DETAILED ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Applicant's amendment and remarks, filed 1/8/26, are acknowledged.
Claims 1, 11, 14, 16, 23, 31-32, 36 have been amended.
Claims 1, 9-16, 23, 31-32, 36, 40-41 are pending.
Claims 40-41 are withdrawn from further consideration by the examiner, 37 CFR 1.142(b), as being drawn to a non-elected invention. Claims 12-14, 17, 31, are withdrawn from further consideration by the examiner, 37 CFR 1.142(b), as being drawn to non-elected species.
Claims 1, 9-11, 15-16, 23, 32, and 36 are being acted upon.
The previous grounds of rejection are withdrawn in view of Applicant’s claim amendments.
The following are new grounds of rejection necessitated by Applicant’s claim amendments.
Claim interpretation
Based on the definitions in the present disclosure:
A matrix protein of the Indiana serotype that includes a GML mutation is being interpreted as the M protein of Indiana serotype (SEQ ID NO: 3), with G21E, M51R, and one of L111A or L111F mutations. rVSVInd-GML is an rVSV of Indiana serotype with said GML mutations.
A matrix protein of New Jersey serotype having a GMM mutation is being interpreted as the M protein of New Jersey serotype (SEQ ID NO: 6), with G23E, M48R, and M51R. . rVSVNJ-GMM is an rVSV of New Jersey serotype with said GMM mutations.
A matrix protein of New Jersey serotype having a GMML mutation is being interpreted as the M protein of New Jersey serotype (SEQ ID NO: 6), with G23E, M48R, M51R, and one of L110A or L110F mutations. rVSVNJ-GMML is an rVSV of New Jersey serotype with said GMML mutations.
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1, 9-11, 15-16, 23, 32, and 36 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claims 1 and 23 are directed to a rVSV carrying a MERS-CoV structural protein or modification thereof, wherein the MERS-CoV structural protein or modification thereof is a full-length spike protein (SF), and wherein the glycoprotein signal peptide at the NH2-terminus of the SF is replaced with a melittin signal peptide and the transmembrane domain of the SF is replaced with a VSV G protein transmembrane domain and cytoplasmic tail (Gtc) at the COOH-terminus of the SF. As an initial matter, the recitation that the rVSV can carry a MERS-CoV structural protein or modification thereof in line 3 of claim 1 is confusing, since the wherein clause limits the protein to a specific modified SF protein. In other words, in line 3 of claim 1, it appears the claims are intending to encompass either a MERS-CoV structural protein, or a modified structural protein, but the claim later limits the scope to a particular modified version of SF, which renders the claims unclear. It is suggested to amend claim 1, line 3 to recite that the VSV carries a gene that encodes for a modified MERS-CoV structural protein, for example. A similar amendment can be made to claim 23.
Furthermore, the claim also recites that the “transmembrane domain of the SF” is replaced with a VGV G protein transmembrane domain and cytoplasmic tail at “the COOH-terminus”. See Du (of record), the COOH-terminus of the SF protein is a cytoplasmic tail region, with a transmembrane region being located N-terminal to the cytoplasmic tail. The present claims recite that the transmembrane domain is replaced, which would appear to require that the protein would have a transmembrane domain and cytoplasmic tail of the VSV G protein in place of the SF protein transmembrane domain, followed by the cytoplasmic tail of the SF (See Fig. 2 of Du, the “TM” portion would be replaced with VSV G). However, the present claims also recite that the replacement is at the COOH-terminus, which is unclear, since the transmembrane domain is not at the COOH-terminus of the SF. Are the claims meant to specify that both the transmembrane and cytoplasmic tail region of the SF are replaced with the VSV transmembrane and cytoplasmic tail? The scope of the claims is unclear and indefinite.
For the purposes of applying prior art, the claims are being interpreted as encompassing replacement of SF transmembrane and cytoplasmic tail with VSV G transmembrane and cytoplasmic tail.
The following is a quotation 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 35 U.S.C. 112 (pre-AIA ), first paragraph:
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.
Claims 1, 9-11, 15-16, 23, 32, and 36 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 pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention. This is a new matter rejection.
The specification and the claims as originally filed do not provide support for the invention as now claimed, specifically:
An avirulent rrVSV carrying a full-length spike protein (SF), and wherein “the glycoprotein signal peptide at the NH2 terminus of the SF is replaced with a melittin signal peptide and the transmembrane domain of the SF is replaced with a VSV G protein transmembrane domain and cytoplasmic tail (Gtc) at the COOH-terminus of the SF (Claims 1 and 23, and dependent claims).
Applicant indicates that support for the new limitations can be found in page 11, lines 10-15 and 25-31.
A review of the specification fails to reveal support for the new limitations.
At page 11, lines 10-15, the instant specification discloses that the S protein (SF or partial length S protein) are modified with a melittin signal peptide at the NH2 terminus and/or VSV G protein transmembrane domain and cytoplasmic tail Gtc) at the COOH terminus of the S protein (SF or partial length S protein). In lines 25-31, the specification discloses that the S protein can be provide as a full-length (SF) protein, a S1 subunit of the SF protein, a S2 subunit of the SF protein, and/or an RBD of the SF protein. However, in the present claims, the modification involves replacing specified portions of a full length-SF (i.e. the signal peptide and the transmembrane domain) with said melittin signal peptide and VSG G protein transmembrane and cytoplasmic tail. Newly added claims or claim limitations must be supported in the specification through express, implicit, or inherent disclosure and a description that merely renders a claimed invention obvious may not sufficiently describe the invention for the purposes of the written description requirement. See MPEP 2163. The specification generally discloses “modifying” full length SF, but does not specifically say what the modification is. In other words, the disclosure of a “modification” is essentially a genus, but no specific species of modification are disclosed. In the examples, the specification discloses adding a melittin signal peptide sequence to the NH2 terminus of a RBD (see page 2 and Fig. 2). Thus, at best, the disclosure would support, for example, adding a signal peptide to the N-terminus of SF or adding a G protein Gtc to the COOH terminus of SF. However, that is not what is claimed. Rather the modification contemplated is a replacement of specified portions of the SF. Even if the modification disclosed in the specification could somehow be construed to mean a replacement (which is not conceded), the present claims appear to encompass replacing the transmembrane domain of SF with a transmembrane domain and cytoplasmic tail of VSVG, i.e. the claimed protein could have said VSV G transmembrane domain and cytoplasmic tail, followed by the cytoplasmic tail of the S protein. This modification is not contemplated anywhere in the instant specification.
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.
Claim 1, 9-11, 15-16, 23, 32, and 36 is/are rejected under 35 U.S.C. 103 as being unpatentable over Ozharovskaia, 2019, in view of Buonocore, 2002, Kapadia, 2005 (of record), and US 2016/0144022.
Ozharovskaia teaches a recombinant viral vector carrying a full length S protein of MERS-CoV, wherein the COOH ER localization signal in the S protein is deleted and replaced with a transmembrane domain of VSV G glycoprotein (see pages 37-38, in particular). Ozharovskaia teaches that doing so allows for the S protein to be expressed as a transmembrane form localized to the plasma membrane of the cell (see page 39, in particular). Ozharovskaia teaches that the recombinant virus carrying said S protein induces a strong antibody and T cell response as well as production of neutralizing antibodies (See page 45, in particular). Although Ozharovskaia does not explicitly state that the G glycoprotein transmembrane includes the cytoplasmic region, or that the deleted ER localization signal of the S protein includes the transmembrane domain, it would be obvious to do so based on the teachings of Buonocore. Buonocore explains that ER retention signals of viral proteins are within the C-terminal transmembrane domain, and that they can be replaced with foreign transmembrane and cytoplasmic domains, such as the transmembrane and cytoplasmic domains of VSV G, to allow for cell surface expression (see page 6865, in particular). Therefore, it would be obvious to the ordinary artisan that one should replace the transmembrane and cytoplasmic domain (i.e. the ER localizing signal) of the S protein, with the transmembrane and cytoplasmic domain of the G-protein to achieve cell surface expression in the viral vectors of Ozharovskaia.
The references differ from the claimed invention in that they do not explicitly teach an avirulent rVSV carrying said MERs-COV S protein with VSV G glycoprotein transmembrane and cytoplasmic domains. The references also do not teach melittin signal peptide.
The ‘022 publication teaches an avirulent rVSV that is capable of inducing immune responses against an antigen of interest, which can replicate to a high titer and has less chance of reverting back to a wild type phenotype (See pages 1-4 and Fig. 2, in particular). The ‘022 publication teaches a recombinant attenuated VSV expresses a VSV G gene and variant M protein that can be used as a VSV based prime-boost vaccine to induce long-lasting immune response against foreign antigens expressed by the VSV carrying foreign genes (see pages 1-4, in particular). The ‘022 publication teaches a M mutant of VSV Indiana serotype (VSVind)-GML) that have an M protein mutation making them avirulent and safer (see , in particular). The ‘022 publication teaches the G21E/L111F/M51R substitutions in an M (i.e. VSVInd see page 8, in particular). The ‘022 publication teaches that the prime boost vaccine combination can be two different VSV serotypes with mutated M, expressing the same foreign gene, and that doing so induces stronger immune responses (See entire document). The ‘022 publication teaches that the antigen of interest can be expressed by replacing the native signal peptide with melittin signal peptide, which dramatically increased the rates of expression and enhanced inducing of T and B cell immune responses (See paragraph 203, in particular).
Likewise, Kapadia teaches that replication competent rVSV carrying a VSV G gene, which has significant advantages over many other vaccine vectors, since it has a relatively small RNA genome, it replicates exclusively in the cytoplasm, and VSV seropositivity is extremely low in the general population. Kapadia teaches using said rVSV for a coronavirus (SARS-CoV).
Therefore, it would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made to use the rVSV of the ‘022 publication and Kapadia, as the recombinant viral vector in Ozharovskaia. The ordinary artisan at the time the invention was made would have been motivated to do so with a reasonable expectation of success, because Kapadia and the ‘022 publication teach that rVSV can be used for expressing a viral antigen, including coronavirus, and that it is advantageous over other vaccine vectors since it has a relatively small RNA genome, it replicates exclusively in the cytoplasm, VSV seropositivity is extremely low in the general population, it can replicate to a high titer and has less chance of reverting back to a wild type phenotype. Furthermore, the ordinary artisan would be motivated to use the melittin signal peptide for expressing the SF protein, since the ‘022 publication teaches that it dramatically increased the rates of expression and enhanced inducing of T and B cell immune responses
Furthermore, the ordinary artisan would be motivated to use the VSVInd serotype with mutated M protein of the ‘022 publication as the type of VSV, since the ‘022 publication teaches that it induces long-lasting immune responses against expressed foreign genes, and is avirulent and safer. Additionally, the ordinary artisan would be motivated to provide a prime-boost combination using said VSVInd with mutated M protein, and a different serotype VSV with mutant M, since the ‘022 publication teaches that such prime -boost combinations can induce stronger immune responses.
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, 9-11, 15-16, 23, 32, and 36 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 6, 10-11, 14, 19-20, 27, 35, 38, 40-41, 44-46 of copending Application No. 18/280,147 in view of Ozharovskaia, 2019 and US 2016/0144022.
The ‘147 application claims a recombinant VSV carrying a VSV G gene and a gene that encodes for a full length spike protein of SARS-CoV-2 (SF). The ‘147 application claims that the SF has a replaced signal peptide of honeybee melittin peptide at the NH2 terminus of the SF protein and a VSV G protein transmembrane domain and cytoplasmic tail replacement at the C-terminus of the SF protein. The ‘147 application claims that the rVSF is rVSVInd serotype have a GML mutation in the matrix protein. The ‘147 application claims a vaccine or immunological composition comprising said rVSV, and a prime boost combination comprising a prime vaccine and a booster vaccine comprising said rVSV, wherein the rVSV is replication competent.
Although the ‘147 application does not claim using the full length spike protein of MERs-CoV, it would be obvious to do so based on the teachings of Ozharovskaia for the same reasons set forth above. Furthermore, it would be obvious to use a rVSV that is avirulent to improve safety as taught by the ‘022 publication.
This is a provisional nonstatutory double patenting rejection.
Claims 1, 9-11, 15-16, 23, 32, and 36 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 7-42 of U.S. Patent No. 9,943,593, or claims 1-14 of 9,630,996, or claims 1-16 of 9,731,006, or claims 1-19 of 9,737,597, or claims 1-12 of 9,248,178, in view of Kapadia, 2005, Buonocore, 2002, and 2016/0144022.
The patents all claim a vaccine comprising a rVSV including a modified matrix protein, wherein the serotype is VSVInd, and wherein the VSV encodes a foreign antigen.
Although the patents do not specifically claim that the foreign antigen is a full length spike protein of MERS-CoV, it would be obvious to use the full length spike protein of MERS-CoV as the foreign antigen with a reasonable expectation of success, in order to induce an immune response to said spike protein based on the teachings of Ozharovskaia, 2019, Kapadia, 2005, and US 2016/0144022 for the reasons set forth above.
The patents also claim that the rVSV encodes a G gene, or alternatively, VSVInd serotype inherently comprises a G gene (or it would be obvious to include the G gene based on Kapadia). The patents claim the GML mutation in said matrix protein, or alternatively said mutations are obvious over the teachings of the ‘022 publication for the reasons set forth above. The patents claims a prime boost composition employing different VSV serotypes. The patents claim that the VSV is attenuated/avirulent, or alternatively this would be an obvious property of the rVSV with the mutated M proteins based on the ‘022 publication.
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 date of this final action.
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Amy E. Juedes
Patent Examiner
Technology Center 1600
/AMY E JUEDES/Primary Examiner, Art Unit 1644