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 .
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claim 15 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 15 recites the second strand forming a complementary bond with the first strand other than a binding site with PNA. It is not clear what “the binding site with PNA” means and what exactly PNA binds to in such binding site.
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.
Claim(s) 14-20 is/are rejected under 35 U.S.C. 103 as being unpatentable over Jin et al (ACS Appl. Bio Mater., 2018, 1: 643-651, cited from IDS) as evidenced by Invitrogen (Invitrogen, printed on 03/13/2026, pages 1-5, of record) and Elbashir et al (Nature, 2001, vol.411, pages 494-498, of record) and in further view of Potenza et al (International Journal of Molecular Sciences, 2008, pages 299-315, cited from IDS) and Lee (US 2013/0273657, October 2013).
Jin teach a method of gene silencing by administering double-stranded siRNA targeting luciferase gene and comprising PNA sequence adjoining antisense strand of siRNA at 3' end (see third structure on Figure 2, page 645, Figure 3). Such siRNA has a sense strand of 30 nucleotides and antisense strand of 21 nucleotides (see third structure on Figure 2). siRNA was administered in combination with intracellular carrier Lipofectamine (see the bottom of second column on page 645). PNA sequence annealed is 9 nucleotides long CACCACCAC, comprising terminal C bases (see Figure 2). Jin do not disclose the sequence of siRNA, just stating that it was purchased from Invitrogen (see Materials section on page 644). Commercially available from Invitrogen luciferase siRNA includes GL2 and GL3 siRNAs (see first page of Invitrogen reference). The sequences of the GL2 and GL3 siRNAs are published by Elbashir in Figure 1, which shows the presence of 3’ terminal GC bases in the antisense strand of GL2 siRNA (not counting the tt overhang). Jin teach that such conjugate has better silencing activity than unconjugated siRNA (see Figure 3). Jin teach that conjugation of siRNA and PNA can be used to attach targeting ligands and chemical moieties to siRNA (see Abstract).
Jin do not teach the presence of two N-terminal bases of PNA selected from G or C.
Potenza teach that PNA modifications of siRNAs result in enhanced nuclease resistance in serum (see Abstract). Potenza teach that siRNAs can comprise two nucleotide overhangs on 3’-end (see Table 1), can comprise 2’ H modifications of sugars and phosphorothioate bonds (see bridging paragraph between pages 300 and 301) and target firefly luciferase mRNA (see page 302).
Lee teach novel siRNAs with elongated antisense strand of 24-121 nucleotides and shorter sense strand of 13-21 nucleotides with increased efficiency of target gene silencing (see Abstract). Examples of such siRNA are shown in Figures 2 and 3, lsiRNA and lasiRNA, wherein antisense strand forms duplex with sense strand in 5’-terminus of the antisense strand, leaving long single-stranded 3’ end of the antisense strand. Such single-stranded region of the siRNA can be PNA modified (see paragraph [0044]).
It would have been obvious to one of the ordinary skill in the art before the effective filing date of the claimed invention to modify any siRNA with PNA arriving at instant invention based on teachings of Jin, Potenza and Lee. One of the ordinary skill in the art would be motivated to do so because Jin teach that such modifications lead to better silencing activity than unmodified siRNAs and allow conjugation of targeting ligands to siRNA, Potenza teach that such modifications lead to enhanced nuclease resistance and Lee teach modifications of single-stranded 3’ end of antisense strand with PNA. Considering an extremely wide variations in siRNA sequences it is inevitable that some modifications with PNA will lead to two G or C on N-terminus of PNA and two G or C on 3’ end of antisense strand of siRNA.
Response to Arguments
Applicant's arguments filed 07/06/2026 have been fully considered but they are not persuasive.
Previous 112 and 102 rejections are withdrawn in view of new amendments, arguments are moot.
Concerning unexpected results Applicant refers to in Example 4 it is noted that all results refer to only one specific siRNA, which is high in G/C content in 3’ end of its antisense strand, while instant claims encompass essentially all possible siRNAs in existence. Therefore, the results shown can be simply specific to this particular siRNA used.
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 EKATERINA POLIAKOVA whose telephone number is (571)270-5257. The examiner can normally be reached Mon-Fri 8-5.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Jennifer Dunston can be reached at (571)272-2916. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/EKATERINA POLIAKOVA-GEORGANTAS/Primary Examiner, Art Unit 1637
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