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 .
Election/Restrictions
Applicant’s election without traverse of Group I, claims 1-4, 6, 9, 12, 21, 30, 35-36, 43, 52, 60, 69, 83, 101, 115 in the reply filed on 06/10/2026 is acknowledged.
Claims 150-153 of Group II are cancelled.
Election of species of species B from claim 101 is acknowledged.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 60 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Claim 60 depends on claim 52, which limits linking functional moiety to antisense strand only. Claim 60 recites linking functional moiety to antisense or sense strand, therefore expanding scope of claim 52 instead of limiting it.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Claim Rejections - 35 USC § 102
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.
Claim(s) 1-3, 6, 21, 30, 36, 43, 69, 159 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Vo-Dihn et al (WO 2021/097390, May 2021, cited from IDS).
Concerning claim 1 Vo-Dihn disclose compounds comprising antisense oligonucleotide (ASO) and siRNA with both strands having 5’ and 3’ ends connected by a linker (see Figure 44).
Concerning claims 2, 3, 6 and 159 the linker can comprise 6 ethylene glycol units (see Figure 44).
Concerning claims 21, 30 and 36 siRNA on Figure 44 comprises 22 nucleotides in each sense and antisense strands, the double-stranded region is formed by 20 base pairs and each strand comprises a single stranded overhang.
Concerning claim 43 siRNA can comprise a phosphorothioate bond (see lines 5-10 on page 26).
Concerning claim 69 ASO on Figure 44 comprises modified nucleotides, LNAs.
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)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claim(s) 1-4, 6, 9, 12, 21, 30, 35-36, 43, 52, 60, 69, 83, 101, 158-161 is/are rejected under 35 U.S.C. 102(a)(1) and 35 U.S.C. 102(a)(2) as being anticipated by Li et al (WO 2022/166849, published 11 August 2022, cited from IDS).
Concerning claim 1 Li disclose compounds comprising covalently linked antisense oligonucleotides (ASO) and duplex (double-stranded) RNA such as siRNA or saRNA (see paragraphs [9-10, 70]). Such siRNA comprises two strands, sense and antisense, each with 5’ and 3’ ends (see paragraph [101]).
Concerning claims 2-3, 9 and 12 Li disclose that linkers connecting ASO and siRNA can be nucleotide or peptide (see paragraph [102]).
Concerning claims 4 and 158 Li disclose propyl-comprising linkers named “Spacer-C3” and “Spacer-C6” (see Table 4 on page 134).
Concerning claims 6 and 159 Li disclose a linker comprising three ethylene glycol units named “Spacer-9” (see Table 4 on page 134).
Concerning claims 21, 30 and 36 Li disclose siRNA with both strands of 21 nucleotides each, double-stranded region of 19 nucleotides and single stranded overhangs (see siRNA in Table 7 on page 139).
Concerning claim 35 Li disclose that siRNA can have blunt-ends (see paragraph [108]).
Concerning claim 43 Li disclose modified internucleotide linkages of siRNAs (see paragraph [123]).
Concerning claims 52 and 60 Li disclose tri-valent compounds comprising two siRNAs and ASO, which can be arranged in any order such as siRNA1-siRNA2-ASO (see paragraph [207]). In this case first siRNA can be considered functional moiety linked to second siRNA. Li disclose that siRNAs can be linked through 5’ or 3’ end of sense or antisense strands (see paragraph [0212]) and linkers of such compound can be different (see paragraph [210]).
Concerning claims 69 and 83 Li disclose that ASO can be in a form of gapmer as shown in Table 16 on page 171, which has 5 2’-MOE modified nucleotides at 5’ and 3’ end and 10 DNA nucleotides in the middle forming 5-10-5 structure.
Concerning claim 101 Li disclose tri-valent compounds comprising siRNA-ASO-siRNA in Table 6 on page 136, compound DAO-12 (see also paragraph [207]). Further Li specify that components of such compound can be connected by different linkers (see paragraph [210]) and ASO can be connected in 3’ to 5’ orientation and siRNAs can be connected through 5’ or 3’ end of sense strands. Therefore Li disclose all structural features of compound of species B of instant claim 1.
Concerning claims 160-161 Li disclose that the linker can comprise eight deoxythymidine nucleotides (see paragraph [144]).
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) 1-4, 6, 9, 12, 21, 30, 35-36, 43, 52, 60, 69, 83, 101, 115, 158-161 is/are rejected under 35 U.S.C. 103 as being unpatentable over Li et al, above, as applied to claims 1-4, 6, 9, 12, 21, 30, 35-36, 52, 60, 69, 83, 101, 158-161, and in further view of Nishina et al (Nature Communications, 2015, 6: 7969, pages 1-13, cited from IDS).
Teachings of Li are discussed above.
Li do not teach a compound comprising siRNA linked to heteroduplex oligonucleotide.
Nishina teach heteroduplex oligonucleotides comprising gapmer ASO with complementary RNA, such oligonucleotide having improved activity compared to ASO by itself (see Abstract).
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 compounds taught by Li to include heteroduplex oligonucleotides taught by Nishina, arriving at instant invention. One of the ordinary skill in the art would be motivated to do so, because heteroduplex oligonucleotides taught by Nishina have improved activity compared to ASO by itself, providing motivation to modify ASO in the compounds taught by Li to heteroduplex oligonucleotide taught by Nishina.
Conclusion
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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/EKATERINA POLIAKOVA-GEORGANTAS/Primary Examiner, Art Unit 1637
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