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. DETAILED ACTION Application status Claims 1-11 and 15-21 are pending in this application. Priority The instant application is the 371 national stage entry of PCT/ GB2021 /0 51679, filed on 07/01/2021. Acknowledgment is made of applicant's claim for foreign priority under 35 U.S.C. 119(a)-(d) to a foreign patent application United Kingdom GB2010075.6 filed on 07/01/2020. Election Applicant's election without traverse of Group I, Claims 1-8 and 20-21 in the response filed on 01/14/2026 , is acknowledged. Claims 9-11 and 15-19 are withdrawn from further consideration by the Examiner, 37 CFR 1.142(b) as being drawn to a non-elected invention. For the reasons provided above, this restriction requirement is deemed proper, and therefore, it is made final. Information Disclosure Statement The information disclosure statements (IDS) submitted on 08/18/2023 are acknowledged. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner. Objections to the Specification The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code on pg. 47, line 34; and pg. 52, line 4 . Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code. See MPEP § 608.01. This application contains sequence disclosures that are encompassed by 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 through 1.825; Applicants’ attention is directed to the final rulemaking notice published at 55 FR 18230 (May 1, 1990), and 1114 OG 29 (May 15, 1990). To be in compliance, Applicants should identify nucleotide sequences of at least 10 nucleotides and amino acid sequences of at least 4 amino acids in the specification by a proper sequence identifier, i.e., “SEQ ID NO:” (see MPEP 2422.01). If these sequences have not been listed in the computer readable form and paper copy of the sequence listing, applicant must provide an initial computer readable form (CRF) copy of the “Sequence Listing”, an initial paper copy of the “Sequence Listing”, as well as an amendment directing its entry into the specification, and a statement that the content of the paper and CRF copies are the same and, where applicable, include no new matter as required by 37 C.F.R. 1.821(e) or 1.821(f) or 1.821(g) or 1.821(b) or 1.825(d). See particularly Figures 1A-B, 2 A- B , and numerous recitations “GGGGCC” and “GCGGCG” throughout the specification containing amino /nucleic acid sequences, and therefore, those sequences should be represented by proper sequence identifier numbers. If the noted sequences are not in a sequence listing as filed, Applicants must provide (1) an updated copy of the sequence listing containing the requisite sequences in computer readable form (CRF), (2) an amendment directing its entry into the specification, (3) a statement that no new matter has been added and (4) an amendment to the specification to identify each of the identified sequences by SEQ ID NO:, and (5) an incorporation by reference statement with the date of creation, sequence file name and size in bytes. – See also MPEP 2422. Appropriate correction is required. Claim Rejections - 35 U.S.C. § 112 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. Claim 8 is rejected under 35 U.S.C. § 112, second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which applicant regards as the invention. Claim 8 recites the limitation "the nucleic acid" in claim 1. There is insufficient antecedent basis for this limitation in the claim. In the interest of advancing prosecution, the instant claim is interpreted as “ A vector comprising the isolated polynucleotide of Claim 1 , wherein the vector is a viral vector derived from retroviruses, adenoviruses, adeno-associated viruses (AAV), herpes simplex virus (HSV), and chimeric viruses .” The following is a quotation of 35 U.S.C. 112(a): (a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention. Claims 1- 8 and 20-21 are rejected under 35 U.S.C. § 112(a), written description, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor(s), at the time the application was filed, had possession of the claimed invention. The instant claims are directed to a n isolated polynucleotide encoding a polypeptide for delivery of an effector peptide to a target cell different to a source cell in which it was expressed; the polynucleotide comprising:(a) a sequence encoding a polypeptide, the polypeptide comprising:( i ) the effector peptide sequence;(ii) a cell secretion peptide sequence operably linked to the effector peptide sequence;(iii) a cell penetration and/or cell localization peptide sequence operably linked to the effector peptide sequence; and(b) a polypeptide expression element operable to cause the polypeptide to be expressed in the source cell in vivo . To satisfy the written description aspect of 35 U.S.C. § 112(a) for a claimed genus of [compositions or methods], it must be clear that: (1) the identifying characteristics of the claimed [compositions or methods] have been disclosed, e.g., structure, physical and/or chemical characteristics, functional characteristics when coupled with a known or disclosed correlation between function and structure, or a combination of these; and (2) a representative number of species within the genus must be disclosed. The Court of Appeals for the Federal Circuit has recently held that a “written description of an invention involving a chemical genus, like a description of a chemical species, ‘requires a precise definition, such as be structure, formula [or] chemical name,’ of the claimed subject matter sufficient to distinguish it from other materials.” University of California v. Eli Lilly and Co., 1997 U.S. App. LEXIS 18221, at *23, quoting Fiers v. Revel, 25 USPQ2d 1601, 1606 (Fed. Cir. 1993) (bracketed material in original). To fully describe a genus of genetic material, which is a chemical compound, applicants must (1) fully describe at least one species of the claimed genus sufficient to represent said genus whereby a skilled artisan, in view of the prior art, could predict the structure of other species encompassed by the claimed genus and (2) identify the common characteristics of the claimed molecules, e.g., structure, physical and/or chemical characteristics, functional characteristics when coupled with a known or disclosed correlation between function and structure, or a combination of these (paraphrased from Enzo Biochemical Inc. v. Gen-Probe Inc. (CAFC (2002) 63 USPQ2d 1609). The specification discloses only a single representative species a genus of any isolated polynucleotides , i.e., expression cassette comprising constitutive promoter/enhancer CMV, DNA encoding SEQ ID NO: 39 which is secretion signal, DNA encoding SEQ ID NO: 44, ENA encoding CPP (SEQ ID NO: 63, and DNA encoding 11-zinc finger peptide fused to a KRAB repressor domain from KOX-1 (see page 69 under method steps) . However, this single disclosed species fails to provide adequate written description for a genus of any isolated polynucleotides as encompassed by the claims, which encompasses a n y isolated polynucleotide encoding a ny polypeptide for delivery of an y effector peptide to a target cell different to a source cell in which it was expressed; the polynucleotide comprising: (a) a ny sequence encoding a polypeptide, the polypeptide comprising: ( i ) any effector peptide sequence ; (ii) any cell secretion peptide sequence operably linked to the effector peptide sequence; (iii) any cell penetration and/or any cell localization peptide sequence operably linked to the effector peptide sequence; and (b) any polypeptide expression element operable to cause the polypeptide to be expressed in the source cell in vivo (italicized for added emphasis) . In this case, the specification fails to describe any identification of structural characteristics or properties of the genus of any isolated polynucleotides encoding [1] any effector peptide, [2] any cell secretion signal sequence, [3] any cell penetration and/or any cell localization peptide sequence , and [4] any polypeptide expression element such that the effector peptide can be delivered to a target cell that is different from the source cell in which the effector peptide was expressed from . The Examiner notes that there is no description of structural characteristics or properties regarding the genus of any components listed above under [1]-[4], and they are all defined by only the functional characteristics of each of the components under [1]-[4]. The Examiner further notes that none of the dependent claims remedy the deficiencies noted above regarding written description requirement. Taken together, the genus of “ isolated polynucleotides ” encompasses widely variant species, having essentially any structure. While M.P.E.P. section 2163 acknowledges that a single species can describe a genus, it also acknowledges that for a genus that encompasses widely variant species, disclosure of a single species within the genus fails to adequately describe all members of the genus. Please refer to the M.P.E.P. section 2163.05 [R-7.2022] under I, B for more details with respect to sufficient number of representative species that should be disclosed to describe a widely variant genus. Given the lack of additional representative species of a genus of claimed invention as noted above , Applicants have failed to sufficiently describe the claimed invention, in such full, clear, concise, and exact terms that a skilled artisan would recognize Applicants were in possession of the claimed invention. Applicant is referred to the revised guidelines concerning compliance with the written description requirement of U.S.C. 112(a) published in the Official Gazette and also available at www.uspto.gov . Claim Rejections - 35 USC § 102 The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action: A person shall be entitled to a patent unless – (a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale , or otherwise available to the public before the effective filing date of the claimed invention. Claim s 1 , 5 and 8 are rejected under 35 U.S.C. 102 (a)(1) as being anticipated by Shen et al. ( Expressed Cell-penetrating Peptides Can Induce a Bystander Effect, but Passage Through the Secretory Pathway Reduces Protein Transduction Activity , Molecular Therapy vol. 19 no. 5, 903–912 may 2011 ) . The instant claims are drawn to a n isolated polynucleotide encoding a polypeptide for delivery of an effector peptide to a target cell different to a source cell in which it was expressed; the polynucleotide comprising:(a) a sequence encoding a polypeptide, the polypeptide comprising:( i ) the effector peptide sequence;(ii) a cell secretion peptide sequence operably linked to the effector peptide sequence;(iii) a cell penetration and/or cell localization peptide sequence operably linked to the effector peptide sequence; and(b) a polypeptide expression element operable to cause the polypeptide to be expressed in the source cell in vivo. Shen et al. teach an adenoviral vector comprising an isolated polynucleotide encoding a polypeptide for delivery of an effector peptide to a target cell different to a source cell in which it was expressed; the polynucleotide comprising: (a) a sequence encoding a polypeptide, the polypeptide comprising: ( i ) the effector peptide sequence , i.e., fluorescent reporter proteins such as DsRed , Cherry or Tomato ; (ii) a cell secretion peptide sequence operably linked to the effector peptide sequence , i.e., (N-terminal secretory signal peptides (SP) (MWWRLWW LLLLLLLLWPMVWA ) ; (iii) a cell penetration peptide (CPP) sequence , i.e., HIV TAT (YGRKKRRQRRR) , operably linked to the effector peptide sequence; and (b) a polypeptide expression element , i.e., AAV viral vector promoter, operable to cause the polypeptide to be expressed in the source H1299 cells in vivo (see Abstract, Figures 1-7 and Materials and Methods ) . Shen et al. further teach that “SP-CherryTatV5 and SP-CherryTatmV5 contain the cDNA for the artificial SP, Cherry, Tat (or Tatm ) and V5 (GKPIPNPLLGLDST) all fused in frame in the order as written” (see page 910, right column, 3 rd to last paragraph), thereby reading on Applicants’ claim 5 ( i ). Teachings of Shen et al. demonstrates that the expressed effector peptide is secreted from the source cell and taken up by different, bystander target cells via CPP, in xenograft tumor models in nude mice in vivo (see Figure 4, its legend and related discussion on page 906). Therefore, teachings of Shen et al. anticipate Applicants’ claim s 1, 5 and 8 . 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. Claims 1- 8 and 20-21 are rejected under 35 U.S.C. 103 as being unpatentable over Shen et al. ( Expressed Cell-penetrating Peptides Can Induce a Bystander Effect, but Passage Through the Secretory Pathway Reduces Protein Transduction Activity , Molecular Therapy vol. 19 no. 5, 903–912 may 2011 ) in view of Oakes et al. (US Patent Application Publication No. 2022/0220508 A1 , with effective filing date of 20190607 ), Chiba- Falek et al. (US Patent Application Publication No. 2021 / 0189361 A1 , with effective filing date of 20180423 ), Baileykobayashi et al. (WO2017/150681) , and KSR International Co. v. Teleflex Inc., 550 U.S.--, 82 USPQ2d 1385 (2007) . The instant claims are drawn to a n isolated polynucleotide encoding a polypeptide for delivery of an effector peptide to a target cell different to a source cell in which it was expressed; the polynucleotide comprising:(a) a sequence encoding a polypeptide, the polypeptide comprising:( i ) the effector peptide sequence;(ii) a cell secretion peptide sequence operably linked to the effector peptide sequence;(iii) a cell penetration and/or cell localization peptide sequence operably linked to the effector peptide sequence; and(b) a polypeptide expression element operable to cause the polypeptide to be expressed in the source cell in vivo . The teachings of Shen et al. are as described above . Shen et al. do not teach the use of [1] one or more NLS; [2] NLS as set forth in SEQ ID NO: 148-150; [3] cell secretion peptide as set forth in SEQ ID NO: 156 (secretion signal from human BMP10 protein) , cell penetration peptide as set forth in SEQ ID NO: 160, or peptide cleavage sequence as set forth in SEQ ID NO: 195; [4] effector peptide which is a transcription factor comprising a zinc finger peptide; and [5] AAV vector which is AAV2/1 or AAV2/9 subtype. Oakes et al. teach the use of a vector for expressing CasX , said vector comprising one or more NLS, wherein said NLS comprises PKKKRKV, which is identical to Applicants’ SEQ ID NO: 148 in a vector (see claims 39 and 180), operably linked to CasX . Oakes et al. further teach that the effector peptide such as CasX inherently possesses a zinc finger domain/peptide (see para [0225]). Chiba- Falek et al. teach the use of AAV vector can be AAV2/1 or AAV2/9 to deliver isolated polynucleotide into host cell (see claims 28, 32; and para [0148]). Baileykobayashi et al. teach the use of cell secretion signal from human BMP10 protein comprising “ MGSLVLTLCALFCLAAYLVSG “ as set forth in SEQ ID NO: 996 which is identical to Applicants’ SEQ ID NO: 156 (see page 95 , with “996” in the 2 nd column of the table). It would have been obvious to a person of ordinary skill in the art (POSITA) prior to the effective filing date of the instant application to make and use the isolated polynucleotide taught by Shen et al. and substitute the effector protein to CasX while using a vector comprising one or more NLS, wherein said NLS comprises PKKKRKV as taught by Oakes et al. or use an alternative AAV2/1 or AAV2/9 vector taught by Chiba- Falek et al. or use a SS comprising “ MGSLVLTLCALFCLAAYLVSG “ as taught by Baileykobayashi et al. A POSITA would have been motivated to make and use an alternative effector peptide, NLS and/or SS in order to optimize the expression of a particular effector peptide to be delivered to target cells . As discussed in KSR International Co. v. Teleflex Inc., 550 U.S.--, 82 USPQ2d 1385 (2007) , it is considered obvious to combine prior art elements known to be used in equivalent fields of endeavor together into a single combination. The reference s of Shen et al., Oakes et al., Chiba- Falek et al. and Baileykobayashi et al. demonstrate that the use of different AAVs, secretion SS sequences , NLS sequences , CPP sequence s for the expression of any effector peptide for the purposes of expressing them in Shen-style secreted - fusion system were known to be used in equivalent fields of endeavor , i.e., in the development of in vivo expression -delivery system for an effector peptide ; thus, it is considered obvious to combine them together . A POSITA would have had a reasonable expectation of success to make and use such composition because all of the required biochemical reagents and techniques were readily available and rampantly used as evidenced by Shen et al., Oakes et al., Chiba- Falek et al. and Baileykobayashi et al. prior to the filing of the instant application. For the reasons provided herein, the invention as claimed is prima facie obvious over the combined teachings of the prior art. Conclusion Claims 1- 8 and 20-21 are rejected for the reasons as stated above. Applicants must respond to the objections/rejections in this Office action to be fully responsive in prosecution. The instant Office action is non-final. Any inquiry concerning this communication or earlier communications from the examiner should be directed to FILLIN "Examiner name" \* MERGEFORMAT JAE W LEE whose telephone number is FILLIN "Phone number" \* MERGEFORMAT (571)272-9949 . The examiner can normally be reached on M-F between 9:00-6:00. If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Manjunath Rao can be reached on ( FILLIN "SPE Phone?" \* MERGEFORMAT 571)272-0939 . The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300. Information regarding the status of an application may be obtained from the Patent Application Information Retrieval (PAIR) system. Status information for published applications may be obtained from either Private PAIR or Public PAIR. Status information for unpublished applications is available through Private PAIR only. For more information about the PAIR system, see http://pair-direct.uspto.gov. Should you have questions on access to the Private PAIR system, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative or access to the automated information system, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000. /JAE W LEE/ Examiner, Art Unit 1656 /MANJUNATH N RAO/ Supervisory Patent Examiner, Art Unit 1656