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. Claims 1-20 are pending. Restriction/Elections Applicant’s election without traverse of Group I (claims 1-9, 15-19 ) in the reply filed on 2/2/2026 is acknowledged. Applicants’ amendment to the claims filed on 2/2/2026 is acknowledged. This listing of claims replaces all prior listings of claims in the application. Claims 10-14, 20 stands withdrawn pursuant to 37 CFR 1.142(b). Claims 1-9, 15-19 are pending. Priority Acknowledgement is made of this national stage entry of PCT/EP2022/060666 of Non-provisional Application No. 18/556,830, filed on 4/22/2022, which claims foreign priority under 35 U.S.C. 119(a)-(d) to European Patent Application No. EP21170068.7 , filing date 4/23/2021 . The certified copy has been filed in the present application on 10/23/2023 . Information Disclosure Statement The information disclosure statement (IDS) submitted on 10/23/2023, 12/4/2024 and 4/29/2025 is acknowledged. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement has been considered by the examiner. Drawings The drawings are objected to because they lack appropriate SEQ ID Nos . Deficiencies are located in Fig. 4A, Fig 4B, Fig. 5, Fig. 14. Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance. Claim Objections Claim 4 is objected to because of the following informalities: the status indicator bracket for claim 4 is partial. Appropriate correction is suggested. Claims 17-19 objected to because of the following informalities: the recitation of ‘ further comprising a further construct .’ Appropriate correction is suggested. 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: Specific deficiency - This application fails to comply with the requirements of 37 CFR 1.821 - 1.825 because it does not contain a "Sequence Listing" as a separate part of the disclosure or a CRF of the “Sequence Listing.” Applicant did not provide the appropriate SEQ ID Nos with the recitation ‘SEQ ID NO: AA1, AA2 within the instant application claims 1, 17, 19 . Applicant is reminded that all SEQ ID Nos must be followed by numerical values. Required response - Applicant must provide: A "Sequence Listing" part of the disclosure; together with An amendment specifically directing its entry into the application in accordance with 37 CFR 1.825(a)(2) ; A statement that the "Sequence Listing" includes no new matter as required by 37 CFR 1.821(a)(4); and A statement that indicates support for the amendment in the application, as filed, as required by 37 CFR 1.825(a)(3). 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) c) or d) above, applicant must also provide: A CRF in accordance with 37 CFR 1.821(e)(1) or 1.821(e)(2) as required by 1.825(a)(5); and A statement according to item 2) a) or b) above. 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. Deficiencies are located in Fig. 4A, Fig 4B, Fig. 5, Fig. 14. 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. Specific deficiency - Sequences appearing in the specification are not identified by sequence identifiers (i.e., “SEQ ID NO:X” or the like) in accordance with 37 CFR 1.831(c). Applicant recites SEQ ID NO: AA1, AA2. Additionally, Applicant recited an amino acid sequence without an appropriate SEQ ID NO on page 19, lines 9-12 ; page 20, lines 6-9; page 21, lines 11-24; page 22, lines 4-6; of the instant application specification . Required response – Applicant must provide: A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3), and 1.125 inserting the required sequence identifiers, 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. Claim Rejections - 35 USC § 112 Written Description The following is a quotation of the first paragraph 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. The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112: 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 of carrying out his invention. Claim s 4, 9, 16 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA), first paragraph, 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 or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention. MPEP 2163.II.A.2.(a). i ) states, “Whether the specification shows that applicant was in possession of the claimed invention is not a single, simple determination, but rather is a factual determination reached by considering a number of factors. Factors to be considered in determining whether there is sufficient evidence of possession include the level of skill and knowledge in the art, partial structure, physical and/or chemical properties, functional characteristics alone or coupled with a known or disclosed correlation between structure and function, and the method of making the claimed invention”. For claims drawn to a genus, MPEP § 2163 states the written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice, reduction to drawings, or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus. See Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406. Claims 4, 16 are drawn to t he vector according to claim 3, wherein the vector comprises an open reading frame comprising or consisting of the nucleotide sequence set forth in SEQ ID NO: 1 or SEQ ID NO: 2, and a second open reading frame encoding firefly luciferase or any other luciferase that uses luciferin as a substrate separated by the coding sequence of a self- cleaving 2A peptide F2A set forth in SEQ ID NO: 6. The structure of any other luciferase other than firefly luciferase is a large number of enzymes. Claim 9 is drawn to t he cell or cell line according to claim 5, wherein the cell or cell line is a metazoan cell or cell line, selected from the group comprising HEK293, HEK293T, K562, U937, Jurkat , Molt-4, HeLa cells, HT1080 cells, ARPE-19, ARPE- 19/HPV-16, insect cell such as Sf9 cells, avian cells such as DT-40, MSB1, or LMH, mouse cells such as L929 cells or the LS variant, Chinese hamster ovary (CHO) cells such as CHO-Ki, CHO- DXB11, CHO-DG44, CHOKISV cells including all variants . The structure and function of CHO variants are a large number of cells. In this case, the specification discloses the following representative luciferase enzymes as encompassed by the claims (i.e. firefly luciferase, Renilla luciferase, Gaussia luciferase, or the novel luciferase derived from Metridia longa ). Furthermore, the specification discloses the following representative CHO cell variants encompassed by the claims (i.e. CHO-Ki, CHO- DXB11, CHO-DG44, CHOKISV ). Other than the above disclosed species, there is no prior-art or disclosed teaching as to the large number of luciferase enzymes and CHO variants that confer improved properties. The breadth of the claims encompass any variant of luciferase enzyme and CHO variant through genetic modification of genes encoding proteins or post-translational modifications, etc. via any modification technique such as deletion, mutation, etc. for improved properties. An adequate written description of a chemical invention also requires a precise definition, such as by structure, formula, chemical name, or physical properties, and not merely a wish or plan for obtaining the chemical invention claimed. See, e.g., Univ. of Rochester v. G.D. Searle & Co., 358 F.3d 916, 927, 69 USPQ2d 1886, 1894-95 (Fed. Cir. 2004). Here, the disclosure fails to teach which luciferase enzyme and CHO variants out of the numerous possibilities for improved properties. Accordingly, one of skill in the art would not accept the disclosure of luciferase enzymes comprising firefly luciferase, Renilla luciferase, Gaussia luciferase, or the novel luciferase derived from Metridia longa and CHO-Ki, CHO- DXB11, CHO-DG44, CHOKISV variants as being representative of all luciferase enzymes and CHO variants as encompassed by the claims. As such, the specification, taken with the pre-existing knowledge in the art of luciferase enzymes and CHO variants , fails to satisfy the written description requirement of 35 U.S.C. 112, first paragraph. Scope of Enablement Claims 4, 9, 16 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA), first paragraph, because the specification, while being enabling for luciferase enzymes such as: firefly luciferase, Renilla luciferase, Gaussia luciferase, or the novel luciferase derived from Metridia longa , it does not reasonably provide enablement for all luciferase enzymes as encompassed by the claims. Furthermore, while the specification being enabling for CHO variant such as CHO-Ki, CHO- DXB11, CHO-DG44, CHOKISV variants , it does not reasonably provide enablement for all CHO variants as encompassed by the claims. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention commensurate in scope with these claims. The test of enablement is not whether any experimentation is necessary, but whether, if experimentation is necessary, it is undue.” In re Angstadt , 537 F.2d 498, 504, 190 USPQ 214, 219 (CCPA 1976). Factors to be considered in determining whether undue experimentation is required are summarized in In re Wands (858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988)) as follows: (A) The breadth of the claims; (B) The nature of the invention; (C) The state of the prior art; (D) The level of one of ordinary skill; (E) The level of predictability in the art; (F) The amount of direction provided by the inventor; (G) The existence of working examples; and (H) The quantity of experimentation needed to make or use the invention based on the content of the disclosure. See MPEP § 2164.01(a). The Factors considered to be most relevant to the instant rejection are addressed in detail below. (A)The breadth of the claims: Claims 4, 16 are drawn to t he vector according to claim 3, wherein the vector comprises an open reading frame comprising or consisting of the nucleotide sequence set forth in SEQ ID NO: 1 or SEQ ID NO: 2, and a second open reading frame encoding firefly luciferase or any other luciferase that uses luciferin as a substrate separated by the coding sequence of a self- cleaving 2A peptide F2A set forth in SEQ ID NO: 6. The structure of any other luciferase is a large number of enzymes. Claim 9 is drawn to t he cell or cell line according to claim 5, wherein the cell or cell line is a metazoan cell or cell line, selected from the group comprising HEK293, HEK293T, K562, U937, Jurkat , Molt-4, HeLa cells, HT1080 cells, ARPE-19, ARPE- 19/HPV-16, insect cell such as Sf9 cells, avian cells such as DT-40, MSB1, or LMH, mouse cells such as L929 cells or the LS variant, Chinese hamster ovary (CHO) cells such as CHO-Ki, CHO- DXB11, CHO-DG44, CHOKISV cells including all variants . The structure and function of CHO variants are a large number of cells. B) The nature of the invention; C)The state of the prior art; (D) The level of one of ordinary skill; and (E) The level of predictability in the art: As noted above, the scope of the claimed luciferase enzymes and CHO variants are a large number of enzymes and cells. The structure of the claimed luciferase enzymes and CHO variants having improved properties are a large number of enzymes and cells. In this regard, it is noted that the reference of Wurum et al. ( 2021, Biotechnology Journal ; examiner cited) discloses It is likely that 200 or more subcultivations have been executed since the cells were named during the 1960–1980 period (page 6, column 2, para 6). The “normal” mutation rate is 10–8 per locus/cell in mammalian systems (page 6, column 2, para 6). In cultures of a suspension mouse cell line, a mutation rate of 1–7 × 10–7/cell/generation (generation = cell duplication) was found (page 6, column 2, para 6). With these numbers in mind, and the large number of duplications in regular maintenance of cell populations occurring, CHO cells will accumulate very fast mutations that will affect phenotypes (page 6, column 2, para 6). It is well-known in the art that b ioluminescence has evolved multiple times in nature, with distinct luciferases and luciferins that accomplish light emission using unique protein and chemical scaffolds ( Adams et al (2020, FEBS, Examiner cited) page 2, para 1). Nature has evolved multiple distinct luciferases and luciferins independently, all of which accomplish the impressive feat of light emission ( Adams et al (2020, FEBS, Examiner cited) abstract) . (F) The amount of direction provided by the inventor and (G) The existence of working examples: The specification discloses the following working examples of luciferase enzymes (i.e. firefly luciferase, Renilla luciferase , Gaussia luciferase , or the novel luciferase derived from Metridia longa ) and CHO variant s (i.e . CHO-Ki, CHO- DXB11, CHO-DG44, CHOKISV cell variants ). Other than the above disclosed species, there is no prior-art or disclosed teaching as to the large number of luciferase enzymes and CHO variants . Other than the above disclosed species, there is no prior-art or disclosed teaching as to the luciferase enzymes and CHO variants through genetic modification of genes encoding proteins or post-translational modifications, etc. via any modification technique such as deletion, mutation, etc. for improved performance . Other than these working examples, the specification fails to disclose any other working examples of luciferase enzymes and CHO variants with improved performance. In view of the overly broad scope of the claims, the lack of guidance and working examples provided in the specification, the high level of unpredictability, and the state of the prior art, undue experimentation would be necessary for a skilled artisan to make and use the entire scope of the claimed invention. Applicants have not provided sufficient guidance to enable one of ordinary skill in the art to make and use the claimed invention in a manner reasonably correlated with the scope of the claims. The scope of the claims must bear a reasonable correlation with the scope of enablement (In re Fisher, 166 USPQ 19 24 (CCPA 1970)). Without sufficient guidance, determination of having the desired biological characteristics is unpredictable and the experimentation left to those skilled in the art is unnecessarily, and improperly, extensive and undue. See In re Wands 858 F.2d 731, 8 USPQ2nd 1400 (Fed. Cir, 1988). 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. Claims 1-9, 15-19 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. Regarding claim 1 (claims 2-9, 15-19 dependent thereof) the phrase " o ne or more nucleotide sequences encoding one or more of the peptide sequences set forth in SEQ ID NO: AA 1 , and/or SEQ ID NO: AA2 " renders the claim indefinite because the numbering of the sequences do not conform to USPTO standards as such they are rendered unsearchable. Appropriate correction is suggested. Regarding claim 4, it simply starts off with the phrase " comprising or consisting of the nucleotide sequence…. " R ender ing the claim indefinite because it is not clear as to what Applicant is claiming. It is not clear as to “what is comprising or consisting of the said nucleotide sequence”. Appropriate correction is suggested. Regarding claims 9, 18-19 , the phrase " such as " renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention or just mere examples, thus rendering the scope undiscernible. See MPEP § 2173.05(d). Regarding claims 17-19 the phrase “further comprising a further construct comprising ” renders the claim indefinite because it is un clear whether Applicant is referring to the polynucleotide constructs recited in the claim upon which claims 17-19 depend, claim 3 , or if they are referencing a separate set of polynucleotides. Appropriate correction is suggested. Regarding claims 6 (claims 17 dependent thereof), 8 (claim 18 dependent thereof), 19 the phrase “heterologous polynucleotide” renders the claim indefinite because it is unclear whether Applicant is referring to the heterologous polynucleotide constructs recited in the claim upon which claims 17-19 depend, or if they are referencing a separate set of heterologous polynucleotides. Appropriate correction is suggested. Regarding claim 9 , the phrase “ CHO-Ki, CHO- DXB11, CHO-DG44, CHOKISV cells including all variants ” renders the claim indefinite because it is unclear which variants Applicant is referring , whether it is “cells” or the “polynucleotides.” Appropriate correction is suggested. Conclusion Status of Claims Claims 1-9, 15-19 are pending. Claims 10-14, 20 stands withdrawn pursuant to 37 CFR 1.142(b). Claims 1-9, 15-19 are rejected. No claims are in condition for allowance. Any inquiry concerning this communication or earlier communications from the examiner should be directed to FILLIN "Examiner name" \* MERGEFORMAT ERICA NICOLE JONES-FOSTER whose telephone number is FILLIN "Phone number" \* MERGEFORMAT (571)270-0360 . The examiner can normally be reached FILLIN "Work Schedule?" \* MERGEFORMAT mf 7:30a - 4:30p . 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 Manjunath Rao can be reached at 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 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. /ERICA NICOLE JONES-FOSTER/ Examiner, Art Unit 1656 /MANJUNATH N RAO/ Supervisory Patent Examiner, Art Unit 1656