Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
DETAILED ACTION
Acknowledgement is hereby made of receipt and entry of the communication filed on May 06, 2026. Claims 1, 3, 6, 15 and 18-20 are pending and are currently examined.
Claim Rejections - 35 USC § 112 (Scope of Enablement)
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.
(Previous rejection-withdrawn) Claims 1-6 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling to show the potent TCDS+ response in mice, that targets multiple epitopes, including the B8, A8, A3, K3, A47 and A42 epitopes in mice on an H2b background (See [0113]), does not reasonably provide enablement for using a method for inducing any type of immune response to any antigen in any subject.
This rejection is withdrawn in view of the amendments filed on May 06, 2026.
Claim Rejections - 35 USC § 112 (Enablement)
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.
(Previous rejection-withdrawn) Claims 7-14 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 any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention commensurate in scope with these claims.
This rejection is withdrawn in view of the amendments filed on May 06, 2026.
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.
(Previous rejection-withdrawn) Claims 6 and 13 are rejected under 35 U.S.C. 103 as being unpatentable over Verardi et al. (Hum Vaccin Immunother. 2012 Jul;8(7):961-70)
This rejection is withdrawn in view of the amendments filed on May 06, 2026.
(New Rejection-necessitated by amendment) Claims 1, 6, 15 and 19 are rejected under 35 U.S.C. 103 as being unpatentable over Bryk P. (Thesis-Ph.D., University of Rochester, 2018. First presented to the public: 12/31/2019) and in view of Verardi et al. (Hum Vaccin Immunother. 2012 Jul;8(7):961-70) as evidenced by Bavarian (Product Monograph Template – Schedule D, Date of Initial Approval: Jul 12, 2017).
The amended base claim 1 is directed to a method for inducing an immune response to a viral antigen in a subject, comprising administering to the subject an effective amount of a recombinant vaccinia virus in which the extracellular virion protein Fl3 has been replaced with MC021, a molluscum contagiosum virus homolog of F13, wherein the recombinant vaccinia virus comprises a nucleic acid encoding an immunogenic epitope of the viral antigen.
The base claim 15 is directed to a pharmaceutical composition comprising (a) a recombinant vaccinia virus in which the extracellular virion protein F13 has been replaced with MC021, a molluscum contagiosum virus homolog of Fl3; (b) a viral antigen; and (c) pharmaceutically acceptable carrier, wherein the pharmaceutical composition is formulated for percutaneous inoculation, subcutaneous injection or intramuscular injection.
Bryk teaches that vaccinia virus (VACV) is the prototypic poxvirus and the protein F13 is conserved across the subfamily Chordopoxvi rinae. It has been shown to be required to produce the wrapped forms of virus that are required for cell-to-cell spread. F13 is included on wrapped forms of virus (Abstract, page ix) and viruses lacking or deficient in the function of F13 are highly attenuated both in vitro and in vivo (See bridging pages 10-11). At the same time, Bryk P. teaches that MOCV (molluscum contagiosum virus) encodes putative homologs of wrapped virion-specific proteins in VACV, of which the homolog of F13, MC021, shares the greatest amino acid sequence identity (See page ix).
Bryk P. further discloses that they have characterized a recombinant vaccinia virus expressing an HA epitope-tagged version of MC021L (MC021L-HA) inserted into the F13L locus under the native VACV promoter (See page 75, paragraph 3) and the plaque phenotype of vMC021L-HA was considerably smaller than that of the C-terminal HA-tagged F13 virus (vF13L-HA) [25], yet appeared slightly larger than that of vΔF13L (Fig. 3.2A) (See page 82 and below), which indicates that the vMC021L-HA is capable of producing EEV at levels greater than vΔF13L and more attenuated at the infections level than vF13L-HA (See page 83). Also, it indicates that that expression of MC021-HA is capable of complementing a deletion of F13L (See page 83). Bryk P. teaches that vMC021L-HA consistently maintained production of EV at a level modestly above that of vΔF13L, ranging from 3- to 12-fold more EV at each time point (Fig. 3.3B) (See page 83).
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Accordingly, Bryk P. teaches a recombinant vaccinia virus in which the extracellular virion protein F13 has been replaced with MC021. The expression of MC021-HA was incorporated into virions, and these virions entered at a rate similar to virions containing F13 (See page 121), where the HA in the construction of MC021-HA is a viral antigen.
Bryk P. also teaches that their work is important for the pursuit of developing a safer vaccine, as targeted mutations within F13 being capable of decreasing the efficiency of infection and increasing the EV particles compared to vΔF13L by replacing vaccinia virus F13L with the MC021L gene (See e.g., pages 23 and 49). Bryk P. teaches their work opens the opportunity to new treatments targeted at preventing the spread of virus early in infection and vaccine development (See page 3), and also teaches constructing a vaccina virus comprises a inserted nucleic acid encoding GFP protein like “recombinant virus vMC021L-HA and vMC-HA/GFP/lacZ were generated by infecting a monolayer of HeLa cells with vΔF13L or vMC021L-HA, respectively” (See page 77, paragraph 1).
Thus, although Bryk does not explicitly point out to induce an immune response to a viral antigen in a subject by administering to the subject an effective amount of a recombinant vaccinia virus as claimed in claim 1 and point out a pharmaceutical composition as claimed in claim 15, Bryk teaches a vaccine development that implies administrating a pharmaceutical composition into a subject. Also, Bryk teaches constructing the MC021L-HA for vaccine development by deleting the F13 for virus attenuation and by adding the MC021 for increasing HA expression, where the construct of rMC021L-HA is the same structure as claimed in the base claim 1 and 15. Therefore, it should have the same function as claimed to induce the immune response by administrating the construct with HA viral antigen and can be used as pharmaceutical composition.
In addition, the limitation “for inducing an immune response to a viral antigen in a subject” in the base claim 1 is not patentable because it is an intended use claim and cannot be considered as a limitation unless it imposes structure differences. (See MPEP 2111.02, Effect of Preamble [R-07.2022]).
Nevertheless, Verardi et al. teaches that a large number of antigens from animal pathogens have been expressed in VACV (vaccinia virus), and the majority elicit protective immune responses (examples shown in Table 2) (See page 963, right column, paragraph 3 and table 2 below), and recombinant VACVs expressing heterologous viral antigens have also been protective against peste-des-petits-ruminants virus, vesicular stomatitis virus, Newcastle disease virus, canine distemper virus, and Rift Valley fever virus in a variety of animal species (See Table 2).
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Verardi et al. also teaches that highly attenuated VACV strain has been extensively tested in humans and has sparked considerable interest because it has been demonstrated to be extremely safe, and discloses number of highly attenuated strains of VACV have been developed and are now being considered as safer smallpox vaccine alternatives, called third-generation smallpox vaccines (Table 1) (See page 963).
In Table 1 (See page 962 and below), Verardi lists some first and next-generation smallpox vaccines. For example, immune responses in phase I and II clinical trials to an MVAbased vaccine developed by Bavarian Nordic (Imvamune®) are dose-dependent and can require two immunizations to achieve immune responses similar to first-generation vaccines (See page 963, left column, paragraph 2), where the Imvamune administration is via a subcutaneous (SC) route. This can be evidenced by Bavarian’s teaching. Bavarian teaches that IMVAMUNE should be administered by subcutaneous injection, preferably in the deltoid region of the non-dominant upper arm. The vaccine must not be administered intravascularly (See page 5). In Table 1 of Bavarian, it shows the Non-medicinal Ingredients (See page 6 and below), where Tris is one type of a pharmaceutical carrier as claimed in claim 15.
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It would have been prima facie obvious for one having ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of Bryk and Verardi to arrive at an invention as claimed. Bryk teaches a method for developing a recombinant vaccinia virus with F13 being replaced by the MC021 (vMC021L-HA) that comprises a viral antigen HA. Verardi teaches the importance to develop a highly attenuated VACV in administering immunogenetic viral antigens into a subject like animal and human to induce an immune response. Thus, one of skill in the art would have been motivated to introduce Verardi’s administration method such as subcutaneous route to Bryk’s study, and there would be a reasonable expectation of success to induce an immune response by administering the vMC021L-HA into a subject as claimed.
The above description also teaches claim 6 at the recombinant vaccinia virus is administered percutaneously, subcutaneously or intramuscularly.
Thus, the invention as a whole was clearly prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention.
Regarding claim 19, it requires that the recombinant vaccinia virus is an enveloped virus and wherein the virus envelop comprises, in addition to MC021, an additional foreign glycoprotein or a portion thereof, wherein the additional foreign glycoprotein is a viral protein from a different virus.
Based on the description above, Bryk teaches that the family Poxviridae encompasses a large group of complex enveloped, linear double stranded DNA viruses that can be divided into two subfamilies; the Entomopoxvirinae infect insects, and the Chordopoxvirinae, which infect vertebrates. Among chordopoxviruses, the genus Orthopoxvirus contains the most members capable of infecting humans, including variola virus (VARV), where vaccinia virus (VACV) is an orthopoxvirus (See page 1). Bryk also teaches that MC021 can replace the F13 of VACV and incorporate into the EV membrane (See e.g., page 75). Furthermore, Bryk teaches that “an HA epitope-tagged MC021L gene was placed under the native F13L promoter and inserted into the F13L locus of a recombinant VACV” (See page 21). Here HA is an viral antigen, an additional foreign glycoprotein beside the MC021.
(New Rejection-necessitated by amendment) Claims 3, 18 and 20 are rejected under 35 U.S.C. 103 as being unpatentable over Bryk P. (Thesis-Ph.D., University of Rochester, 2018. First presented to the public: 12/31/2019) in view of Verardi et al. (Hum Vaccin Immunother. 2012 Jul;8(7):961-70) evidenced by Bavarian as applied to claims 1, 6, 15 and 19 above and further in view of Tscheme et al. (bioRxiv preprint doi: https://doi.org/10.1101/2021.01.09.426032, this version posted January 11, 2021).
Claims 3, 18 and 20 further require the viral antigen is from SARS-COV-2 virus.
Based on the description above, Bryk, in view of Verardi teaches a method for inducing an immune response by administering a recombinant vaccinia virus comprising a nucleic acid encoding an immunogenic epitope of the antigen, where the F13 is replaced by the MC021. However, it is silent on the antigen is from SARS-COV-2.
Tscherne et al. teaches that they describe the construction and preclinical characterization of a recombinant MVA expressing full-length SARS-CoV-2 spike (S) protein (MVA-SARS-2-S). Genetic stability and growth characteristics of MVA-SARS-2-S, plus its robust synthesis of S antigen, make it a suitable candidate vaccine for industrial scale production. Vaccinated mice produced S antigen specific CD8+ T cells and serum antibodies binding to S glycoprotein that neutralized SARS-CoV-2. Prime-boost vaccination with MVA-SARS-2-S protected mice sensitized with a human ACE2-expressing adenovirus from SARS-CoV-2 infection. MVA-SARS-2-S is currently being investigated in a phase I clinical trial as aspirant for developing a safe and efficacious vaccine against COVID-19 (See Abstract).
It would have been prima facie obvious for one having ordinary skill in the art before the effective filing date of the claimed invention to introduce the teaching of Tscherne into the studies of Bryk and Verardi to arrive at an invention as claimed. The SARS-CoV-2 spike (S) protein serves as the most important target antigen for vaccine development, and Tscherne shows the SARS-CoV-2 Spike can be expressed by the attenuated vaccinia virus, MVA, and induced antibody/T cell responses in mice. One of skill in the art would have been motivated to introduce the SARS-CoV-2 Spike as an immunogenetic antigen to construct a VACV of Verardi and Bryk to encode the antigen of SARS-COV-2 and evaluate the effect for inducing the immune responses in vivo. There would be a reasonable expectation of success to develop such a method and composition to use the recombinant vaccinia virus of Verardi and Bryk to express the antigen of SARS-COV-2 based on Tscherne’s teachings.
Responses to Applicant’s Remarks
Applicant’s arguments filed on May 06, 2026, has been received and fully considered.
Applicant’s amendment regarding the rejection under 35 U.S.C. § l 12(a) (Scope of Enablement) is considered. The rejection is withdrawn.
Applicant’s amendment regarding the rejection under 35 U.S.C. § l 12(a) ( Enablement) is considered. The rejection is withdrawn.
Applicant’ argument regarding the rejection Under 35 U.S.C §103 is not found persuasive as follows:
1). Applicant argued that Veradi generally mentions using VACV as a vector for vaccine development and cancer treatment (See Remarks, page 6) and a person of ordinary skill in the art would not be motivated to use the claimed chimeric recombinant vaccinia virus to induce an immune response to a viral antigen in a subject, as recited in amended claim 1or amended claim 15 (See Remarks, page 7). The argument regarding Veradi is moot.
Based on applicant’s amendment, Veradi is not applied as a primary prior art in the current office action. Thus, the argument regarding Veradi as a primary art is moot.
2). Applicant argued that a person skilled in the art would expect that a recombinant vaccinia virus of Bryk with F 13 being replaced with MC021 would exhibit reduced immunogenicity, and would not be motivated to use the claimed chimeric recombinant vaccinia virus to induce an immune response to a viral antigen in a subject, as recited in amended claim 1 or amended claim 15.
The argument is not persuasive (See Remarks, page 7).
(i). BryK does not teach or imply the recombinant vaccinia virus with F 13 being
replaced with MC021 would exhibit reduced immunogenicity. In fact, BryK teaches the opposite by stating that the vMC021L-HA expression level is higher than the vΔF13L (See e.g., page 83), which means more HA is expressed, which can increase the immunogenicity.
(ii). For the reducing point, Bryk teaches the plaque size being reduced in the MC021L-HA construct by disclosing “MC021L-HA was inserted into the F13L locus of an F13L-deletion virus. Extracellular virion production was increased to levels similar to that of an F13-HA-expressing virus, however plaque size was considerably reduced, yet larger than an F13L-deletion virus” (See page 72). Here the reduced plaque size general means that the virus has reduced ability to spread and replicate, which makes it an excellent starting candidate for a live-attenuated vaccine.
3). Applicant argued an unexpected result for the chimeric virus being substantially higher levels of glycoproteins A33 (3 fold) and B5 (2 fold) incorporated into the EV than the parent Fl3 virus and the claimed chimeric virus, although exhibiting attenuated infectivity, induces the comparable levels of immune response as the parent F 13 virus (See Remarks, page 7).
The argument is not persuasive.
(i). The instant claims do not cite limitations on the expression of A33 and B5.
(ii). Bryk discloses EEV lacking F13 still incorporated EV-specific proteins A33 and B5 (See page 55, paragraph 2), and MC021-HA, B5 and A33 were found to be incorporated into the EV membrane, suggesting EEV produced by vMC021L-HA incorporates the full complement of WV-specific proteins (See page 84, paragraph 2). Therefore, the alleged unexpected results need to be compared with Bryk’s data on B5 and A33.
(iii). As for the alleged unexpected result of “…comparable levels of immune response as the parent F 13 virus”, Bryk teaches that “ characterization of the MC021-HA expressing recombinant virus, termed vMC021L-HA, revealed production of EV at levels similar to that of WR”(See page 22, paragraph 1), and “Expression of the MC021-HA protein in place of F13 resulted in production of similar levels of EV compared to an F13-HA-expressing virus” (See page 75, paragraph 3), which indicates that a comparable level of immune response would be achieved with a similar MC021-HA protein expression.
(iii). Based on the description above, Applicant’s attention is directed to MPEP 716.02(b)-(e) for how unexpected results can be established. E.g., to evaluate if the claimed invention produces unexpected results, one must consider if the results produced by the claimed invention are commensurate in scope with the claims and how the results compare with the closest prior art. See MPEP Section 716.02(d) and (e). Here, applicant has not provided sufficient information for the Office to consider if the results produced by the claimed invention are commensurate in scope with the claims and how the results compare with the closest prior art.
Applicant also argued against the secondary references of Tscheme and Kaufman.
The argument is not persuasive.
Tscheme and Kaufman are used to support a specific claim. It is applicable to combine the teachings of Bryk, Veradi, Tscheme and Kaufmanin in the current action. For example, Veradi in view of Tscheme is to teach the viral antigen of SARS-COV-2.
Conclusion
No claims are allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any extension fee pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to RUIXUE WANG whose telephone number is (571)272-7960. The examiner can normally be reached Monday-Friday 8:00 am-5:00 pm, EST.
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/RUIXUE WANG/Examiner, Art Unit 1672
/NICOLE KINSEY WHITE/Primary Examiner, Art Unit 1672
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