CTNF 18/033,980 CTNF 89123 DETAILED ACTION Disposition of Claims Claims 1-60 are pending. Examiner’s Note All paragraph numbers (¶) throughout this office action, unless otherwise noted, are from the US PGPub of this application US20230405109A1, Published 12/21/2023. Applicant is encouraged to utilize the new web-based Automated Interview Request (AIR) tool for submitting interview requests; more information can be found at https://www.uspto.gov/patent/laws-and-regulations/interview-practice. Of note, there is not an attorney of record on file due to a lack of an official power of attorney of record. While a customer number has been provided on the ADS submitted 04/26/2023, this is not the equivalent of a power of attorney or an authorization to act in a representative capacity. In order to expedite prosecution in the instant application, it is suggested that a power of attorney be filed as per MPEP §402 or MPEP §1807, or an Authorization to Act in a Representative Capacity be filed as per MPEP §403 in order for the Office to freely and openly discuss the merits of the case with the applicant's representative(s). Please refer to https://www.uspto.gov/about-us/contact-us if you have questions regarding the proper filing of a power of attorney. Optional Authorization to Initiate Electronic Communications The Applicant’s representative may wish to consider supplying a written authorization in response to this Office action to correspond with the Examiner via electronic mail (e-mail). This authorization is optional on the part of the Applicant’s representative, but it should be noted that the Examiner may not initiate nor respond to communications via electronic mail unless and until Applicant’s representative authorizes such communications in writing within the official record of the patent application. A sample authorization is available at MPEP § 502.03, part II. If Applicant’s representative chooses to provide this authorization, please ensure to include a valid e-mail address along with said authorization. Information Disclosure Statement 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. Specification 06-16 AIA Applicant is reminded of the proper language and format for an abstract of the disclosure. The abstract should be in narrative form and generally limited to a single paragraph on a separate sheet within the range of 50 to 150 words in length. The abstract should describe the disclosure sufficiently to assist readers in deciding whether there is a need for consulting the full patent text for details. The language should be clear and concise and should not repeat information given in the title. It should avoid using phrases which can be implied, such as, “The disclosure concerns,” “The disclosure defined by this invention,” “The disclosure describes,” etc. In addition, the form and legal phraseology often used in patent claims, such as “means” and “said,” should be avoided. The abstract of the disclosure is objected to because of the use of legal phraseology (e.g. “inter alia”). A corrected abstract of the disclosure is required and must be presented on a separate sheet, apart from any other text. See MPEP § 608.01(b). The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code. 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. See ¶[0060] “www.ncbi.nlm.nih.gov/BLAST/” ; see in “References” after ¶[0286] “https://cov.lanl.gov/content/index” 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 reference to at least one drawing executed in color (See e.g. legends in specification for Figs. 2-3 and 13). 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). 06-22 AIA The drawings are objected to because Figures 2-3 and 13 reference color when only black and white drawings have been provided . 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 07-29-01 AIA Claim 30 is objected to because of the following informalities: the definition of the abbreviation “SARS-CoV-2” is not provided. For clarity, it is requested that the first recitation of an abbreviation within a claim set be preceded by its full-length name (i.e. … severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2)...) . Appropriate correction is required. 07-45 AIA Claim s 48-60 are objected to under 37 CFR 1.75(c) as being in improper form because a multiple dependent claim cannot depend upon another multiple dependent claim . See MPEP § 608.01(n). Accordingly, the claim s have not been further treated on the merits . 07-30-03-h AIA Claim Interpretation The claims in this application are given their broadest reasonable interpretation using the plain meaning of the claim language in light of the specification as it would be understood by one of ordinary skill in the art. Claim 1 is drawn to a protein having at least 85% sequence identity to SEQ ID NO:2, SEQ ID NO:4, SEQ ID NO:6, SEQ ID NO:8, SEQ ID NO:10, SEQ ID NO:12, SEQ ID NO:14, or SEQ ID NO:16. Further limitations on the protein of claim 1 are wherein the protein is having at least 90% (claim 2), at least 95% (claim 3), or is having 100% (claim 4) sequence identity to SEQ ID NO:2, SEQ ID NO:4, SEQ ID NO:6, SEQ ID NO:8, SEQ ID NO: 10, SEQ ID NO: 12, SEQ ID NO: 14, or SEQ ID NO:16; wherein the protein does not comprise an HA-tag having SEQ ID NO:31 (YPYDVPDYA)(claim 5); Claim 6 is drawn to a nucleic acid encoding the protein of claim 1. Further limitations on the nucleic acid of claim 6 are wherein said nucleic acid is having at least 90% (claim 8) or at least 95% (claim 9) sequence identity to SEQ ID NO: 1, SEQ ID NO:3, SEQ ID NO:5, SEQ ID NO:7, SEQ ID NO:9, SEQ ID NO: 11, SEQ ID NO:13, or SEQ ID NO:15. Claim 7 is drawn to a nucleic acid having at least 85% sequence identity to SEQ ID NO:1, SEQ ID NO:3, SEQ ID NO:5, SEQ ID NO:7, SEQ ID NO:9, SEQ ID NO: 11, SEQ ID NO: 13, or SEQ IDNO:15. Further limitations on the nucleic acid of claim 7 are wherein the nucleic acid does not comprise an HA- tag having SEQ ID NO:30 (claim 10). Claim 11 is drawn to a protein comprising an amino acid sequence of formula (I): R1-L1-R2-L2-R3-R4-R5 wherein: R1 is an amino acid sequence having at least 85% sequence identity to SEQ ID NO:46; L1 is SEQ ID NO:20, absent, -S(G 4 S)x-, -(G 4 S)x-, -S(G 3 S)x-, or -(G 3 S)x-; wherein x is an integer from 1 to 10; R2 is an amino acid sequence having at least 85% sequence identity to SEQ ID NO:47; L2 is SEQ ID NO:21, absent, -S(G 4 S)x-, -(G 4 S)x-, -S(G 3 S)x-, or -(G 3 S)x-; wherein x is an integer from 1 to 10; R3 is an amino acid sequence having at least 85% sequence identity to SEQ ID NO:48; R4 is absent, an amino acid sequence having at least 85% sequence identity to SEQ ID NO:41, or a truncated transmembrane domain; and R5 is absent or a truncated cytoplasmic domain; provided that R5 is absent when R4 is absent or a truncated transmembrane domain. Further limitations on the protein of claim 11 are wherein R1 is an amino acid sequence having at least 90% sequence identity to SEQ ID NO:46; R2 is an amino acid sequence having at least 90% sequence identity to SEQ ID NO:47; and R3 is an amino acid sequence having at least 90% sequence identity to SEQ ID NO:48 (claim 12), wherein R1 is an amino acid sequence having at least 95% sequence identity to SEQ ID NO:46; R2 is an amino acid sequence having at least 95% sequence identity to SEQ ID NO:47; and R3 is an amino acid sequence having at least 95% sequence identity to SEQ ID NO:48 (claim 13), wherein R1 is an amino acid sequence having SEQ ID NO:46; R2 is an amino acid sequence having SEQ ID NO:47; and R3 is an amino acid sequence having SEQ ID NO:48 (claim 14); wherein R4 is an amino acid sequence having at least 90% sequence identity to SEQ ID NO:41 (claim 15), wherein R4 is an amino acid sequence having at least 95% or 100% (claim 17) sequence identity to SEQ ID NO:41 (claim 16); wherein R5 is absent (claim 18); wherein R5 is a truncated cytoplasmic domain (claim 19); wherein both R4 and R5 are absent (claim 20); wherein R4 is a truncated transmembrane domain and R5 is absent (claim 21); wherein L1 is absent, -S(G 4 S)x-, -(G 4 S)x-, -S(G 3 S)x-, or - (G 3 S)x-; wherein x is an integer from 1 to 10; and L2 is absent, -S(G 4 S)x-, -(G 4 S)x-, -S(G 3 S)x-, or -(G 3 S)x-; wherein x is an integer from 1 to 10 (claim 22), wherein L1 and L2 are both absent (claim 23), wherein L1 is -S(G 4 S)x-, -(G 4 S)x-, -S(G 3 S)x-, or -(G 3 S)x-;wherein x is an integer from 1 to 6; and L2 is -S(G 4 S)x-, -(G 4 S)x-, -S(G 3 S)x-, or -(G 3 S)x-;wherein x is an integer from 1 to 6 (claim 24), wherein L1 is -(G 4 S)x- or -(G 3 S)x-; where x is an integer from 1 to 3; and L 2 is -(G 4 S)x- or -(G 3 S)x-; where x is an integer from 1 to 3 (claim 25); further comprising an amino acid sequence of a human MIP3-alpha protein (claim 26), wherein the human MIP3-alpha protein has the amino acid sequence of SEQ ID NO:29 (claim 27), and wherein the human MIP3-alpha protein is located at position on the N-terminus of R1 (claim 28). Claim 29 is drawn to a nucleic acid encoding the protein of claim 11. Claim 30 is drawn to a severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) spike (S) protein comprising a truncated cytoplasmic domain. Further limitations on the S protein of claim 30 are wherein the SARS-CoV-2 spike (S) protein has at least 85% sequence identity to SEQ ID NO:44 or has at least 85% sequence identity to SEQ ID NO:45 (claim 32); wherein the S1/S2 protease cleavage site in the SARS-CoV-2 spike (S) protein is absent or replaced with a peptide linker (claim 34), wherein the S1/S2 protease cleavage site in the SARS-CoV-2 spike (S) protein is absent and the S2' protease cleavage site in the SARS-CoV-2 spike (S) protein is absent (claim 39); wherein the S2' protease cleavage site in the SARS-CoV-2 spike (S) protein is absent or replaced with a peptide linker (claim 35), wherein the S1/S2 protease cleavage site is replaced with a peptide linker and the S2' protease cleavage site is replaced with a peptide linker (claim 36), wherein the peptide linker is - S(G 4 S)x-, -(G 4 S)x-, -S(G 3 S)x-, or -(G 3 S)x-; wherein x is an integer from 1 to 6 (claim 37), where the peptide linker is - (G4S)3-(claim 38); and further comprising a human MIP3-alpha protein (claim 40). Claim 31 is drawn to a SARS-CoV-2 S protein comprising a truncated transmembrane domain; wherein the protein does not comprise the amino acid sequence of SEQ ID NO:42. Claim 33 is drawn to a SARS-CoV-2 spike (S) protein having at least 85% sequence identity to SEQ ID NO:44 or has at least 85% sequence identity to SEQ ID NO:45; provided that SEQ ID NO:44 and SEQ ID NO:45 do not comprise the amino acid sequence of SEQ ID NO:40. Claim 41 is drawn to a nucleic acid encoding the SARS-CoV-2 spike (S) protein of any one of claims 30 to 41. Claim 42 is drawn to a plasmid comprising the nucleic acid of claim 6. Further limitations on the plasmid of claim 42 are wherein the plasmid is further comprising a nucleic acid encoding a human MIP3-alpha protein (claim 43); further comprising a ubiquitous promoter (claim 44), wherein the ubiquitous promoter is a CMV promoter (claim 45); further comprising a polyadenylation signal located 113 downstream of the nucleic acid encoding the protein (claim 46), wherein the polyadenylation signal is a rabbit beta-globulin polyadenylation signal (claim 47). Claim Rejections - 35 USC § 101 07-04-01 AIA 07-04 35 U.S.C. 101 reads as follows: Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title. Claims 1-3, 5-6, 11-23, 29-33, 41-42, and 46 are rejected under 35 U.S.C. 101 because the claimed invention is directed to naturally-occurring severe acute respiratory syndrome coronavirus type 2 (SARS CoV-2) sequences, namely spike (S) protein and protein-encoding nucleic acid sequences, without significantly more. The claims recite proteins with at least 85% identity to any one of SEQ ID NOs: 2, 4, 6, 8, 10, 12, 14, or 16, or nucleic acids which encode said proteins. This judicial exception is not integrated into a practical application because the sequences, as claimed, are drawn to naturally-occurring viral sequences from SARS CoV-2 viral proteins, namely S protein. With respect to the protein sequences, for instance, claim 11 is drawn to a protein that minimally comprises R1-R2-R3, wherein R1 is at least 85% identical to SEQ ID NO: 46, R2 is at least 85% identical to SEQ ID NO: 47, and R3 is at least 85% identical to SEQ ID NO: 48. When all three are combined into one sequence and searched, they are part of a wild-type SARS CoV-2 S protein at 100% identity (See attached NCBI BLAST sequence search alignment). When SEQ ID NO: 41 is added, this appears to be part of the naturally-occurring S protein transmembrane (TM) domain, and aligns with 100% identity to known S protein sequences (See attached NCBI BLAST sequence search alignment.) Sequences of instant claims 1-3 at the percent identity claimed align to known wild-type SARS CoV-2 S protein sequences (see ABSS sequence search data in file wrapper.) Sequences with at least 85% identity to SEQ ID NO: 44 or 45 lacking SEQ ID NO: 40 are fragments of S proteins lacking the TM and cytoplasmic domains, and still read upon naturally occurring sequences. With respect to the nucleic acid sequences, the nucleic acid sequences or plasmids encoding said proteins are recited at such a high level of generality that they can reasonably read upon naturally occurring SARS CoV-2 nucleic acid sequences and genomes. The claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception because the sequences have sufficient claimed percent identity to naturally occurring wild-type SARS CoV-2 sequences. The sequences claimed do not comprise elements that markedly or significantly distinguish the product from its naturally occurring counterpart. In order to overcome this rejection, it is suggested that limitations from pending and examined claims not included in this rejection be incorporated into independent claims. Additionally, the sequences can be amended to read on non-naturally occurring sequences (e.g. sequences with heterologous protein tags, such as HA tags, sequences which are codon-optimized, sequences which include heterologous linkers (e.g. ser/gly linkers), fusion proteins of heterologous sequences, plasmids which encode the protein but are heterologous to the virus and/or include heterologous regulatory elements (e.g. enhancers, promoters, etc.); etc.) Additionally, Applicant is invited to present persuasive arguments that the claims are drawn to patent eligible subject matter. For at least these reasons, the noted claims are not drawn to patent eligible subject matter. Claim Rejections - 35 USC § 112(b); Second Paragraph 07-30-02 AIA 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 applicant regards as his invention. Claim 11 and dependent claims 12-29 thereof are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention. Claim 11 is rejected for claiming the limitation of “truncated transmembrane domain” without noting what would be considered a “full-length transmembrane domain” for the claimed protein. Further dependent claims state said protein may also have a “truncated cytoplasmic domain” (instant claim 19), again without providing what would be considered a “full-length cytoplasmic domain” for the claimed protein. As it is unclear what type of protein is encompassed by instant claim 11 and dependent claims thereof, only that they must have the structure noted by instant claim 11 and a certain percent identity to specific regions comprising R1, R2, etc., it is unclear what would, and what would not, be considered a “truncated” domain with respect to a cytoplasmic region and/or transmembrane region from the resulting protein. Note that similar language was presented in instant claims 30 and 31, but the proteins of claims 30 and 31 are clearly “SARS CoV-2 S proteins” comprising a truncated cytoplasmic/transmembrane domain while instant claim 11 (and dependent claims thereof) are drawn generically to any protein , so long as it comprises the R and L groups claimed, so it is not bound by the definitions of “truncated cytoplasmic domain” as presented in ¶[0031] or “truncated transmembrane domain” as presented in ¶[0033] of the specification. One suggestion to overcome this rejection would be to amend claim 11 to recite that the generically recited protein is “A SARS CoV-2 S protein comprising an amino acid sequence of formula (I):…” Since a skilled artisan would not be reasonably apprised as to the metes and bounds of the claimed invention, instant Claim 11 is rejected on the grounds of being indefinite. Claims 12-29 are also rejected since they depend from claim 11, but do not remedy these deficiencies of claim 11. 07-34-01 Claim 41 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention. Claim 41 is drawn to a nucleic acid encoding the S protein of claims 30 to 41. A claim cannot depend upon itself. The claim will be interpreted as being drawn to the S protein of claims 30 to 40, but must be amended for further clarification. Claim Rejections - 35 USC § 102 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. 07-07-aia AIA 07-07 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 – 07-08-aia AIA (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. 07-12-aia AIA (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. 07-15-03-aia AIA Claim s 1-3, 5-6, 10-17, 19, 22-23, 29-30, 32-33, 41-42, and 44-46 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Landau et. al. (US20220056429A1; Priority 08/18/2020; hereafter “Landau”) . The Prior Art Landau teaches polypeptides that bind to angiotensin-converting enzyme 2 (ACE2) ectodomains, such as coronavirus (CoV) spike (S) proteins, as well as compositions comprising said CoV S proteins and therapeutic administration thereof (entire document; see abstract.) Landau teaches SEQ ID NO: 44, which is a SARS CoV-2 S protein sequence that comprises an HA tag at the C-terminus and has a truncation of the 19 carboxy-terminal amino acids (Δ19) of the S protein (Fig. 1; Table 1; ¶[0090]). SEQ ID NO: 44 has the following percent identities with the claimed instant sequences: Instant SEQIDNO: % identity to reference SEQ ID NO:44 2 97.7 4 91.7 6 97.2 8 91.0 10 96.8 12 90.6 14 94.0 16 88.1 41 100 44 100 45 100 46 100 47 100 48 100 Landau therefore teaches the proteins of instant claims 1-3 and 30 . SEQ ID NO: 44 of Landau also comprises instant SEQ ID NOs: 41, 44, 45, 46, 47, and 48 at 100% identity (see attached NCBI BLAST alignment; instant claims 11-17, 19, 22-23, 32-33 .) Landau teaches the SARS CoV-2 may or may not have the C-terminal HA tag, and can be encoded by a lentivirus vector (Fig. 1; ¶[0016]; instant claims 5-6, 10, 29, 41-42 ). Landau teaches the SARS CoV-2 S protein sequence can be encoded by a codon-optimized nucleic acid sequence (¶[0016][0070][0088].) Landau teaches that truncation of the cytoplasmic tail of the S protein allows for better incorporation of the S protein in pseudotyped viruses (¶[0088]). Landau teaches the deletion of the transmembrane (TM) and/or cytoplasmic portions of the ACE2 protein (¶[0008]), as well as the utilization of linker sequences between the segments of the fusion protein generated from ACE2 fused to other protein carriers (¶[0041]). Landau teaches the S protein is synthesized as a single polypeptide that is cleaved by cellular proteases such as furin into S1 and S2 subunits in the endoplasmic reticulum (¶[0006]). Landau teaches the SARS CoV-2 S protein sequences were cloned into pcDNA6 vectors, which inherently utilizes the ubiquitous, constitutively-active CMV promoter and comprises both the bovine growth hormone (bGH) poly(A) signal and the SV40 early poly(A) signal (¶[0070]; instant claims 44-46 ). For at least these reasons, Landau expressly or inherently teaches the limitations of instant claims 1-3, 5-6, 10-17, 19, 22-23, 29-30, 32-33, 41-42, 44-46 , and anticipates the invention encompassed by said claims . 07-15-03-aia AIA Claim s 1-3, 5-6, 10-25, 29-39, and 41-42 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Smith et. al. (US20220125914A1, Priority 01/27/2020; hereafter “Smith”.) Smith teaches SARS CoV-2 S proteins and nanoparticles comprising said proteins (entire document; see abstract.) Smith teaches SEQ ID NOs: 1 and 36, which both have 97.0% identity to instant SEQ ID NO: 2 ( instant claims 1-3, 11 .) Smith teaches the S protein sequence may or may not have tags, such as HA tags (¶[0130]; instant claim 5 ). Smith teaches that a nucleic acid may encode the S protein, and may be within a plasmid (¶[0199]; instant claims 5-6, 10, 29, 41-42 ). SEQ ID NO: 1 of Smith has the following percent identities with the claimed instant sequences: Instant SEQIDNO: % identity to reference SEQ ID NO:1 2 97.0 41 100 44 100 45 100 46 100 47 100 48 100 SEQ ID NO: 1 of Smith also comprises instant SEQ ID NOs: 41, 44, 45, 46, 47, and 48 at 100% identity (see attached NCBI BLAST alignment; instant claims 11-17, 19, 22-23, 32-33 .) Smith teaches that the S protein has a furin cleavage site (RRAR)(¶[0009]) that is a typical polybasic cleavage site to cleave the full length S protein (S0) into S1/S2 subunits (¶[0074]). Smith teaches mutation of this site so that the S protein is expressed as an inactive S0 single chain protein (¶[0087]). Smith also references that one or more of the amino acids of the cleavage site may be replaced with glycine and/or serine (¶[0088-0093]; instant claim 34 ). Smith also identifies additional protease cleavage sites which may also comprise the noted mutations, such as deletion or substitution with serine and/or glycine amino acids (¶[0093-0097]; Table 1; instant claims 34-36, 39 ). Smith teaches that one or more amino acids in the transmembrane and cytoplasmic domains may be deleted from the S protein in order to increase the solubility of the resulting protein (¶[0085][0099][0134]; instant claims 18, 20-21, 30-31 ). Smith teaches the S protein may comprise polypeptide linkers, such as serine/glycine linkers of sequence (SGGG)n (which can also reasonably be interpreted as (GGGS)n repeating units) or (GGGGS)n, wherein n is an integer from 1 to 50 (¶[0107-0112]; instant claim 24-25, 37-38 ). For at least these reasons, Smith teaches the limitations of instant claims 1-3, 5-6, 10-25, 29-39, and 41-42 , and anticipates the invention encompassed by said claims . 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 7-10, 26-28, 40, 43, and 47 are rejected under 35 U.S.C. 103 as being unpatentable over Landau as applied to claims 1-3, 5-6, 10-17, 19, 22-23, 29-30, 32-33, 41-42, 44-46 above, and alternatively over Smith as applied to claims 1-3, 5-6, 10-25, 29-39, and 41-42 , above and further in view of Yu et. al. (CN111588843A, Priority 08/28/2020; hereafter “Yu”); Bancel et. al. (US20140010861A1, Pub. 01/09/2014; hereafter “Bancel”); and Lanoix et. al. (Lanoix J, et. al. EMBO J . 1988 Aug;7(8):2515-22.; hereafter “Lanoix”.) The Prior Art The teachings of Landau and Smith have been set forth supra . While both Landau and Smith teach SARS CoV-2 S proteins of the instant claims, and that said protein may comprise additional heterologous materials, neither teach that said protein may be a fusion protein comprising MIP-3-alpha (CCL20) at the N-terminus of the S protein. Additionally, while Landau and Smith teach nucleic acids which can encode the SARS CoV-2 S protein, and Landau teaches their nucleic acid is codon-optimized for their system, neither teach the specific codon-optimized sequences as instantly claimed. However, such optimizations of the teachings of Landau or Smith would be obvious to a skilled artisan, given the teachings of Yu. Yu teaches a DNA vaccine, wherein the DNA plasmid encodes a viral antigen, such as a viral antigen from SARS CoV-2, and encodes an adjuvanting immune enhancer (entire document; see abstract, reference claim 1). Said immune enhancing agent may be a chemokine, such as MIP-3-alpha (CCL20) (p. 2, “Background” ¶6) and said antigen may be the S protein from SARS CoV-2 (reference claim 10). As evidenced by Bancel, at least one known sequence of human MIP-3-alpha aligns with 100% identity to instant SEQ ID NO: 29 (SEQ ID NO: 41009; See alignment below; instant claims 26-27 ). SEQIDNO29 1 MCCTKSLLLAALMSVLLLHLCGESEAS 27 ||||||||||||||||||||||||||| Bancel 1 MCCTKSLLLAALMSVLLLHLCGESEAS 27 Bancel teaches that polynucleotides which encode the proteins of interest may be codon optimized (¶[0186]) and that codon optimization methods and tools are known in the art (¶[0188-0189]). As codon-optimization, the rationale behind codon-optimization, and multiple software programs are available to perform codon-optimization for known nucleotide and/or protein sequences, and as the sequences disclosed for SEQ ID NOs: 2, 4, 6, 8, 10, 12, 14, and 16 were known in the art with at least 85%, at least 90%, and at least 95% identity, it would be obvious to generate codon-optimized nucleic acid sequences for said protein sequences at the percent identities claimed, thus making the limitations of instant claims 7-10 obvious for a skilled artisan to arrive upon, given the combined teachings of Smith (or Landau) and Bancel. Bancel teaches that the nucleic acids may comprise poly-A tails (¶[0037][0047][0175-0181]), and poly-A tails were well known in the art, such as rabbit beta-globin polyA signals which direct efficient termination of transcription of viral transcription, as evidenced by Lanoix (entire document; see abstract.) Given the teachings of Landau or Smith, one of skill in the art would be apprised to useful SARS CoV-2 S protein constructs. Given the teachings of Landau or Smith, one of skill in the art would be apprised as to the generation of fusion proteins comprising said S protein along with heterologous materials to increase the solubility, isolation, immunogenicity, and/or expression of said protein. Given the teachings of Yu, one of skill in the art would find it obvious to use such immunogenic proteins as MIP- 3-alpha along with S protein, and to generate the fusion protein with the heterologous material at the N- or C-terminus of said protein. Given the teachings of Bancel, one of skill in the art would be apprised as to sequences available for such heterologous immune enhancing agents, and would be further apprised as to regulatory elements and techniques, such as the use of specific promoters, enhancers, and polyA tails, or the use of codon-optimization of genes encoding known proteins. Given the teachings of Lanoix, one of skill in the art would be apprised as to specific polyA tail sequences which were known to enhance transcription. Therefore, given the related teachings of Landau or Smith in view of Yu, Bancel, and Lanoix, one of skill would find it obvious to arrive at the limitations of instant claims 7-10, 26-28, 40, 43, and 47 . It would have been obvious to one of ordinary skill in the art to modify the compositions taught by Landau or Smith in order to utilize specific biomolecular techniques to express the protein efficiently and increase its immunogenicity, thereby generating nucleic acids that would encode the SARS CoV-2 protein and recombinant constructs thereof. One would have been motivated to do so, given the suggestion by Yu that the SARS CoV-2 S protein could have a heterologous immunogen, such as MIP-3-alpha, fused to it to increase immunogenicity. There would have been a reasonable expectation of success, given the knowledge that techniques, such as codon optimization software and regulatory elements, were well-known and utilized in the art to increase expression of a protein, as taught by Yu, Bancel, and Lanoix. Thus, the invention as a whole was clearly prima facie obvious to one of ordinary skill in the art at the time the invention was made . Allowable Subject Matter 12-151-08 AIA 07-43 12-51-08 Claim 4 is objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims. 13-03-01 AIA The following is a statement of reasons for the indication of allowable subject matter: SEQ ID NOs: 2, 4, 6, 8, 10, 12, 14, and 16 appear to be novel at 100% identity . Conclusion No claims are allowed. 07-96 AIA The prior art made of record and not relied upon is considered pertinent to applicant's disclosure. US20250222090A1, Priority 04/11/2022. Post-filing art that teaches Mycobacterium tuberculosis ( Mtb ) vaccine wherein a Mtb antigen is fused to MIP3α. WO2025029562A1, Priority 08/28/2023. Post-filing art that teaches SARS CoV-2 vaccine wherein the S protein RBD is fused to MIP3α. Gordy JT, et. al. A SARS-CoV-2 RBD vaccine fused to the chemokine MIP-3α elicits sustained murine antibody responses over 12 months and enhanced lung T-cell responses. Front Immunol . 2024 Feb 2;15:1292059. Post-filing art that teaches SARS CoV-2 vaccine wherein the S protein RBD is fused to MIP3α. Meza J, et. al. Novel Vaccines Targeting the Highly Conserved SARS-CoV-2 ORF3a Ectodomain Elicit Immunogenicity in Mouse Models. Vaccines ( Basel ). 2025 Feb 22;13(3):220. Post-filing art that teaches SARS CoV-2 vaccine wherein the ORF3a protein is fused at its N-terminal ectodomain to MIP3α. Any inquiry concerning this communication or earlier communications from the examiner should be directed to RACHEL B GILL whose telephone number is (571)272-3129. The examiner can normally be reached on M to F 8:00 AM to 5:00 PM Eastern. 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, MICHAEL ALLEN can be reached on 571-270-3497. 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. /RACHEL B GILL/ Primary Examiner, Art Unit 1671 Application/Control Number: 18/033,980 Page 2 Art Unit: 1671 Application/Control Number: 18/033,980 Page 3 Art Unit: 1671 Application/Control Number: 18/033,980 Page 4 Art Unit: 1671 Application/Control Number: 18/033,980 Page 5 Art Unit: 1671 Application/Control Number: 18/033,980 Page 6 Art Unit: 1671 Application/Control Number: 18/033,980 Page 7 Art Unit: 1671 Application/Control Number: 18/033,980 Page 8 Art Unit: 1671 Application/Control Number: 18/033,980 Page 9 Art Unit: 1671 Application/Control Number: 18/033,980 Page 10 Art Unit: 1671 Application/Control Number: 18/033,980 Page 11 Art Unit: 1671 Application/Control Number: 18/033,980 Page 12 Art Unit: 1671 Application/Control Number: 18/033,980 Page 13 Art Unit: 1671 Application/Control Number: 18/033,980 Page 14 Art Unit: 1671 Application/Control Number: 18/033,980 Page 15 Art Unit: 1671 Application/Control Number: 18/033,980 Page 16 Art Unit: 1671 Application/Control Number: 18/033,980 Page 17 Art Unit: 1671 Application/Control Number: 18/033,980 Page 18 Art Unit: 1671