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 March 27, 2024. Claims 1-20 are pending and currently examined.
Specification – Sequence Compliance
This application contains sequence disclosures that are encompassed by the definitions for nucleotide and/or amino acid sequences set forth in 37 CFR 1.821(a)(1) and (a)(2). However, this application fails to comply with the requirements of 37 CFR 1.821 through 1.825 for the reason(s) as follows:
The specification does not contain sequence identifiers (SEQ ID NO:) in all locations where sequences are disclosed, see at least claim 10 and Table 1. Applicant must assign sequence identifiers to all of the sequences disclosed in the application based on 37 CFR 1.821(a)(1) and (a)(2). If the prior filed Sequence Listing does not contain updated sequences, Applicant is also required to submit a replacement Sequence Listing that includes all updated sequences.
Full compliance with the sequence rules is required in response to this Office Action. A complete response to this office action should include both compliance with the sequence rules and a response to the Office Action set forth below. Failure to fully comply with both these requirements in the time period set forth in this Office Action will be held non-responsive.
Claim Rejections - 35 USC § 101
The following is a quotation of 35 U.S.C. 101:
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, 7, 9 and 10 are rejected under 35 U.S.C. 101 because the claimed invention is directed to non-statutory subject matter. A claim directed to a judicial exception must be analyzed to determine whether the elements of the claim, considered both individually and as an ordered combination, are sufficient to ensure that the claim as a whole amounts to significantly more than the exception itself. To be patent-eligible, a claim that is directed to a judicial exception must include additional features to ensure that the claim describes a process or product that applies the exception in a meaningful way, such that it is more than a drafting effort designed to monopolize the exception.
Claims 1, 7 and 9-10 are directed to a recombinant microorganism comprising an antigen of SARS-CoV-2 expressed on the surface of the microorganism, wherein the recombinant microorganism is capable of inducing an immune response against a SARS-CoV-2 infection in a subject. The claims do not specify the microorganism, which may read on a SARS-CoV-2 virus itself, since a SARS-CoV-2 virus displays SARS-CoV-2 antigens on its surface. Additionally, merely reciting the word “recombinant” does not render the “recombinant microorganism” structurally different from the naturally occurring counterpart.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claims 1, 7 and 9-10 are rejected under 35 U.S.C. 102(1) as being anticipated by GenBank: MN908947.3 (Severe acute respiratory syndrome coronavirus 2 isolate Wuhan-Hu-1, complete genome; dated Mar. 18, 2020).
These claims are described in the 101 rejection above. I.e., they read on a SARS-CoV-2 virus itself.
GenBank: MN908947.3 discloses a strain of SARS-CoV-2, which comprises all of the antigens of the virus.
Regarding claim 9, the SARS-CoV-2 of GenBank: MN908947.3 encodes the recited proteins, and at least the Orf3a, which is a transmembrane protein, is displayed on the virus surface.
Regarding claim 10, the recited peptide sequences are included in SARS-CoV-2 proteins, except for i) AGLFQRHGEGTKATVGEPV, which exists in a gram-negative porin. E.g., the peptide ii) KDGIIWVATEGALNT exist in the SARS-CoV-2 NP protein; peptide iii) LSYYKLGASQRVAGD exist in the SARS-CoV-2 membrane glycoprotein (M); and iV) QYIKWPWYI exist in the spike protein (S), etc..
Therefore, GenBank: MN908947.3 anticipates claims 1, 7 and 9-10.
Claims 1, 2 and 7 are rejected under 35 U.S.C. 102(1) as being anticipated by Wang et al. (International Journal of Biological Macromolecules 160 (2020) 736–740; submitted in IDS filed on Jun. 12, 2025).
These claims are directed to a recombinant microorganism comprising an antigen of SARS-CoV-2 expressed on the surface of the microorganism, wherein the recombinant microorganism is capable of inducing an immune response against a SARS-CoV-2 infection in a subject.
Wang teaches that coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become a global pandemic in the past four months and causes respiratory disease in humans of almost all ages. The authors described the construction of a recombinant Lactobacillus plantarum strain expressing the SARS-CoV-2 spike protein. The results showed that the spike gene with optimized codons could be efficiently expressed on the surface of recombinant L. plantarum and exhibited high antigenicity. Recombinant L. plantarum may provide a promising food-grade oral vaccine candidate against SARS-CoV-2 infection. See Abstract.
Wang teaches that they optimized the codons of the S gene of the SARS-CoV-2 isolate Wuhan-Hu-1 (GenBank: MN908947) according to the codon usage bias of L. plantarum (Lp18) and synthesized the gene, followed by linking the sequence of the endogenous signal peptide 1320 (ALX04_001320) of L. plantarum to the 5′ terminus of the optimized S gene and the target peptide D (DCpep: FYPSYHSTPQRP) and HA genes to the 3′ terminus of the gene, resulting in a fragment named 1320-tSDH. Then, the fragment was amplified using the primers F01 and R01 and subcloned into pSIP411 with Nco I and Xba I using the Gibson Assembly® Cloning Kit (NEB, USA), producing the expression plasmid pLP-tS. Thereafter, the expression plasmid was electro-transformed into competent Lp18 cells as described previously [11]. A positive colony, designated L. plantarum Lp18:S, was grown and verified by colony PCR using the primers F01 and R01 and sequencing analysis (Fig. 1A). See page 738, left column, and Fig. 1A below.
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Accordingly, Wang teaches each and every aspect of claims 1-2 and 7.
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.
Claims 1-10 and 12-13 are rejected under 35 U.S.C. 103 as being unpatentable over Lee et al. (JOURNAL OF VIROLOGY, Apr. 2006, Vol. 80, No. 8, p. 4079–4087; submitted in IDS filed on Sep. 11, 2023) and Mou et al. (Antiviral Research 131 (2016) 74-84; submitted in IDS filed on Jun. 12, 2025), in view of GenBank: MN908947.3 (Severe acute respiratory syndrome coronavirus 2 isolate Wuhan-Hu-1, complete genome; dated Mar. 18, 2020).
These claims are directed to a recombinant microorganism comprising an antigen of SARS-CoV-2 expressed on the surface of the microorganism, wherein the recombinant microorganism is capable of inducing an immune response against a SARS-CoV-2 infection in a subject. Claims 2-6 specify that the microorganism is a bacterium, specifically a bacterium of Bacillus genus, and more specifically, Bacillus subtilis.
Lee teaches that induction of mucosal immunity may be important for preventing SARS-CoV infections. For safe and effective delivery of viral antigens to the mucosal immune system, the authors have developed a novel surface antigen display system for lactic acid bacteria using the poly-g-glutamic acid synthetase A protein (PgsA) of Bacillus subtilis as an anchoring matrix. Recombinant fusion proteins comprised of PgsA and the Spike (S) protein segments SA (residues 2 to 114) and SB (residues 264 to 596) were stably expressed in Lactobacillus casei. Surface localization of the fusion protein was verified by cellular fractionation analyses, immunofluorescence microscopy, and flow cytometry. Oral and nasal inoculations of recombinant L. casei into mice resulted in high levels of serum immunoglobulin G (IgG) and mucosal IgA, as demonstrated by enzyme-linked immunosorbent assays using S protein peptides. More importantly, these antibodies exhibited potent neutralizing activities against severe acute respiratory syndrome (SARS) pseudoviruses. Orally immunized mice mounted a greater neutralizing-antibody response than those immunized intranasally. Three new neutralizing epitopes were identified on the S protein using a peptide neutralization interference assay (residues 291 to 308, 520 to 529, and 564 to 581). These results indicate that mucosal immunization with recombinant L. casei expressing SARS-associated coronavirus S protein on its surface provides an effective means for eliciting protective immune response against the virus. See Abstract.
Specifically, Lee teaches that the authors generated expression vectors encoding PgsA fused to two fragments of the SARS-CoV S protein, SA and SB, containing amino acid residues 2 to 114 and 264 to 596, respectively (pHAT:pgsA-SA and pHAT:pgsA-SB) (Fig. 1A). These sequences include the B-cell epitopes and the receptor-binding domain (RBD) located at the N terminus of the S protein (33). E. coli harboring the plasmids was grown overnight at 37°C. The cells were harvested, and expression of the expected chimeric proteins was confirmed by immunoblotting using anti-PgsA and anti-SARS S polyclonal antibodies (data not shown). L. casei cells were then transformed with the plasmids and cultured at 30°C. Expression of the PgsA-SA and PgsA-SB fusion proteins was monitored by immunoblotting whole-cell lysates of serially passaged recombinant L. casei (Fig. 1B, lane 2). Both PgsA-SA and PgsA-SB were stably expressed through more than 10 serial passages and maintained their predicted molecular masses (55 kDa and 79 kDa, respectively). See para spanning pages 4080-4081.
Lee teaches that to determine cellular localization of the proteins, membrane and cytoplasmic fractions of L. casei cells were subjected to Western immunoblotting. As expected, both PgsA-SA and PgsA-SB fusion proteins were detected in the membrane, but not the cytoplasmic fraction (Fig. 1B, lanes 4 and 3, respectively). See page 4081, left column, para 2.
Mou teaches a study on immune responses induced by recombinant Bacillus subtilis expressing the spike protein of transmissible gastroenteritis virus in pigs. Mou teaches that, to develop an effective, safe, and convenient vaccine for the prevention of Transmissible gastroenteritis (TGE), the authors have constructed a recombinant Bacillus subtilis strain (B. subtilis CotGSG) displaying the transmissible gastroenteritis virus (TGEV) spike (S) protein and discussed its immune function to intestinal submucosal dendritic cells (DCs). Their results showed that the recombinant B. subtilis had the ability to recruit more DCs to sample B. subtilis CotGSG, migrate to MLNs, and induce immune responses. Immunized piglets with B. subtilis CotGSG could significantly elevate the specific SIgA titers in feces, IgG titers and neutralizing antibodies in serum. Collectively, their results suggested that recombinant B. subtilis CotGSG expressing the TGEV S protein could effectively induce immune responses via DCs, and provided a perspective on potential novel strategy and approach that may be applicable to the development of the next generation of TGEV vaccines. See Abstract.
Mou further teaches that recombinant B. subtilis CotGSG was constructed, which could display TGEV S protein on the surface of spores. The B. subtilis CotGSG spores could be sampled by intestinal submucosal DCs and could induce BM-DCs maturation, T cells proliferation, and cytokine secretion. In addition, the efficacy of B. subtilis CotGSG spores oral immunization was evaluated in piglets. See page 75, left column, para 2. Here, the transmissible gastroenteritis virus (TGEV) is a coronavirus that infects pigs.
According, both Lee and Mou teach the construction of a recombinant bacterium (Lactobacillus casei by Lee and Bacillus subtilis by Mou) expressing a coronavirus antigen on the surface of the bacterium (Spike antigen of SARS-CoV by Lee and Spike antigen of TGEV by Mou) for use as a vaccine candidate. However, Lee and Mou are silent on the surface displayed antigen being a SARS-CoV-2 antigen.
GenBank: MN908947.3 discloses the complete genome sequence and the encoded protein sequences of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) isolate Wuhan-Hu-1, indicating that SARS-CoV-2 is present and biological/molecular information is known at the time of 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 combine the teachings of Lee, Mou and GenBank: MN908947.3 to arrive at the invention as claimed, one would have been motivated to do so to construct a recombinant bacillus bacterium expressing a SARS-CoV-2 antigen on the surface and test its vaccine potential against SARS-CoV-2, in a way similar to those in the studies disclosed in Lee and Mou for SARS-CoV and TGEV. There is a reasonable expectation of success that such a recombinant bacterium construct can be made based on the teachings of Lee, Mou and GenBank: MN908947.3.
Regarding claims 9-10, Lee and Mou are silent on expressing the specified SARS-CoV-2 genes (in claim 9) or the sequences (claim 10). However, since these genes and sequences are all from SARS-CoV-2, disclosed in GenBank: MN908947.3, one of skill in the art would have found it obvious to test them as antigens to be expressed on the surface of a bacterial carrier, and test their vaccine antigen potential, as having been done for the S protein in Lee and Mou, unless there is evidence that the claimed genes or sequences are critical.
Regarding claim 13, Mou teaches that CotG gene of Bacillus subtilis was used making the fusion protein with the viral S antigen. See page 75, left column, para 4.
Claim 14 is rejected under 35 U.S.C. 103 as being unpatentable over Lee et al. (JOURNAL OF VIROLOGY, Apr. 2006, Vol. 80, No. 8, p. 4079–4087; submitted in IDS filed on Sep. 11, 2023) and Mou et al. (Antiviral Research 131 (2016) 74-84; submitted in IDS filed on Jun. 12, 2025), in view of GenBank: MN908947.3 (Severe acute respiratory syndrome coronavirus 2 isolate Wuhan-Hu-1, complete genome; dated Mar. 18, 2020), as applied above, further in view of Chen et al. (J Mol Microbiol Biotechnol 2017; 27:159–167).
Claim 14 specifies that the SARS-CoV-2 is fused with the membrane protein CotY.
Relevance of Lee, Mou and GenBank: MN908947.3 is set forth above. Briefly, these references combined suggest a recombinant bacterium (e.g., Bacillus subtilis) expressing a SARS-CoV-2 antigen on its surface by fusing to a bacterial surface protein, including CotG of Bacillus subtilis. However, they are silent on the bacterial membrane protein CotY.
Chen reviews progress in Bacillus subtilis spore surface display technology towards environment, vaccine development, and biocatalysis. Chen teaches that B. subtilis spores contain different spore coat proteins, CotA, CotB, CotC, CotD, CotE, CotF, CotG, CotH, CotJA, CotJC, CotM, CotS, CotSA, CotT, CotX, CotY, CotZ, SpoIVA, SpoVID, YabG, and YrbA [Takamatsu and Watabe, 2002], but the most preferred anchored proteins are the outer coat proteins. The most commonly used outer coat proteins are CotB [Duc le et al., 2007; Hinc et al., 2010b], CotG [Hinc et al., 2010b; Kwon et al., 2007], and CotC [Yuan et al., 2013]. See page 161, right column, para 1.
Accordingly, teachings of Chen suggest that CotY, among other B. subtilis spore coat proteins, can be used as a membrane carrier protein for surface display of foreign antigens.
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 combine the teachings of Lee, Mou, GenBank: MN908947.3 and Chen to arrive at the invention as claimed (i.e. using the the B. subtilis spore coat protein CotY as the membrane carrier for surface display of a SARS-CoV-2 antigen). One would have been motivated to do so to evaluate the effectiveness of the CotY protein as a membrane display carrier.
Claim 15 is rejected under 35 U.S.C. 103 as being unpatentable over Lee et al. (JOURNAL OF VIROLOGY, Apr. 2006, Vol. 80, No. 8, p. 4079–4087; submitted in IDS filed on Sep. 11, 2023) and Mou et al. (Antiviral Research 131 (2016) 74-84; submitted in IDS filed on Jun. 12, 2025), in view of GenBank: MN908947.3 (Severe acute respiratory syndrome coronavirus 2 isolate Wuhan-Hu-1, complete genome; dated Mar. 18, 2020), and further in view of Potocki et al. (Microb Cell Fact (2017) 16:151).
Claim 15 specifies that the recombinant microorganism of claim 1 further displays a protein adjuvant on the surface of the microorganism.
Relevance of Lee, Mou and GenBank: MN908947.3 is set forth above. Briefly, these references combined suggest a recombinant bacterium (e.g., Bacillus subtilis) expressing a SARS-CoV-2 antigen on its surface by fusing to a bacterial surface protein. However, they are silent on if the recombinant microorganism further displays a protein adjuvant.
Potocki teaches a study on use of recombinant and non‑recombinant Bacillus subtilis spore display technology for presentation of antigen and adjuvant on single spore. The authors have used a combined approach to adsorb and display FliD protein of Clostridium difficile on the surface of recombinant IL-2-presenting spores. Such spores presented FliD protein with efficiency comparable to FliD-adsorbed spores produced by wild-type 168 strain and elicited FliD-specific immune response in intranasally immunized mice. See Abstract. Potocki teaches that their idea was to present on spore surface both, an adjuvant and antigen, therefore they decided to use recombinant spores produced by BKH121 strain, which display human IL-2 as fusion with CotB protein joined by a peptide linker. Single spore of this strain presents an average number of 9.5 × 104 IL-2 molecules [10]. Since robust display of proteins on spore surface can be achieved using adsorption method [13–15] we also decided to apply this approach to present FliD protein of C. difficile. The entire FliD was overproduced in E. coli, purified and used for adsorption on surface of spores produced by the wild-type strain 168 and the recombinant strain BKH121. See page 2, right column, para 1.
Accordingly, teachings of Potocki indicate that it was contemplated and practiced to display a protein adjuvant (IL-2) on the surface of a B. subtilis to enhance the host immune response to a heterologous target antigen (FliD protein of C. difficile) that is also displayed on the surface of the bacterium.
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 combine the teachings of Lee, Mou, GenBank: MN908947.3 and Potocki to arrive at the invention as claimed (i.e. displaying an IL-2 protein on a recombinant B. subtilis displaying a SARS-CoV-2 antigen). One would have been motivated to do so to introduce the adjuvant effect of the IL-2 into the recombinant B. subtilis construct suggested by the combined teachings of Lee, Mou and GenBank: MN908947.3.
Claims 11, 16 and 18-20 rejected under 35 U.S.C. 103 as being unpatentable over Lee et al. (JOURNAL OF VIROLOGY, Apr. 2006, Vol. 80, No. 8, p. 4079–4087; submitted in IDS filed on Sep. 11, 2023) and Mou et al. (Antiviral Research 131 (2016) 74-84), in view of GenBank: MN908947.3 (Severe acute respiratory syndrome coronavirus 2 isolate Wuhan-Hu-1, complete genome; dated Mar. 18, 2020), and further in view of Rahman et al. (PeerJ. 2020 Jul 27: 8:e9572).
Claim 11 is directed to a recombinant microorganism of claim 1, wherein the antigen of SARS-CoV-2 includes a fusion of epitopes related to different SARS-CoV-2 proteins. Claims 16 and 18-20 are directed to a recombinant microorganism displaying a fusion protein at its surface, wherein the fusion protein comprises: i) a receptor binding portion of a SARS-CoV-2 protein, ii) a multi-epitope chimeric portion of SARS-CoV-2 proteins; and a membranal protein of the microorganism; and wherein the recombinant microorganism is capable of inducing an immune response against epitopes related to different SARS-CoV- 2 proteins infection in a subject.
Relevance of Lee, Mou and GenBank: MN908947.3 is set forth above. However, they are silent on if the SARS-CoV-2 antigen can be a fusion protein comprising i) a receptor binding portion of a SARS-CoV-2 protein and ii) a multi-epitope chimeric portion of SARS-CoV-2 proteins.
Rahman teaches a study on in silico designing of an epitope-based chimeric peptide vaccine against S, M and E proteins of SARS-CoV-2. An immuno-informatics approach along with comparative genomics was applied to design a multi-epitope-based peptide vaccine against SARS-CoV-2 combining the antigenic epitopes of the S, M, and E proteins. The tertiary structure was predicted, refined and validated using advanced bioinformatics tools. The candidate vaccine showed an average of >90.0% world population coverage for different ethnic groups. Molecular docking and dynamics simulation of the chimeric vaccine with the immune receptors (TLR3 and TLR4) predicted efficient binding. Immune simulation predicted significant primary immune response with increased IgM and secondary immune response with high levels of both IgG1 and IgG2. It also increased the proliferation of T-helper cells and cytotoxic T-cells along with the increased IFN-g and IL-2 cytokines. The codon optimization and mRNA secondary structure prediction revealed that the chimera is suitable for high-level expression and cloning. Overall, the constructed recombinant chimeric vaccine candidate demonstrated significant potential and can be considered for clinical validation to fight against this global threat, COVID-19. See Abstract.
Rahman teaches that considering the facts, the authors have proposed the development of a multi-epitope vaccine candidate, which differs from all the previous studies in the aspect of containing whole RBD and NTD regions of the spike protein along with specific epitopes of M and E proteins, giving an excellent chimeric conformation and might lead to the generation of a more potent protective immune responses since smaller epitopes have less ability to give better immune protection. Hence, they can assume that chimeric vaccine targeting multiple epitopes on the RBD and NTD segments of the S protein, M and E proteins would be a potentially effective vaccine candidate in combatting COVID-19 pandemic, and therefore, could be used against the could be used against the highly pathogenic SARS-CoV-2. See page 3, para 3.
Accordingly, Rahman teaches the design of a chimeric polypeptide as a potential SARS-CoV-2 vaccine antigen, comprising the receptor binding domain (RBD) of the spike protein as well as epitopes from the M and E proteins of SARS-CoV-2.
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 combine the teachings of Lee, Mou, GenBank: MN908947.3 and Rahman to arrive at the invention as claimed (i.e. displaying on a recombinant B. subtilis a multi-epitope chimeric SARS-CoV-2 antigen). One would have been motivated to do so to introduce the multi-epitope chimeric SARS-CoV-2 antigen disclosed in Rahman into the recombinant B. subtilis construct suggested by the combined teachings of Lee, Mou and GenBank: MN908947.3.
Claim 17 is rejected under 35 U.S.C. 103 as being unpatentable over Lee et al. (JOURNAL OF VIROLOGY, Apr. 2006, Vol. 80, No. 8, p. 4079–4087; submitted in IDS filed on Sep. 11, 2023) and Mou et al. (Antiviral Research 131 (2016) 74-84) and GenBank: MN908947.3 (Severe acute respiratory syndrome coronavirus 2 isolate Wuhan-Hu-1, complete genome; dated Mar. 18, 2020), in view of Rahman et al. (PeerJ. 2020 Jul 27: 8:e9572), and further in view of Potocki et al. (Microb Cell Fact (2017) 16:151) and Lee et al. (CLINICAL AND VACCINE IMMUNOLOGY, Nov. 2010, p. 1647–1655, Vol. 17, No. 11; referred to hereinafter as Lee-2010).
Claim 17 is directed to the recombinant microorganism of claim 16, further displaying an enzyme having an enzyme activity that is absent in the microorganism in the wild.
Relevance of Lee, Mou, GenBank: MN908947.3, Rahman and Potocki is set forth above. However, they are silent on a recombinant microorganism displaying a fusion antigen from SARS-CoV-2 and further displaying an enzyme having an enzyme activity that is absent in the microorganism in the wild. (Potocki discloses a B. subtilis displaying a vaccine antigen and a protein adjuvant, IL-2.)
Lee-2010 teaches a study on development of a bacillus subtilis-based rotavirus vaccine. Bacillus subtilis vaccine strains engineered to display rotavirus VP6 were tested in adult mice for their ability to induce immune responses and provide protection against rotavirus challenge. Mice were inoculated intranasally with spores or vegetative cells of the recombinant strains of B. subtilis. To enhance mucosal immunity, whole cholera toxin (CT) or a mutant form (R192G) of Escherichia coli heat-labile toxin (mLT) were included as adjuvants. See Abstract. These teachings indicate that cholera toxin (CT) or E. coli heat-labile toxin (LT) are known to be effective as adjuvant that enhances immune response of vaccine antigens displayed B. subtilis. Here, the CT and LT are enzymes with enzymatic activities.
It would have been prima facie obvious for one of ordinary skill in the art at the time of invention to combine the teachings of Lee, Mou, GenBank: MN908947.3, Rahman, Potocki and Lee-2010 to arrive at the invention as claimed. One would have been motivated to do so, e.g., to substitute the protein adjuvant IL-2 of Potocki with the protein adjuvant CT or LT of Lee-2010 to test the immune enhancing effect CT or LT when used with a recombinant microorganism displaying a SARS-CoV-2 antigen.
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