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. Election/Restrictions Applicant’s election without traverse of Group I and the species of Chikungunya in the reply filed on February 18, 2026 is acknowledged. Applicant requests rejoinder of method claims if the elected product is found allowable. Applicant’s attention is hereby directed to the following is a recitation of MPEP § 821.04 regarding the restriction of claims to a product and processes of using the product, Rejoinder: Where product and process claims drawn to independent and distinct inventions are presented in the same application, applicant may be called upon under 35 U.S.C. 121 to elect claims to either the product or process. See MPEP § 806.05(f) and § 806.05(h). The claims to the nonelected invention will be withdrawn from further consideration under 37 CFR 1.142. See MPEP § 809.02© and § 821 through § 821.03. However, if applicant elects claims directed to the product, and a product claim is subsequently found allowable, withdrawn process claims which depend from or otherwise include all the limitations of the allowable product claim will be rejoined. Where product and process claims are presented in a single application and that application qualifies under the transitional restriction practice pursuant to 37 CFR 1.129(b), applicant may either (1) elect the invention to be searched and examined and pay the fee set forth in 37 CFR 1.17(s) and have the additional inventions searched and examined under 37 CFR 1.129(b)(2), or (2) elect the invention to be searched and examined and not pay the additional fee (37 CFR 1.129(b)(3)). Where no additional fee is paid, if the elected invention is directed to the product and the claims directed to the product are subsequently found patentable, process claims which either depend from or include all the limitations of the allowable product will be rejoined . If applicant chooses to pay the fees to have the additional inventions searched and examined pursuant to 37 CFR 1.129(b)(2), even if the product is found allowable, applicant would not be entitled to a refund of the fees paid under 37 CFR 1.129(b) by arguing that the process claims could have been rejoined. 37 CFR 1.26 states that "[m]oney paid by actual mistake or in excess will be refunded, but a mere change of purpose after the payment of money...will not entitle a party to demand such a return..." The fees paid under 37 CFR 1.129(b) were not paid by actual mistake nor paid in excess, therefore, applicant would not be entitled to a refund. In the event of rejoinder, the rejoined process claims will be fully examined for patentability in accordance with 37 CFR 1.104 - 1.106. Thus, to be allowable, the rejoined claims must meet all criteria for patentability including the requirements of 35 U.S.C. 101, 102, 103, and 112. If the application containing the rejoined claims is not in condition for allowance, the subsequent Office action may be made final, or, if the application was already under final rejection, the next Office action may be an advisory action. The following is a recitation from paragraph five, “Guidance on Treatment of Product and Process Claims in light of In re Ochiai, In re Brouwer and 35 U.S.C. §103(b)” (1184 TMOG 86(March 26, 1996)): “However, in the case of an elected product claim, rejoinder will be permitted when a product claim is found allowable and the withdrawn process claim depends from or otherwise includes all the limitations of an allowed product claim. Withdrawn process claims not commensurate in scope with an allowed product claim will not be rejoined.” (emphasis added) In accordance with MPEP §821.04 and In re Ochiai, 71 F.3d 1565, 37 USPQ 1127 (Fed. Cir. 1995), rejoinder of product claims with process claims commensurate in scope with the allowed product claims will occur following a finding that the product claims are allowable. Until, such time, a restriction between product claims and process claims is deemed proper. Additionally, in order to retain the right to rejoinder in accordance with the above policy, Applicant is advised that the process claims should be amended during prosecution to maintain either dependency on the product claims or to otherwise include the limitations of the product claims. Failure to do so may result in a loss of the right to rejoinder. Claims 55-65, 67, 68, and 70-74 are pending; claims 67, 68, 72, 73 , and the species of a modified Sindbis virus (SINV) genome or replicon RNA , are withdrawn due to non-elected inventions; and claims 55-65, 70, 71, and 74 are under consideration. Information Disclosure Statement The information disclosure statement (IDS) submitted on 7/31/2023; 11/1/2024; and 9/5/2025 have been considered by the examiner. 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. Specification The preliminary amendment to the instant specification filed January 26, 2023 is objected to because it does not conform to 37 CFR 1.125(b) and (c) due to lack of compliance under MPEP § 2414.02 (2): (2) An amendment to the specification to incorporate by reference the material in the "Sequence Listing XML" by reciting in a separate paragraph of the specification the name of the file, the date of creation, and the size of the file in bytes (37 CFR 1.835(a)(2) and 37 CFR 1.835(c)) The January 26, 2023 preliminary amendment lists the sequence listing size in KB. The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code , see paragraph [0080] in the instant published disclosure, USPgPub 2023/0398200 . Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01. The use of at least terms: “ Genbank ”, recited in at least paragraph [0138] of the instant published disclosure (USPgPub 2023/0398200), is a trade names or marks used in commerce. The terms should be accompanied by the generic terminology; furthermore the term 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. Applicant is required to properly annotate all trade names and/or marks present in the instant specification, if any additional trade names and/or marks are discovered. Applicant' s cooperation is requested in correcting any errors of which applicant may become aware in the specification. Applicant is reminded that the incorporation of essential material in the specification by reference to a foreign application or patent, or to a publication is improper , i.e., Lynn D. E., Available lepidopteran insect cell lines . Methods Mol Biol. 2007; 388:117-38 , recited in paragraph [0088] and all of the references incorporated by reference listed in paragraph [0135]. Applicant is required to amend the disclosure to include the material incorporated by reference. The amendment must be accompanied by an affidavit or declaration executed by the applicant, or a practitioner representing the applicant, stating that the amendatory material consists of the same material incorporated by reference in the referencing application. See In re Hawkins, 486 F.2d 569, 179 USPQ 157 (CCPA 1973); In re Hawkins, 486 F.2d 579, 179 USPQ 163 (CCPA 1973); and In re Hawkins, 486 F.2d 577, 179 USPQ 167 (CCPA 1973). Claim Rejections - 35 USC § 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. 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 55-65, 70, 71, and 74 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. C laim 55 recites, "a nucle ic acid construct comprising a nucleotide sequence encoding (i) a modified Chikungunya virus (CHIKV) genome or replicon RNA …”. It is unclear whether the nucleotide sequence is intended to encompass the entire length of the modified Chikungunya virus (CHIKV) genome or replicon RNA or any sequence fragment of indeterminable length within " modified Chikungunya virus (CHIKV) genome or replicon RNA ” . This rejection could be ameliorated if the claim is amended to language such as, “ a nucle ic acid construct comprising the nucleotide sequence encoding (i) a modified Chikungunya virus (CHIKV) genome or replicon RNA…” . Claim 61 lists genes of interest (GOI) encoding, “ a therapeutic polypeptide, a prophylactic polypeptide, a diagnostic polypeptide, a nutraceutical polypeptide, an industrial enzyme, and a reporter polypeptide ”. It is unclear what structural attributes possessed by each of the claimed polypeptides are attributed to the descriptive functions. Claim 62 is rejected on the basis that it contains an improper Markush grouping of alternatives. See In re Harnisch, 631 F.2d 716, 721-22 (CCPA 1980) and Ex parte Hozumi, 3 USPQ2d 1059, 1060 (Bd. Pat. App. & Int. 1984). A Markush grouping is proper if the alternatives defined by the Markush group (i.e., alternatives from which a selection is to be made in the context of a combination or process, or alternative chemical compounds as a whole) share a "single structural similarity" and a common use. A Markush grouping meets these requirements in two situations. First, a Markush grouping is proper if the alternatives are all members of the same recognized physical or chemical class or the same art-recognized class, and are disclosed in the specification or known in the art to be functionally equivalent and have a common use. Second, where a Markush grouping describes alternative chemical compounds, whether by words or chemical formulas, and the alternatives do not belong to a recognized class as set forth above, the members of the Markush grouping may be considered to share a "single structural similarity" and common use where the alternatives share both a substantial structural feature and a common use that flows from the substantial structural feature. See MPEP § 2117 . The Markush grouping of an antibody, an antigen, an immune modulator, an enzyme, a signaling protein, and a cytokine, is improper because the alternatives defined by the Markush grouping do not share both a single structural similarity and a common use for the following reasons: A n antibody, an antigen, an immune modulator, an enzyme, a signaling protein, and a cytokine are not all members of the same recognized physical or chemical class or the same art-recognized class . The members are also not considered to be functionally equivalent and have a common use; and none of the alternatives share both a substantial structural feature and a common use that flows from the substantial structural feature. See MPEP § 2117 . To overcome this rejection, a pplicant may set forth each alternative (or grouping of patentably indistinct alternatives) within an improper Markush grouping in a series of independent or dependent claims and/or present convincing arguments that the group members recited in the alternative within a single claim in fact share a single structural similarity as well as a common use. Claim 62 lists an “immune modulator” . There is no description for what is intended by an immune modulator since the term encompasses stimulation, inhibition, or both. Since the immune system is a complex network of skin, mucous membranes, lymphoid tissues, and a myriad of white blood cell types inducing innate, humoral, and cellular responses, it is unclear what is intended by a modulator of an immune response. Claim 62 also lists “a signaling protein” as an option for the GOI. However, the only mention of “ signaling ” involving proteins in the instant disclosure is “ JAK-STAT signal ing ” in paragraphs [0046 and 0047]. However, as evidenced by Figure s 1 -3 of H u et al. ( Frontiers in bioengineering and biotechnology. 2023 Feb 23; 11: 1110765 ), there are a number of proteins involved in the JAK-STAT signaling pathway. Since “a signaling protein” is not limited to those in the JAK-STAT signaling pathway, t he metes and bounds for what is considered a signaling protein cannot be determined. Claim 63 states that the coding sequence of GOI “is optimized for expression at a level higher than the expression level of a reference coding sequence.” T he specification does not provide a standard for ascertaining the requisite degree of a higher level of expression. Claim Rejections - 35 USC § 112 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 61 and 62 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. This is a written description rejection . Claim 61 lists genes of interest (GOI) encoding, “ a therapeutic polypeptide, a prophylactic polypeptide, a diagnostic polypeptide, a nutraceutical polypeptide, an industrial enzyme, and a reporter polypeptide ”. There are no structural motifs attribut able to the descriptive functions of each type of polypeptide listed . The skilled artisan would not predict that any polypeptide is therapeutic , prophylactic , diagnostic , nutraceutical , an industrial enzyme, or a reporter . Claim 62 lists an “immune modulator”. There is no description for what is intended by an immune modulator since the term encompasses stimulation, inhibition, or both. Since the immune system is a complex network of skin, mucous membranes, lymphoid tissues, and a myriad of white blood cell types inducing innate, humoral, and cellular responses, it is unclear what is intended by a modulator of an immune response. There is no description provided for the immune modulator claimed. Claim 62 also lists “a signaling protein” as an option for the GOI. However, the only mention of “signaling” involving proteins in the instant disclosure is “ JAK-STAT signal ing ” in paragraphs [0046 and 0047]. However, as evidenced by Figures 1-3 of H u et al. ( Frontiers in bioengineering and biotechnology. 2023 Feb 23; 11: 1110765 ), there are a number of proteins involved in the JAK-STAT signaling pathway. Since “a signaling protein” is not limited to those in the JAK-STAT signaling pathway, a signaling protein is not adequately described . There is a lack of structure s or polypeptides identifying a therapeutic polypeptide, a prophylactic polypeptide, a diagnostic polypeptide, a nutraceutical polypeptide, an industrial enzyme, a reporter polypeptide , an immune modulator, or a signaling protein c laimed. The skilled artisan would be unable to recognize any of the polypeptides, immune modulator, or a signaling protein c laimed because there are no structural features or characteristics that would identify itself as a therapeutic polypeptide, a prophylactic polypeptide, a diagnostic polypeptide, a nutraceutical polypeptide, an industrial enzyme, a reporter polypeptide , an immune modulator, or a signaling protein. Strzelec et al. ( Front iers in Immunol ogy. 2023; 14: 1127704 ) review the state of the art of immunomodulatory compounds, including pathogen associated molecular patterns (PAMPs), cytokines, interferons, antibodies, corticosteroids, non-steroidal anti-inflammatory drugs (NSAIDs) , the CRISPR/Cas9 system , RNA interference (RNAi), and mesenchymal stem cell . Due to the vast genus of known immune modulators, the skilled artisan would not predict whether a particular material modulates immunity without further guidance . The applicable standard for the written description requirement can be found in MPEP 2163; University of California v. Eli Lilly , 43 USPQ2d 1398 at 1407; PTO Written Description Guidelines; Enzo Biochem Inc. v. Gen-Probe Inc ., 63 USPQ2d 1609; Vas- Cath Inc. v. Mahurkar , 19 USPQ2d 1111; and University of Rochester v. G.D. Searle & Co ., 69 USPQ2d 1886 (CAFC 2004). To provide adequate written description and evidence of possession of a claimed genus, the specification must provide sufficient distinguishing identifying characteristics of the genus. The factors to be considered include disclosure of complete or partial structure, physical and/or chemical properties, functional characteristics, structure/function correlation, methods of making the claimed product, or any combination thereof. In this case, the re are no such distinctions identifying a therapeutic polypeptide, a prophylactic polypeptide, a diagnostic polypeptide, a nutraceutical polypeptide, an industrial enzyme, a reporter polypeptide , an immune modulator, or a signaling protein in the specification . In the absence of sufficient recitation of distinguishing identifying characteristics, the specification does not provide adequate written description of the instant TCM. A definition by function alone is not sufficient because it is only an indication of what a thing does, rather than what it is. Eli Lily , 119 F.3 at 1568, 43 USPQ2d at 1406. MPEP § 2163 offers the following discussion ( emphasis added in bold ): “… written description requirement may be satisfied through disclosure of function and minimal structure when there is a well-established correlation between structure and function. In contrast, without such a correlation, the capability to recognize or understand the structure from the mere recitation of function and minimal structure is highly unlikely . In this latter case, disclosure of function alone is little more than a wish for possession; it does not satisfy the written description requirement. See Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406 (written description requirement not satisfied by merely providing “a result that one might achieve if one made that invention”); In re Wilder, 736 F.2d 1516, 1521, 222 USPQ 369, 372-73 (Fed. Cir. 1984) (affirming a rejection for lack of written description because the specification does “little more than outline goals appellants hope the claimed invention achieves and the problems the invention will hopefully ameliorate”). Further, in the same section in the MPEP: “ It is not sufficient to define it solely by its principal biological property , e.g., encoding human erythropoietin, because an alleged conception having no more specificity than that is simply a wish to know the identity of any material with that biological property. We hold that when an inventor is unable to envision the detailed constitution of a gene so as to distinguish it from other materials, as well as a method for obtaining it, conception has not been achieved until reduction to practice has occurred, i.e., until after the gene has been isolated.”) (citations omitted). In such instances the alleged conception fails not merely because the field is unpredictable or because of the general uncertainty surrounding experimental sciences, but because the conception is incomplete due to factual uncertainty that undermines the specificity of the inventor’s idea of the invention. Burroughs Wellcome Co. v. Barr Laboratories Inc., 40 F.3d 1223, 1229, 32 USPQ2d 1915, 1920 (Fed. Cir. 1994). Reduction to practice in effect provides the only evidence to corroborate conception (and therefore possession) of the invention. Id.” In the instant case, there is no minimal structure that is required to be maintained to achieve the desired and required function attributed to the claimed polypeptides recited in instant claims 61 and 62 . The court clearly states in Vas-Cath Inc. v. Mahurkar , 19 USPQ2d 1111, that “applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention. The invention is, for purposes of the ‘written description’ inquiry, whatever is now claimed.” (See page 1117.) The specification does not clearly allow persons of ordinary skill in the art to recognize that the inventors invented what is claimed. As discussed above, the skilled artisan cannot envision the distinguishing, identifying characteristics of the encompassed therapeutic polypeptide, a prophylactic polypeptide, a diagnostic polypeptide, a nutraceutical polypeptide, an industrial enzyme, a reporter polypeptide , an immune modulator, and a signaling protein claimed. Applicant is reminded that Vas-Cath makes clear that the written description provision of 35 U.S.C. §112 is severable from its enablement provision (see page 1115). Claims 55-6 5 , 70, 71, and 74 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 enablement requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention. Instant claim 55 recites, "a nucle ic acid construct comprising a nucleotide sequence encoding (i) a modified Chikungunya virus (CHIKV) genome or replicon RNA…”. T he nucleic acid , nucleic acid construct, and cell in claims 56-65 encompass a cell within a transgenic animal or a transgene therein given that the term "isolated" is not denoted in describing the host cell or nucleic acid construct . Support for transgenes integrated into the host chromosome within a host is supported in the instant published disclosure, USPgPub 20 23/0398200 , in at least paragraphs [00 48 , 0087, and 0090- 0 094 ], referring to cells expressing transgenes and transgenic organisms and paragraph [0103] describing gene therapy, gene replacement, cardiovascular diseases, age- related pathologies, encompassed by the preamble of the kit in claim 74 to prevent and/or treat a ny health condition . With respect to the un-isolated host cells and transgenes as "nucleic acids" of the instant claims discussed above, the state of the art at the time of filing was such that one of skill could not predict the phenotype of transgenics. The art of transgenic animals has for many years stated that the unpredictability lies, in part, with the site or sites of transgene integration into the target genome and that "the position effect" as well as unidentified control elements are recognized to cause aberrant expression of a transgene (Wall et a l., Theriogenology, Vol. 45, Pg. 57-68, 1996). The elements of the particular construct used to make transgenic animals are also held to be critical, and they must be designed case by case without general rules to obtain good expression of a transgene; e.g., specific promoters, presence or absence of introns, etc. (Houdebine et al., Journal of Biotechnology, Vol. 34, Pg. 269-287, 1994, abstract only). Furthermore, transgenic animals are regarded to have within their cells, cellular mechanisms that prevent expression of the transgene, such as methylation or deletion from the genome (Kappell et al., Current Opinions in Biotechnology, Vol. 3, Pg. 548-553, 1992). Houdebine (Comparative Immunology, Microbiology, and Infectious Diseases, Vol. 32, Pg. 107-121, 2009) teaches progress has been made in the field of transgenic animals for production of foreign proteins (Abstract); however, constructing an efficient expression vector to produce a therapeutic protein is not a standard operation (Pg. 116, Paragraph, second). Therefore, undue experimentation is required to make and use a transgene and transgenic animal expressing a nucleic acid construct comprising a modified CHIKV genome or replicon RNA, devoid of at least a portion of a nucleic acid sequence encoding one or more structural proteins, and further encoding a gene of interest, asserted by the instant claims. There is no discussion, data, or working example provided in the instant disclosure for transgenic expression of the scope of nucleic acids and fragments thereof, encompassed by the instant claims. The skilled artisan would not predict success expressing the instant nucleic acids, or fragments thereof, as transgenes. Remenyi et al. (Journal of Virology. 2018; 92 (16): 92:e00477-18 ) characterize the interaction between CHIKV nsP3 and cellular components during persistent replication and evaluate the persistence of cytoplasmic granules composed of viral and cellular proteins. Remenyi et al. do not predict long-term consequences of the persistence of CHIKV viral protein complexes to control and treat chronic infection and disease symptoms . To determine intracellular distribution of CHIKV nsp3, Remenyi et al. develop a stable human-origin cell line, see “Development of a stable human-origin cell line carrying a SNAP-tagged CHIKV replicon and super resolution microscopy of nsP3-G3BP-containing granules” and Figure 1. There is no indication in the instant disclosure that any cell encompassed by the instant claims would be susceptible or adequately express a nucleic acid construct comprising a modified CHIKV genome or replicon RNA, devoid of at least a portion of a nucleic acid sequence encoding one or more structural proteins, and further encoding a gene of interest. Examples in the literature aptly demonstrate that even closely related species carrying the same transgene construct can exhibit widely varying phenotypes. Mullins et al. (1993, Hypertension, Vol. 22, No. 4, pp. 630-633) state that not all animals express a transgene sufficiently to provide a model for a disease as the integration of a transgene into different species of animal has been reported to give divergent phenotypes. For example, several animal models of human diseases have relied on transgenic rats when the development of mouse models was not feasible. Mullins (1990, Nature, Vol. 344, 541-544) produced outbred Sprague-Dawley X WKY rats with hypertension caused by expression of a mouse Ren-2 renin transgene. Hammer (1990, Cell, Vol. 63, 1099-1112) describes spontaneous inflammatory disease in inbred Fischer and Lewis rats expressing human class I major histocompatibility allele HLA-B27 and human 02- microglobulin transgenes. Both investigations were preceded by the failure to develop human disease-like symptoms in transgenic mice expressing the same transgenes that successfully caused the desired symptoms in transgenic rats (Mullins, 1989, EMBO J., Vol. 8, pages 4065-4072). Thus, the use of nonmurine species for transgenesis will continue to reflect the suitability of a particular species for the specific questions being addressed, bearing in mind that a given construct may react very differently from one species to another. For all these reasons, transgenes and hosts comprising transgenes are not enabled. At the time of filing, the phenotype of a transgene and transgenic cell contained within any animal was unpredictable. The claims as written, encompassing a transgene and cell in a transgenic animal, is not adequately described in the specification as to prevent excessive experimentation by the public to generate and use the invention. Applicants can obviate the instant rejection by amending the claim to recite the term "isolated" before the recitation, "nucleic construct" in claim s 55, 70, 74, and "cell" in claim s 6 4 , 65 , 70, and 74. Applicant may consider using purified in such claims if description is appropriate for such a term and it is not redefined away from standard meaning. Method claims using these products should also carry the appropriate adjectives above. In view of the lack of the predictability of the art to which the invention pertains as evidenced by the art above, the lack of guidance and direction provided by instant disclosure, and the absence of working examples, it is determined that an undue quantity of experimentation would be required to make and use the nucleic acids claimed as transgenes and expression in a transgenic animal. 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. (a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention. Claim s 55- 58, 60-6 5, and 70 are rejected under 35 U.S.C. 102 (a)(1) as being anticipated by Zhang et al. (Journal of Virology. 2019; 93:e00504-19). Zhang et al. anticipate a nucleic acid construct comprising a nucleic acid sequence encoding a modified chikungunya vi rus (CHIKV) genome or replicon RNA, devoid of at least a portion of the nucleic acid sequence encoding one or more viral structural proteins , see the abstract : “ In this study, we generated a novel live attenuated vaccine (LAV) candidate for CHIKV with a complete deficiency of capsid ( Δ C -CHIKV) , anticipating instant claim 55. In “Plasmid construction” and Figure 1 , Zhang et al. anticipate a eGFP reporter virus vector lacking the full sequence of capsid , ΔC-CHIKVeGFP, containing a repeated subgenomic promoter operably linked to a reporter eGFP gene between 5’ and 3’ UTRs , anticipating instant claims 56-58 and 60. ΔC-CHIKVeGFP protein (green signal) expression is detected by immunofluorescence assay (IFA) and western blot, see Figure 2A and 2B, anticipating instant claims 61 and 62. Since no requisite degree for “expression at a higher level than the expression level of a reference coding sequence” is provided for instant claim 63, expression of GFP in ΔC-CHIKVeGFP by Zhang et al. meets the requisite limitation. The recombinant plasmid was propagated in BHK-21 cells . See “ ΔC-CHIKV is considerably stable in cell culture” and Figure 7, antic ipating instant claims 64 and 65 . In “Mouse experiments”, ΔC-CHIKV, is subcutaneously delivered in a pharmaceutically acceptable carrier, anticipating instant claim 70. Claim s 55-65 and 70 are rejected under 35 U.S.C. 102 (a)(1)/ (a)(2) as being anticipated by Kamrud (WO 2018075235) . Kamrud anticipates a nucleic acid molecule comprising a modified Chikungunya virus (CHIKV) genome or a replicon RNA, comprising a modified 5'-UTR (heterologous) and is devoid of at least a portion of a nucleic acid sequence encoding viral structural proteins , see paragraphs [0012, 0021, 0029, 0086, 0087], Figure 1A, and claims 1-8, 10, and 16-19, anticipating instant claims 55, 58, and 59. Claim 9 of Kamrud anticipates t he nucleic acid molecule further comprising one or more expression cassettes, wherein each of the expression cassettes comprises a promoter operably linked to a heterologous nucleic acid sequence , anticipating instant claims 56 and 57. Paragraph [0011] of Kamrud states: …the heterologous nucleic acid sequence of at least one of the expression cassettes as disclosed herein includes a coding sequence of a gene of interest (GOI). In some embodiments, the GOI encodes a polypeptide selected from the group consisting of a therapeutic polypeptide, a prophylactic polypeptide, a diagnostic polypeptide, a neutraceutical polypeptide, an industrial enzyme, and a reporter polypeptide. In some embodiments, the GOI encodes a polypeptide selected from the group consisting of an antibody, an antigen, an immune modulator, and a cytokine. In some particular embodiments, the coding sequence of the GOI is optimized for expression at a level higher than the expression level of a reference coding sequence. Also see paragraphs [0020, 0046, and 0083-0085]. These teachings anticipate instant claims 60-63. Paragraphs [0095, 0110] and claims 20-22 anticipate a cell culture comprising the recombinant nucleic acid, as recited in claims 64 and 65. Claims 44 and 45 of Kamrud anticipate a pharmaceutical composition comprising the nucleic acid construct and recombinant cell, anticipating instant claim 70. 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 71 and 74 are rejected under 35 U.S.C. 103 as being unpatentable over Zhang et al. as applied to claim s 55-58, 60-65, and 70 above, or alternatively, as being unpatentable over Kamrud as applied to claims 55-65 and 70 and further in view of Kamrud et al. (USPgPub 20 18/0171340 ). See the teachings of Zhang et al. or, alternatively, Kamrud above. Neither reference teaches the recombinant CHIKV genome or replicon RNA devoid of at least a portion of a nucleic acid sequence encoding at least one structural protein formulated in a lipid nanoparticle, recited in instant claim 71 or in a kit, recited in instant claim 74. Kamrud et al. teach lipid nanoparticles comprising CHIV genome or replicon RNA formulated in a lipid nanoparticle and a kit, see paragraphs [ 0067 (kit), 0091, 0110, 0126, 0203-0205, and 210-217] . One of ordinary skill in the art prior to the instant effective filing date would have been motivated to have formulated the recombinant CHIKV genome or replicon RNA devoid of at least a portion of a nucleic acid sequence encoding at least one structural protein of Zhang et al. or Kamrud in a lipid nanoparticle, as taught by Kamrud et al. to improve delivery of the pharmaceutical, see paragraph [0210]. One of ordinary skill in the art prior to the instant effective filing date would have had a reasonable expectation of success to have formulated the recombinant CHIKV genome or replicon RNA devoid of at least a portion of a nucleic acid sequence encoding at least one structural protein of Zhang et al. or Kamrud in a lipid nanoparticle, as taught by Kamrud et al., because Kamrud et al. teach replicon RNA does not contain coding sequences for at least one of the structural viral proteins and is substituted with one or more heterologous sequences such as, for example, a coding sequence for a gene of interest (GOI) , see paragraph [0126]. It would have been prima facie obvious to one of ordinary skill in the art prior to the instant effective filing date to have incorporated the recombinant CHIKV genome or replicon RNA of Zhang et al. or Kamrud into the kit of Kamrud et al. for ease of transport, storage, and preparation. 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