) by editing the SCN9A gene in the subject; the method comprises administering sgRNA/S. pyogenes Cas9 to a neuronal cell to introduce double or single-strand DNA breaks to eliminate SCN9A function via deletions within the SCN9A gene; the sgRNA comprises a spacer sequence complementary to the SCN9A gene and the sgRNA/Cas9 is expressed from an AAV vector (i.e., DNA) (claims 1, 13, and 14) (see p. 8, line 32 through p. 9, line 2; p. 10, line 5 and 28-29; p. 15, lines 16-23; p. 20, lines 13-17; p. 28, lines 8-10; p. 29, lines 21-33; p. 63, lines 7-17; p. 74, lines 20-27; paragraph bridging p. 76 and 77; p. 77, lines 25-32; Example 1).
While Greenberg et al. teach that the method could be also applied to treat pain associated with SCN10A, SCN10A is disclosed as part of a genus of voltage-gated sodium channels (see p. 2, lines 13-15; p. 11, lines 14-19; p. 70, lines 16-25). However, in view of the prior art specifically teaching that, similar to SCN9A, SCN10A is associated with pain (see Huang et al., Abstract), one of skill in the art would have found obvious to apply the method of Greenberg et al. to subjects experiencing pain associated with mutations in the SCN10A gene (claims 1 and 14) to achieve the predictable result of treating pain in these subjects.
Greenberg et al. and Huang et al. do not specifically teach the spacers recited in claims 1-3 and 14-16). However, the prior art teaches that finding the optimal target sites only entails routine experimentation. For example, Zhu teaches that finding the target sites is easily achieved by just using scanning for the PAM sequences; further identifying those unique target sites which can be efficiently cleaved with low off-target effects (high specificity) could be done by using available software tools such as CRISPRseek (see Abstract; p. 290, column 2, first full paragraph; p. 291, column 1, first full paragraph and Table 1; p. 291, paragraph bridging columns 1 and 2; p. 292-293). Thus, using PAM scanning and software tools was routine in the prior art and obvious to one of skill in the art to achieve the predictable result of identifying the optimal target sites within the SCN10A gene; as evidenced by Zhu, designing the spacers targeting these sites and testing them to confirm their optimal activity would have only entailed routine experimentation (see p. 291, paragraph bridging columns 1 and 2). Routine optimization is not considered inventive and no evidence has been presented that the selection the claimed sequences was other than routine or that the results should be considered unexpected in any way as compared to the closest prior art (see MPEP 2144.05 II).
Thus, the claimed invention was prima facie obvious at the time of its effective filing date.
13. Claims 1-3, 7-10, and 13-16 are rejected under 35 U.S.C. 103 as being unpatentable over Greenberg et al. taken with both Huang et al. and Zhu, in further view of Hendel et al. (Nature Biotechnol., 2015, 33: 985-989; of record in the parent application 16/315,540).
The teachings of Greenberg et al., Huang et al., and Zhu are applied as above for claims 1-3 and 13-16. Greenberg et al., Huang et al., and Zhu do not teach chemically modified sgRNA nor do they teach a precomplex (claims 7-10). Hendel et al. teach that delivering chemically modified sgRNA enhances genome editing; Hendel et al. teach that the chemically modified sgRNA could be delivered as a precomplex with Cas9 protein (see Abstract; p. 985, paragraph bridging column 1 and 2 and column 2, first full paragraph; p. 987, column 2; p. 988, paragraph bridging columns 1 and 2). Modifying the method of Greenberg et al., Huang et al., and Zhu by using a chemically modified sgRNA precomplexed with Cas9 would have been obvious to one of skill in the art to achieve the predictable result of efficiently treating pain in the subjects.
Thus, the claimed invention was prima facie obvious at the time of its effective filing date.
14. Claims 1-3 and 11-16 are rejected under 35 U.S.C. 103 as being unpatentable over Greenberg et al. taken with both Huang et al. and Zhu, in further view of Cong et al. (Science, 2013, 339: 819-823; of record in the parent application 16/315,540).
The teachings of Greenberg et al., Huang et al., and Zhu are applied as above for claims 1-3 and 13-16. Greenberg et al., Huang et al., and Zhu do not teach an NLS (claims 11 and 12). Cong et al. teach attaching at least one NLS to the Cas9 N- and/or C-terminus (i.e., at 50 amino acids from the N- and/or C-terminus) to ensure nuclear localization (see p. 820; 822, Fig. 4A). One of skill in the art would have found obvious to modify the teachings of Greenberg et al., Huang et al., and Zhu by attaching at least one NLS to Cas9 to achieve the predictable result of efficiently treating subjects affected by pain associated with mutations in the SCN10A gene.
Thus, the claimed invention was prima facie obvious at the time of its effective filing date.
15. Claims 1-3, 5, 6, and 13-16 are rejected under 35 U.S.C. 103 as being unpatentable over Greenberg et al. taken with both Huang et al. and Zhu, in further view of Ryan et al. (Meth. Enzymol., 546: 473-489).
The teachings of Greenberg et al., Huang et al., and Zhu are applied as above for claims 1-3 and 13-16. Greenberg et al., Huang et al., and Zhu do not teach spacer and tracrRNA extensions (claims 5 and 6). Ryan et al. teach increasing the sgRNAs levels inside cells by extended the spacer with stabilizing sequences (such as ribozymes) and adding a 3’ terminator sequence (i.e., extending the tracrRNA) (see paragraph bridging p. 479 and 480; p. 480-481). One of skill in the art would have found obvious to modify the teachings of Greenberg et al., Huang et al., and Zhu by using a stabilizing sequence and terminator sequence to achieve the predictable result of efficiently treating subjects affected by pain associated with mutations in the SCN10A gene.
Thus, the claimed invention was prima facie obvious at the time of its effective filing date.
16. No claim is allowed.
Claims 1-3 and 5-16 are rejected.
Claim 4 is objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
Claim 4 is free of the prior art of record because the gRNA targeting SEQ ID NO: 21893 exhibits the beneficial and superior combination of high target cleavage activity, ability to introduce mutations at the target site, and lack of off-target cleavage (see applicant’s remarks filed on 05/08/2023 in the parent application 15/315,540). Such a gRNA would not have been predictably identified based on the software tools available in the prior art.
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/ILEANA POPA/Primary Examiner, Art Unit 1633