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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 08/25/2025 has been entered.
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) 1-2, 8-9, 12-14, 42-43, 48-52 is/are rejected under 35 U.S.C. 103 as being unpatentable over Huber et al (WO 2019/048645, March 2019, of record) and in further view of Schlegal et al (WO 2018/098117, May 2018, cited from IDS).
Concerning claims 1-2 and 52 Huber et al teach double-stranded RNA, siRNA, with antisense and sense strands complementary to each other, with antisense strand having complementarity with the target RNA (see paragraphs [0078-0079, 0087]). Such double-stranded RNA can effectively and specifically downregulate target RNA transcript (see paragraph [0056]). In one embodiment the sense strand of such double-stranded RNA can comprise 1-10 nucleotide overhang at the 3’ or 5’ end, such overhang can comprise abasic nucleotides connected to the rest of the strand with 5’-5’ linkage (see paragraphs [0090, 00135]). Such inverted abasic modification may encourage preferential loading of antisense strand (see paragraph [00135]). Huber et al teach that GalNAc ligand can be connected to 3’ end of sense strand through a linker (see paragraph [00196]). Concerning claims 8, 9 and 12 Huber et al teach that such double-stranded RNA can be modified (see paragraph [00118]), such modification can be 2’-Me or 2’-F and can be present on each strand (see paragraph [00191]). Concerning claims 13 and 49 Huber et al teach the presence of at least one GNA in the double-stranded RNA (see paragraph [00137]). Concerning claims 42 and 43 Huber et al teach the presence of at least one phosphorothioate linkage in the strands (see paragraph [00134]). Concerning claim 48 Huber et al teach pharmaceutical compositions comprising double-stranded RNA of the invention and at least one pharmaceutically acceptable carrier (see paragraph [00213]).
Huber et al do not teach 3’-5’ linkage between two terminal abasic nucleotides, or the inclusion of GNA in one or more positions 1-9 of antisense strand, or RNA having a melting temperature between 40 and 80 C, or presence of phosphorothioate linkages between three consecutive positions in near terminal region of sense strand or in 5’ terminal region of antisense strand.
Schlegal et al teach double-stranded RNAs for inhibiting gene expression, siRNA or RNAi (see lines 20- 25 on page 2, lines 15-30 on page 20). Such double-stranded RNAs can be further improved to reduce off-target effects by including thermally destabilizing modification at positions 2-9 of antisense strand and/or having melting temperature of double-stranded RNA between 40 and 80C (see lines 27-36 on page 2). Such destabilizing modification can be inclusion of GNA (see lines 25-30 on page 7). Further Example on lines 25-30 on page 7 shows inclusion of phosphorothioate linkages between three consecutive positions in 5’ terminal region of antisense strand (see line 27 on page 7). Schlegal et al further teach phosphorothioate linkages on every nucleotide in a sense and/or antisense strand (see lines 10-15 on page 70).
It would have been obvious to one of the ordinary skill in the art before the effective filing date of the claimed invention to include modifications taught by Schlegal et al into siRNA taught by Huber et al arriving at instant invention. One of the ordinary skill in the art would be motivated to do so to further improve siRNA of Huber et al to reduce off-target effects by including modifications taught by Schlegal et al. The references do not teach the 3’-5’ linkage between abasic nucleotides as instantly claimed, but there are only several ways to make such a connection, therefore it would be obvious to choose one between several limited options.
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 1-2, 8-9, 12-14, 42-43, 48-52 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 58, 61-65 of copending Application No. 18/106,158 in view of Schlegal et al, above. Claims from ‘158 recite a GalNAc compound connected to 3’ terminal end of the sense strand of double-stranded RNA (siRNA). Specification from ‘158 teach that such RNA can have abasic nucleotides overhang identical to instantly claimed (see paragraph [0067] from ‘158), GNA modification at position 9 of sense strand (see paragraph [0402] from ‘158) and can include phosphorothioate modifications (see paragraph [0148] from ‘158). Teachings of Schlegal et al are discussed above. It would have been obvious to include modifications taught by Schlegal et al into double-stranded RNAs from ‘158 to reduce off-target effects arriving at instant invention.
This is a provisional nonstatutory double patenting rejection.
Claims 1-2, 8-9, 12-14, 42-43, 48-52 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-19 of U.S. Patent No. 12,338,438 in view of Schlegal et al, above. Claims from ‘438 recite a compound comprising double-stranded RNA (siRNA) comprising abasic nucleotides, which is conjugated to a ligand. Specification from ‘438 teach that such RNA can have abasic nucleotides overhang identical to instantly claimed (see lines 20-30 in column 22), GNA modification at position 9 of sense strand (see lines 5-15 in column 116), can include phosphorothioate modifications (see lines 40-50 in column 26) and the ligand can be GalNAc attached to 3’ terminus of sense strand through a linker (see Figure 26B). Teachings of Schlegal et al are discussed above. It would have been obvious to include modifications taught by Schlegal et al into double-stranded RNAs from ‘438 to reduce off-target effects arriving at instant invention.
Claims 1-2, 8-9, 12-14, 42-43, 48-52 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-41 of U.S. Patent No. 10,995,336 in view of Huber et al, above. Claims from ‘336 recite specific double-stranded RNAs (siRNAs) comprising abasic nucleosides, GNA and phosphorothioate linkages. Claims do not recite abasic nucleoside overhangs or GalNAc connected to 3’ terminus of sense strand as in instant claims. Teachings of Huber et al are discussed above. It would have been obvious to include overhangs and GalNAc as taught by Huber et al into RNAs from ‘336 to encourage preferential loading of antisense strand arriving at instant invention.
Claims 1-2, 8-9, 12-14, 42-43, 48-52 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 3, 5-7, 11-13, 15, 19-20, 22-24, 37, 43 of copending Application No. 18/698,235. Claims from ‘235 recite the same double-stranded RNA (siRNA) comprising abasic nucleotides as in instant claims, which is connected to a ligand attached to 3’ terminus of sense strand. Specification from ‘235 teach the presence of phosphorothioate modifications at the same regions as instantly claimed (see paragraphs [0109-0110] from ‘235) and that the ligand can be GalNAc (see paragraph [0278] from ‘235).
This is a provisional nonstatutory double patenting rejection.
Response to Arguments
Applicant's arguments filed 08/25/2025 have been fully considered but they are not persuasive.
Concerning 103 rejection Applicant argues that the references do not teach or suggest claimed siRNA. In response the references teach all the elements of the siRNAs as instantly claimed, providing a finite number of identified and predictable solutions to such elements. According to MPEP 2143, Section I, example (E) it is obvious to try by choosing from a finite number of identified, predictable solutions with a reasonable expectation of success.
Further Applicant argues that the Declaration submitted on 08/25/2025 shows unexpected results. In response the Declaration does show that siRNAs with elements as instantly claimed are active, but it does not provide any comparison with siRNAs with different types of elements such as missing abasic nucleotides or having different linkage between them, etc. Therefore, it is not clear from the results shown that specific elements in specific arrangement as claimed provide unexpected activity. It is suggested to provide such evidence to overcome obviousness rejection.
Double patenting rejections are maintained for the reasons of record.
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.
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