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
Priority
This application claims the benefit of U.S. Provisional Application No. 63/080,862, filed September 21, 2020, and U.S. Provisional Application Serial No. 63/217,361, filed July 1, 2021, that is hereby acknowledged by the Examiner.
Status of the Claims
The amendment dated 12/17/2025 is acknowledged. Claims 1, 5-6 and 11-27 are pending and under examination.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 12/17/2025 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement(s) is/are being considered by the Examiner.
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.
(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.
(Withdrawn) Claims 1-2 rejected under 35 U.S.C. 102(a)(1) as being anticipated by Li et al. “Li” (mBio-American Society for Microbiology, 2020, 11(2):1-12) is hereby withdrawn in view of Applicant’s amendment to the claims.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103(a) which forms the basis for all obviousness rejections set forth in this Office action:
(a) A patent may not be obtained though the invention is not identically disclosed or described as set forth in section 102 of this title, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter pertains. Patentability shall not be negatived by the manner in which the invention was made.
This application currently names joint inventors. In considering patentability of the claims under 35 U.S.C. 103(a), the examiner presumes that the subject matter of the various claims was commonly owned at the time any inventions covered therein were made absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and invention dates of each claim that was not commonly owned at the time a later invention was made in order for the examiner to consider the applicability of 35 U.S.C. 103(c) and potential 35 U.S.C. 102(e), (f) or (g) prior art under 35 U.S.C. 103(a).
(Withdrawn) Claims 3-4 rejected under 35 U.S.C. 103(a) as being unpatentable over Li et al. “Li” (mBio-American Society for Microbiology, 2020, 11(2):1-12) in view of Walls et al. “Walls” (PNAS, 2017, 114(42):11157-11162) are hereby withdrawn in view of Applicant’s amendment to the claims.
(New rejection- Necessitated by Amendment) Claims 1 and 11 are rejected under 35 U.S.C. 103(a) as being unpatentable over Li et al. “Li” (mBio-American Society for Microbiology, 2020, 11(2):1-12) in view of Walls et al. “Walls” (PNAS, 2017, 114(42):11157-11162).
The claims are directed to a viral expression vector comprising a parainfluenza virus 5 (PIV5) genome comprising a heterologous nucleotide sequence expressing a heterologous polypeptide,
wherein the heterologous polypeptide comprises a coronavirus spike (S) protein; wherein the coronavirus S protein comprises the coronavirus S protein of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2); wherein the cytoplasmic tail of the coronavirus S protein has been replaced with the cytoplasmic tail of the fusion (F) protein of PIV5; and wherein the heterologous nucleotide sequence is inserted between the small hydrophobic protein (SH) gene and the hemagglutinin-neuraminidase (HN) gene of the PIV5 genome; replaces the SH gene nucleotide sequence; is inserted between the hemagglutinin-neuraminidase (HN) gene and the large RNA polymerase protein (L) gene of the PIV5 genome; is inserted closer to the leader than between the hemagglutinin-neuraminidase (HN) gene and the large RNA polymerase protein (L) gene of the PIV5 genome; is inserted upstream of the nucleocapsid protein (NP) gene of the PIV5 genome; is inserted immediately downstream of the leader sequence of the PIV5 genome; is inserted between the fusion (F) protein gene and the SH gene of the PIV5 genome; is inserted between the VP gene and the matrix protein (M) gene of the PIV5 genome; is inserted between the M gene and the F gene of the PIV5 genome; is inserted between the nucleocapsid protein (NP) gene and the V/P gene of the PIV5 genome; is inserted between the leader sequence and the nucleocapsid protein (NP) gene of the PIV5 genome; is inserted wherein a portion of the F or HN gene of PIV5 has been replaced with the heterologous nucleotide sequence; is inserted within the SH gene nucleotide sequence, is inserted within the NP gene nucleotide sequence, is inserted within the V/P gene nucleotide sequence, is inserted within the M gene nucleotide sequence, is inserted within the F gene nucleotide sequence, is inserted within the HN gene nucleotide sequence, and/or is inserted within the L gene nucleotide sequence.
Regarding claims 1 and 11, Li discloses a viral expression vector comprising a parainfluenza virus 5 (PIV5) genome (Abstract, page 1) comprising a heterologous nucleotide sequence expressing a heterologous polypeptide, wherein the heterologous polypeptide comprises a coronavirus spike (S) protein (PIV5 expressing MERS S (page 8 para. 3). Li discloses the plasmid containing the cDNA clone of PIV5 with MERS-S was inserted between SH and HN genes of the of the PIV5 genome (page 8 last para). Li also discloses the viral expression vector of claim 1 and states “SARS-CoV-2 (2019-nCoV) was identified in Wuhan, China, in late 2019. This is a novel zoonotic CoV related to the SARS-CoV that can cause severe respiratory disease (COVID-19). To date, this virus resulted in a significant disease burden, with more than 465,000 cases reported in 199 countries and an estimated case fatality rate of ~2%. The finding that PIV5 expressing MERS S protected mice against lethal MERS-CoV challenge at a single low dose of 104 PFU suggests its potential use as a vaccine vector for emerging viruses such as SARS-CoV-2” (SARS-CoV-2 (2019-nCoV, page 8 para. 3).
Li does not explicitly disclose the cytoplasmic tail of the coronavirus S protein has been replaced with the cytoplasmic tail of the fusion (F) protein of PIV5.
Walls, however, discloses the similarity between post-fusion coronavirus S and paramyxovirus F structures demonstrate that a conserved refolding trajectory mediates entry of these viruses and supports the evolutionary relatedness of their fusion subunits; and characterization of said proteins provide a structural framework for understanding the mode of neutralization of antibodies targeting the fusion machinery and for engineering next-generation subunit vaccines or inhibitors against this medically important virus family. Walls discloses characterizing mutations of the S protein to better elucidate fusion machinery (page 11160 Mapping of Mutations That Affect Membrane Fusion). Moreover, Walls discloses the cytoplasmic tail of the coronavirus S protein has been replaced with the cytoplasmic tail of the fusion (F) protein of PIV5 (page 11157 column 1 para. 3) (instant claims 1 and 11).
Accordingly, it would have been obvious to one of ordinary skill in the art to generate the viral expression vector as disclosed by Li whereby the cytoplasmic tail of the coronavirus protein has been replaced with the cytoplasmic tail of the fusion (F) protein of PIV5 disclosed by Walls. One of ordinary skill in the art would have been motivated to do so with a reasonable expectation of success in order to provide the capability to use the S spike protein of the coronavirus as taught by Walls in order to understand the mode of neutralization of antibodies targeting the fusion machinery and for engineering next-generation subunit vaccines or inhibitors against this medically important virus family (page 11157 column 1 para 3). Therefore, the claimed invention would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention.
Double Patenting
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 claims at issue 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); and 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 a nonstatutory double patenting ground provided the reference application or patent either is shown to be commonly owned with this application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. 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 Web site contains terminal disclaimer forms which may be used. Please visit http://www.uspto.gov/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.
(Withdrawn) Claims 1-2, 11-15 and 17-20 rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-4, 19-20 of copending Application No. 18433149 are hereby withdrawn in view of Applicatn’s amendment to the claims.
(Withdrawn) Claims 1-4, 7-15, 17-20 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-6, 8-10, 12-14 and 16-18 of copending Application No. 17933812.
(New rejection- Necessitated by Amendment) Claims 1 and 11-21 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-6, 8-10, 12-14, 16 and 18 of copending Application No. 17933812. Although the claims at issue are not identical, they are not patentably distinct from each other because the claims are coextensive in scope and species with one another. This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
The claims of the present invention are directed to a viral expression vector comprising a parainfluenza virus 5 (PIV5) genome comprising a heterologous nucleotide sequence expressing a heterologous polypeptide, wherein the heterologous polypeptide comprises a coronavirus spike (S) protein; wherein the coronavirus S protein comprises SARS-CoV-2; and wherein the cytoplasmic tail of the coronavirus S protein has been replaced with the cytoplasmic tail of the fusion (F) protein of PIV5.
The co-pending claims are directed to
1. (Original) A viral expression vector comprising a parainfluenza virus 5 (PIV5) genome having a heterologous nucleic acid sequence with at least 98% sequence identity to SEQ ID NOs: 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, or 80, wherein the viral expression vector expresses a heterologous polypeptide comprising a coronavirus spike (S) and/or nucleocapsid (N) proteins (instant claim 1, note: instant application vector SEQ ID NO: 1 has at least 98% sequence identity to co-pending application SEQ ID NOs:63-65, 72-73, 75-79).
2. (Original) The viral expression vector of claim 1, wherein the coronavirus S protein is a coronavirus S protein of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV- 2), a variant of interest or a variant of concern of SARS-CoV-2 and the coronavirus N protein is the coronavirus N protein of SARS-CoV-2, a variant of interest or a variant of concern of SARS-CoV-2 (instant claim 1).
3. (Original) The viral expression vector of claim 1, wherein the coronavirus S protein is the coronavirus S protein of a SARS-CoV-2 beta variant, a SARS-CoV-2 gamma variant, a SARS-CoV-2 delta variant, or a SARS-CoV-2 omicron variant and the coronavirus N protein is the coronavirus N protein of a SARS-CoV-2 beta variant, a SARS-CoV-2 gamma variant, a SARS-CoV-2 delta variant, or a SARS-CoV-2 omicron variant (instant claim 12).
4. (Original) The viral expression vector of claim 1, wherein the coronavirus S protein comprises the coronavirus S protein of SARS-CoV-2 and wherein the cytoplasmic tail of the coronavirus S protein has been replaced with the cytoplasmic tail of the fusion (F) protein of PIV5 (instant claim 1).
5. (Original) The viral expression vector of claim 1, wherein the coronavirus S protein of a variant of SARS-CoV-2 has been inserted between the PIV5 small hydrophobic (SH) and hemagglutinin (HN) genes and the coronavirus N protein of a variant of SARS-CoV-2 has been inserted between the PIV5 HN and polymerase (L) genes (instant claim 1).
6. (Original) The viral expression vector of claim 1, wherein the coronavirus S protein of a variant of SARS-CoV-2 has been inserted between the PIV5 HN and polymerase (L) genes (instant claim 1).
8. (Original) The viral expression vector of claim 1, wherein the PIV5 small hydrophobic (SH) gene has been replaced with the coronavirus N protein of SARS-CoV-2 (instant claim 13).
9. (Original) The viral expression vector of claim 1, wherein the PIV5 genome further comprises one or more mutations comprising a mutation of the V/P gene, a mutation of the shared N-terminus of the V and P proteins, a mutation of residues 26, 32, 33, 50, 102, and/or 157 of the shared N-terminus of the V and P proteins, a mutation lacking the C-terminus of the V protein, a mutation lacking the small hydrophobic (SH) protein, a mutation of the fusion (F) protein, a mutation of the phosphoprotein (P), a mutation of the large RNA polymerase (L) protein, a mutation incorporating residues from canine parainfluenza virus, a mutation inducing apoptosis, or a combination thereof (instant claims 11 and 12).
10. (Original) The viral expression vector of claim 9, wherein the one or more mutations comprise PIV5 VAC, PIV5ΔSH, PIV5-P-S308G, or a combination thereof (instant claims 13-15).
12. (Original) The viral expression vector of claim 11, wherein the amino acid substitution at amino acid residue S157 comprises a substitution of serine (S) to phenylalanine (F) and the amino acid substitution at amino acid residue S308 comprises a substitution of serine (S) to alanine (A) or Glycine (G) (instant claims 11 and 12).
13. (Original) The viral expression vector of claim 1, wherein a viral particle comprises the viral expression vector (instant claim 14).
14. (Currently amended) A composition comprising a viral expression vector comprising a parainfluenza virus 5 (PIV5) genome having a heterologous nucleic acid sequence with at least 98% sequence identity to SEQ ID NOs: 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, or 80, wherein the viral expression vector expresses a heterologous polypeptide comprising a coronavirus spike (S) and/or nucleocapsid (N) proteins (instant claims 1 and 15).
16. (Currently amended) A method of inducing an immune response in a subject having coronavirus disease 2019 (COVID-19), the method of comprising administering a composition comprising a viral expression vector or a viral particle comprising a parainfluenza virus 5 (PIV5) genome having a heterologous nucleic acid sequence with at least 98% sequence identity to SEQ ID NOs: 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, or 80, wherein the viral expression vector expresses a heterologous polypeptide comprising a coronavirus spike (S) and/or nucleocapsid (N) proteins, and wherein the immune response comprises a humoral immune response and/or a cellular immune response (instant claims 16-19, 21).
18. (Original) The method of claim 16, wherein the composition is administered intranasally, intramuscularly, topically, or orally (instant claim 20).
There is no patentable difference between the claimed composition and the patented composition in that the copending No. 17933812 discloses a viral expression vector comprising a parainfluenza virus 5 (PIV5) genome comprising a heterologous nucleotide sequence expressing a heterologous polypeptide, wherein the heterologous polypeptide comprises a coronavirus spike (S) protein; wherein the coronavirus S protein comprises SARS-CoV-2; and wherein the cytoplasmic tail of the coronavirus S protein has been replaced with the cytoplasmic tail of the fusion (F) protein of PIV5.
Moreover, The MPEP states “where the claimed and prior art products are identical or substantially identical in structure or composition, or are produced by identical or substantially identical processes, a prima facie case of either anticipation or obviousness has been established. In re Best, 562 F.2d 1252, 1255, 195 USPQ 430, 433 (CCPA 1977).
Conclusion
Claims 5-6 and 22-27 are allowed. As allowable subject matter has been indicated, applicant's reply must either comply with all formal requirements or specifically traverse each requirement not complied with. See 37 CFR 1.111(b) and MPEP § 707.07(a).
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.
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Any inquiry concerning this communication or earlier communications from the examiner should be directed to Barry Chestnut whose telephone number is 571-270-3546. The examiner can normally be reached on M-F (8:00-4:00). If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Thomas Visone can be reached on 571-270-0684. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
/BARRY A CHESTNUT/Primary Examiner, Art Unit 1672