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 .
Response to Amendment
This action is written in response to applicant’s amendments received on 2/25/26.
The objection to the claims are overcome by amendment.
The rejection of the claims under 35 USC 102 is overcome by amendment.
Amended claims 1, 10, 11, 15, 20-23, and 33 are under examination herein.
Election/Restrictions
Applicant’s election without traverse of Group 1, claims 1, 10, 11, 15, 20-23 and 32-33 in the reply filed on 8/11/25 is acknowledged.
Claims 4-6, 8, and 35-36 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected inventions, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 8/11/25.
Applicant’s election without traverse of histone acetyltransferase, VPR, binding to a nucleic acid sequence that is not more than 500 nucleotides upstream from the transcription start site of FXN, Zn finger, and SEQ ID NO:33 in the reply filed on 8/11/25 is acknowledged.
Priority
Application claims priority to 62/904,391 provisional application with an effective filing date of 9/23/19. Claims of the instant application are supported by the provisional application and thus have a priority date of 9/23/19.
Information Disclosure Statement
The IDS filed on 2/25/26 has been fully considered except where references have been lined through.
Claim Rejections - 35 USC § 103
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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
New rejection necessitated by amendment. Claims 1, 11, 15, 20, and 23 are rejected under 35 U.S.C. 103 as being unpatentable over Cherqui (US20220009977A1) and Tremblay (US20180170985A1).
Regarding claim 1, Cherqui teaches methods of treating mitochondrial diseases (title). Cherqui teaches the treatment can comprise a nucleic acid (abstract). Cherqui teaches the nucleic acid can comprise a gene editing system that removes a trinucleotide repeat found in FXN (abstract). Cherqui teaches that this trinucleotide repeat leads to reduced expression of FXN ([0008]). Cherqui teaches that the repeats are associated with DNA methylation and silenced chromatin (epigenetic modifying moiety) ([0010]). Cherqui teaches that the vector removes the trinucleotide sequence and thereby treats the disease (effector moiety comprising an epigenetic modifying moiety increases expression of FXN) ([0014]). As the trinucleotide sequence is removed, the DNA methylation and therefore the silenced chromatin would be unable to be formed resulting in increased gene expression of FXN. Cherqui teaches that the nucleic acid can comprise a target sequence (targeting moiety) ([0043-0049]). Cherqui teaches a promoter can be targeted ([0013]).
Cherqui does not explicitly teach targeting the nucleic acid sequence that is not more than 500 nucleotides upstream from the transcription start of FXN
Tremblay teaches methods and products for increasing FXN expression (abstract). Tremblay teaches this is accomplished by targeting the promoter region of FXN (claim 1). Tremblay teaches that the promoter can be targeted ~150bp from the transcription start (fig 2 and [0074]). Tremblay teaches that fig 2 shows SEQ ID NO 11 ([0074]). As evidenced by SEQ ID NO 11, this matches a region on the GRCH37 of 71649439-71650938 (appendix). This overlaps with the claimed ranges (for example o-r) and therefore the claimed ranges are prima facia obvious. Further, it would be obvious to one of ordinary skill in the arts to experiment within different loci within the locations taught by Tremblay to arrive at the specific claimed coordinates in the absence of a declaration of unexpected results or benefits.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to incorporate a promoter targeting sequence of Tremblay in the method of Cherqui. One of ordinary skill in the art would be motivated to do so because Tremblay teaches this increases FXN expression. There would be a reasonable expectation of success as both Cherqui and Tremblay are in the same field of endeavor of increasing FXN expression.
Regarding claims 11, Trembly teaches that VP64 can be used (claim 25).
Regarding claim 15, Cherqui teaches that Cas9 can be included ([0101]).
Regarding claim 20, Cherqui teaches the targeting moiety can be Zn fingers ([0014]).
Regarding claim 23, Cherqui teaches that the nucleic acid can comprise a promoter functionally linked to FXN ([0015]).
Claim 10 is rejected under 35 U.S.C. 103 as being unpatentable over Cherqui (US20220009977A1) and Tremblay (US20180170985A1), as applied to 1, 11, 15, 20, and 23 above, and further in view of Piatek ("Targeted genome regulation via synthetic programmable transcriptional regulators." Critical reviews in biotechnology 37.4 (2017): 429-440)
Regarding claim 10, Cherqui and Tremblay does not explicitly teach where the epigenetic modifying moiety is a histone acetyltransferase.
Piatek reviews genetic regulation via programmable transcriptional regulators (title). Piatek teaches that cas9 has been fused to a histone acetyltransferase to increase gene expression (p426 left column).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to incorporate a histone acetyltransferase to increase gene expression as taught by Piatek in the composition of Cherqui and Tremblay. One of ordinary skill in the art would be motivated to do so because these fused histone acetyltransferases have been successfully used to increase gene expression, and one skilled in the art could have combined the elements as claimed by known methods with no change in their respective functions, and the combination yielded nothing more than predictable results to one of ordinary skill in the art. There would be a reasonable expectation of success as Cherqui, Tremblay and Piatek are in the same field of endeavor of increasing gene expression.
Claims 21-22 and 33 is rejected under 35 U.S.C. 103 as being unpatentable over Cherqui (US20220009977A1) and and Tremblay (US20180170985A1), as applied to claims 1, 11, 15, 20, and 23, and further in view of Chen (WO2020163017A1). While Chen was published after the effective filing date of instant application, Chen claims priority to 2/6/19 and therefore is valid prior art under 35 U.S.C. 102(a)(2).
Regarding claims 21 and 33, Trembly teaches that VP64 can be used (claim 25). Cherqui, Tremblay, and Piatek do not teach the sequence of the zinc finger coupled to the VPR sequence.
Chen teaches an 84% match to claimed SEQ ID NO 33 (appendix). Chen teaches it is a zinc finger coupled to a VPR domain (appendix).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to use the SEQ ID of Chen in the method of Cherqui, Trembly and Piatek above. One of ordinary skill in the art would be motivated to do so because as the explicit sequence was not disclosed, one of ordinary skill in the arts would seek out a disclosed sequence for a zinc finger-VPR. There would be a reasonable expectation of success as Piatek and Chen are in the same field of endeavor of zinc finger-VPR.
Regarding claim 22, Chen teaches that multiple zinc finger proteins can be used including 3 or more ([00114])
Response to Arguments
Applicant’s arguments with respect to the claims have been considered but are moot because the new ground of rejection does not rely on any reference applied in the prior rejection of record for any teaching or matter specifically challenged in the argument.
Applicant argues that Chen does not discuss FXN (p10-11 bridging paragraph). Chen is not relied upon for the targeting to FXN, only the zinc finger coupled to the VPR domain.
Applicant argues that Tremblay does not teach the specific genomic coordinates (p11-12 bridging paragraph). Tremblay does teach the claimed coordinates, see the rejection above. As the entire range of coordinates are taught by Tremblay, a deceleration of unexpected results commensurate in scope with the claims could aid in overcoming the obvious conclusion.
Conclusion
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). 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 TREVOR L KANE whose telephone number is (571)272-0265. The examiner can normally be reached M-F 7:00 am-4:00pm.
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/TREVOR KANE/Examiner, Art Unit 1657
/ROBERT J YAMASAKI/Primary Examiner, Art Unit 1657
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