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 Aug. 4, 2026. Claims 1, 2, 6, 7, 9-11, 14, 15, 18-23, 25-27 and 29 are pending. Claims 18-19, 21, 22 and 25 are withdrawn. Claims 1, 2, 6, 7, 9-11, 14, 15, 20, 23, 26-27 and 29 are currently examined.
Election/Restrictions
Corrections
The Requirement for Election/Restrictions in the Office actions mailed on Jun. 4, 2026 has flaws. The following grouping replaces that in the previous Office action:
Group I, claims 1-2, 6-7, 9-11, 14-15, 20 (in part), 23 (in part), 27, and 29, drawn to a transgene encoding i) a viral surface glycoprotein component, ii) a viral nucleoprotein component, and iii) a viral RNA polymerase component.
Group II, claims 18-19, 20 (in part), 21, 23 (in part), drawn to a replication-incompetent E1/E3-deleted adenoviral vector.
Group III, claims 22 (in part), and 26 (in part), drawn to a method of vaccinating a mammal comprising administering a vaccine comprising a transgene of Group I.
Group IV, claims 22 (in part), 25 and 26 (in part), drawn to a method of vaccinating a mammal comprising administering a vaccine comprising an adenoviral vector in Group II or an adenoviral vector in general (claim 25).
Claims 20, 22, 23 and 26 are linking claims.
Applicant’s Response
Applicant's election without traverse of Group I (Claims 1, 2, 6-7, 9-11, 14-15, 20, 23, 27, 29), directed to a transgene encoding a viral surface glycoprotein component, a viral nucleoprotein component and a viral RNA polymerase component, in the reply filed on Aug. 4, 2026, is acknowledged. For the species election requirement, Applicant elects: 1) for the transmembrane domain, viral transmembrane domain as defined in claim 2, and 2) for the vaccine, a viral-vectored vaccine as defined in claim 15.
Accordingly, claims 18-19, 21, 22 and 25-26 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected Group.
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.
Claims 1, 2, 6, 7, 9-11, 14, 15, 20, 23, 27 and 29 are rejected under 35 U.S.C. 112(b) as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor regards as the invention.
The base claim 1 recites “A trivalent transgene for use in a viral vaccine, wherein said trivalent transgene encodes: i) a viral surface glycoprotein component comprising a signal peptide and a viral surface glycoprotein coupled to a transmembrane domain that functions to anchor the surface glycoprotein for extracellular expression; ii) a viral nucleoprotein component that complexes or associates with viral RNA; and iii) a viral RNA polymerase component.”
Neither the claim nor the specification defines the phrase “trivalent transgene”. The term “trivalent” has a conventional meaning of having a chemical valence of three, or providing immunity against three distinct strains or pathogens. See “Trivalent definition” (Merriam-webster dictionary, downloaded online Aug. 30, 2026; https://www.merriam-webster.com/dictionary/trivalent”. However, the term “trivalent” is not used in the claims to define a chemical or a vaccine providing immunity against three distinct strains or pathogens. It is, instead, used to define a “transgene” which is required to “encode” three “components”. It appears that the three “components” represent three different antigens that induce three different immune responses. However, it is not clear how to interpret that the trivalent transgene “encodes” the recited components of i)-iii). E.g., by using “encodes”, it is not clear if the “trivalent transgene” as claimed comprises or consists of the three recited components. Applicant must clarify.
Claim 27 recites “wherein the second protein complexes or associates with the viral RNA polymerase component, and wherein the first glycoprotein component and the second protein are linked with a self-cleaving peptide” renders the claim indefinite because the limitation does not have sufficient antecedent basis. Claim 1 which claim 27 depends from does not recite a “first glycoprotein component” and a “second protein”.
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 of this title, 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.
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.
Claims 1, 2, 6, 7, 9-11, 14, 15, 20, 23, 27 and 29 are rejected under 35 U.S.C. 103 as being unpatentable over Rice et al. (bioRxiv 2021.03.22.436476; posted online Mar. 23, 2021), Gambotto et al. (US 2023/0241202 A1, published on Aug. 3, 2023, PCT filed on May 28, 2021), and Yan et al. (US 2021/0268102 A1, published on Sep. 2, 2021; filed on Feb. 25, 2021),
These claims are directed to a trivalent transgene for use in a viral vaccine, wherein said trivalent transgene encodes: i) a viral surface glycoprotein component comprising a signal peptide and a viral surface glycoprotein coupled to a transmembrane domain that functions to anchor the surface glycoprotein for extracellular expression; ii) a viral nucleoprotein component that complexes or associates with viral RNA; and iii) a viral RNA polymerase component.
As indicated in the 112(b) rejection above, the term “trivalent transgene” renders the claims unclear. To facilitate examination, the term “trivalent transgene” is interpreted as reading on a nucleic acid sequence encoding a fusion polypeptide consisting of the three components as claimed, as examplified in Figure 1A of the instant specification. See below:
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Rice teaches a study for development of dual-antigen human adenovirus serotype 5 (hAd5) COVID-19 vaccine expressing both the SARS-CoV-2 spike (S) and nucleocapsid (N) proteins using an hAd5 platform with E1, E2b, and E3 sequences deleted (hAd5[E1-, E2b-, E3-]) that is effective even in the presence of hAd5 immunity. Rice teaches that on the vaccine, S is modified (S-Fusion) for enhanced cell-surface display to elicit humoral responses and N is modified with an Enhanced T-cell Stimulation Domain (N-ETSD) to direct N to the endosomal/lysosomal pathway to increase MHC I and II presentation. See Abstract.
Rice teaches that the hAd5 S-Fusion + N-ETSD vaccine used in the study comprises a wildtype spike (S) sequence [accession number YP009724390] modified with a proprietary linker peptide sequence as well as a wildtype nucleocapsid (N) sequence [accession number YP009724397] with a an Enhanced T-cell Stimulation Domain (ETSD) signal sequence to direct translated N to the endosomal/lysosomal pathway, that the SARS-CoV-2 S protein is found on the viral surface and the N protein is found in the interior of the virus (Fig. S1B). See page 25. Fig, S1 is shown below.
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Gambotto teaches a vaccine against SARS-CoV-2 comprising a replication-defective adenovirus infectious unit comprising a genome comprising a gene for expressing a polypeptide comprising an immunogenic amino acid sequence of SARS-CoV-2. See [0006]. Gambotto teaches that embodiment of the invention may include a nucleic acid encoding, or comprising a gene for expressing a polypeptide comprising, in frame SARS-CoV-2 S1 protein amino acid sequence and one or both of an epitope string comprising one or more epitopes of SARS-CoV-2 polypeptide; and/or acid sequence of protein of SARS-CoV-2, such as an M protein, an N protein, an ORF1ab protein, an ORF3 protein, an epitope of any of the preceding, or any combination thereof. See [0011]. Fig. 14 of Gambotto presents embodiments of the polypeptides of the invention, including ones expressing fusion protein of S1 (of the spike protein) and NP (nucleoprotein) of SARS-CoV-2, e.g., pAd/SARS-CoV-2 S1-3-NP, pAd/SARS-CoV-2 S1-3-2A-NP, pAd/SARS-CoV-2 S1-3fRS09-NP, and pAd/SARS-CoV-2 S1-3fRS09-2ANP. See below:
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Accordingly, both Rice and Gambotto teach adenovirus-vector-based vaccines comprising transgenes expressing SARS-CoV-2 spike protein antigens (which is a viral surface glycoprotein) and SARS-CoV-2 NP (or N, which is a viral nucleoprotein that complexes or associates with viral RNA). Teachings of Rice suggest that the S protein expressed by the transgene comprises a modified full-length S protein (S-fusion), which is expected to contain a signal peptide and a transmembrane domain, as evidenced by Xia et al. (Viruses 2021, 13, 109). See Figure 1 of Xia.
However, Rice and Gambotto are silent on a “trivalent” transgene that comprises a viral RNA polymerase component. On the other hand, Gambotto teaches that additional viral immunogens besides the S and NP can be included in the adenovirus-vector-based vaccine, mentioning an ORF1ab protein. It is known in the art that the SARS-CoV-2 RNA-dependent RNA polymerase (also referred to as the nsp12 protein) is a protease-cleavage product of the ORF1ab polyprotein.
Yan teaches an invention relating to nucleic acid molecules encoding SARS-CoV-2 antigens, immunogenic compositions, and vaccines and their use in inducing immune responses and protecting against or treating a Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) infection in a subject. See Abstract. Yan teaches that the immunogenic compositions may comprise a nucleic acid molecule encoding a SARS-CoV-2 antigen, a fragment thereof, a variant thereof, or a combination thereof (see [0113]), and that the SARS-CoV-2 antigen can be a SARS-CoV-2 spike protein, a SARS-CoV-2 RNA polymerase, a SARS-CoV-2 nucleocapsid protein, a SARSCoV-2 envelope protein, a SARS-CoV-2 matrix protein, a fragment thereof, a variant thereof, or a combination thereof (see [0114]-[0118]).
Accordingly, Yan teaches that antigens from many SARS-CoV-2 proteins, including the spike protein, nucleocapsid protein (also called nucleoprotein or N protein), and RNA polymerase (also called RNA-dependent RNA polymerase or RdRp), as claimed, can be used as antigens encoded by the nucleic acid molecules of the invention.
It would have been prima facie obvious for one of ordinary skill in the art before the effective filing date of the current invention to introduce the RNA polymerase protein of SARS-CoV-2 taught in Yan into the studies of Rice and Gambotto to build a adenovirus-vectored vaccine construct expressing three SARS-CoV-2 antigens, i.e., a spike antigen, a nucleoprotein antigen, and a RNA polymerase antigen, so that the vaccine construct may have the potential to induce immune response to all three of the included SARS-CoV-2 antigens.
Regarding claims 1-2, the full-length spike protein contains a signal peptide and a transmembrane domain. See discussion above.
Regarding claim 7, Gambotto teaches that different antigens can be linked by peptide 2A which is a self-cleaving peptide. See discussion above.
Regarding claims 20 and 22, both Gambotto teaches that the adenovirus vector used in the studies is replication-deficient with E1/E3 deletions. See [0277].
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to NIANXIANG (NICK) ZOU whose telephone number is (571)272-2850. The examiner can normally be reached on Monday - Friday, 8:30 am - 5:00 pm, EST. If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, MICHAEL ALLEN, on (571) 270-3497, can be reached. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300. Information regarding the status of an application may be obtained from the Patent Application Information Retrieval (PAIR) system. Status information for published applications may be obtained from either Private PAIR or Public PAIR. Status information for unpublished applications is available through Private PAIR only. For more information about the PAIR system, see http://pair-direct.uspto.gov. Should you have questions on access to the Private PAIR system, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative or access to the automated information system, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/NIANXIANG ZOU/
Primary Examiner, Art Unit 1671
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