RECOMBINANT VACCINIA VIRUS

DETAILED ACTION Non-Final Rejection Notice of Pre-AIA or AIA Status 1. The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA . Continued Examination Under 37 CFR 1.114 2. A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 08/06/2026 has been entered. Priority 3. This application is 371 of PCT/JP2021/029240 filed on 07/30/2021 and claims foreign priority to JP2020-130717 filed on 07/31/2020, JP2020-215454 filed on 12/24/2020 and JP2021-078781 filed on 05/06/2021. Status of Claims 4. Claims 1-3, 5, and 7-17 as amended and filed on 08/06/2026 are pending. Specification 5. A minor amendment to the specification filed on 08/06/2026 that does not introduce a new matter is entered. 6. The objection to specification raised in final office action mailed on 05/07/2026 is withdrawn. Withdrawn Rejection under 35 U.S.C. 112(b) 7. The rejection of claims 1-3, 5 and 7-17 under 35 USC 112(b) as raised in final office action mailed on 05/07/2026 is withdrawn. Information Disclosure Statement 8. The information disclosure statement (IDS) submitted on 04/10/2023, 10/03/2023, 01/17/2025, 04/11/2025 and 08/06/2026 are in compliance with the provisions of 37 CFR 1.97 and are considered by the examiner. Drawings 9. Drawings filed on 01/27/2023 are considered and acknowledged. Claim Objections 10. Claims 1 and 3 are objected to because of the following informalities: Claim 1 limitation recites a limitation, (i) wherein the cDNA encoding nonstructural protein is any of DNAs shown in (a) and (b), (ii) wherein the cDNA encoding a structural protein is any of DNAs shown in (c) and (d). It is interpreted that the limitation is intended to comprise any one of DNAs shown in (a) and (b), and any one of DNAs shown in (c) and (d). Applicant may insert “one” as recited above to amend the claim for better clarity of the claim. Claim 2 recites “strain DIs”. If known / there is support in the specification, the applicant may write the full form of “strain DIs” at least once in the claims. Appropriate correction is required to overcome the objection. Claim Rejections - 35 USC § 112 (New) 11. 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. Claims 1 and dependent claims 2-3, 5, and 7-17 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. Claims 1-3, 5, and 7-17 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 1 limitation recites a limitation, (i) wherein the cDNA encoding nonstructural protein is any of DNAs shown in (a) and (b), (ii) wherein the cDNA encoding a structural protein is any of DNAs shown in (c) and (d). It is not clear whether the limitation is intended to comprise any one of DNAs shown in (a) and (b), and any one of DNAs shown in (c) and (d). Applicant may insert “one” as recited above to amend the claim. Claim 2 recites “strain DIs”. It is not clear what the “strain DIs” stand for. Applicant may write the full form at least once in the claim. Appropriate correction is required to overcome the rejection. Claim Rejections - 35 USC § 112 (Written Description) 12. 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. Claims 1-3, 5, and 7-17 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. Claims 1 and dependent claims are directed to recombinant vaccinia virus comprising the whole or part of cDNA encoding nonstructural proteins or structural protein derived from SARS-CoV-2 with an alternative limitation (b) DNA consisting of the nucleotide sequence that shares 80% or more identity with DNA consisting of the nucleotide sequence shown in SEQ ID NO: 3 and encodes a nonstructural protein derived from SARS-CoV-2, wherein the DNA. The claim also recites a limitation (d) DNA consisting of the nucleotide sequence that shares 80% or more identity with DNA consisting of the nucleotide sequence shown in SEQ ID NO: 7 and encodes a structural protein derived from SARS-CoV-2. The invention is directed to vaccine composition intended to induce protective immune response against a SARS-CoV-2 coronavirus and confer protection and thus implicitly comprise a functional limitation an induction of protective immune response against a SARS-CoV-2 coronavirus. The instant claims 1 recites a broad genus of SARS-CoV-2 nonstructural protein (limitation b) and structural protein (limitation d) encoding cDNA that has a large degree of claimed variation (20% variation). When there is substantial variation within the genus, as here, one must describe a sufficient variety of species to reflect the variation within the genus to provide a “representative number” of species. The claimed genus comprises innumerable number of sequences that arise due to the claimed variation. The specification has not adequately described the species of the genus, nor successfully reduced to practice the variant species of the genus. The claims recite 80% identity without disclosing any structure of the variant SARS-CoV-2 nonstructural protein (limitation b) and structural protein (limitation d). Under BRI the variation can comprise substitutions of amino acids in the claimed protein encoding sequence or deletion or insertion of amino acid or nucleotide sequences that can affect the B and T cell epitopes and thus can affect protective immune response (humoral and cellular) against a coronavirus. One of ordinary skills in the art cannot conclude that Applicant was in possession of the innumerable variant species of Nucleocapsid sequences encompassed by the claimed genera. Absent the disclosed positions of variation along the sequence, the skilled artisan would not be able to visualize or otherwise predict, a priori, each individual variant sequence of the claimed SARS-CoV-2 nonstructural protein (limitation b) and structural protein (limitation d) in comparison to the reference sequences SEQ ID NO: 3 and 7. Thus, it is clear that the breadth of the claimed genus overreaches the Applicant’s contribution. In the absence of a representative number of examples, the specification must at least describe the structural features that are required for the claim function. In the instant case, the specification should explain the structure of the variant nonstructural protein (limitation b) and structural protein (limitation d) that is required to induce protective immune response. However, the specification fails to describe any substantive structural limitations as to establish the criteria necessary to design a nonstructural protein (limitation b) and structural protein (limitation d) encoding cDNA comprising recombinant vaccinia virus that is intended to induce protective anti-coronavirus immune response. The disclosure of an antigen fully characterized by its structure, formula, chemical name, physical properties, or deposit in a public depository does not, without more, provide an adequate written description of an antibody claimed by its binding affinity to that antigen, even when preparation of such an antibody is routine and conventional. Describing a composition by its function alone typically will not suffice to sufficiently describe the composition. See Eli Lilly, 119 F.3 at 1568, 43 USPQ2d at 1406 (Holding that description of a gene’s function will not enable claims to the gene "because it is only an indication of what the gene does, rather than what it is."); see also Fiers, 984 F.2d at 1169-71, 25 USPQ2d at 1605-06 (discussing Amgen Inc. v. Chugai Pharm. Co., 927 F.2d 1200, 18 USPQ2d 1016 (Fed. Cir. 1991)). 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 Univ. of Rochester v. G.D. Searle & Co., 358 F.3d 916, 927, 69 USPQ2d 1886, 1894-95 (Fed. Cir. 2004). See MPEP 216. One having ordinary skill in art cannot determine the structures encompassed by the claimed genus. Overall, the claims as currently written are not adequately described and one of ordinary skills in that art would have readily appreciated that Applicant was not in possession of the claimed genus of variant nonstructural protein (limitation b) and structural protein (limitation d) sequence at the time of filing. "The purpose of [the written description requirement] is to ensure that the scope of the right to exclude, as set forth in the claims, does not overreach the scope of the inventor’s contribution to the field of art as described in the patent specification"); LizardTech Inc. v. Earth Resource Mapping Inc., 424 F.3d 1336, 1345, 76 USPQ2d 1724, 1732 (Fed. Cir. 2005). This requirement is separate and distinct from the enablement requirement. To satisfy the written description requirement for a claimed genus, the specification must describe the claimed invention in sufficient detail that one skilled in the art can reasonably conclude that the inventor had possession of the claimed invention at the time of filing. See In re Reiffin v. Microsoft Corp., 214 F.3d 1342, 1345, 54 USPQ2d 1915, 1917 (Fed. Cir. 2000). “Even if a claim is supported by the specification, the language of the specification, to the extent possible, must describe the claimed invention so that one skilled in the art can recognize what is claimed. The appearance of mere indistinct words in a specification or a claim, even an original claim, does not necessarily satisfy that requirement.” See In re Enzo Biochem, Inc. v. Gen–Probe, Inc., 323 F.3d 956, 968, 63 USPQ2d 1609, 1616 (Fed. Cir. 2002). See also MPEP § 2163. The written description requirement 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 In re University of California v. Eli Lilly & Co., 119 F.3d 1559, 1566, 43 USPQ2d 1398, 1404 (Fed. Cir. 1997); and Juno Therapeutics, Inc. v. Kite Pharma, Inc., 10 F.4th 1330, 1337, 2021 USPQ2d 893 (Fed. Cir. 2021). A “representative number of species” means that the species which are adequately described are representative of the entire genus. Thus, when there is substantial variation within the genus, the applicant must describe a sufficient variety of species to reflect the variation within the genus. See In re AbbVie Deutschland GMBH v. Janssen Biotech, 759 F.3d 1285, 1300, 111 USPQ2d 1780, 1790 (Fed. Cir. 2014). The disclosure of only one species encompassed within a genus adequately describes a claim directed to that genus only if the disclosure "indicates that the patentee has invented species sufficient to constitute the gen[us]." See In re Enzo Biochem, 323 F.3d at 966, 63 USPQ2d at 1615; Noelle v. Lederman, 355 F.3d 1343, 1350, 69 USPQ2d 1508, 1514 (Fed. Cir. 2004) (Fed. Cir. 2004). "A patentee will not be deemed to have invented species sufficient to constitute the genus by virtue of having disclosed a single species when … the evidence indicates ordinary artisans could not predict the operability in the invention of any species other than the one disclosed." See In re Curtis, 354 F.3d 1347, 1358, 69 USPQ2d 1274, 1282 (Fed. Cir. 2004). The Federal Circuit has clarified the application of the written description requirement to inventions in the field of biotechnology. The Court stated that a written description of an invention requires a precise definition, one that defines the structural features of the chemical genus that distinguishes it from other chemical structures. A definition by function does not suffice to define the genus because it is only an indication of what the genus does, rather than what it is. This is because functionally defined genus claims can be inherently vulnerable to invalidity challenge for lack of written description support, especially in technology fields that are highly unpredictable, where it is difficult to establish a correlation between structure and function for the whole genus or to predict what would be covered by the functionally claimed genus. Further, the Court held that to adequately describe a claimed genus, an applicant must describe a representative number of species of the claimed genus, and that one of skill in the art should be able to “visualize or recognize the identity of the members of the genus.” The description needed to satisfy the written description varies depending on the nature and scope of the claims and on the complexity and predictability of the relevant technology. See In re University of California v. Eli Lilly and Co., 119 F.3d 1559, 1568, 43 USPQ2d 1398, 1406 (Fed. Cir. 1997); In re AbbVie Deutschland GMBH v. Janssen Biotech, 759 F.3d 1285, 1300, 111 USPQ2d 1780, 1790 (Fed. Cir. 2014); In re Ariad Pharms., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 94 USPQ2d 1161 (Fed. Cir. 2010); and In re Capon v. Eshhar, 418 F.3d at 1357, 76 USPQ2d at 1084. The legal standard for sufficiency of a patent's (or a specification’s) written description is whether that description "reasonably conveys to the artisan that the inventor had possession at that time of the claimed subject matter", Vas-Cath, Inc. v. Mahurkar, 19 USPQ2d 1111 (Fed. Cir. 1991). In the instant case, the specification does not convey to the artisan that the applicant had possession at the time of invention of the claimed invention. The full breadth of the claims does not meet the written description provision of 35 U.S.C. 112, first paragraph. Claim Rejections - 35 USC § 112 (Scope of Enablement) 13. Claims 1-3, 5, and 7-17 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 100% identity to the SEQ ID NOs: 3 and 7, does not reasonably provide enablement for 80% identity to the SEQ ID NOs: 3 and 7. 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 use the invention commensurate in scope with these claims. The specification does not reasonably provide enablement for the instant claims 1 recombinant vaccinia virus comprising 80% identity to the SEQ ID NOs: 3 and 7 encoding respectively for non-structural and structural proteins of SARS-CoV-2. Because the claim 1 inherently comprise a functional limitation as the recombinant vaccinia virus is intended to be used as a vaccine that has a function to induce protective immune response against SARS-CoV-2. The claimed sequences (SEQ ID NOs: 3 and 7) with 80% identity may not be as effective and efficacious to induce immune response and confer protection as that of the claimed sequences (SEQ ID NOs: 3 and 7) with 100% sequence identity. The claims depending on the base claim 1 inherit the limitations. In order to determine compliance with the enablement requirement of 35 U.S.C. 112(a), the Federal Circuit has developed a framework of factors in In re Wands, 858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988), referred to as the Wands factors, to assess whether any necessary experimentation required by the specification is "reasonable" or is "undue." The factors considered include, but are not limited to: (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 in the art; (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. Breadth of the claims and nature of the invention: Claim 1 and the dependent claims inventions are drawn to a recombinant vaccinia virus comprising 80% identity to the SEQ ID NOs: 3 and 7 encoding respectively for non-structural and structural proteins of SARS-CoV-2. The claimed sequences recited in SEQ ID NOs: 3 and 7 comprise a large degree of variation by claiming 80% identity (comprise 20% variation) and thus comprise a broad genus comprising a large number of species of variant sequences and thus the claims are very broad. The dependent claims inherit the limitations of base claim 1. The claims are intended and directed to a functional limitation of induction of protective immune response against a SARS-CoV-2 coronavirus. The level of one of ordinary skills in the art: The required level of skills in art is that of Ph.D. level scientists and medical doctors (D.O. and/or M.D.). Amount of direction and existence of working examples: The instant application does not represent even one example of a recombinant vaccinia virus comprising variant sequences derived from SEQ ID NOs: 3 and 7 due to claimed 80% identity (reads on 20% variation). Working Example: The instant application does not represent even one example comprising a recombinant vaccinia virus comprising variant sequences derived from SEQ ID NOs: 3 and 7 due to claimed 80% identity (reads on 20% variation) reduced to practice inducing reasonably protective immune response against a SARS-CoV-2 coronavirus. The instant disclosure does not offers reasonable guidance or direction. State of the prior art and unpredictability in the art: The prior art (See, Rahman et al 2020 on Evolutionary dynamics of SARS-CoV-2 nucleocapsid (N) protein and its consequences) teaches a large number of variations in the Nucleocapsid protein encoding gene of a coronavirus (SARS-CoV-2). Sanches et al 2021 and Singh et al 2021 teaches amino acid variation is spike protein of SARS-CoV-2 virus and variants thereof belonging to different antigenic clades (See, Sanches et al 2021 and Singh et al 2021). It is not clear to one of the ordinary skills which variations in the SEQ ID NOs: 3 and 7 sequence are claimed in the instant claims 1 and dependent claims and how the mutations/variations could affect/influence induction of a protective immune response against a SARS-CoV-2 coronavirus after immunization/vaccination with the claimed recombinant vaccinia virus and thus there is unpredictability in the art. Quantity of experimentation needed: At a minimum the art teaches that a skilled artisan would consider the predictive function of a variant sequence derived from SEQ ID NOs: 3 and 7. Thus, one of skills in the art would neither expect nor predict the appropriate function of sequences with 20% variation as compared to the reference SEQ ID NOs: 3 and 7 for induction of protective immune response. Any and all enablement of the claimed variants of SEQ ID NOs: 3 and 7 that has up to 20% variability in sequence must therefore come from the instant disclosure. The claims are clearly not enabled to their full scope. Moreover, the claims not containing elements critical or essential to the practice of the invention, such as specific amino acid residue variation as compared to the reference sequences SEQ ID NOs: 3 and 7, are not enabled by the disclosure to induce protective immune response against SARS-CoV-2 coronavirus. In this context, see, claims that contain materials demonstrated not to bind to the critical element of the invention are also not enabled by the disclosure. See In re Mayhew, 527 F.2d 1229, 188 USPQ 356 (CCPA 1976). For the reasons discussed above, “undue and unreasonable experimentation” is required to practice the claimed invention commensurate with the scope of the claims. Reasonable correlation must exist between the scope of the claims and scope of enablement set forth. It would take undue trials and errors to practice the claimed invention in view of the quantity of experimentation necessary, the limited working examples, the unpredictability of the art, the lack of sufficient guidance in the specification, and the breadth of the claims. Therefore, the instant disclosure is not enabled for any variant of a recombinant vaccinia virus comprising variant sequences derived from SEQ ID NOs: 3 and 7 due to claimed 80% identity (reads on 20% variation) as presently written but rather is only enabled for 100% identity to the claimed SEQ ID NOs: 3 and 7. Thus, claims 1 and dependent claims limitations that do not further limit the SEQ ID NOs: 3 and 7 identity requirement to 100% are not enabled. This includes elected claims 1-3, 5, and 7-17. Claim Interpretation (Modified) 14. 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: A recombinant vaccinia virus, which comprises the whole or part of cDNA encoding nonstructural proteins or structural protein derived from SARS-CoV-2, and an expression promoter, wherein the cDNA encoding nonstructural protein is any of DNAs shown in (a) and (b) below: (a) DNA consisting of the nucleotide sequence shown in SEQ ID NO: 3; and (b) DNA consisting of the nucleotide sequence that shares 80% or more identity with DNA consisting of the nucleotide sequence shown in SEQ ID NO: 3 and encodes a nonstructural protein derived from SARS-CoV-2, wherein the DNA of (b) is a DNA in which the bases corresponding to the bases at positions 2445, 2448, 4998, 5001 and 6000 in the nucleotide sequence shown in SEQ ID NO: 3 are cytosine, and the base corresponding to the base at position 2539 in the nucleotide sequence shown in SEQ ID NO: 3 is adenine, wherein the cDNA encoding a structural protein is any of DNAs shown in (c) and (d) below: (c) DNA consisting of the nucleotide sequence shown in SEQ ID NO: 7; and (d) DNA consisting of the nucleotide sequence that shares 80% or more identity with DNA consisting of the nucleotide sequence shown in SEQ ID NO: 7 and encodes a structural protein derived from SARS-CoV-2, wherein the DNA of (d) is a DNA in which the bases corresponding to the bases at positions 99, 102, 2364, 2367, 3213, 3216, 3417 and 3420 in the nucleotide sequence shown in SEQ ID NO: 7 are cytosine. Under BRI, instant claim 1 is interpreted to comprise an alternative limitation comprising (b) non-structural protein with 80% identity to SEQ ID NO: 3, and (d) structural protein with 80% identity to SEQ ID NO: 7. Thus the claimed variation in the sequence SEQ ID NO: 3 and SEQ ID NO: 7 reads on 20% variation that introduces a broad genus with many different variant species of SEQ ID NO: 3 and SEQ ID NO: 7. Allowable Subject Matter 15. The following is a statement of reasons for the indication of allowable subject matter: Claim 1. The instant claim 1 limitation (a) DNA consisting of the nucleotide sequence shown in SEQ ID NO: 3 (reads on 100% identity) and (c) DNA consisting of the nucleotide sequence shown in SEQ ID NO: 7 (reads on 100% identity) are free of prior art. Conclusion 16. No claim is allowed. 17. Any inquiry concerning this communication or earlier communications from the examiner should be directed to SAMADHAN J JADHAO whose telephone number is (703)756-1223. The examiner can normally be reached M-F 8:00-5:00. 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, Thomas J Visone can be reached at 571-270-0684. 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. /SAMADHAN JAISING JADHAO/Examiner, Art Unit 1672 /BENNETT M CELSA/Primary Examiner, Art Unit 1600