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 .
Application Status
This action is written in response to applicant’s correspondence received 10/7/2025. Claims 63, 72, 80, 94-96, 98, and 100 are currently pending.
Applicant's elected Group I, claims 63, 72, 80, 94-96, 98, and 100, without traverse in the reply filed 6/16/2025. Claims 1-2, 10, 12, 16, 17, 31, 37, 50, 62, 102 and 110-111 are withdrawn from prosecution as being drawn to non-elected subject matter. The restriction requirement mailed 4/16/2025 is still deemed proper. Applicant cancelled claims 1-62, 64-71, 73-79, 81-93, 97, 99, and 101-114. Accordingly, claims 63, 72, 80, 94-96, 98, and 100 are examined herein.
Any rejection or objection not reiterated herein has been overcome by amendment. Applicant’s amendments and arguments have been thoroughly reviewed, but are not persuasive to place the claims in condition for allowance for the reasons that follow.
Priority
This application is a CON of 16/088,159 (filed 09/25/2018) - PAT 11597924 (issued 03/07/2023), which is a 371 of PCT/US2017/024110 (filed 03/24/2017), which
has PRO 62/313,247 (filed 03/25/2016). Thus, the earliest priority date is 03/25/2016.
Drawings - withdrawn
Objection to drawings for citing “Fig.” or “Fi.” Instead of “FIG.” is withdrawn in view of Applicant’s amendment to drawings filed 10/7/2025.
Drawings – new necessitated by amendment
The drawings are objected to because the application file contains at least one drawing executed in color in FIGs. 1A, 1B, 2A and 2B. Copies of this patent or patent application publication with color drawing(s) will be provided by the Office upon request and payment of the necessary fee. If applicant did not intend to file color drawings, the applicant should file an updated version of their drawings that do not contain color.
Color photographs and color drawings are not accepted in utility applications unless a petition filed under 37 CFR 1.84(a)(2) is granted. Any such petition must be accompanied by the appropriate fee set forth in 37 CFR 1.17(h), one set of color drawings or color photographs, as appropriate, if submitted via the USPTO patent electronic filing system or three sets of color drawings or color photographs, as appropriate, if not submitted via the via USPTO patent electronic filing system, and, unless already present, an amendment to include the following language as the first paragraph of the brief description of the drawings section of the specification:
Color photographs will be accepted if the conditions for accepting color drawings and black and white photographs have been satisfied. See 37 CFR 1.84(b)(2).
Specification - withdrawn
Objection to the specification is withdrawn in view of Applicant’s amendment filed 10/7/2025 to add proper symbols for trade names and marks.
Claim Rejections - 35 USC § 102 - maintained
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 (i.e., changing from AIA to pre-AIA ) 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 the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claims 63, 72, 80, 94-96, 98, and 100 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Weschler et al. (WO2014130955A1; published 08/28/2014; cited in the IDS filed 07/15/2024). This rejection is maintained in view of Applicant’s amendment to claim 63 adding magnitudes of change “by at least 0.1-fold” and/or “by at least 5-fold” to parts A) through I).
Regarding claim 63, Weschler teaches methods and compositions for enhancing nuclease-mediated gene disruption using DNA repair inhibitors (see abstract and paras 0009 and 0012). Wechsler further teaches methods and compositions for increasing efficiency of targeted gene disruption by contacting cells with a nuclease (e.g., ZFN or TALEN) or nuclease system (e.g., CRISPR/Cas with engineered single guide RNA) and inhibiting repair via classic and alternative NHEJ mechanisms in cells (see paras 0009 and 0012). Wechsler teaches that the nuclease can be a zinc finger protein, a CRISPR/Cas system and combinations thereof (see claims 8 and 9) and that the repair enzyme can be heterologous (exogenous) (see paras 0048-0050). Wechsler further teaches that there was a 2-3 fold increase in mutagenic repair (“%indels”) in nuclease-treated cells (see Example 1 and Figs 2, 3A and 3C) and that, with the addition of Rad52 mRNA, there was a 2-to 4-fold increase in plasmid donor-based target integration and further by about 5-fold with the addition of DNA-PKcs inhibitor NU7441 (see Example 2; Figs. 4E and 4F). Weschler further teaches modulating Artemis with inhibitors to control gene deletion events (see paras 0012 and 0025, Fig. 1; claims 1-3). Weschler teaches that RPA and Rad51 can play a role in gene correction via targeted integration (see paras 0011, 0016, and 0024-0025; and Fig. 1).
Regarding claim 72, Weschler teaches that the RMEM Rad52 is mRNA encoding the RMEM protein (see Example 2).
Regarding claim 80, Weschler teaches that the RNA-guided nuclease molecule can be a Cas9 molecule (see paras 0101-0111).
Regarding claim 94, Weschler teaches a cell comprising the genome editing systems (see paras 0011-0014).
Regarding claim 95, Weschler teaches a population of cells where each cell comprises the genome editing system (see paras 0142 and 0163).
Regarding claim 96, Weschler teaches pharmaceutical compositions comprising cells comprising genome editing systems (see paras 0131-0133 and 0151).
Regarding claim 98, Weschler teaches RNA or DNA polynucleotide viral based systems encoding gene editing systems (see paras 0128-135).
Regarding claim 100, Weschler teaches vector systems comprising one or more nucleic acids encoding genome editing systems (see paras 0133-0150).
Weschler teaches each and every limitation of claims 63, 72, 80, 94-96, 98, and 100, therefore, Weschler anticipates claims 63, 72, 80, 94-96, 98, and 100.
Response to Arguments
Applicant's arguments filed 10/7/2025 have been fully considered but they are not persuasive. Applicant argues that Office has not established that Wechsler teaches or suggests any genome editing systems comprising: (a) a gRNA molecule; (b) a RNA-guided nuclease molecule; and (c) a heterologous Repair-Modulating Enzyme Molecule (RMEM), wherein the gRNA molecule and the RNA-guided nuclease molecule are configured to associate with a target nucleic acid, resulting in a cleavage event; wherein the cleavage event is repaired by at least one DNA repair pathway that is modulated by the RMEM wherein the formation of a deletion in the nucleic acid after repair is suppressed by at least 0.1-fold, the formation of a deletion the nucleic acid after repair is enhanced by at least 0.1-fold, the gene conversion is suppressed by at least 0.1-fold, the gene conversion is enhanced by at least 0.1-fold, the gene correction is suppressed by at least 0.1-fold, the gene correction is enhanced by at least 5-fold, the formation of an insertion in the nucleic acid after repair is suppressed by at least 0.1-fold, and/or the formation of an insertion in the nucleic acid after repair is enhanced by at least 0.1-fold; in the cell or in the population of cells, relative to a cell or a population of cells not contacted with the RMEM, as required by the pending claims. Applicant further argues that the Office has not established that the art on record teaches or suggests each and every element of the invention recited in the amended claims.
The Office disagrees. Claim 63 requires the amended limitations in the alternative wherein only one scenario within any given alternative from parts A) through I) is required. The Office detailed in the above 102 rejection that Wechsler teaches that, with the addition of Rad52 mRNA, there was a 2-to 4-fold increase in plasmid donor-based target integration and further by about 5-fold with the addition of DNA-PKcs inhibitor NU7441 (see Example 2; Figs. 4E and 4F). Therefore, Wechsler teaches a genome editing system comprising a gRNA, a ZFN molecule, and a heterologous Rad52 RMEM wherein a frequency of the DNA repair pathway repairing the target nucleic acid using gene correction is increased by at least 5-fold. Accordingly, the rejection is maintained.
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 63, 72, 80, 94-96, 98, and 100 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 3-6, 8-9, 13-14, and 18-19 of U.S. Patent No. 11597924, cited on an IDS. Although the claims at issue are not identical, they are not patentably distinct from each other because there is significant overlap in the claims. This rejection is modified in view of Applicant’s amendment to claim 63 to add magnitudes of change “by at least 0.1-fold” and/or “by at least 5-fold” to parts A) through I).
Claims 1, 3-6, 8-9, 13-14, and 18-19 of the ‘924 patent encompass a genome editing system comprising a cell or a population of cells with (a) a gRNA molecule; (b) a RNA-guided nuclease molecule; and (c) a heterologous Repair-Modulating Enzyme Molecule (RMEM); wherein the gRNA molecule and the RNA-guided nuclease molecule interact with the nucleic acid, resulting in a cleavage event, and wherein the cleavage event is repaired by at least one DNA repair pathway that is modulated by the RMEM, wherein i) the RMEM is Rad52 or TdT, and the RMEM suppresses formation of a deletion in the nucleic acid at the target position in the cell, or in the population of cells; ii) the RMEM is Artemis, and the RMEM enhances formation of a deletion in the nucleic acid at the target position in the cell, or in the population of cells; iii) the RMEM is Rad52, TdT, Rad51, RPA, or ERCC1, and the RMEM suppresses gene conversion of the nucleic acid at the target position in the cell, or in the population of cells; iv) the RMEM is TdT, Rad51, or T5 exonuclease, and the RMEM suppresses gene correction of the nucleic acid at the target position in the cell, or in the population of cells; v) the RMEM is Rad52 or 53BP1 dominant negative, and the RMEM enhances gene correction of the nucleic acid at the target position in the cell, or in the population of cells; vi) the RMEM is 53BP1 dominant negative or T5 exonuclease, and the RMEM suppresses formation of an insertion in the nucleic acid at the target position in the cell, or in the population of cells; or vii) the RMEM is TdT, and the RMEM enhances formation of an insertion in the nucleic acid at the target position in the cell, or in the population of cells, and wherein the formation of a deletion in the nucleic acid after repair is suppressed by at least 0.1-fold, the formation of a deletion the nucleic acid after repair is enhanced by at least 0.1-fold, the gene conversion is suppressed by at least 0.1-fold, the gene conversion is enhanced by at least 0.1-fold, the gene correction is suppressed by at least 0.1-fold, the gene correction is enhanced by at least 5-fold, the formation of an insertion in the nucleic acid after repair is suppressed by at least 0.1-fold, and/or the formation of an insertion in the nucleic acid after repair is enhanced by at least 0.1-fold; in the cell or in the population of cells, relative to a cell or a population of cells not contacted with the RMEM, thereby altering the nucleic acid at the target position in the cell, or in the population of cell. Claims 1, 3-6, 8-9, 13-14, and 18-19 of the ‘924 patent further encompass the RNA-guided nuclease molecule is a Cas9 molecule and that the RMEM is a protein or nucleic acid encoding the RMEM.
Response to Arguments
Applicant's arguments filed 10/7/2025 have been fully considered but they are not persuasive. Applicant argues that they will address the foregoing rejection once all other rejections are overcome with the filing of a terminal disclaimer, if appropriate. However, such a response is not a proper reply to the outstanding rejection of record.
Conclusion
No claim is allowed.
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to KHALEDA B HASAN whose telephone number is (571)272-0239. The examiner can normally be reached IFP, Monday - Friday 7:30am-5pm.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Neil Hammell can be reached at (571) 270-5919. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/KHALEDA B HASAN/Examiner, Art Unit 1636
/BRIAN WHITEMAN/Primary Examiner, Art Unit 1636