DETAILED ACTION
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 .
Election/Restrictions
2. Applicant’s election of Group I claims 1-6, 8-9, 12 and 14-15 with species election “mammalian cell” in the reply filed on 02/13/2026 is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
The Restriction/Election is made final.
Status of Claims (modified)
3. Claims 1, 4-6, 8-9, 12, 14-16, 18, 23, 25-27, 29, and 31-32 as per amended claims filed on 08/13/2026 are pending.
4. Claims 16,18,23,25-27,29 and 31-32 withdrawn as non-elected groups of invention due to Restriction/Election.
5. Claims 1, 4-6, 8-9, 12, and 14-15 are under examination.
Priority
6. This 18/275,226 application is 371 of PCT/CN2022/077527 filed on 02/23/2022 and claims an earlier priority to date of filing date 03/31/2021 to CN202110348881.6 filed in country People’s Republic of China.
Information Disclosure Statement
7. The information disclosure statement (IDS) submitted on 07/05/2024 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Withdrawn Objections to Specification
8. Withdrawn objections to specification in view of amendment filed on 08/13/2026.
Objections to Specification (maintained)
9. 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) set forth below or on the attached Notice To Comply With Requirements For Patent Applications Containing Nucleotide Sequence And/Or Amino Acid Sequence Disclosures.
The specification is objected to because there is no incorporation by reference statement of the Sequence Listing. This statement is required. Applicants must comply with sequence rules in order to be considered a complete response to this Office Action.
Withdrawn Objections Claims
10. Withdrawn objections claims in view of amendments filed on 08/13/2026.
Withdrawn Rejections of Claims - 35 USC § 112
11. Withdrawn rejection of claims 1-6, 8-9, 12 and 14-15 in view of claim amendment filed on 08/13/2026.
Withdrawn Rejections of Claims - 35 USC § 101
12. Withdrawn rejection of claims 12, and 14-15 under 35 U.S.C. 101 in view of claim amendment filed on 08/13/2026.
Claim Interpretation (modified)
13. 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: The instant claim 1 is directed to an S-RBD trimer protein for a SARS-CoV-2, the S-RBD trimer protein for the SARS-CoV-2 comprises an amino acid sequence shown as SEQ ID NO: 1.
According to the instant specification, an S-RBD trimer protein is composed of amino acid fragments at positions 319-537 in an RBD domain of an S protein of the novel coronavirus in a trimer form (para [010]). The trimer protein in the present invention may be formed by self- assembly of three polypeptide subunits including a same sequence (para [012]). In one embodiment of the present invention, the primary structure of the trimer protein is formed by linking three of the amino acid fragments in an order from an N terminal to a C terminal (para [013]).
Claim Rejections - 35 USC § 102 (New)
14. In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1, 4-6, 9, 12, and 14-15 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Gao et al 2022 (WO2022089471A1, 05/05/2022, with earlier priority of 10/27/2020 to CN 202011165603.9).
Claim 1: Gao et al 2022 is drawn to a beta coronavirus (novel coronavirus reads on SARS CoV-2) multimer antigen expression, application as immunogen and induction of neutralizing antibodies in a subject (see, abstract, Figures 1, 5, 7, Example 1). Gao et al 2022 disclosed SEQ ID NO: 1 (Claim 8) that is identical to the instant claimed SEQ ID NO: 1 (except M at position 1 which is inherently present when the protein is expressed in the prior art Gao et al 2022 recited below in the office action (see, Example 1, para [0044]-[0045]) because Methionine (M) being a first amino acid coded by a start codon). Gao et al 2022 disclosed that the three directly connected in series are from the 319-537 region of the receptor binding region of the 2019-nCoV spike protein (reads on SARS-CoV-2), and the sequence is shown in SEQ ID NO.1, namely R319-K537-R319-K537-R319-K537 (see, para [0020], claim 8).
Qy 2 RVQPTESIVRFPNITNLCPFGEVFNATRFASVYAWNRKRISNCVADYSVLYNSASFSTFK 61
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 RVQPTESIVRFPNITNLCPFGEVFNATRFASVYAWNRKRISNCVADYSVLYNSASFSTFK 60
Qy 62 CYGVSPTKLNDLCFTNVYADSFVIRGDEVRQIAPGQTGKIADYNYKLPDDFTGCVIAWNS 121
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 CYGVSPTKLNDLCFTNVYADSFVIRGDEVRQIAPGQTGKIADYNYKLPDDFTGCVIAWNS 120
Qy 122 NNLDSKVGGNYNYLYRLFRKSNLKPFERDISTEIYQAGSTPCNGVEGFNCYFPLQSYGFQ 181
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 NNLDSKVGGNYNYLYRLFRKSNLKPFERDISTEIYQAGSTPCNGVEGFNCYFPLQSYGFQ 180
Qy 182 PTNGVGYQPYRVVVLSFELLHAPATVCGPKKSTNLVKNKRVQPTESIVRFPNITNLCPFG 241
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 PTNGVGYQPYRVVVLSFELLHAPATVCGPKKSTNLVKNKRVQPTESIVRFPNITNLCPFG 240
Qy 242 EVFNATRFASVYAWNRKRISNCVADYSVLYNSASFSTFKCYGVSPTKLNDLCFTNVYADS 301
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 241 EVFNATRFASVYAWNRKRISNCVADYSVLYNSASFSTFKCYGVSPTKLNDLCFTNVYADS 300
Qy 302 FVIRGDEVRQIAPGQTGKIADYNYKLPDDFTGCVIAWNSNNLDSKVGGNYNYLYRLFRKS 361
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 301 FVIRGDEVRQIAPGQTGKIADYNYKLPDDFTGCVIAWNSNNLDSKVGGNYNYLYRLFRKS 360
Qy 362 NLKPFERDISTEIYQAGSTPCNGVEGFNCYFPLQSYGFQPTNGVGYQPYRVVVLSFELLH 421
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 361 NLKPFERDISTEIYQAGSTPCNGVEGFNCYFPLQSYGFQPTNGVGYQPYRVVVLSFELLH 420
Qy 422 APATVCGPKKSTNLVKNKRVQPTESIVRFPNITNLCPFGEVFNATRFASVYAWNRKRISN 481
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 421 APATVCGPKKSTNLVKNKRVQPTESIVRFPNITNLCPFGEVFNATRFASVYAWNRKRISN 480
Qy 482 CVADYSVLYNSASFSTFKCYGVSPTKLNDLCFTNVYADSFVIRGDEVRQIAPGQTGKIAD 541
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 481 CVADYSVLYNSASFSTFKCYGVSPTKLNDLCFTNVYADSFVIRGDEVRQIAPGQTGKIAD 540
Qy 542 YNYKLPDDFTGCVIAWNSNNLDSKVGGNYNYLYRLFRKSNLKPFERDISTEIYQAGSTPC 601
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 541 YNYKLPDDFTGCVIAWNSNNLDSKVGGNYNYLYRLFRKSNLKPFERDISTEIYQAGSTPC 600
Qy 602 NGVEGFNCYFPLQSYGFQPTNGVGYQPYRVVVLSFELLHAPATVCGPKKSTNLVKNK 658
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 601 NGVEGFNCYFPLQSYGFQPTNGVGYQPYRVVVLSFELLHAPATVCGPKKSTNLVKNK 657
Claim 4: Gao et al 2022 teaches instant claim 4, a fusion protein, comprising the S-RBD trimer protein for the SARS-CoV-2 according to claim 1 by disclosing Three directly linked regions 319-537 from the receptor-binding region of the 2019-nCoV spike protein, sequenced as SEQ ID NO.1, i.e., R319-K537-R319-K537-R319-K537 (see, para [020], claim 8, SEQ ID NO: 1).
Claim 5: Gao et al 2022 teaches instant claim 5, the fusion protein according to claim 4, further comprising one or more of a signal peptide, a tag six histidine (HHHHHHH) or an immune-enhancing peptide (see, Example 1, para [0042], [0044]).
Claims 6 and 9: Gao et al 2022 teaches instant claims 6 and 9, a nucleic acid molecule, comprising a nucleotide sequence encoding the S-RBD trimer protein for the SARS-CoV-2novel coronavirus according to claim 1. Gao et al 2022 disclosed a human codon to obtain the DNA sequence encoding the claimed RBD trimer for expression in human cells (e.g. HEK293T cells) in a plasmid DNA vector is disclosed (see, Example 1, para [0044]-[0045]).
Claims 12 and 14-15: Gao et al 2022 teaches instant claims 12 and 14 by disclosing expression and purification of nCoV-RBD-trimer by transfection of the plasmid vector in HEK293T cells (a mammalian cells) is disclosed (Example 2, para [0046]-[0047]). The cells of the expression system include mammalian cells, insect cells, yeast cells, or bacterial cells, optionally; The mammalian cells include 293T cells or CHO cells, and the bacterial cells include E. coli cells (See, claims 10).
Thus, as recited supra, claims 1, 4-6, 9, 12, and 14-15 are anticipated by Gao et al 2022.
Claim Rejections - 35 USC § 103 (modified)
15. In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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.
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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
16. Claims 1, 4-6, 8-9, 12, and 14-15 are rejected under 35 U.S.C. 103 as being unpatentable over Gao et al 2022 (WO2022089471A1, 05/05/2022, with earlier priority of 10/27/2020 to CN 202011165603.9), and further in view of Dai et al 2020 (Cell. 2020 Aug 6;182(3):722-733.e11), Webb et al 2017 (Curr Protoc Bioinformatics; 54: 5.6.1–5.6.37), and Cai et al 2020 (Science, 369(6511), 1586-1592).
Claims 1, 4-6, 9, 12, and 14-15: The teachings of Gao et al 2022 (WO2022089471A1) that anticipated instant claims as recited supra are incorporated here in entirety to render obvious the claims 1, 4-6, 9, 12, and 14-15.
Claim 8: Gao et al 2022 teaches the amino acid sequence encoded by the nucleic acid sequence claimed in SEQ ID NO: 2. However, does not teach added limitation of instant claim 8, the nucleotide sequence disclosed in instant SEQ ID NO: 2.
Gao et al 2022 teaches human codon optimization to obtain the DNA sequence to construct and obtain the plasmid vector expressing trimeric RBD (see, para [044]).
Additionally, Dai et al 2020 teaches design of RBD dimer protein with amino acid residues 319-537 expression is taught in mammalian cells (See, page e6) by disclosing that the coding sequence for RBD protein of SARS-CoV-2 were codon-optimized for mammalian cell expression in a construct for clinical grade CHO-K1 (Chinese hamster ovary ) cell line to express RBD. A strategy for codon-optimized MERS-CoV RBD dimer (reads on RBD of SARS-CoV-2) for cloning into the baculovirus transfer vector pFastBac1, insect cells, expression is disclosed (See, page e4- Methods). The HEK293T mammalian cell-expressed recombinant RBD proteins is disclosed with codon optimized sequences, these constructs were cloned into the pCAGGS vector, respectively, and transiently transfected into HEK293T cells (See, page e4- Methods).
It would have been obvious to one of the ordinary skills in the art before the effective filing date of the claimed invention to modify the prior art teachings of Gao et al as applied to claim 1 with additional teachings of Dai et al 2020 on species specific codon optimization and expression of the claimed RBD trimer protein to reasonably arrive at the inventions of claim 8 comprising . One of the ordinary skills would have been motivated to increase the nucleic acid molecule comprises the nucleotide sequence shown as SEQ ID NO: 2. There would have been a reasonable expectation of success in desired codon optimization for reasonably high expression compared to the wild type of nucleotide sequence absent any evidence to the contrary. The motivation would be to develop efficacious immunogen or vaccine against SARS-CoV-2 virus and for commercial success because Gao et al 2022 disclosed that a SARS‑CoV‑2 RBD multimer (reads on trimer) induce an immune response that is strong and in addition, a neutralizing antibody titer produced by the induced by the RBD trimer in mice is significantly different (reads on higher) from that of a SARS‑CoV‑2 RBD monomer and dimer (see, Gao et al 2022, abstract, Figure 8, also see Figures 4-6 for RBD trimer binding to human ACE2 receptor). There would be a reasonable expectation of success given the applied prior art teachings in the art as recited supra. This is analogous to some teaching, suggestions, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the invention as claimed in claims 1, 4-6, 8-9, 12, and 14-15. See KSR Int'l Co. v. Teleflex Inc., 550 U.S. 398, 415-421, 82 USPQ2d 1385, 1395-97 (2007) (see MPEP § 2143, example of rationales, A -G).
Double Patenting
17. The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1, 4-6, 9, 12, and 14-15 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 10-12, and 18-22 of U.S. Patent No. US20240325520A1 in view of Gao et al 2022 (WO2022089471A1, 05/05/2022, with earlier priority of 10/27/2020 to CN 202011165603.9).
US20240325520A1 Patented claim 1: A recombinant Severe Acute Respiratory Syndrome(SARS)-Coronavirus(CoV)-2 receptor binding domain(RBD) trimer protein capable of generating broad-spectrum cross neutralization activity, wherein the trimer protein is composed of subunits of three SARS-CoV-2 protein RBD regions, and the amino acid sequence of the trimer protein is the amino acid sequence shown in SEQ ID NO: 4.
The Instant claim 1 SEQ ID NO: 1 (Qy) and the amino acid sequence disclosed by the patented application claim 1 SEQ ID NO: 4 (Db) has 99.3 % amino acid sequence identity.
Gao et al 2022 taught SEQ ID NO: 1 is identical to instant claimed SEQ ID NO: 1 (see, as recited supra in office action).
It would have been obvious to substitute patented SEQ ID NO: 4 with SEQ ID NO: 1 of Gao et al 2022 to arrive at the instant claim 1 with a reasonable expectation of success because the prior art is in the same subject matter.
Response to Arguments
18. Applicant’s arguments with respect to rejection of claims 1-6, 8-9, 12, and 14-15 under 35 USC 103 obviousness in the non-final office action mailed on 04/14/2026 have been considered but are moot because the new ground of rejection is based on the applicant’s substantially amended claims, and the instant office action does not rely only on the reference applied in the prior non-final rejection office action of record for teaching or matter specifically challenged in the argument considering substantially amended independent claim 1 and dependent claims thereof.
Applicant’s arguments
Response to Claim Reiections-35 USC 103:
The applicant has traversed the prior art rejections under 35 U.S.C. § 103 set forth in Items 19-21 (claims of the 1-6, 8-9, 12, and 14-15) in the non-final office action mailed on 04/14/2026 (See, Arguments/Remarks filed on 08/13/2026).
In Response:
The applicant has traversed the prior art rejections under 35 U.S.C. § 103 for substantially amended claims 1-6, 8-9, 12, and 14-15 as filed on 08/13/2026 that required additional search and consideration of the prior art and SEQ ID NO:1 in the substantially amended claim 1 and affected dependent claims that has changed the scope of the amended claims. The instant office action that has applied additional prior arts and combined teachings, as recited supra, rendered obvious the substantially amended claims filed on 08/13/2026. Therefore, the Dia et al is not the primary reference applied for the modified obviousness of claim 1 comprising a substantial amendment comprising RBD trimer with amino acid sequence shown in the SEQ ID NO: 1 because Gao et al 2022 has anticipated as well as rendered obvious substantially amended instant claim 1 as recited supra in the office action.
The instant amended claim 1 SEQ ID NO: 1 amino acid sequence (RBD trimer) is rendered obvious by Gao et al 2022 in the office action as recited supra. Therefore, the codon optimized nucleotide sequence SEQ ID NO: 2 encoding the RBD trimer as claimed is rendered obvious because Gao et al 2022 teaches requirement for codon optimization. The exact codon optimized nucleotide sequence as claimed in instant SEQ ID NO: 2 is not required for a reasonable high-level expression of the RBD trimer because the codon optimization algorithm would provide output for more than one species of codon optimized SEQ ID NO: 2. The applicant has not provided contrary evidence (e.g. results and data) that an alternate wild type or alternative codon optimized SEQ ID NO: 2 would not induce a reasonably similar immune response on basis of same quantity microgram dose.
See, MPEP 2145. Rebuttal evidence and arguments can be presented in the specification, In re Soni, 54 F.3d 746, 750, 34 USPQ2d 1684, 1687 (Fed. Cir. 1995), by way of an affidavit or declaration under 37 CFR 1.132, e.g., Soni, 54 F.3d at 750, 34 USPQ2d at 1687; In re Piasecki, 745 F.2d 1468, 1474, 223 USPQ 785, 789-90 (Fed. Cir. 1984), or otherwise presented during prosecution. See, e.g., MPEP §§ 714 to 716 et seq. However, arguments presented by applicant cannot take the place of factually supported objective evidence. See, e.g., In re Schulze, 346 F.2d 600, 602, 145 USPQ 716, 718 (CCPA 1965); In re De Blauwe, 736 F.2d 699, 705, 222 USPQ 191, 196 (Fed. Cir. 1984).
In response to applicant’s argument that there is no teaching, suggestion, or motivation to combine the references, the examiner recognizes that obviousness may be established by combining or modifying the teachings of the prior art to produce the claimed invention where there is some teaching, suggestion, or motivation to do so found either in the references themselves or in the knowledge generally available to one of ordinary skill in the art. See In re Fine, 837 F.2d 1071, 5 USPQ2d 1596 (Fed. Cir. 1988), In re Jones, 958 F.2d 347, 21 USPQ2d 1941 (Fed. Cir. 1992), and KSR International Co. v. Teleflex, Inc., 550 U.S. 398, 82 USPQ2d 1385 (2007). In this case, see the prior and instant office action.
As recited in the prior office action mailed on 04/14/2026, the combined prior art teachings rendered obvious the commensurate scope of the elected claims (claim listing version 08/01/2023) with reasonable success and motivation recited in the office action (see, office action, 04/14/2026).
Applicants’ arguments filed on 08/13/2026 have been fully considered but they are not persuasive in view of the prior office action, and instant modified office action to render obvious substantiative amendment of the claims.
19. Relevant Prior Art:
Webb 2016. Comparative protein structure modeling using MODELLER. Current protocols in bioinformatics, 54(1), 5-6. Webb et al 2017 is in the protein modeling art and teaches comparative protein structure modeling using MODELLER to predicts the three-dimensional structure of a given protein sequence (target) based primarily on its alignment to one or more proteins of known structure (templates) (See, abstract, entire article, and figures).
Cai et al 2020. Distinct conformational states of SARS-CoV-2 spike protein. Science, 369(6511), 1586-1592. Cai et al 2020 is in the art and teaches distinct conformational states of SARS-CoV-2 spike protein and RBD protein (See, abstract, Fig. 5, entire article).
Jurasze et al 2021. Stabilizing the closed SARS-CoV-2 spike trimer. Nat Commun 12, 244.
Dai et al 2020 (CN111592602A, 08/28/2020). Beta coronavirus antigen, preparation method and application thereof.
Zeng et al 2020 (CN111991556A, 11/27/2020). SARS-CoV-2 RBD Conjugated Nanoparticle Vaccine.
Conclusion
20. No claim is allowed.
21. 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).
22. 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 nonprovisional extension fee (37 CFR 1.17(a)) 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 mailing date of this final action.
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.
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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.
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/SAMADHAN JAISING JADHAO/Examiner, Art Unit 1672
/BENNETT M CELSA/Primary Examiner , Art Unit 1600
