Prosecution Insights
Last updated: April 19, 2026
Application No. 18/256,707

APTAMER-siRNA FUSIONS

Non-Final OA §103§DP
Filed
Jun 09, 2023
Examiner
POLIAKOVA-GEORGAN, EKATERINA
Art Unit
1637
Tech Center
1600 — Biotechnology & Organic Chemistry
Assignee
Apterna Limited
OA Round
1 (Non-Final)
65%
Grant Probability
Favorable
1-2
OA Rounds
2y 8m
To Grant
81%
With Interview

Examiner Intelligence

Grants 65% — above average
65%
Career Allow Rate
434 granted / 668 resolved
+5.0% vs TC avg
Strong +16% interview lift
Without
With
+16.2%
Interview Lift
resolved cases with interview
Typical timeline
2y 8m
Avg Prosecution
55 currently pending
Career history
723
Total Applications
across all art units

Statute-Specific Performance

§101
5.4%
-34.6% vs TC avg
§103
28.6%
-11.4% vs TC avg
§102
22.8%
-17.2% vs TC avg
§112
24.2%
-15.8% vs TC avg
Black line = Tech Center average estimate • Based on career data from 668 resolved cases

Office Action

§103 §DP
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 1-3, 5-6, 8-10, 12-16, 25 in the reply filed on 02/10/2026 is acknowledged. Claims 19-24 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected Group, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 02/10/2026. 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) 1-3, 5-6, 8-10, 12-16, 25 is/are rejected under 35 U.S.C. 103 as being unpatentable over Yoon et al (Molecular Therapy Nucleic Acids, published online on December 6 2019, vol.18, pages 142-154, cited from IDS) and in further view of Saertrom (WO 2015/075557, May 2015), Rossi et al (WO 2017/173247, October 2017) and Birkus et al (US 2019/0185509, June 2019). Yoon teach using transferrin receptor aptamers to deliver various therapeutic payloads such as siRNAs to cancer cells expressing such receptor (see first column on page 143). One of such aptamers is shown in Table 1 on page 143 as TR14 ST1-3, which is 22 nucleotides long and identical to instant SEQ ID NO: 1. Such aptamer can deliver double-stranded RNA, saRNA, to cancer cells (see second column on page 145) such as hepatocellular carcinoma (see second column on page 143). Aptamer is conjugated to RNA through nucleotide linker (see Table 3). Such aptamer is capable of binding to TfR on a cell surface (see bridging paragraph between columns on page 145) and can internalize into a cell (see first column on page 145). Yoon teach pharmaceutical compositions comprising the aptamer bound to double-stranded RNA (see second column on page 145). Yoon do not teach conjugation of the aptamer to C/EBPβ siRNA of SEQ ID NO: 9 which comprises substituted 2’ ribose, or using disulphide bridge linker for conjugation, or using such conjugate in combination with gemcitabine. Saertrom teaches siRNA targeting C/EBPβ of SEQ ID NO: 29 (see Table 3 on page 26), which can be used for treatment of hepatocellular carcinoma and breast cancer (see paragraph [00266]). Saetrom teaches that siRNA can comprise 2’ ribose modifications (see paragraph [00134] and can be delivered by conjugation to aptamers (see paragraph [00143]). Rossi teach aptamers conjugated to anticancer compounds through disulphide bonds (see paragraphs [0072-0073]). Birkus teach treatment of hepatocellular carcinoma by administering gemcitabine (see paragraph [0838]). It would have been obvious to one of the ordinary skill in the art before the effective filing date of the claimed invention to create a conjugate of aptamer taught by Yoon with siRNA targeting C/EBPβ taught by Saertrom for treatment of hepatocellular carcinoma using conjugation through disulphide bonds as taught by Rossi and combining such conjugate with gemcitabine as taught by Birkus. One of the ordinary skill in the art would be motivated to do so, because Yoon teach the aptamer conjugate for delivery of siRNAs for treatment of hepatocellular carcinoma, Saetrom teach a specific siRNA which also can be used for the same cancer treatment, leading to creation of aptamer conjugate as instantly claimed. Further, Rossi teach using disulphide bond for conjugation of aptamer and siRNA, which can be used in a new conjugate. Lastly, Birkus teach that gemcitabine can be administered for hepatocellular carcinoma treatment, motivating adding gemcitabine to a pharmaceutical composition comprising new aptamer-siRNA conjugate. It is obvious to combine things known separately to have same effect (In re Kerkhoven, MPEP 2144.06). Double Patenting The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969). A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b). The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13. The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer. Claims 1, 6, 8-10, 12-16 and 25 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-14 of U.S. Patent No. 11,236,341 in view of Saertrom, Rossi and Birkus, above. Claims from ‘341 recite transferrin receptor aptamers which can be conjugated to siRNAs for such siRNA delivery for cancer treatments. Teachings of Saertrom, Rossi and Birkus are discussed above. It would have been obvious to create conjugates of aptamers from ‘341 with siRNA taught by Saertrom to administer in cancer treatments, arriving at instant invention. Claims 1-3, 5-6, 8-10, 12-16 and 25 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-21 of U.S. Patent No. 11,427,826 in view of Saertrom, Rossi and Birkus, above. Claims from ‘826 recite transferrin receptor aptamer of SEQ ID NO: 1, which is identical to instant SEQ ID NO: 1 and can be conjugated to siRNAs for such siRNA delivery for cancer treatments. Teachings of Saertrom, Rossi and Birkus are discussed above. It would have been obvious to create conjugates of aptamer from ‘826 with siRNA taught by Saertrom to administer in cancer treatments, arriving at instant invention. Claims 1, 6, 8-10, 12-16 and 25 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-21 of U.S. Patent No. 11,219,635 in view of Saertrom, Rossi and Birkus, above. Claims from ‘635 recite bi-specific aptamers comprising transferrin receptor aptamers which can be conjugated to siRNAs for such siRNA delivery for cancer treatments (see lines 60-66 in column 7). Teachings of Saertrom, Rossi and Birkus are discussed above. It would have been obvious to create conjugates of aptamers from ‘635 with siRNA taught by Saertrom to administer in cancer treatments, arriving at instant invention. Claims 1, 6, 8-10, 12-16 and 25 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-23 of U.S. Patent No. 12,138,279 in view of Saertrom, Rossi and Birkus, above. Claims from ‘279 recite bi-specific aptamers comprising transferrin receptor aptamers which can be conjugated to siRNAs for such siRNA delivery for cancer treatments (see lines 55-65 in column 7). Teachings of Saertrom, Rossi and Birkus are discussed above. It would have been obvious to create conjugates of aptamers from ‘635 with siRNA taught by Saertrom to administer in cancer treatments, arriving at instant invention. Claims 1-3, 5-6, 8-10, 12-16 and 25 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 44-63 of copending Application No. 17/615,695 in view of Saertrom, Rossi and Birkus, above. Claims from ‘695 recite transferrin receptor aptamer of SEQ ID NO: 6, which is identical to instant SEQ ID NO: 1 and can be conjugated to siRNAs for such siRNA delivery for cancer treatments. Teachings of Saertrom, Rossi and Birkus are discussed above. It would have been obvious to create conjugates of aptamer from ‘695 with siRNA taught by Saertrom to administer in cancer treatments, arriving at instant invention. This is a provisional nonstatutory double patenting rejection. Claims 1-3, 5-6, 8-10, 12-16 and 25 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-13 of copending Application No. 18/582,785 in view of Yoon, Rossi and Birkus, above. Claims from ‘785 recite C/EBPβ siRNAs, which are identical to several instantly claimed siRNAs (see claim 4 from ‘785) and can be administered for cancer treatments (see claim 13 from ‘785). Teachings of Yoon, Rossi and Birkus are discussed above. It would have been obvious to create conjugates of aptamer taught by Yoon with siRNA from ‘785 to administer in cancer treatments, arriving at instant invention. This is a provisional nonstatutory double patenting rejection. 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. Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice. 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. Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000. /EKATERINA POLIAKOVA-GEORGANTAS/Primary Examiner, Art Unit 1637
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Prosecution Timeline

Jun 09, 2023
Application Filed
Mar 19, 2026
Non-Final Rejection — §103, §DP (current)

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Study what changed to get past this examiner. Based on 5 most recent grants.

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Prosecution Projections

1-2
Expected OA Rounds
65%
Grant Probability
81%
With Interview (+16.2%)
2y 8m
Median Time to Grant
Low
PTA Risk
Based on 668 resolved cases by this examiner. Grant probability derived from career allow rate.

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