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 .
Status of Application/Amendment/Claims
This Office action is in response to the communications filed on May 20, 2026.
Currently, claims 1, 3, 10-11, 14-17, 28, and 145 are pending and under examination on the merits in the instant application.
The following rejections are either newly applied or are reiterated and are the only rejections and/or objections presently applied to the instant application.
Response to Arguments and Amendments
Withdrawn Rejections
Any rejections/objections not repeated in this Office action are hereby withdrawn.
Maintained Rejections
Claim Rejections - 35 USC § 103
Claims 1, 3, 10-11, 14-17, 28, and 145 remain rejected under 35 U.S.C. 103 as being unpatentable over Turunen et al. in view of Li et al. and Jaenisch et al. for the reasons as set forth in the Office action mailed on January 20, 2026 and for the reasons stated below.
Applicant's arguments filed on May 20, 2026 have been fully considered but they are not persuasive. Applicant argues that the claims as amended are not obvious because there is no motivation for one of ordinary skill in the art to arrive at the claimed subject matter by modifying the teachings of Turunen, whose oligonucleotides are already modified with 2’-F providing nuclease protection, wherein arabinose configuration is “among the various sugar modifications” that “may provide stability or affinity benefits”. In response, applicant’s arguments pertaining to the lack of motivation because Turunen’s 2’-F-modified oligonucleotide is already beneficial are not found persuasive because the “increased RNA affinity” provided by Li’s FANA is not taught in Turunen’s 2’-F-modified oligonucleotide. As such, one of ordinary skill in the art desiring to further enhance the properties of Turunen’s oligonucleotide would have been motivated to use Li’s FANA within the G6055A mutation-causing triplet sequence so as to enable the therapeutic oligonucleotide to bind to the disease-causing sequence, thereby effectively editing the disease-causing sequence. In addition, applicant’s argument that there are “various” modification choices to choose from is not found persuasive to show the asserted nonobviousness of using Li’s FANA in place of 2’-F because both FANA and 2’-F-RNA comprise fluorine (F) at the 2’ position of the sugar, which is taught to be “small enough not to cause steric interference with ADAR2”, wherein such property/feature of 2’-F is critical in providing the ADAR enzyme-mediated base editing for correcting the G6055A mutation associated with Parkinson’s disease. That is, one of ordinary skill in the art would have readily understood the significance of the small size of 2’-F in the ADAR-mediated base editing methodology thus would have been motivated to utilize a 2’-F-containing sugar modification or a similar modification known to be “small enough not to cause steric interference with ADAR2” in order to practice the art-recognized method of editing LRRK2 mutation.
Applicant asserts that one of ordinary skill in the art would have been cautious of inserting a FANA at the triplet where ADAR editing occurs because the “steric implications would be unknown and certainly unpredictable” and one of ordinary skill in the art would have had “no reasonable expectation that such an orientation would be successful for an ADAR-editing oligonucleotide.” In response, it is noted that applicant’s argument is not supported by any objective, factual evidence showing that a FANA-containing base, unlike Turunen’s 2’-F base, was known to cause steric hindrance for ADAR-mediated base editing, nor is there any teaching in any of the cited references of record that the arabino configuration of FANA is unsuitable because it disrupts ADAR enzyme recruitment. Hence, applicant’s conjecture and the asserted unpredictable nature of the FANA modification are not found persuasive to support that one of ordinary skill in the art would have been “even more leery” of using a FANA for base editing purpose.
Applicant argues that Li compares FANA only to an unmodified RNA or unmodified DNA thus the examiner failed to establish a motivation to introduce FANA to replace 2’-F of Turunen. In response, applicant’s attention is directed to the fact that FANA comprising 2’-F in arabinose configuration was compared to arabinonucleic acid (ANA) without 2’-F, wherein FANA has a far significantly higher RNA heteroduplex stability compared to ANA as expressly disclosed at page 4141: “the observed trend for the stability of heteroduplexes between RNA and antisense oligonucleotides (AONs) is as follows: FANA > RNA > DNA > PS-DNA >> ANA”. Hence, ANA having 2’-F (thus FANA) was known to form a significantly stable heteroduplex with a complementary RNA compared to ANA without 2’-F, thereby providing a desirability of using FANA in a target RNA-binding oligonucleotide for stable target RNA binding activity. The mere fact that Li does not experimentally compare FANA with 2’-F RNA for RNA binding stability is not sufficient to show lack of a motivation to use FANA in place of 2’-F RNA because it has long been recognized in the relevant art that both FANA comprising 2’-F in the arabino configuration and 2’-F RNA have similar properties in terms of target RNA-binding affinity as evidenced by the long-held art-accepted scientific knowledge at page 4149 such that “a 2’-fluorine substituent, either in the ribo (2’F-RNA) or arabino configuration (FANA), promotes conformational properties that result in significantly higher RNA affinities of 2’-fluoro analogues compared to the corresponding oligonucleotides with a 2’-OH substituent (RNA and ANA, respectively).” (emphasis added). Hence, in view of the art-accepted, art-recognized similar properties shared by FANA and 2’-F-RNA as expressly disclosed by Li, one of ordinary skill in the art would have had a sufficient reason to use the art-recognized alternative 2’-F-containing RNA in arabino configuration in place of 2’-F RNA so as not to disrupt the ADAR recruitment/binding for the ADAR-mediated base editing in the G6055A mutation of the LRRK2 RNA while improving or retaining the target RNA binding affinity and stability against nuclease compared to the 2’-F-containing base-editing oligonucleotide, thereby practicing Turunen’s suggested method of editing LRRK2 G6005A mutation without the need “to cause steric interference with ADAR2”.
In view of the foregoing, this rejection is maintained.
Double Patenting
Claims 1, 3, 10-11, 14-17, 28, and 145 remain rejected on the ground of nonstatutory double patenting as being unpatentable over claims 18-19 and 21 of U.S. Patent No. 12,173,285 B2 in view of Klein et al. for the reasons as set forth in the Office action mailed on January 20, 2026 because applicant did not provide any substantial rebuttal arguments addressing the supposed errors of this rejection.
Claims 1, 3, 10-11, 14-17, 28, and 145 remain provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 52 and 61 of Application No. 18/290,062 in view of Klein et al., Turunen et al., and Li et al. for the reasons as set forth in the Office action mailed on January 20, 2026 because applicant did not provide any substantial rebuttal arguments addressing the supposed errors of this rejection.
Claims 1, 3, 10-11, 14-17, 28, and 145 remain provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 41 and 50 of Application No. 18/570,918 in view of Klein et al., Turunen et al., and Li et al. for the reasons as set forth in the Office action mailed on January 20, 2026 because applicant did not provide any substantial rebuttal arguments addressing the supposed errors of this rejection.
Claims 1, 3, 10-11, 14-17, 28, and 145 remain provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 46 and 55 of Application No. 18/570,938 in view of Klein et al., Turunen et al., and Li et al. for the reasons as set forth in the Office action mailed on January 20, 2026 because applicant did not provide any substantial rebuttal arguments addressing the supposed errors of this rejection.
Claims 1, 3, 10-11, 14-17, 28, and 145 remain provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 24-25 and 27 of Application No. 18/941,793 in view of Klein et al. for the reasons as set forth in the Office action mailed on January 20, 2026 because applicant did not provide any substantial rebuttal arguments addressing the supposed errors of this rejection.
Claims 1, 3, 10-11, 14-17, 28, and 145 remain provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 29-30 of Application No. 19/189,150 in view of Klein et al., Turunen et al., and Li et al. for the reasons as set forth in the Office action mailed on January 20, 2026 because applicant did not provide any substantial rebuttal arguments addressing the supposed errors of this rejection.
Claims 1, 3, 10-11, 14-17, 28, and 145 remain provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-3, 5-11, 15-27, and 30-41 of Application No. 19/479,642 in view of Klein et al., Turunen et al., and Li et al. for the reasons as set forth in the Office action mailed on January 20, 2026 because applicant did not provide any substantial rebuttal arguments addressing the supposed errors of this rejection.
Claims 1, 3, 10-11, 14-17, 28, and 145 remain provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 33 of Application No. 19/493,944 in view of Klein et al. for the reasons as set forth in the Office action mailed on January 20, 2026 because applicant did not provide any substantial rebuttal arguments addressing the supposed errors of this rejection.
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 DANA H SHIN whose telephone number is (571)272-8008. The examiner can normally be reached Monday-Thursday: 8am - 6:30pm.
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/DANA H SHIN/Primary Examiner, Art Unit 1635
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