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 .
Applicant’s response filed 04/22/2026 has been received and considered entered. This is a response to amendments and arguments filed 04/22/2026.
Election/Restrictions
Claims 48, 51-53 stand withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 09/26/2025.
Applicant’s election without traverse of the species SEQ ID NO:41 in the reply filed on 09/26/2025 is acknowledged. However, the species election requirement has been withdrawn.
Claims Status
Claims 2, 4, 6-10, 19, 24-46, 49-50, 54-83 is/are cancelled and claims 84-85 is/are newly added. Claims 1, 3, 5, 11-18, 20-23, 47-48, 51-53, 84-85 is/are currently pending with claims 48, 51-53 withdrawn. Claims 1, 3, 5, 11-18, 20-23, 47, 84-85 is/are under examination.
Claim Rejections - 35 USC § 103
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 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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
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.
WO2011135396A1:
Claim(s) 1, 3, 5, 11-18, 47, 84-85 is/are rejected under 35 U.S.C. 103 as being unpatentable over Duchateau (WO2011135396A1, of record), in view of Shukla (2010) and as evidenced by Dana (2017). This is a new rejection necessitated by amendments.
Regarding claims 1, 3, 5, 84, and 85, Duchateau teaches a modified oligonucleotide (a “chemically modified” siRNA or other inhibitory RNA, page 42) consisting of a sequence targeting SEQ ID NO:736 (SEQ ID NO:736 comprises a sequence of 21 consecutive nucleotides 100% identical to nucleotides 12706-12726 of instant SEQ ID NO:2 and 19 consecutive nucleotides 100% complementary to instant SEQ ID NO:16, see alignments below) (page 45; claims 1-10, 17-18).
SEQ ID NO:736 to instant SEQ ID NO:16:
PNG
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162
660
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Greyscale
SEQ ID NO:736 to instant SEQ ID NO:2:
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163
660
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Greyscale
Regarding claim 47, Duchateau teaches a composition comprising the modified oligonucleotide and a pharmaceutically-acceptable carrier (page 56 lines 3-6).
However, Duchateau teaches that the oligonucleotide is an siRNA or other inhibitory RNA, wherein siRNA are double-stranded.
Dana teaches that siRNA is processed in a cell such that a single-stranded oligonucleotide is formed.
Regarding claim 1, Dana teaches that double-stranded siRNA is processed in a cell by AGO2, which ejects the passenger strand, creating a single-stranded RNA oligonucleotide (Fig. 3). Duchateau teaches that the siRNA is introduced into cells, wherein the double-stranded RNA would convert the double-stranded RNA taught by Duchateau into two single-stranded RNA molecules (claims 34, 36). The “isolated eukaryotic cell” comprising the siRNA, and compositions comprising said cell, would thus inherently comprise a single-stranded oligonucleotide comprising 21 consecutive nucleotides 100% complementary to instant SEQ ID NO:2.
However, Duchateau does not teach specific chemical modifications of the taught siRNAs.
Shukla teaches chemical modifications of siRNA.
Regarding claims 11-12, Shukla teaches that 2’-MOE and 2’-OMe modified sugars in an siRNA are common modifications and provide the benefits of improved nuclease resistance and enhanced silencing activity (page 337; Fig. 4b).
Regarding claim 13, Shukla teaches that bicyclic sugars (such as LNA, ENA, OXE, and ALN) are common modifications of siRNA and provide the benefit of enhanced hybridization to a target sequence (page 338; Fig. 4b).
Regarding claim 14, Shukla teaches that the LNA modification consists of a 4’-CH2-O-2’ chemical bridge (Fig 4b).
Regarding claims 15-17, Shukla teaches that phosphorothioate modifications are commonly used in siRNAs to provide “improved nuclease resistance and favorable pharmacokinetic properties” (page 336). Shukla teaches that at least one linkage in an siRNA may be so modified, rendering obvious siRNA comprising a mix of phosphorothioate and phosphodiester linkages, and siRNA comprising only phosphorothioate linkages (page 336).
Regarding claim 18, Shukla teaches that siRNAs may comprise 5-methylcytidine nucleotides (inherently comprising a 5-methylcytosine base) (page 341).
It would have been obvious to an artisan at the time of filing to improve the siRNA of Duchateau by adding 2’-MOE or 2’-OMe modifications, bicyclic sugars, and phosphorothioate linkages in order to provide resistance to nucleases (pages 335, 337 of Shukla), thus increasing the stability of the siRNA.
Response to Arguments
Applicant's arguments filed 04/22/2026 have been fully considered but they are not fully persuasive. The arguments regarding Kenyon et al. are considered persuasive and the rejections of claims under 35 USC 102(a)(1) and 103 over Kenyon are withdrawn.
As described above, while Duchateau does not explicitly disclose a single-stranded oligonucleotide, Duchateau does teach eukaryotic cells comprising the double-stranded siRNA, and the nature of siRNA processing in cells would inherently result in the eukaryotic cells and compositions comprising these siRNAs of Duchateau comprising single--stranded oligonucleotides in addition to double-stranded oligonucleotides.
Allowable Subject Matter
Claims 20-23 are 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.
The following is a statement of reasons for the indication of allowable subject matter: Claims 20-23 require that the oligonucleotide be a gapmer. The prior art teaches that a gapmer is an antisense oligonucleotide, not an siRNA, miRNA, or shRNA, as required by Duchateau, the closest prior art. An antisense oligonucleotide is structurally and functionally distinct from an siRNA, miRNA, or shRNA, and as such would not be rendered obvious by an siRNA, miRNA, or shRNA.
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 AFRICA M MCLEOD whose telephone number is (703)756-1907. The examiner can normally be reached Mon-Fri 9:00AM-6:00PM EST.
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/AFRICA M MCLEOD/ Examiner, Art Unit 1635
/KIMBERLY CHONG/ Primary Examiner, Art Unit 1636
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