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
Response to Amendment and Arguments
The Amendment filed on 2/13/2026 in response to the previous Non-Final Office Action (8/13/2025) is acknowledged and has been entered.
Claims 5, 9-12, 16-17 have been cancelled.
Claims 1-4, 6-8, 13-15, and 18-71 are pending.
Claims 24-71 were withdrawn previously from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention and species (claim 14), there being no allowable generic or linking claim.
Claim 1 has been amended to include species of tail mutants of SEQ ID NO: 4, 5, 6,7 or 8. Since applicant does not indicate which SEQ ID NO is elected in the amended claim, the Office currently selects species of sequence SEQ ID NO: 7 for examination in this Office action.
Thus, claims 1-4, 6-8, 13-15, and 18-23, drawn to a recombinant vesicular stomatitis virus (rVSV) comprising a nucleic acid sequence encoding a variant of coronavirus spike protein (S) SEQ ID NO:1 replaced at residues 1193-1273 with the mutant of SEQ ID NO:7, are under consideration.
The following office action contains NEW GROUNDS of rejection
Rejections/Objection Withdrawn
It is acknowledged that the specification has been amended to comply with sequence requirement.
The objection of claims 2-3 are withdrawn in view of the amendment to claims.
The objection of claims 12 and 16-17 are moot in view of the cancellation of the claims.
The rejection of the claims 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requirement of claimed rVSV having portion of SEQ ID NO: 1 or 80% sequence identity to the protein of SEQ ID NO: 1 is withdrawn in view of the claim amendment.
The rejections of Claim(s) under 35 U.S.C. 103 as being unpatentable over Park et al (WO2021/168318, priority to Feb 2020) in view of Victor Gilbert Georges et al (as evidenced by the sequence alignments are withdrawn in view of the claim amendment and cancellation of claim 10.
The arguments are moot in view of withdrawals of the rejection(s).
Rejection Maintained and Response to Arguments
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)(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.
Claim(s) 1-4, 6-8, 13, 15, and 18-23 remain and are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Park et al (WO2021/168318, priority to Feb 2020) as evidenced by the sequence alignment (newly searched).
The claims are modified based on the amended claims.
The Spike S protein is examined to the extent of a SARS-CoV-2 spike S protein comprising a variant of SEQ ID NO:1 modified by replacing the amino acid residues 1193-1273 of SEQ ID NO: 1 with the sequence of SEQ ID NO: 7.
Park et al disclose recombinant vesicular stomatitis virus (rVSV) comprising a nucleic acid encoding a coronavirus spike protein (S) or an immunogenic variant thereof having 90% or up sequence identity, which is used as a vaccine for inducing immune response to SARS-Cov-2 infection by the virus (abstract and entire document). Park et al disclose that the spike protein S replaces the endogenous VSV viral glycoprotein G and the rVSV keeps at least a portion of the genes including N, P, and M (figure 4 shown below).
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Park et al further disclose rVSV comprising mutants of Spike S protein E484D, 484G and C-terminal deletion and replacement (p14-u, 93-(21), and P167-u., fig 1P). Park et al also teach that the rVSV is encapsulated with VSV-N and transcribed and replicated and release of infectious progeny virion indicating the rVSV being a live virus (bridging page 59-60), that meets the limitation of claim 23.
Park et al then teach a vaccine and pharmaceutical composition comprising the rVSV and adjuvant comprising CpG polynucleotide etc. (page 100 or [00239]). The wild type and mutant form Spike S protein have the identical sequence as instant SEQ ID NO: 1 as sequence alignment and shown in figure 1P:
QY=SEQ ID NO:1
DT 14-OCT-2021 (first entry)
DE SARS-CoV-2 S protein (WT), SEQ ID 1.
KW S protein; Spike protein; coronavirus infection; immune stimulation;
KW immunogenicity; prophylactic to disease; protein engineering;
KW respiratory-gen.; vaccination; vaccine, antiviral; vector; virucide;
KW virus-like particle.
OS Severe acute respiratory syndrome coronavirus 2.
CC PN WO2021168318-A1.
CC PD 26-AUG-2021.
CC PA (ITAI-) INT AIDS VACCINE INITIATIVE INC.
CC PA (MERI ) MERCK SHARP & DOHME CORP.
CC PI Parks CL, Yuan M, Feinberg M, Espeseth A, Bett AJ;
CC PT New recombinant vesicular stomatitis virus (VSV) vector having portion of
CC PT VSV genome and nucleic acid encoding severe acute respiratory syndrome
CC PT coronavirus-2 (SARS-CoV-2) spike protein, used to generate immune
CC PT response against SARS-CoV-2.
CC The present invention relates to a novel recombinant vesicular stomatitis
CC virus (VSV) vector comprising at least a portion of a VSV genome
CC comprising at least a VSV-N gene, VSV-P gene, VSV-M gene, and VSV-L gene,
CC and a nucleic acid sequence encoding a severe acute respiratory syndrome
CC coronavirus 2 (SARS-CoV-2) S protein or its immunogenic variant. The
CC invention further provides: (1) a recombinant VSV particle comprising the
CC vector and displaying the S protein or its immunogenic variant on the
CC surface of the VSV particle; (2) an immunogenic recombinant protein
CC comprising a SARS-CoV-2 S protein or its immunogenic variant expressed by
CC the recombinant VSV vector or recombinant VSV particle; (3) a SARS-CoV-2
CC vaccine comprising the recombinant VSV vector, the recombinant VSV
CC particle, or the immunogenic recombinant protein; (4) a method for
CC producing the recombinant VSV particle; (5) a recombinant cell comprising
CC the recombinant VSV vector or the recombinant VSV particle; (6) a method
CC for generating an immune response against SARS-CoV-2; and (7) a vaccine
CC composition for preventing coronavirus disease. The immunogenic
CC compositions comprising the SARS-CoV-2 vaccines, the recombinant VSV
CC vectors, the recombinant replicable VSV particles and/or the immunogenic
CC recombinant proteins may be used for inducing an immune response to the
CC SARS-CoV-2, preventing infection by the SARS-CoV-2, vaccinating against
CC the SARS-CoV-2 and/or producing adaptive mutants of the recombinant
CC replicable VSV particles.
SQ Sequence 1273 AA;
Query Match 100.0%; Score 6722; Length 1273;
Best Local Similarity 100.0%;
Matches 1273; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 MFVFLVLLPLVSSQCVNLTTRTQLPPAYTNSFTRGVYYPDKVFRSSVLHSTQDLFLPFFS 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 MFVFLVLLPLVSSQCVNLTTRTQLPPAYTNSFTRGVYYPDKVFRSSVLHSTQDLFLPFFS 60
Qy 61 NVTWFHAIHVSGTNGTKRFDNPVLPFNDGVYFASTEKSNIIRGWIFGTTLDSKTQSLLIV 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 NVTWFHAIHVSGTNGTKRFDNPVLPFNDGVYFASTEKSNIIRGWIFGTTLDSKTQSLLIV 120
Qy 121 NNATNVVIKVCEFQFCNDPFLGVYYHKNNKSWMESEFRVYSSANNCTFEYVSQPFLMDLE 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 NNATNVVIKVCEFQFCNDPFLGVYYHKNNKSWMESEFRVYSSANNCTFEYVSQPFLMDLE 180
……………………………………………………………………………………………
Qy 1081 ICHDGKAHFPREGVFVSNGTHWFVTQRNFYEPQIITTDNTFVSGNCDVVIGIVNNTVYDP 1140
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1081 ICHDGKAHFPREGVFVSNGTHWFVTQRNFYEPQIITTDNTFVSGNCDVVIGIVNNTVYDP 1140
Qy 1141 LQPELDSFKEELDKYFKNHTSPDVDLGDISGINASVVNIQKEIDRLNEVAKNLNESLIDL 1200
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1141 LQPELDSFKEELDKYFKNHTSPDVDLGDISGINASVVNIQKEIDRLNEVAKNLNESLIDL 1200
Qy 1201 QELGKYEQYIKWPWYIWLGFIAGLIAIVMVTIMLCCMTSCCSCLKGCCSCGSCCKFDEDD 1260
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1201 QELGKYEQYIKWPWYIWLGFIAGLIAIVMVTIMLCCMTSCCSCLKGCCSCGSCCKFDEDD 1260
Qy 1261 SEPVLKGVKLHYT 1273
|||||||||||||
Db 1261 SEPVLKGVKLHYT 1273
For currently amended claims, the residues 1193-1273 of S protein of SEQ ID NO: 1 are replaced by a tail mutant peptide of SEQ ID NO: 7, Park et al teach the identical sequence as evidenced by sequence alignment:
QY= amino acid residues 1193-1273 of SEQ ID NO: 1 are replaced by the sequence of SEQ ID NO: 7:
CC PN WO2021168318-A1.
CC PI Parks CL, Yuan M, Feinberg M, Espeseth A, Bett AJ;
CC PT New recombinant vesicular stomatitis virus (VSV) vector having portion of
CC PT VSV genome and nucleic acid encoding severe acute respiratory syndrome
CC PT coronavirus-2 (SARS-CoV-2) spike protein, used to generate immune
CC PT response against SARS-CoV-2.
CC PS Claim 9; SEQ ID NO 7; 291pp; English.
SQ Sequence 1263 AA;
Query Match 100.0%; Score 6635; Length 1263;
Best Local Similarity 100.0%;
Matches 1263; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 MFVFLVLLPLVSSQCVNLTTRTQLPPAYTNSFTRGVYYPDKVFRSSVLHSTQDLFLPFFS 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 MFVFLVLLPLVSSQCVNLTTRTQLPPAYTNSFTRGVYYPDKVFRSSVLHSTQDLFLPFFS 60
Qy 61 NVTWFHAIHVSGTNGTKRFDNPVLPFNDGVYFASTEKSNIIRGWIFGTTLDSKTQSLLIV 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 NVTWFHAIHVSGTNGTKRFDNPVLPFNDGVYFASTEKSNIIRGWIFGTTLDSKTQSLLIV 120
………………………………………………………
Qy 841 LGDIAARDLICAQKFNGLTVLPPLLTDEMIAQYTSALLAGTITSGWTFGAGAALQIPFAM 900
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 841 LGDIAARDLICAQKFNGLTVLPPLLTDEMIAQYTSALLAGTITSGWTFGAGAALQIPFAM 900
Qy 961 TLVKQLSSNFGAISSVLNDILSRLDKVEAEVQIDRLITGRLQSLQTYVTQQLIRAAEIRA 1020
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 961 TLVKQLSSNFGAISSVLNDILSRLDKVEAEVQIDRLITGRLQSLQTYVTQQLIRAAEIRA 1020
Qy 1021 SANLAATKMSECVLGQSKRVDFCGKGYHLMSFPQSAPHGVVFLHVTYVPAQEKNFTTAPA 1080
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1021 SANLAATKMSECVLGQSKRVDFCGKGYHLMSFPQSAPHGVVFLHVTYVPAQEKNFTTAPA 1080
Qy 1081 ICHDGKAHFPREGVFVSNGTHWFVTQRNFYEPQIITTDNTFVSGNCDVVIGIVNNTVYDP 1140
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1081 ICHDGKAHFPREGVFVSNGTHWFVTQRNFYEPQIITTDNTFVSGNCDVVIGIVNNTVYDP 1140
Qy 1141 LQPELDSFKEELDKYFKNHTSPDVDLGDISGINASVVNIQKEIDRLNEVAKNLNESLIDL 1200
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1141 LQPELDSFKEELDKYFKNHTSPDVDLGDISGINASVVNIQKEIDRLNEVAKNLNESLIDL 1200
Qy 1201 QELGKYEQYIKWPWYIWLGFIAGLIAIVMVTIMLRVGIYLCIKLKHTKKRQIYTDIEMNR 1260
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1201 QELGKYEQYIKWPWYIWLGFIAGLIAIVMVTIMLRVGIYLCIKLKHTKKRQIYTDIEMNR 1260
Qy 1261 LGK 1263
|||
Db 1261 LGK 1263
wherein the residues 1193-1273 are replaced by the sequence of SEQ ID NO:7:
LNESLIDLQELGKYEQYIKWPWYIWLGFIAGLIAIVMVTIMLRVGIYLCIKLKHTKKRQIYTDIEMNRLGK
which is highlighted and underlined in the sequence above. Thus, Park et al teach the amended claim 1 as well as the dependent claims.
Response to Applicant’s argument:
At page 14, applicant argues the independent claim 1 has been amended and Park et al fail to disclose and suggest the limitation as defined rVSV.
In response, the amended claims are still anticipated by Park since the referecen also disclosed fusion sequence comprising portion of SEQ ID NO:1 and tail sequence of SEQ ID NO: 7 as claimed.
The following is a New Ground of rejection-based on amendment to the claims
Claim Rejections - 35 USC § 112
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.
Drawn to New Matter:
Claims 1-4, 6-8, 13-15, and 18-23 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.
Independent claims 1-3 have been amended to
1. (currently amended) A recombinant vesicular stomatitis virus (rVSV) comprising a nucleic acid sequencef a coronavirus (SARS- CoV-2) spike protein according to SEQ ID NO: 1, wherein residues 1193-1273 of SEQ ID NO: 1 are replaced with a tail mutation selected from SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, and SEQ ID NO: 8.
2. (currently amended) A recombinant vesicular stomatitis virus (rVSV) construct or vaccine platform comprising:
at least a portion of a vesicular stomatitis virus (VSV); and
a coronavirus (SARS-CoV-2) spike protein according to SEQ ID NO: 1, wherein residues 1193-1273 of SEQ ID NO: 1 are replaced with a tail mutation selected from SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, and SEQ ID NO: 8.
3. (currently amended) A recombinant vesicular stomatitis virus (rVSV) comprising in its genome a nucleic acid sequence encoding a coronavirus (SARS-CoV-2 protein according to SEQ ID NO: 1, wherein residues 1193-1273 of SEQ ID NO: 1 are replaced with a tail mutation selected from SEQ ID NO: 4, SEQ ID NO: 5.SEQ ID NO: 6, SEQ ID NO: 7, and SEQ ID NO: 8.
The amendments are NOT supported by the instant specification. The instant specification as filed, although provides teaching on that the spike protein of SEQ ID NO: 1 or functional variant could be functional mutation, insertion, deletion or substitution thereof (page 2, and original claim 9) and provides the SEQ ID NOs: 4-8 are a spike protein or functional portion thereof.
The specification as filed does not provide sufficient support for the amended claims reciting the residues 1193-1273 of SEQ ID NO: 1 are replaced with a tail mutation selected from SEQ ID NO: 4, 5, 6, 7 or 8. The specification does not provide any teaching on the functional variant of spike protein could be a fusion protein comprising portions of the spike proteins and no mention the tail part form 1193 could be replaced by other amino acids of spike protein.
If applicant believes that support for the above-mentioned phrases or terms is present in the specification, claims, or drawing as originally filed, applicant must in responding to this action, point out with particularity, where such support may be found.
Applicant in the remarks filed with the amendment merely states:
Support for amendments can be found throughout applicant’s specification and claims as originally filed, which is obviously no support for the amended claims.
The Federal Circuit has pointed out that under United States law, disclosure in an application that merely renders the later-claimed (by amendment) invention obvious is not sufficient to meet the written description requirement of 35 USC 112, first paragraph. Lockwood v. American Airlines, Inc., 107 F.3d 1565, 1572, 41 USPQ2d 1961, 1966 (Fed. Cir. 1997). See MPEP 2163.
The Federal Circuit has pointed out that under United States law, a description that does not render a claimed invention obvious cannot sufficiently describe the invention for the purposes of the written description requirement of 35 U.S.C. 112. Eli Lilly, 119 F.3d at 1567, 43 USPQ2d at 1405.
Claim Objection
Amended claims 1-3 are objected to for the clause “
A recombinant vesicular stomatitis virus (rVSV) comprising a nucleic acid sequence encoding a coronavirus (SARS- CoV-2) spike protein according to SEQ ID NO: 1, wherein residues 1193-1273 of SEQ ID NO: 1 are replaced with a tail mutation selected from SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, and SEQ ID NO: 8.
Thus, it is not clear the nucleic acid sequence encoding SAR-CoV-2 protein of SEQ ID NO: 1 and a fusion protein comprising 5’ portion of SEQ ID NO:1 plus replaced tail mutant at position 1193-1273. Amending the claims as following would be appreciated.
……..a nucleic acid sequence encoding a variant of coronavirus (SARS- CoV-2) spike protein of SEQ ID NO: 1, wherein the variant has the amino acid residues 1193-1273 of sequence of SEQ ID NO: 1 replaced with the mutant of S protein selected from SEQ ID NO: 4, 5, ……
Conclusion
No claim is 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 mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Lei Yao, whose telephone number is (571) 272-3112. The examiner can normally be reached on 8:00am-6:00pm Monday-Friday.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Samira Jean-Louis, can be reached on (571) 270-3503. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/LEI YAO/Primary Examiner, Art Unit 1642