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. Response to Restriction/Election Requirement Applicant’s Response to Restriction/Election Requirement , filed 24 October 2025, in response to the non-final office action dated 29 July 2025, is acknowledged. In the Response, Applicant has elected a single species as follows: A cell-targeting peptide with a peptide extender as described in claims 10, 26, 28, and 31. A specific cell-targeting peptide and peptide extender as represented by SEQ ID NO:5, which is a composite of SEQ ID NO: 49 (peptide extender) and SEQ ID NO: 32 (cell-targeting peptide) wherein X and X1 are 2-azido-acetyl lysine. Claims 1, 8, 10, 22-26, 28, 106-107, 115-116, 118-119, 122, 129, and 132 read on the elected species. SEQ ID NO: 5 was searched and the exact sequence was not identified in those searches. Therefore, the election requirement is fully withdrawn and claims 1, 8, 10, 22-26, 28, 31, 106-107, 115-116, 118-119, 122, 129, and 132 are currently under examination. In view of the withdrawal of the restriction requirement, applicant(s) are advised that if any claim presented in a divisional application is anticipated by, or includes all the limitations of, a claim that is allowable in the present application, such claim may be subject to provisional statutory and/or nonstatutory double patenting rejections over the claims of the instant application. Once the restriction requirement is withdrawn, the provisions of 35 U.S.C. 121 are no longer applicable. See In re Ziegler , 443 F.2d 1211, 1215, 170 USPQ 129, 131-32 (CCPA 1971). See also MPEP § 804.01. Claim Status Claims 1- 166 were pending in the present application. By virtue of a n Amendment, filed by Applicant on 27 June 2023, claims 1 , 8, 10, 22-26, 28, 31, 106-107, 115-116, 118-119, 122, 129, and 132 were amended and claims 2-7, 9, 11-21, 27, 29-30, 32-105, 108-114, 117, 120-121, 123-128, 130-131, and 133-166 were cancelled. Therefore, claims 1, 8, 10, 22-26, 28, 31, 106- 107, 115-116, 118-119, 122, 129, and 132 were pending. As a result of the Restriction/Election requirement and Applicant’s election of species detailed above, claims 1, 8, 10, 22-26, 28, 31, 106-107, 115-116, 118-119, 122, 129, and 132 read on the elected species. However, the election was fully withdrawn and claims 1, 8, 10, 22-26, 28, 31, 106-107, 115-116, 118-119, 122, 129, and 132 are currently under examination . Priority Acknowledgment is made of applicant's claim for priority based on a parent application filed on 18 May 2020. The instant application filed on 07 November 2022 is a 371 of PCT/US2021/032906 filed 18 May 2021, which is a provisional of application 63/026,648 filed 18 May 2020 and which finds full support for the instant claims. Therefore, the effective filing date of the instant application is 18 May 2020. Information Disclosure Statement (IDS) The IDS (1) filed on 27 June 2023 has been considered by the examiner. A signed copy is enclosed. Applicant is reminded of their duty to disclose to the Office all information known to the person to be material to patentability as defined in 37 CFR 1.56. As stated therein, “[e]ach individual associated with the filing and prosecution of a patent application has a duty of candor and good faith in dealing with the Office, which includes a duty to disclose to the Office all information known to that individual to be material to patentability as defined in this section.” Claim Formatting Objections The formatting of the claims is objected for the following informalities: in the Amendment, filed 27 June 2023, the claim listing contains text pertaining to other parts of the Amendment. See 37 CFR 1.121(c)(1). Specifically, claims 132 (currently amended) and 133-166 (cancelled) share a page with Applicant Remarks (see p. 5 of Applicant Argument/Remarks). Appropriate correction is required. Claim Rejections - 35 USC § 112 (b) 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 appl icant regards as his invention. Claim s 10, 26 , and 28 are 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 10 recites, for example, the following limitation: “…wherein the amino acid sequence of the peptide extender and cell-targeting peptide together is at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% identical to an amino acid sequence selected from XPPPAGSSPGLYENKPRRPYIL (SEQ ID NO: 5)…wherein X is lysine or azido-acetyl lysine.” However, the sequence listing submitted by the Applicant is as follows: \ Applicant has indicated the wildcard, X, is selected from lysine or 2-azido-acetyl lysine. What is claimed in instant claim 10 does not correspond with Applicant’s sequence submission (e.g., 2-azido-acetyl lysine) and therefore, claim 10 is indefinite as one of ordinary skill in the art could not determine the metes and bounds of the claim. Claim 26 recites, for example, the following limitation: “…wherein the peptide extender comprises an amino acid sequence that is at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% identical to X 1 PPPAGSSPG (SEQ ID NO: 49)…wherein X 1 is selected from lysine, 2-azido-acetyl lysine, D-lysine, L-lysine, N 6 -(2-azido-acetyl)-D-lysine, and N 6 -(2-azido-acetyl)-L-lysine.” However, the sequence listing submitted by the Applicant is as follows: Applicant has indicated the wildcard, X, can be any naturally occurring amino acid. W hat is claimed in instant claim 26 does not correspond with Applicant’s sequence submission (e.g., 2-azido-acetyl lysine is not naturally occurring) and therefore, claim 26 is indefinite as one of ordinary skill in the art could not determine the metes and bounds of the claim. Claim 28 recites, for example, the following limitation: “…wherein the peptide extender comprises an amino acid sequence that is at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% identical to XPPPAGSSPG (SEQ ID NO: 49)…wherein X is any amino acid.” However, the sequence listing submitted by the Applicant is as follows: Applicant has indicated the wildcard, X, can be any naturally occurring amino acid. What is claimed in instant claim 28 does not correspond with Applicant’s sequence submission (e.g., any naturally occurring amino acid vs. any amino acid) and therefore, claim 28 is indefinite as one of ordinary skill in the art could not determine the metes and bounds of the claim. 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: 1. Determining the scope and contents of the prior art. 2. Ascertaining the differences between the prior art and the claims at issue. 3. Resolving the level of ordinary skill in the pertinent art. 4. 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. Claim s 1, 106, 107, and 132 are rejected under 35 U.S.C. 103 as being unpatentable over Beliveau (WO 2017/088058 A1; published 1 June 2017) . Beliveau discloses peptide compounds and conjugate compounds, processes, methods and uses thereof for treating cancer and increasing cellular internalization of said peptide compounds (abstract). Regarding instant claim 1, Beliveau discloses “Katana Biopharma Peptide Family 2 peptide compounds” which refers to peptides derived from neurotensin ([0069]). Beliveau provides nonlimiting examples of such compounds and indicates these compounds can be derived from neurotensin having an amino acid sequence represented by SEQ ID NO: 22. SEQ ID NO: 22 disclosed by Beliveau is 100% identical to instant SEQ ID NO:32 as shown below: Beliveau further discloses the peptide compounds disclosed can be linked to an oligonucleotide ([00222]) using a variety of linkers ([0099]). Regarding instant claim 106, Beliveau discloses the linker comprises maleimide ([0097], [0098], [00101]). Regarding instant claim 107, Beliveau discloses click chemistry can be used for conjugation on the peptide ([00117]). Beliveau further discloses the linker is phosphoramidited for incorporation onto an oligonucleotide sequence ([00117]). Regarding instant claim 132, Beliveau discloses embodiments comprising more than one peptide compound and/or more than one conjugate compound ([00297]). Beliveau discloses a cell-targeting peptide neurotensin linked to an oligonucleotide, thereby meeting the limitations of instant claim 1. Beliveau discloses various potential embodiments of the oligonucleotide complex and one of ordinary skill in the art could pick and choose from the embodiments disclosed by Beliveau to meet the limitations of instant claims 1, 106, 107, and 132. Therefore, it would have been prima facie obvious, before the effective filing date of the claimed invention, to select from the various embodiments disclosed by Beliveau to arrive at the currently claimed invention. One of ordinary skill would have predicted the prior art embodiments in Beliveau are capable of combination because Beliveau taught success in doing so. Claim s 22, 115-116, 118-119, 122, and 129 are rejected under 35 U.S.C. 103 as being unpatentable over Beliveau (WO 2017/088058 A1; published 1 June 2017) in further view of Prakash (“Evaluation of the effect of 2’-O-methyl, fluoro hexitol, bicyclo and Morpholino nucleic acid modifications on potency of GalNAc conjugated antisense oligonucleotides in mice,” published: 10 October 2028). The disclosures of Beliveau are discussed above. While Beliveau does not explicitly disclose the limitations of instant claims 22, 115 - 116, 118-119, 122, and 129 , these limitation s are made obvious in further view of Prakash . Prakash teaches antisense oligonucleotide (ASO) drugs and evaluated in vivo potency after ASO modification (abstract). Regarding instant claim 22, Prakash teaches the ASOs are connected to a linker at the 5’ end of the oligonucleotide ( p. 3775; p. 3776, Scheme 1) as shown below: Regarding instant claim 115, Prakash teaches short ASOs containing 20 linked nucleosides (p. 3776, Scheme 1). Regarding instant claims 116 and 118, Prakash teaches nucleoside modifications commonly used in ASO therapeutic applications include 2’-O-Me and 2’-O-MOE (p. 3775, Fig. 2). Regarding instant claim 119, Prakash teaches constrained ethyl bicyclo nucleic acid ( cEt BNA) is another ASO modification that significantly improves potency (abstract; p. 3775, Fig. 2). Prakash further teaches cEt BNA have proven to be effective tools for tailoring the hybridization affinity of oligonucleotides (p. 3776). Regarding instant claim 122, Prakash teaches ASOs containing cEt BNA modification at the 5’-wing, a 2’-O-MOE modification at the 3’-wing, and DNA gap region ( p. 3775, Fig. 2; p. 3777). According to the various embodiments of ASOs disclosed by Prakash, ASOs 4, 6, and 7 contain a 5’ region of 5 linked nucleosides modified by 2’-O-Me, a DNA region of 10 linked nucleosides, and a 3’ region of 5 linked nucleosides modified by 2’-O-Me (p. 3776, Scheme 1). Regarding instant claim 129, Prakash teaches ASOs containing phosphorothioate modifications (p. 3777). Prakash teaches PS ASOs bind more avidly to proteins than phosphodiester ASOs (p. 3777). Beliveau discloses a cell-targeting peptide neurotensin linked to an oligonucleotide, thereby meeting the limitations of instant claim 1. Prakash teaches modifications to oligonucleotide therapeutics to improve potency. Prakash teaches the modifications claimed in instant claims 22, 115-116, 118-119, 122, and 129. Prakash demonstrates these modifications to oligonucleotides were widely known in the art and available to the skilled artisan before the effective filing date of the claimed invention. Therefore, it would have been prima facie obvious, before the effective filing date of the claimed invention, apply the modifications taught by Prakash to the oligonucleotide complex disclosed by Beliveau. One of ordinary skill would have been motivated to do so because Prakash teaches these modifications significantly improve oligonucleotide potency in vivo . Allowable Subject Matter Claims 8, 2 3 -2 5 , and 31 are objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims. Prior art and the disclosed sequences were extensively searched. The incorporation of a peptide extender and specific oligonucleotide orientation as described in instant claims 8, 10, 2 3 -26, 28, and 31 is free from prior art, but objected to because of dependency upon rejected claim 1. Regarding the incorporation of a peptide extender, Beliveau discloses the peptide compounds can be modified at the C- and/or N-terminal by the addition of one or more amino acid residues in order to obtain or increase preferential binding sites at the peptide terminal end ([00221]). DiMarchi (WO 2013/074910 A1; published: 23 May 2013) discloses glucagon superfamily peptides exhibiting glucocorticoid receptor activity (title). DiMarchi specifically discloses peptide conjugates represented by the formula: Q-L-Y, where Q is a glucagon superfamily peptide; Y is a GR ligand, and L is a linking group or bond ([0011]). DiMarchi discloses Q can be conjugated with a heterologous moiety which can include one or more nucleic acid molecules ([00245]). Furthermore, DiMarchi discloses an extension attached to the C-terminus of Q comprising an amino acid sequence of SEQ ID NO: 1610 (GPSSGAPPPS). DiMarchi teaches this extension may further increase solubility, stability, and/or glucagon activity ([00301]-[00302]). Pertaining to the structure, DiMarchi teaches the extension in reverse order, attached to a peptide and linker as shown below ([00779]): However, there is nothing in Beliveau, DiMarchi , or other prior art which teaches or suggests a cell-targeting peptide comprising SEQ ID NOs: 3, 32, and 72-75 , attached to a peptide extender comprising SEQ ID NOs: 48-58, and 81-83, linked to an oligonucleotide via linker. Conclusion Claims 8, 23-25, and 31 are objected to. Claims 1, 10, 22, 26, 28, 106-107, 115-116, 118-119, 122, 129, and 132 are rejected. No claim is allowed. Communication Any inquiry concerning this communication or earlier communications from the examiner should be directed to FILLIN "Examiner name" \* MERGEFORMAT Julia A Rossi whose telephone number is FILLIN "Phone number" \* MERGEFORMAT (571) 272-0138 . The examiner can normally be reached FILLIN "Work Schedule?" \* MERGEFORMAT M-F 8:30-5:00 . 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 Daniel E Kolker can be reached at FILLIN "SPE Phone?" \* MERGEFORMAT (571) 272-3181 . 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. /JULIA A ROSSI/ Examiner, Art Unit 1644 /DANIEL E KOLKER/ Supervisory Patent Examiner, Art Unit 1644