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. Application Status This action is written in response to applicant’s correspondence received 03/13/2026 . Claims 1-21 are currently pending. Claim s 17-21 are withdrawn from prosecution as being drawn to non-elected subject matter. Accordingly, claims 1-16 are examined herein. The restriction requirement mailed 01/28/2026 is still deemed proper. Applicant elected the invention of Group I, claims 1-16, drawn to an aptamer-POEGMA conjugate and method of making it, with out traverse in the reply filed 03/13/2026 . Election/Restrictions Applicant's election with out traverse of the invention of Group I in the reply filed on 03/13/2026 is acknowledged. C laim s 17-21 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention, there being no allowable generic or linking claim. Nucleotide and/or Amino Acid Sequence Disclosures REQUIREMENTS FOR PATENT APPLICATIONS CONTAINING NUCLEOTIDE AND/OR AMINO ACID SEQUENCE DISCLOSURES Items 1) and 2) provide general guidance related to requirements for sequence disclosures. 37 CFR 1.821(c) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.821(a) must contain a "Sequence Listing," as a separate part of the disclosure, which presents the nucleotide and/or amino acid sequences and associated information using the symbols and format in accordance with the requirements of 37 CFR 1.821 - 1.825. This "Sequence Listing" part of the disclosure may be submitted: In accordance with 37 CFR 1.821(c)(1) via the USPTO patent electronic filing system (see Section I.1 of the Legal Framework for Patent Electronic System (https://www.uspto.gov/PatentLegalFramework), hereinafter "Legal Framework") as an ASCII text file, together with an incorporation-by-reference of the material in the ASCII text file in a separate paragraph of the specification as required by 37 CFR 1.823(b)(1) identifying: the name of the ASCII text file; ii) the date of creation; and iii) the size of the ASCII text file in bytes; In accordance with 37 CFR 1.821(c)(1) on read-only optical disc(s) as permitted by 37 CFR 1.52(e)(1)(ii), labeled according to 37 CFR 1.52(e)(5), with an incorporation-by-reference of the material in the ASCII text file according to 37 CFR 1.52(e)(8) and 37 CFR 1.823(b)(1) in a separate paragraph of the specification identifying: the name of the ASCII text file; the date of creation; and the size of the ASCII text file in bytes; In accordance with 37 CFR 1.821(c)(2) via the USPTO patent electronic filing system as a PDF file (not recommended); or In accordance with 37 CFR 1.821(c)(3) on physical sheets of paper (not recommended). When a “Sequence Listing” has been submitted as a PDF file as in 1(c) above (37 CFR 1.821(c)(2)) or on physical sheets of paper as in 1(d) above (37 CFR 1.821(c)(3)), 37 CFR 1.821(e)(1) requires a computer readable form (CRF) of the “Sequence Listing” in accordance with the requirements of 37 CFR 1.824. If the "Sequence Listing" required by 37 CFR 1.821(c) is filed via the USPTO patent electronic filing system as a PDF, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the PDF copy and the CRF copy (the ASCII text file copy) are identical. If the "Sequence Listing" required by 37 CFR 1.821(c) is filed on paper or read-only optical disc, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the paper or read-only optical disc copy and the CRF are identical. Specific deficiencies and the required response to this Office Action are as follows: 1. Specific deficiency – Nucleotide and/or amino acid sequences appearing in the drawings are not identified by sequence identifiers in accordance with 37 CFR 1.821(d). Sequence identifiers for nucleotide and/or amino acid sequences must appear either in the drawings or in the Brief Description of the Drawings. Please see FIGs. 2A and 11A. Required response – Applicant must provide: Replacement and annotated drawings in accordance with 37 CFR 1.121(d) inserting the required sequence identifiers; AND/OR A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3) and 1.125 inserting the required sequence identifiers into the Brief Description of the Drawings, consisting of: A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version); A copy of the amended specification without markings (clean version); and A statement that the substitute specification contains no new matter. 2. Specific deficiency - This application contains sequence disclosures in accordance with the definitions for nucleotide and/or amino acid sequences set forth in 37 CFR 1.821(a)(1) and (a)(2). However, this application fails to comply with the requirements of 37 CFR 1.821 - 1.825. The sequence disclosures are located on page 37 of the specification and in FIGs. 2A and 11A. There appears to be a discrepancy between SEQ ID NO: 1 / R B 00 5 as it is disclosed in the specification and SEQ ID NO: 1 as it is disclosed in the sequence listing. On page 37 of the specification, SEQ ID NO: 1 is disclosed to be 5'-mGmUmGmGmAfCfUmAfUmAfCfCmGfCmGfUmAmAfUmGfCmUrGmCfCfUmCmCmAmCidT-3'. Aptamer RB005 has the same sequence and modifications, per FIGs. 2A and 11A. However, the sequence listing discloses SEQ ID NO: 1 to be 5'-mGmUmGmAfCfUmAfUmAfCmGfCmGfUmAfUmGfCmUrGmCfCfUmCmAmCidT-3'. Aligning SEQ ID NO: 1 from the sequence listing against SEQ ID NO: 1 from the specification, we can see that they are not the same sequence: 5'-mGmUmGmGmAfCfUmAfUmAfCfCmGfCmGfUmAmAfUmGfCmUrGmCfCfUmCmCmAmCidT-3' 5'-mGmUmG-- mAfCfUmAfUmAfC -- mGfCmGfUmA -- fUmGfCmUrGmCfCfUmC --mAmCidT-3' It appears that the discrepancy may be due to a typographical error and the aptamer disclosed in the specification and drawings may be the correct sequence. This is supported by Moreno (Anti-PEG antibodies inhibit the anticoagulant activity of PEGylated aptamers. Cell Chem Biol. 2019 May 16; 26(5): 634–644.e3. ; of record, applicant’s own submission). Moreno shares inventors with the instant application and depicts aptamer RB006, the PEG-conjugated version of RB005, which matches what is presented in the instant specification and drawings. In the interests of customer service and compact prosecution, the Examiner will assume, based on the preponderance of evidence, that SEQ ID NO: 1 as it is disclosed in the sequence listing has typographical errors, and SEQ ID NO: 1 on page 37 of the specification and in FIGs. 2A and 11A is the sequence Applicant actually intended to claim. Any claims reciting SEQ ID NO: 1 will be interpreted and examined accordingly. Required response – Applicant must provide: A "Sequence Listing" part of the disclosure, as described above in item 1); as well as An amendment specifically directing entry of the "Sequence Listing" part of the disclosure into the application in accordance with 1.825(b)(2) ; A statement that the "Sequence Listing" includes no new matter in accordance with 1.825(b)(5) ; and A statement that indicates support for the amendment in the application, as filed, as required by 37 CFR 1.825(b)(4). If the "Sequence Listing" part of the disclosure is submitted according to item 1) a) or b) above, Applicant must also provide: A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3) and 1.125 inserting the required incorporation-by-reference paragraph, consisting of: A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version); A copy of the amended specification without markings (clean version); and A statement that the substitute specification contains no new matter; If the "Sequence Listing" part of the disclosure is submitted according to item 1) b), c), or d) above, Applicant must also provide: A replacement CRF in accordance with 1.825(b)(6) ; and Statement according to item 2) a) or b) above. 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. The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows: Determining the scope and contents of the prior art. Ascertaining the differences between the prior art and the claims at issue. Resolving the level of ordinary skill in the pertinent art. 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. Claims 1 , 8-9, 11, and 15-16 are rejected under 35 U.S.C. 103 as being unpatentable over WIPO Publication 2017 / 11282 5 A2 to Ganson (of record, applicant’s submission, hereinafter ‘ Ganson ’) in view of Joh ( Architectural Modification of Conformal PEG-Bottlebrush Coatings Minimizes Anti-PEG Antigenicity While Preserving Stealth Properties . Adv. Healthcare Mater.2019, 8, 1801177 .; of record, applicant’s submission). Ganson teaches molecule-polymer conjugates having reduced or eliminated antigenicity compared to a control, the conjugate comprising a backbone and plurality of side chains, each side chain covalently attached to the backbone , where in each side chain is a linear polymer (claim 3 9 ) , the branched polymer comprises poly[oligo(ethylene glycol) methyl ether methacrylate] (POEGMA) , and wherein the POEGMA has a backbone comprising poly(methyl methacrylate) and a plurality of side chains covalently attached to the backbone (claim 5 5 ), each side chain comprising 1 (claim 5 6 ), 2 (claim 5 7 ), 3 (claim 60 ), or 3-9 (claim 6 1 ) monomers of ethylene glycol repeated in tandem. Ganson confirms that, “ Breaking up and appending PEG as short o l igomeric side-chains of optimized length on the conjugated POEGMA not only retains the long circulation of the POEGMA conjugates, but also eliminates their reactivity toward patient-derived PEG antibodies ” (para [00031]). Specifically, they note that a 3-monomer repeat side chain, “ completely eliminated the reactivity of the conjugate toward anti-PEG antibodies present in the patient plasma samples. ” (para [0001 50 ]). Ganson differs from the instant claims in that Ganson exemplifies a peptide (exendin) but does not exemplify an aptamer conjugated to POEGMA. However, Ganson notes that, “ PEGylation, or the covalent conjugation of therapeutics with the "stealth" polymer PEG, is one of the most widely used approaches to increase the circulation half-life and stability and to reduce the immunogenicity of biomolecule therapeutics such as polypeptides and polynucleotides. ” (para [0005]), but, “ the immunogenicity of PEG has recently attracted much attention ” (para [0006]) and that, “ High levels of such pre-existing anti-PEG antibodies have recently been linked to serious first-exposure allergic reactions to a PEGylated RNA aptamer ” ( Id .). In claim 63, Ganson recites wherein the molecule (i.e., biomolecule) conjugated to POEGMA may be an aptamer. While Ganson does not explicitly state that POEGMA may be readily substituted for PEG, Joh teaches that POEGMA is a, “n ext-generation, PEG-derived polyme r” and that, “ the use of POEGMA, rather than transitioning to non-PEG derived polymers, may be logistically favorable given PEG’s long history of use in humans and its pervasive role in commercial, research, and clinical settings .”. It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the peptide-POEGMA conjugate, as taught by Ganson , by substituting an aptamer as the biomolecule, also as taught by Ganson . Ganson teaches that PEGylation of polynucleotides, including aptamers, was one of the most commonly used approaches to increase circulation half-life and stability and reduce immunogenicity of biomolecule therapeutics. Ganson further teaches that there was an art-recognized need for less immunogenic alternatives to PEG , and provides POEGMA as that alternative. The ordinary artisan would have been motivated to conjugate an aptamer to POEGMA instead of PEG to produce a less immunogenic aptamer therapeutic . The ordinary artisan would further have had a reasonable expectation of success based on Ganson’s teachings that aptamers were one of the possible biomolecule conjugates and on Joh’s teachings that POEGMA was developed as a logistically favorable substitute for PEG. Regarding claim s 8 and 15 , Ganson teaches wherein the POEGMA has a number average molecular weight of about 5-50 kDa (see Table 1). Regarding claim s 9 and 16 , Ganson teaches wherein each side chain comprises 3 monomers of EG repeated in tandem (see above). Regarding claim 11, Ganson teaches various methods of making a peptide-POEGMA conjugate (para [0009] ). Claim s 2-7, 10, and 1 3 -14 are rejected under 35 U.S.C. 103 as being unpatentable over Ganson (cited above) and Joh (cited above) in view of Moreno ( Anti-PEG antibodies inhibit the anticoagulant activity of PEGylated aptamers . Cell Chem Biol. 2019 May 16;26(5):634-644.e3 .; of record, applicant’s own submission) . Ganson and Joh render obvious the aptamer-POEGMA conjugate from which the instantly rejected claims depend, as described above. Ganson and Joh do not teach a modified, 15-100 nucleotide aptamer capable of binding a blood protein and comprising SEQ ID NO: 1. Regarding claim 4, Moreno teaches pegnivacogen /RB006, “ a novel fast acting and rapidly reversible anticoagulant RNA aptamer targeting coagulation Factor IXa ( FIXa ) ” , i.e., capable of binding a blood protein (p. 3). Regarding claims 2 and 13, Moreno further teaches that the aptamer was 31 nucleotides long (p. 12, Figure 1a): RB006, a 31 nucleotide 2’ modified RNA aptamer conjugated to 40 kDa methoxy polyethylene glycol (Figure 1a ) Regarding claim s 3, 5, 6 and 14 , Moreno teaches that RB006 comprises SEQ ID NO: 1 , is modified, and comprises at least one stem and at least one loop : Regarding claim 7, Moreno teaches that the conjugate comprising POEGMA is not reactive with pre-existing anti-PEG antibodies in a subject, as already discussed with regard to claim 1. Regarding claim 10 , Moreno teaches wherein PEG is conjugated to a 5’ end of the aptamer, and Ganson in view of Joh renders obvious the substitution of PEG with POEGMA, as already discussed above. Moreno further provides a teaching, suggestion or motivation to modify RB006 by teaching that administration of RB006 conjugated to PEG resulted in, “serious adverse advents in 0.6% of the patients, resulting in early termination of the study. Subsequent investigation correlated the severity of the allergic reactions to the presence of pre-existing anti-PEG antibodies”. It would have been prima facie obvious to a person having ordinary skill in the art before the effective filing date of the claimed invention to have combined the teachings of Ganson and Joh, which disclose that POEGMA eliminates reactivity towards pre-existing anti-PEG antibodies and may be conjugated to aptamers in place of PEG, with those of Moreno, which teaches that the specific PEGylated aptamer, RB006, led to serious adverse events in patients due to the presence of pre-existing anti-PEG antibodies. The ordinary artisan would have been motivated to ameliorate the immunogenicity of RB006 based on Moreno’s disclosures, and would have recognized, based on Ganson and Joh’s disclosures, that POEGMA was a suitable substitute for PEG which would predictably have achieved the desired outcome of an aptamer conjugate with reduced immunogenicity . Claim 12 is rejected under 35 U.S.C. 103 as being unpatentable over Ganson (cited above) and Joh (cited above) in view of Fletcher ( Designed multifunctional polymeric nanomedicines: long-term biodistribution and tumour accumulation of aptamer-targeted nanomaterials . Chem. Commun ., 2018, 54, 11538 .). Ganson and Joh render obvious the conjugate of claim 1 and method of making it of claim 11, from which claim 12 depends, as discussed above. Ganson and Joh do not teach wherein the POEGMA is functionalized with an azide group and the aptamer is functionalized with a dibenzocyclooctyne group . Fletcher teaches the conjugation of hyperbranched polymeric nanoparticles comprising a Poly(ethylene glycol)methacrylate ( PEG MA) backbone to an aptamer (Abstract, Title, Scheme 1, p. 1153 8- 9). Fletcher further teaches that the PEGMA backbone was functionalized with an azide group, and that the aptamer was functionalized with a dibenzocyclooctyne (DBCO) group (Scheme 1 and p. 11539, quoted below): The previously reported aptamer RNV66 was synthesised in-house incorporating a DBCO phosphoramadite at the 50 terminus and incubated overnight with the azido functionalized HBP3 to produce HBP3-A It would have been prima facie obvious to a person having ordinary skill in the art before the effective filing date of the claimed invention to have synthesized the aptamer-POEGMA conjugate, as taught by Ganson and Joh, using the methods taught by Fletcher. Ganson and Joh render obvious aptamer-POEGMA conjugates comprising aptamers and PEGMA backbones , and Fletcher provides an effective method suitable for conjugating aptamers to PEGMA backbones . Based on Fletcher’s disclosures and the fact that both Fletcher’s nanoparticles and Ganson and Joh’s POEGMA nanoparticles shared a key structure, i.e., a PEGMA backbone, the ordinary artisan would have had a reasonable expectation that Fletcher’s approach would have successfully produced an aptamer-POEGMA conjugate. 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 . Claim s 1 and 9 are rejected on the ground of nonstatutory double patenting as being unpatentable over claim 17 of U.S. Patent No. 10,364,451 . Although the claims at issue are not identical, they are not patentably distinct from each other because patented claim 17 depends from patented claim 13, which recites a molecule-polymer conjugate having reduced or eliminated antigenicity and comprising a POEGMA backbone and a plurality of 2-9 EG side chains attached to the backbone, while patented claim 17 specifically recites that the molecule may be an aptamer. Conclusion No claims are allowed at this time. Any inquiry concerning this communication or earlier communications from the examiner should be directed to FILLIN "Examiner name" \* MERGEFORMAT AMANDA M ZAHORIK whose telephone number is FILLIN "Phone number" \* MERGEFORMAT (703)756-1433 . The examiner can normally be reached FILLIN "Work Schedule?" \* MERGEFORMAT M-F 8:00-16:00 EST . 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, FILLIN "SPE Name?" \* MERGEFORMAT Neil Hammell can be reached on FILLIN "SPE Phone?" \* MERGEFORMAT (571) 270-5919 . 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. /AMANDA M ZAHORIK/ Examiner, Art Unit 1636