CTNF 18/272,158 CTNF 71972 DETAILED ACTION Notice of Pre-AIA or AIA Status 07-03-aia AIA 15-10-aia 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 08-25-02 Applicants’ election of Group I (claims 1-5, 7-8, 12-13, 16, 19, 21, 25-26, and 28) in the reply filed on April 22, 2026 is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)). 08-06 AIA Claim s 29-32, 34-35, 39-40, 43, 46, 48, 50, 53-55, 57, 59-62, and 64-68 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention , there being no allowable generic or linking claim. Election was made without traverse in the reply filed on April 22, 2026 . In addition, Applicants also elected the species Gag polypeptide, PEG10, and G envelope protein. However, upon further consideration the election of species requirement is withdrawn. Claims 1-5, 7-8, 12-13, 16, 19, 21, 25-26, and 28 will be examined in their entirety . Information Disclosure Statement The Information Disclosure Statements filed April 22, 2026 (2) and July 13, 2023 have been considered. 06-49-06 AIA The listing of references in the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered. Drawings 06-24-01 AIA Color photographs and color drawings are not accepted in utility applications unless a petition filed under 37 CFR 1.84(a)(2) is granted. Any such petition must be accompanied by the appropriate fee set forth in 37 CFR 1.17(h), one set of color drawings or color photographs, as appropriate, if submitted via the USPTO patent electronic filing system or three sets of color drawings or color photographs, as appropriate, if not submitted via the via USPTO patent electronic filing system, and, unless already present, an amendment to include the following language as the first paragraph of the brief description of the drawings section of the specification: The patent or application file contains at least one drawing executed in color ( see Figure 37). Copies of this patent or patent application publication with color drawing(s) will be provided by the Office upon request and payment of the necessary fee. Color photographs will be accepted if the conditions for accepting color drawings and black and white photographs have been satisfied. See 37 CFR 1.84(b)(2). Nucleotide and/or Amino Acid Sequence Disclosures Summary of Requirements for Patent Applications Filed On Or After July 1, 2022, That Have Sequence Disclosures 37 CFR 1.831(a) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.831(b) must contain a “Sequence Listing XML”, 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 1.831-1.835. This “Sequence Listing XML” part of the disclosure may be submitted: 1. In accordance with 37 CFR 1.831(a) using the symbols and format requirements of 37 CFR 1.832 through 1.834 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”) in XML format, together with an incorporation by reference statement of the material in the XML file in a separate paragraph of the specification (an incorporation by reference paragraph) as required by 37 CFR 1.835(a)(2) or 1.835(b)(2) identifying: a. the name of the XML file b. the date of creation; and c. the size of the XML file in bytes; or 2. In accordance with 37 CFR 1.831(a) using the symbols and format requirements of 37 CFR 1.832 through 1.834 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 statement of the material in the XML format according to 37 CFR 1.52(e)(8) and 37 CFR 1.835(a)(2) or 1.835(b)(2) in a separate paragraph of the specification identifying: a. the name of the XML file; b. the date of creation; and c. the size of the XML file in bytes. SPECIFIC DEFICIENCIES AND THE REQUIRED RESPONSE TO THIS NOTICE ARE AS FOLLOWS: Specific deficiency - Sequences appearing in the drawings are not identified by sequence identifiers in accordance with 37 CFR 1.831(c). Sequence identifiers for sequences (i.e., “SEQ ID NO:X” or the like) must appear either in the drawings or in the Brief Description of the Drawings. See Figures 12, 114B, 122B, and 132. Required response – Applicant must provide: Amended 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 (i.e., “SEQ ID NO:X” or the like) 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. Specification 07-29 AIA The disclosure is objected to because of the following informalities: All genus and species names should be italicized. The use of the terms TEXAS RED® at paragraph [0372]; TALEN® at paragraph [0600]; LIPOFECTAMINE® at paragraph [0682]; PROTOSCRIPT® at paragraph [0683]; PHUSION® at paragraph [0683]; GIBSON ASSEMBLY® at paragraph [0683]; NANODROP® at paragraph [0684]; IBLOT® at paragraph [0684]; CHEMIDOC® at paragraphs [0684] and [0761]; DIRECT-ZOL® at paragraphs [0683], [0685], [0686], [0701], [0702], [0762], [0763], [0780], and [0781]; SYBR® at paragraphs [0685], [0700], [0762], and [0779]; LIGHTCYCLER® at paragraph [0685]; DURAPORE® at paragraphs [0686] and [0763]; MICROFLUIDIZER® at paragraphs [0689] and [0767]; STREP TACTIN® at paragraphs [0689] and [0767]; AKTA PURE® at paragraph [0689]; CRYOPLUNGE® at paragraph [0689]; SUPERDEX® at paragraph [0689]; ULTRASCAN® at paragraph [0689]; EASY-SPRAY® at paragraphs [0696], [0697], and [0775]; DIONEX® at paragraph [0696]; XCALIBUR at paragraphs [0696], [0697], and [0775]; SEQUEST at paragraphs [0697] and [0777]; OPTIPREP® at paragraphs [0700] and [0779]; NEBNEXT® at paragraphs [0702] and [0781]; QUBIT® at paragraph [0704]; MISEQ® at paragraphs [0704] and [0783]; NUPAGE® at paragraph [0707]; TRYPLE® at paragraph [0713]; CYTOFLEX® at paragraph [0714]; AMICON® at paragraph [0779]; NEXTSEQ® at paragraph [0781]; AMPURE® at paragraph [0783]; and BIORUPTOR® at paragraph [0784]; which are trade names or marks used in commerce, has been noted in this application. The terms should be accompanied by the generic terminology; furthermore the terms should be capitalized wherever they appear or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term. Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks . Appropriate correction is required. Claim Objections 07-29-01 AIA Claim s 2, 4, 5, 8, and 28 are objected to because of the following informalities: At claim 2, line 2, and claim 5, line 3, “the cargo polynucleotide” should be changed to “the one or more heterologous cargo polynucleotides.” At claim 4, line 1, “PEG10” should be changed to “paternally expressed gene 10 (PEG10).” At claim 4, line 2, “RTL1” should be changed to “retrotransposon Gag Like 1 (RTL1).” At claim 4, line 2, “RTL3” should be changed to “retrotransposon Gag Like 3 (RTL3).” At claim 4, line 2, “RTL5” should be changed to “retrotransposon Gag Like 5 (RTL5).” At claim 4, line 2, “RTL6” should be changed to “retrotransposon Gag Like 6 (RTL6).” At claim 8, lines 9, 10, and 13, each occurrence of “derived” should be changed to “obtained.” At claim 28, lines 3-4, “configured such that the targeting moiety is present” should be changed to “comprises a targeting moiety present.” Appropriate correction is required. Claim Rejections - 35 USC § 112 07-34-01 Claims 2-3, 5, 8, 12, 16, 21, 25-26, 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. A broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). In the present instance, claim 2 recites the broad recitation “a fusogenic polypeptide,” and the claim also recites “optionally wherein the fusogenic polypeptide is specific for a target cell type to which the cargo polynucleotide is targeted for delivery,” which is the narrower statement of the range/limitation. In the present instance, claim 3 recites the broad recitation “an endogenous Gag polypeptide,” and the claim also recites “optionally a Sushi family polypeptide or orthologue thereof,” which is the narrower statement of the range/limitation. While claim 4 depends from claim 3, claim 4 is directed solely to the Gag polypeptide. Thus, claim 4 is not included in this rejection. In the present instance, claim 5 recites the broad recitation “one or more modifications,” and the claim also recites “optionally wherein the one or more modifications are in the polynucleotide encoding the endogenous LTR retroelement polypeptide at the boundary between the nucleocapsid domain encoding region and the protease domain encoding region,” which is the narrower statement of the range/limitation. In the present instance, claim 12 recites the broad recitation “an endogenous Gag polypeptide,” and the claim also recites “optionally a Sushi family polypeptide,” which is the narrower statement of the range/limitation. While claim 13 depends from claim 3, claim 4 is directed solely to the Gag polypeptide. Thus, claim 13 is not included in this rejection. In the present instance, claim 16 recites the broad recitation “the fusogenic polypeptide is a tetraspanin (TSPAN), a G envelope protein,” and the claim also recites “optionally wherein (a) the TSPAN is CD81, CD9, CD63, or a combination thereof; or (b) the G envelope protein is a vesicular stomatitis virus G envelope protein (VSV-G),” which is the narrower statement of the range/limitation. In the present instance, claim 21 recites the broad recitation “one or more heterologous cargo polynucleotides are RNA, DNA, or hybrid RNA/DNA,” and the claim also recites “optionally, wherein at least one of the one or more heterologous cargo polynucleotides encodes an RNA guided nuclease system,” “optionally an RNA guided nuclease,” “optionally wherein the RNA guided nuclease system is a Cas-based system or an IscB system and wherein the optional RNA guided nuclease is a Cas polypeptide or an IscB polypeptide,” which are the narrower statements of the ranges/limitations. Claims 25-26 depend from claim 21, and are therefore included in this rejection. In the present instance, claim 28 recites the broad recitation “the polynucleotide encoding an endogenous long-terminal repeat (LTR) retroelement polypeptide,” and the claim also recites “optionally the capsid domain,” which is the narrower statement of the range/limitation. The claims are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims. Claim 5 recites the limitation "the nucleocapsid domain encoding region" in line 7. There is insufficient antecedent basis for this limitation in the claim. It is suggested that “encoding region” be deleted. Claim 5 recites the limitation "the protease domain encoding region" in line 7. There is insufficient antecedent basis for this limitation in the claim. It is suggested that “encoding region” be deleted. At claim 8, lines 2, 3, 4, 6, 8, 13, and 15, the term “portion” is indefinite because it is not clear how much of the 3’ and 5’ untranslated regions (UTRs) are required in order for the “portion” to be effective as an UTR. Is a single nucleotide enough to be considered a “portion?” Claim Rejections - 35 USC § 103 07-06 AIA 15-10-15 In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status. 07-20-aia AIA 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. 07-23-aia AIA 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. 07-20-02-aia AIA 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. 07-21-aia AIA Claim s 1-5, 7-8, 12-13, 16, 19, 21, 25-26, and 28 are rejected under 35 U.S.C. 103 as being unpatentable over Lu et al. (PCT Patent Application Publication No. WO 2019/213257, published November 7, 2019, and cited in the Information Disclosure Statement filed July 13, 2023) in view of Abed et al. (14(4) PLoS ONE e0214110, 1-18 (2019), and cited in the Information Disclosure Statement filed July 13, 2023) . Regarding claim 1, Lu discloses that the lentiviral Env protein VSV-G promotes extracellular vesicle production (Example 1). Lu discloses a polynucleotide encoding a long-terminal repeat (LTR) retroelement polypeptide comprising a capsid domain, a nucleocapsid domain, a protease domain and a reverse transcriptase domain (paragraphs [0026], [0067], and [0239] and Figure 10D). Lu discloses that the LTR retroelement comprises a lentivirus packaging signal (paragraph [0067]). Lu discloses one or more heterologous cargo polynucleotides (paragraph [0130). Lu discloses that the LTR retroelement comprises one or more packaging elements operatively coupled to the one or more heterologous cargo polynucleotides (paragraph [0026]). Regarding claim 2, Lu discloses a polynucleotide encoding a fusogenic polypeptide, which may be an envelope glycoprotein (claim 35). Regarding claims 3 and 12, Lu discloses that the LTR retroelement is a Gag polypeptide (abstract and Figure 1) Regarding claim 5, Lu discloses modification to enhance the packaging of SaCas9 mRNA in vesicles (paragraph [0026] and Figure 7). Regarding claim 16, Lu discloses that the fusogenic polypeptide can be a tetraspanin (TSPAN) or a G envelop protein, such as vesicular stomatitis virus G envelope protein (claim 35). Regarding claim 19, Lu discloses that the components of the vesicle can be encoded on one or more vectors and that the vectors can also include one or more regulatory elements (paragraphs [0019], [0024], [0067]. And [0070] and Figure 5). Regarding claim 21, Lu discloses that the heterologous cargo polynucleotides can be RNA, DNA, or an RNA/DNA hybrid (paragraph [0130]). Regarding claims 25 and 26, Lu discloses that the heterologous polynucleotides can encode a CRISPR-Cas protein and a guide molecule, which are operably coupled to the packaging elements (paragraphs [0026] and [0130] and Figure 7. Regarding claim 28, Lu discloses the use of aptamers and fusion proteins for packaging SaCas9 mRNA in vesicles (paragraphs [0026] and [0067] and Figure 7). Lu fails to disclose or suggest that the Gag polypeptide is PEG10. Lu fails to disclose or suggest that the packaging elements can complex with the LTR retroelement polypeptide. Lu fails to disclose or suggest that the packaging elements comprise 5’ or 3’ untranslated regions (UTRs). While Lu does disclose the use of aptamers and fusion proteins for packaging SaCas9 mRNA in vesicles, Lu does not explicitly disclose a targeting moiety on an external capsid surface. Abed teaches an endogenous long-terminal repeat (LTR) which can be PEG10, which is an imprinted gene that is derived from an LTR retrotransposon (abstract). Abed discloses that this LTR retains Gag and Pol-like domains (abstract and page 2, first and second paragraphs). Abed discloses that the Gag domain of PEG1O can promote vesicle generation (page 5, final paragraph to page 6, second full paragraph). Abed discloses that PETG10 binds to 3’ UTRs (Figure 7). It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to use the PEG1O of Abed could be used as an endogenous LTR polypeptide for the system of Lu in order to package a non-viral protein, such as Cas9, which may be targeted to cells in need of modulation or editing by the Cas9 of Lu. It would also have been obvious to one with ordinary skill in the art before the effective filing date of the claimed invention that the aptamers of Lu could be used on the surface of a vesicle, as disclosed and suggested by Lu and Abed in order to provide the heterologous cargo polynucleotide encoding a CRISPR-Cas protein and guide molecule to a specific cell in order to edit the specifically targeted cell . Double Patenting 08-33 AIA 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 1-5, 7, 12-13, 16, 21, 25-26, and 28 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 7, 17, 23, 30, 34-36, 39, 45, 47-50, 52, 58, 60, 62-64, 70, 73, and 87 of copending Application No. 17/761,641 (reference application) in view of Sandmeyer et al. (7(6) RNA Biology 642-654 (2010)). Although the claims at issue are not identical, they are not patentably distinct from each other because both the ‘641 application and the instant application claim a delivery system comprising polynucleotides encoding a PEG10 gene, where the delivery system is a vesicle and a cargo can be packaged within the delivery vesicle. Regarding claims 1, 3-4, 12-13, the ‘641 application claims an engineered vesicle generation system comprising a gag-homology protein, which is an long-terminal repeat (LTR) retroelement. While the ‘641 application does not specifically claim an mRNA, the ‘641 application claims a polynucleotide encoding the gag protein, which is deemed to encompass an mRNA encoding the gag protein. Regarding claims 2 and 28, the ‘641 application claims a targeting moiety that specifically binds to a target cell. Regarding claims 5 and 7, the ‘641 application claims packaging a cargo within the system and complexing the with domains of the LTR retroelement ( i.e. , gag protein). Regarding claim 16, the ‘641 application claims a G envelope protein, which can be a vesicular virus G envelope protein. Regarding claims 21 and 25-26, the ‘641 application claims a system where the cargo is a genetic modulating agent, which is a CRISPR-Cas system comprising a Cas protein and a guide molecule. The ‘641 application does not claim a capsid domain, a nucleocapsid domain, a protease domain and a reverse transcriptase domain. Sandmeyer discloses that long terminal repeat retrotransposons ( i.e. , retroelements) provide insight into genomic mobility, gRNA recognition, dimer stabilization, packaging, primer annealing, cDNA strand transfers, multimerization, suppression of premature reverse transcription, and mediation of localization on complex interactions with host cellular environment (abstract and paragraph bridging pages 650 and 651). Sandmeyer discloses that these structures comprises a variety of domains including capsid, nucleocapsid, protease, and reverse transcriptase domains (Figure 1). It would have been obvious to one with ordinary skill in the art before the effective filing date of the claimed invention that the LTR retroelement of the ‘641 application would comprise the elements of a capsid domain, a nucleocapsid domain, a protease domain, and a reverse transcriptase domain because, as disclosed by Sandmeyer, the LTR retroelements generally comprise these components, which provide, along with the cargo and the packaging elements, for the generation of a delivery vesicle for the delivery of a variety of cargo polynucleotides. Therefore, the claims are not deemed to be patentably distinct. This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented. Claims 1-5, 7-8, 12-13, 16, 19, 21, 25-26, and 28 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-5, 7, 9-11, 15-17, 21, 25, 27, 33-34, 36, 38, 40, 44, 48, 52, 56, 58, 61, and 66-67 of copending Application No. 18/726,460 (reference application) in view of Sandmeyer et al. (7(6) RNA Biology 642-654 (2010)). Although the claims at issue are not identical, they are not patentably distinct from each other because both the ‘460 application and the instant application claim a delivery system comprising polynucleotides encoding a PEG10 gene, where the delivery system is a vesicle and a cargo can be packaged within the delivery vesicle. Regarding claims 1, 3-4, 12-13, the ‘460 application claims an engineered vesicle generation system comprising an LTR retroelement polypeptide, which can be a gag-homology protein, which is an long-terminal repeat (LTR) retroelement. The ‘460 application claims an mRNA encoding the gag protein. The ‘460 application claims that the LTR retroelement comprises a capsid domain, Regarding claims 2 and 28, the ‘460 application claims a targeting moiety that specifically binds to a target cell. Regarding claims 5 and 7, the ‘460 application claims packaging a cargo within the system and complexing the with domains of the LTR retroelement ( i.e. , gag protein). Regarding claim 8, the ‘460 application claims that the packaging elements comprise a 5’ untranslated region (UTR) and/or a 3’ UTR, which can be derived from an mRNA encoding an endogenous LTR retroelement polypeptide. Regarding claim 16, the ‘460 application claims a G envelope protein, which can be a vesicular virus G envelope protein. Regarding claim 19, the ‘460 application claims a vector or vectors encoding regulatory elements and the LTR retroelement, the heterologous cargo polynucleotides, the packaging elements and a targeting element for delivery to a cell. Regarding claims 21 and 25-26, the ‘460 application claims a system where the cargo is a genetic modulating agent, which is a CRISPR-Cas system comprising a Cas protein and a guide molecule. The ‘460 application does not claim a nucleocapsid domain, a protease domain and a reverse transcriptase domain. Sandmeyer discloses that long terminal repeat retrotransposons ( i.e. , retroelements) provide insight into genomic mobility, gRNA recognition, dimer stabilization, packaging, primer annealing, cDNA strand transfers, multimerization, suppression of premature reverse transcription, and mediation of localization on complex interactions with host cellular environment (abstract and paragraph bridging pages 650 and 651). Sandmeyer discloses that these structures comprises a variety of domains including capsid, nucleocapsid, protease, and reverse transcriptase domains (Figure 1). It would have been obvious to one with ordinary skill in the art before the effective filing date of the claimed invention that the LTR retroelement of the ‘460 application would comprise the elements of a capsid domain, a nucleocapsid domain, a protease domain, and a reverse transcriptase domain because, as disclosed by Sandmeyer, the LTR retroelements generally comprise these components, which provide, along with the cargo and the packaging elements, for the generation of a delivery vesicle for the delivery of a variety of cargo polynucleotides. Therefore, the claims are not deemed to be patentably distinct. This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented. Claims 1-5, 7-8, 12-13, 16, 19, 21, 25-26, and 28 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1,3, 6-15, 17, 19, 21, 24-25, 28-29, 31, 35-37. 39, 40, 43, and 45 of copending Application No. 18/276,514 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because both the ‘514 application and the instant application claim a delivery system comprising polynucleotides encoding an RTL1, RTL3, RTL5, or RTL 6 gene, where the delivery system is a vesicle and a cargo can be packaged within the delivery vesicle. Regarding claims 1, 3-4, 12-13, the ‘514 application claims an engineered vesicle generation system comprising an LTR retroelement polypeptide comprising a capsid domain, a nucleocapsid domain, a protease domain, and a reverse transcriptase domain, a heterologous cargo polypeptide, and one or more packaging elements coupled to the cargo polypeptide(s). The ‘514 application claims an mRNA encoding the Sushi protein. Regarding claims 2 and 28, the ‘514 application claims a targeting moiety that specifically binds to a target cell. Regarding claims 5 and 7, the ‘514 application claims packaging a cargo within the system and complexing the with domains of the LTR retroelement ( i.e. , gag protein). Regarding claim 8, the ‘514 application claims that the packaging elements comprise a 5’ untranslated region (UTR) and/or a 3’ UTR, which can be derived from an mRNA encoding an endogenous LTR retroelement polypeptide. Regarding claim 16, the ‘514 application claims a G envelope protein, which can be a vesicular virus G envelope protein or a tetraspanin (TSPAN) protein, which can be CD81, CD9, or CD63. Regarding claim 19, the ‘514 application claims a vector or vectors encoding regulatory elements and the LTR retroelement, the heterologous cargo polynucleotides, the packaging elements and a targeting element for delivery to a cell. Regarding claims 21 and 25-26, the ‘514 application claims a system where the cargo is a genetic modulating agent, which is a CRISPR-Cas system comprising a Cas protein and a guide molecule. Therefore, the claims are not deemed to be patentably distinct. This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented. Conclusion 07-96 AIA The prior art made of record and not relied upon is considered pertinent to applicant's disclosure. Berglund et al. (25(5) Nucleic Acids Research 1042-1049 (1997), and cited in the Information Disclosure Statement filed July 13, 2023) disclose a packaging element comprising a polynucleotide having the sequence of UNNUU, where N can be any of A, T, C, G, or U, which sequence is an optional limitation of instant claim 8 (abstract, page 1043 column 1, and Figures 1 and 2). Any inquiry concerning this communication or earlier communications from the examiner should be directed to NANCY J LEITH whose telephone number is (313)446-4874. The examiner can normally be reached Monday - Thursday 8:00 AM - 6:30 PM. 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, NEIL HAMMELL can be reached at (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. NANCY J. LEITH Primary Examiner Art Unit 1636 /NANCY J LEITH/Primary Examiner, Art Unit 1636 Application/Control Number: 18/272,158 Page 2 Art Unit: 1636 Application/Control Number: 18/272,158 Page 3 Art Unit: 1636 Application/Control Number: 18/272,158 Page 4 Art Unit: 1636 Application/Control Number: 18/272,158 Page 5 Art Unit: 1636 Application/Control Number: 18/272,158 Page 6 Art Unit: 1636 Application/Control Number: 18/272,158 Page 7 Art Unit: 1636 Application/Control Number: 18/272,158 Page 8 Art Unit: 1636 Application/Control Number: 18/272,158 Page 9 Art Unit: 1636 Application/Control Number: 18/272,158 Page 10 Art Unit: 1636 Application/Control Number: 18/272,158 Page 11 Art Unit: 1636 Application/Control Number: 18/272,158 Page 12 Art Unit: 1636 Application/Control Number: 18/272,158 Page 13 Art Unit: 1636 Application/Control Number: 18/272,158 Page 14 Art Unit: 1636 Application/Control Number: 18/272,158 Page 15 Art Unit: 1636 Application/Control Number: 18/272,158 Page 16 Art Unit: 1636 Application/Control Number: 18/272,158 Page 17 Art Unit: 1636 Application/Control Number: 18/272,158 Page 18 Art Unit: 1636
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