DETAILED ACTION
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 .
Applicant’s amendment filed on 07/30/2026 has been entered.
Amended claims 1-10 are pending in the present application.
Applicant elected previously without traverse Group I, which is drawn to a heat-controlled replication-competent controlled alpha-herpesvirus whose replication can be transiently activated in infected nonneural cells but that cannot be activated in infected neural cells.
Applicant also elected previously the following species: (i) HSV-1 virus as a species of an alpha-herpesvirus; and (ii) an influenza virus surface antigen or parts thereof.
Claims 9-10 were withdrawn previously from further considerations because they are directed to a non-elected invention. Claims 5 and 7 were also withdrawn previously from further considerations because they are directed to non-elected species.
Accordingly, amended claims 1-4, 6 and 8 are examined on the merits herein with the above elected species.
Priority
This application is a CIP of U.S. Patent Application No. 17,300,287, filed on 05/12/2021, now US Patent No. 12,257,300; which is a 371 of PCT/EP2019/080138, filed on 11/04/2019; which claims the benefit of U.S. Provisional Patent Application No. 62/917,066, filed on 11/19/2018 and the Foreign Application EPO EP18207121.7, filed on 11/19/2018.
Upon reviewing the specifications for the above U.S. Patent Application, Provisional Patent Application and Foreign Application, it is determined that the pending claims have at best the priority date 11/04/2019. This is because none of the Provisional Application and the Foreign Application described at least a heat-controlled replication-competent controlled alpha-herpesvirus whose replication can be transiently activated in infected nonneural cells but that cannot be activated in infected neural cells.
Response to Amendment
The rejection under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, for Lack of Written Description was withdrawn in light of currently amended independent claim 1, and upon further considerations.
Claim Rejections - 35 USC § 112
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.
Amended claims 1-4, 6 and 8 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. This is a new ground of rejection necessitated by Applicant’s amendment.
Independent claim 1 recites the limitation "the intended inoculation site" in the recited elements (b)(1) and (b)(2). There is insufficient antecedent basis for this limitation in the claim. This is because prior to this limitation there is no recitation of any intended inoculation site. Accordingly, which particular the intended inoculation site does the limitation refer to? Clarification is requested because the metes and bounds of the claim are not clearly determined.
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, 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.
Amended claims 1-4, 6 and 8 are rejected under 35 U.S.C. 103 as being unpatentable over Voellmy et al (Expert Rev. Vaccines 14:637-649, 2015) in view of Martuza et al (WO 96/39841). This is a modified rejection necessitated by Applicant’s amendment.
The instant claims encompass a composition comprising a replication-competent controlled alpha-herpesvirus (e.g., HSV-1, HSV-2 or a varicella-zoster virus) whose replication can be transiently activated in infected nonneural cells by application of an activating heat dose but that cannot be activated in infected neural cells by application of an activating heat dose, the replication-competent controlled alpha-herpes virus comprises:
(a) a first heterologous promoter that is a nucleic acid sequence that is a heat shock promoter, the first heterologous promoter controlling the expression of a first replication-essential gene of the replication-competent controlled alpha-herpesvirus, wherein the first heterologous promoter is functionally linked to the first replication-essential gene of the replication-competent controlled alpha-herpesvirus,
(b) a second heterologous promoter, wherein the second heterologous promoter is a promoter active in nonneural cells of an intended inoculation site but also is essential inactive in neural cells and the second promoter is functionally linked to a second replication-essential gene of the replication-competent controlled alpha-herpes virus; and a vaccine composition comprising an effective amount of the same heat-controlled replication-competent controlled alpha-herpesvirus and a pharmaceutically acceptable carrier or excipient.
Voellmy et al already disclosed at least a replication-competent controlled HSV-1 virus, in which genome the promoter of at least one replication-essential viral gene would be replaced with an HSP70B promoter, and for safety reasons, it may be prudent to subject at least two replication-essential genes to HSP promoter control (see section titled “Immunization by means of a replication-competent controlled virus” on pages 641-644; particularly at page 642, left column, middle two complete paragraphs at page 642; and Fig. 1A). Figure 1A is reproduced below.
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Voellmy et al taught that the resulting recombinant HSV-1 should be capable of infecting host cells and, subsequent to a transient activating heat treatment of the host cells, undergo a single round of replication; and further rounds of virus replication may be induced by further activating heat treatments. Voellmy et al also disclosed that replication-essential genes include immediate early (RL1 [ICP0], RS1 [ICP4]), early (UL9, UL29) as well as late (UL38, UL48) genes (left column, last complete paragraph at page 642). Voellmy et al stated “Inoculation of a subject with such a replication-competent controlled virus in a location in which viral replication will not cause illness or undue distress followed by localized activation of one or more rounds of controlled virus replication would be expected to induce a similarly potent immune response as infection with wild-type virus, but without the negative consequences of illness, malaise and enablement of secondary infection” (page 641, right column, bottom of first paragraph); and “The inoculation site may be, for example, an area skin of an upper extremity or a mucosal surface” (page 641, right column, top of first full paragraph). Voellmy et al also disclosed that the replication-competent controlled virus can be used as an immunization platform, with an inserted gene encoding a heterologous antigen (e.g., influenza virus antigen) that may be subjected to the same control as vector replication or may be driven by a constitutively active promoter (right column, second last paragraph at page 645); and hemagglutinin (HA) is the major surface antigen (an influenza virus spike protein) against which a host antibody response is directed (left column, last paragraph at page 638) and present vaccines rely largely on the induction of HA antibodies (right column, last full paragraph at page 639). Voellmy et al further disclosed that additional modifications of the HSV backbone could be envisioned to further enhance the immune response, including deletion of the ICP47 gene (right column, last sentence of third full paragraph at page 645). Moreover, Voellmy et al also stated “To attain a high margin of safety, replication of a controlled virus ought to be subject to dual regulation. Our preferred solution would be to subject one or, better, two replication-essential genes to the control of both an HSP promoter and a small-molecule regulator (SMR)-activated gene switch (FIGURE 1B). Alternatively, one may place one replication-essential gene under the control of an HP promoter and another under the control of a SMR-activated gene switch (FIGURE 1C)” (page642, right column, top of first full paragraph).
Voellmy et al did not teach explicitly at least a heat-controlled replication-competent controlled alpha-herpesvirus with a dual regulation comprising: (a) a heat shock promoter that is functionally linked to a first replication-essential gene of the replication-competent controlled alpha-herpesvirus, and (b) a second heterologous promoter that is active in nonneural cells of an intended inoculation site but also is essentially inactive in neural cells, and the second promoter is functionally linked to a second replication-essential gene of the replication-competent controlled alpha-herpesvirus; and a vaccine composition comprising an effective amount of the heat-controlled replication-competent controlled HSV-1 and a pharmaceutically acceptable carrier or excipient.
Before the effective filing date of the present application (11/04/2019), Martuza et al already taught at least a replication competent herpes simplex virus vector with an essential herpes simplex virus gene (e.g., an HSV gene encodes a protein which is essential to viral replication such as the immediately-early genes ICP4 and ICP27) is driven by a cell-specific or tissue-specific promoter, including a keratin promoter which is a skin-specific promoter, to ablate the specific target cell (e.g., keratinocytes/epithelial cells responsible for wart) via cell-specific viral replication; and a pharmaceutical composition comprising the same replication competent herpes simplex virus vector and a pharmaceutically acceptable vehicle (e.g., aqueous solutions, non-toxic excipients such as salts, preservatives, buffers and the like) for the vector (at least Abstract; Summary of the Invention; particularly page 9, line 35 continues to line 6 at page 10; page 16, lines 14-18, lines 27-29; page 17, lines 18-34; page 48, lines 23-35; page 49, lines 8-22; and Table 1). Martuza et al stated “[t]he HSV immediate-early genes are the preferred HSV genes to be placed under the control of the cell-, tissue- or tumor-specific promoter in the HSV of the invention. The immediate-early HSV genes ICP4 and ICP27 are preferred because they are transcriptional regulatory genes. For example, ICP4 must be turned on before the other genes essential to HSV replication” (lines 28-34 at page 17). Martuza et al also taught that the tissue specific recombinant HSV vectors may further include other coding sequences, such as for immune modulatory products, which can be placed under control of viral early and late promoters (page 34, lines 26-30); and they may be additionally engineered to disrupt expression of the endogenous γ34.5 gene and/or the ribonucleotide reductase gene (page 40, lines 17-33). Martuza et al also taught that a replication-competent HSV that is incapable of expressing one or both of (i) a functional γ34.5 gene product and (ii) a ribonucleotide reductase can be used as a vaccine to protect an animal against HSV infection (page 9, lines 15-21; and Examples 6 and 8)
Accordingly, it would have been obvious for an ordinary skilled artisan before the effective filing date of the present application to modify the teachings of Voellmy et al by also at least replacing the endogenous promoter of the immediate-early HSV ICP4 gene with a heterologous keratin promoter (a skin-specific promoter) to be operably linked to the replication-essential ICP 4 gene, in addition to an HSP70B promoter operably linked to another replication-essential gene of HSV to have a dual regulation for the replication of a heat-controlled replication-competent controlled HSV virus to increase a margin of safety, particularly to prevent the replication or reactivation of the heat-controlled replication-competent controlled alpha-herpesvirus in infected neural cells with accidental application of an activating heat dose (e.g., a high fever); as well as formulating a vaccine composition comprising an effective amount of the heat-controlled replication-competent controlled recombinant HSV-1 virus with a pharmaceutically acceptable carrier or excipient, in light of the teachings of Martuza et al as presented above.
An ordinary skilled artisan would have been motivated to carry out the above modifications because Martuza et al already taught the use of a keratin promoter (a skin-specific promoter) that is functionally linked to an essential herpes simplex virus gene (e.g., the immediate-early ICP4 gene which must be turned on before the other genes essential to HSV replication) to control replication of a replication competent herpes simplex virus vector to ablate target keratinocytes/epithelial cells that are responsible for wart; and a pharmaceutical composition comprising the same replication competent herpes simplex virus vector and a pharmaceutically acceptable vehicle (e.g., aqueous solutions, non-toxic excipients such as salts, preservatives, buffers and the like). Please note that the primary Voellmy reference already stated explicitly “To attain a high margin of safety, replication of a controlled virus ought to be subject to dual regulation”.
An ordinary skilled artisan would have a reasonable expectation of success in light of the teachings of Voellmy et al and Martuza et al as set forth above; coupled with a high level of skill of an ordinary skilled artisan in the relevant art.
The modified compositions resulting from the combined teachings of Voellmy et al and Martuza et al are indistinguishable and encompassed by the presently claimed invention. The modified heat-controlled replication-competent controlled alpha-herpesvirus with at least the additional replication-essential viral ICP4 gene under the control of a skin cell-specific keratin promoter in infected neural cells cannot be activated and/or replicated by application of an activating heat dose alone.
Therefore, the claimed invention as a whole was prima facie obvious in the absence of evidence to the contrary.
Response to Arguments
Applicant’s arguments related to the above modified 103 rejection in the Amendment filed on 07/30/2026 (pages 7-10) have been fully considered, but they are respectfully not found persuasive for the reasons discussed below.
Applicant argued that the Office Action has used hindsight reconstruction to arrive at the presently claimed invention. Basically, Voellmy discloses confinement of viral replication in infected cells in a skin inoculation but does not teach or suggest the use of skin cell-specific promoters, which were known in 2015. Instead, Voellmy teaches the use of a heat shock promoter controlling two replication essential viral genes, or a heat shock promoter in combination with a small molecule regulator (SMR) activated transactivator because the heat shock promoter is the only system that responds to a physical stimulus and, when present to control two replication essential viral genes or together with a SMR-activated transactivator (activated by administration of the SMR), can satisfy the requirements for safe, dual regulation. Applicant further argued that a cell-specific promoter as taught by Martuza is not a gene switch or system that responds to a physical stimulus and can be activated by technology in the field and, thus, cannot satisfy the requirements set out by Voellmy for a dually regulated safe replication-competent herpesvirus. Accordingly, an ordinary skill in the art would at the time of the current application would not have an apparent reason to combine Voellmy and Martuza. Although Applicant acknowledges that “preferred” embodiments do not constitute a teaching away from a broader disclosure or nonpreferred embodiments, Applicant argues the Voellmy does not provide a “broader disclosure” or “non-preferred embodiments”, but simply alternatives, none of which includes any teaching or suggestion of using a non-regulatable, cell-specific promoter. Applicant further argued that based on the combined references, one skilled in the art would not have been motivated to modify Voellmy to use, instead of Voellmy’s heat shock promoter and small molecule regulator activator promoter, a non-regulatable cell promoter, even one specific to a certain cell or tissue as disclosed by Martuza because such modification would substantially alter Voellmy’s dual controlled replication competent herpesvirus platform by removing one to the externally regulatable promoter-based control mechanisms, the combination would render Voellmy’s dually controlled replication competent herpesvirus unsatisfactory for its intended purpose.
First, with respect to Applicant’s argument on impermissible hindsight reconstruction Examiner would like to recite a paragraph from in re Oetiker, 977, F.2d 1443, 1448 (Fed. Cir. 1992).
"[T]here must be some teaching, reason, suggestion, or motivation found "in the prior art" or "in the prior art references" to make a combination to render an invention obvious within the meaning of 35 U.S.C. 103 (1998). Similar language appears in a number of opinions and if taken literally would mean that an invention cannot be held to have been obvious unless something specific in a prior art reference would lead an inventor to combine the teachings therein with another piece of prior art. This restrictive understanding of the concept of obviousness is clearly wrong…. While there must be some teaching, reason, suggestion, or motivation to combine existing elements to produce the claimed device, it is not necessary that the cited references or prior art specifically suggest making the combination…. In sum, it is off the mark for litigants to argue, as many do, that an invention cannot be held to have been obvious unless a suggestion to combine the prior art teachings is found in a specific reference."
Although the cited artisans do not specifically point out a motivation to in their disclosure, an ordinarily skilled artisan would have been able to identify the need for the combination of the teachings without the disclosure of the instant application. It must be recognized that any judgment on obviousness is in a sense necessarily a reconstruction based upon hindsight reasoning. But so long as it takes into account only knowledge which was within the level of ordinary skill at the time the claimed invention was made, and does not include knowledge gleaned only from the applicant's disclosure, such a reconstruction is proper. See In re McLaughlin, 443 F.2d 1392, 170 USPQ 209 (CCPA 1971). Please refer to the above modified 103 rejection for more details and the provided motivation.
Second, since the above rejection was made under 35 U.S.C. 103 none of the cited references individually have to teach every limitation of the instant claims. For example, the Voellmy reference does not have to disclose the use of any tissue-selective promoter for any reason, let alone one that is essentially inactive in neural cells. Similarly, the Martuza reference does not have to teach a transient activation of a replication-competent controlled alpha-herpes virus replication in infected nonneural cells by application with an activating heat dose. It is also apparent that Applicant considered each of the cited references in total isolation one from the other, without considering the specific combination of Voellmy et al and Martuza et al.
Third, Voellmy et al teach specifically to engineer replication-competent alpha-herpesviruses to replicate like wild-type virus, and in effect lyse cells at the inoculation site such as an area of skin on an upper extremity to be a superior immunization agent when compared with either a corresponding attenuated virus with a diminished replication or a non-replicating virus (the paragraph bridging left and right columns at page 641). Voellmy et al also stated “Based on the above-discussed results, one may reasonably argue that if an attenuated virus capable of some degree of replication induces a more potent and complete immune response in a subject than a corresponding non-replication virus, an even more potent and complete immune response would be elicited by a virus that replicates more efficiently than the latter attenuated virus” (left column, second last full paragraph at page 641). Similarly, Martuza et al teach the use of a keratin promoter (a skin-specific promoter) that is functionally linked to an essential herpes simplex virus gene (e.g., the immediate-early ICP4 gene which must be turned on before the other genes essential to HSV replication) to control replication of a replication competent herpes simplex virus vector to ablate target keratinocytes/epithelial cells that are responsible for wart. Please note that the primary Voellmy reference already stated explicitly “To attain a high margin of safety, replication of a controlled virus ought to be subject to dual regulation”. Accordingly, an ordinary skill in the art before the effective filing date of the present application (11/04/2019) would readily recognize that the use of a heat shock promoter in combination with a skin-specific promoter such as a keratin promoter, wherein each of which is functionally linked to a different essential herpes simplex virus gene would constitute a dual regulation for a controlled replication of a replication-competent virus.
Fourth, the heat- and SMR-controlled RCCHV is only a preferred vaccine construct with a high margin of safety that is disclosed in the Voellmy reference as evidenced by the following statements “To attain a high margin of safety, replication of a controlled virus ought to be subject to dual regulation. Our preferred solution would be to subject one or, better, two replication-essential genes to the control of both an HSP promoter and a small-molecule regulator (SMR)-activated gene switch (FIGURE 1B). Alternatively, one may place one replication-essential gene under the control of an HP promoter and another under the control of a SMR-activated gene switch (FIGURE 1C)” (page 642, right column, top of first full paragraph). Voellmy et al also disclosed at least a replication-competent controlled HSV-1 virus, in which genome the promoter of at least one replication-essential viral gene would be replaced with an HSP70B promoter, and for safety reasons, it may be prudent to subject at least two replication-essential genes to HSP promoter control (see section titled “Immunization by means of a replication-competent controlled virus” on pages 641-644; particularly at page 642, left column, middle two complete paragraphs at page 642; and Fig. 1A). Figure 1A is reproduced below.
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Thus, the teachings of Voellmy et al already suggest at least that the use of a gene-switch is not the only and absolute means to make a replication-competent controlled alpha-herpesvirus safe.
Fifth, as set forth in the above modified 103 rejection it would have been obvious for an ordinary skilled artisan before the effective filing date of the present application to modify the teachings of Voellmy et al by also at least replacing the endogenous promoter of the immediate-early HSV ICP4 gene with a heterologous keratin promoter (a skin-specific promoter) to be operably linked to the replication-essential ICP 4 gene, in addition to an HSP70B promoter operably linked to another replication-essential gene of HSV to have a dual regulation for the replication of a heat-controlled replication-competent controlled HSV virus to increase a margin of safety, particularly to prevent the replication or reactivation of the heat-controlled replication-competent controlled alpha-herpesvirus in infected neural cells with accidental application of an activating heat dose (e.g., a high fever) because Martuza et al already taught the use of a keratin promoter (a skin-specific promoter) that is functionally linked to an essential herpes simplex virus gene (e.g., the immediate-early ICP4 gene which must be turned on before the other genes essential to HSV replication) to control replication of a replication competent herpes simplex virus vector to ablate target keratinocytes/epithelial cells that are responsible for wart.
Sixth, please note that the standard under 35 U.S.C. 103 is a “reasonable” expectation of success.
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 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.
Amended claims 1-4, 6 and 8 are still rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-10 of U.S. Patent No. 12,257,300 (IDS).
Although the claims at issue are not identical, they are not patentably distinct from each other because a heat-controlled or heat- and small-molecule regulators-controlled replication-competent controlled alpha-herpesvirus whose replication can be transiently activated in nonneural cells infected with said replication-competent controlled alpha-herpesvirus but that cannot be transiently in neural cells infected with said replication-competent controlled alpha-herpevirus, wherein the replication-competent controlled alpha-herpesvirus is a recombinant alpha-herpesvirus derived from a virus of the group consisting of a herpes simplex virus type 1 (HSV-1), a herpes simplex virus type 2 (HSV-2) and a varicella-zoster virus, said replication-competent controlled alpha-herpesvirus comprising the recited elements (a)-(b); and a vaccine composition comprising an effective amount of the same replication-competent controlled alpha-herpesvirus and a pharmaceutically acceptable carrier or excipient in claims 1-10 of U.S. Patent No. 11,565,001 anticipate a composition comprising a heat-controlled replication-competent controlled alpha-herpesvirus whose replication can be transiently activated in infected nonneural cells but that cannot be activated in infected neural cells by application of an activating heat dose in the application being examined and, therefore, a patent to the genus would, necessarily, extend the rights of the species or sub- should the genus issue as a patent after the species of sub-genus.
Response to Argument
Applicant’s argument related to the above nonstatutory double patenting rejection in the Amendment filed on 07/30/2026 (middle of page 10) has been fully considered, but it is respectfully not found persuasive for the reason discussed below.
Applicant argued simply that currently amended claims are not obvious over the claims of the cited patent. Additionally, Applicant stated that Applicant would consider filing a terminal disclaimer should an allowable subject matter is indicated in the present application.
The claims of the cited patent anticipate a composition comprising a heat-controlled replication-competent controlled alpha-herpesvirus of the present application as claimed, particularly claim 1 of US Patent No. 12,257,300 recites the limitation “wherein (1) the first heterologous promoter is functionally linked to the first replication-essential gene of the replication-competent controlled alpha-herpesvirus……and (b) a second heterologous promoter that is known to be active in nonneural cells of a mammalian subject to which the replication-competent controlled alpha-herpesvirus is to be administered but is also known to be essentially inactive in neural cells of the mammalian subject, the second heterologous promoter being functionally linked to a second replication-essential gene of the replication-competent controlled alpha-herpesvirus”. Additionally, there is no terminal disclaimer being filed.
Amended claims 1-3, 6 and 8 are still provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-2 and 7-10 of copending Application No. 17/803,699 (reference application).
Although the claims at issue are not identical, they are not patentably distinct from each other because a replication-competent controlled herpesvirus capable of delivering an antigen of a SARS-CoV-2 virus, comprising inserted in the genome of an alpha-herpesvirus: (a) a first exogenous promoter that is a nucleic acid sequence that acts as a heat shock promoter, the first promoter controlling expression of a first replication-essential gene of the alpha-herpesvirus, (b) a second exogenous promoter and a functionally linked exogenous gene for an antigen of a SARS-CoV-2 virus, and further comprising (c) a third exogenous promoter that is functionally linked to a second replication essential gene of the replication-competent controlled herpesvirus, wherein the third exogenous promoter is selected from the group consisting of promoters of a KRT1, a KRT4, a KRT5, a KRT6A, a KRT10, a KRT13, a KRT14, a KRT77, and a FLG gene (dependent claim 2); and a vaccine composition comprising an effective amount of the replication-competent controlled herpesvirus encompassed in claims 1-2 and 7-10 of copending Application No. 17/803,699 anticipate/encompass a composition comprising a heat-controlled replication-competent controlled alpha-herpesvirus whose replication can be transiently activated in infected nonneural cells by application of an activating heat dose but that cannot be activated in infected neural cells by application of an activating heat dose in the application being examined and, therefore, a patent to the genus would, necessarily, extend the rights of the species or sub- should the genus issue as a patent after the species of sub-genus.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Response to Argument
Applicant’s argument related to the above provisional nonstatutory double patenting rejection in the Amendment filed on 07/30/2026 (pages 10-11) has been fully considered, but it is respectfully not found persuasive for the reason discussed below.
Applicant argued basically that currently amended claims are not obvious over claims 1-2 and 7-10 of the co-pending application 17/0803,699. Additionally, Applicant also noted that the current application has a priority date of 11/04/2019 while the co-pending application 17/803,699 has a priority date of April 24, 2020; and Applicant requested that the rejection be withdrawn according to MPEP 804(I)(B)(1(b)(i).
Claims 1-2 and 7-10 of the co-pending application 17/0803,699 still anticipate/encompass a heat-controlled replication-competent controlled alpha-herpesvirus of the present application as claimed. Additionally, it is noted that the above provisional nonstatutory double patenting rejection is not the only rejection remaining in the present application.
Conclusions
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 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 Quang Nguyen, Ph.D., at (571) 272-0776.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s acting SPE, James Douglas (Doug) Schultz, Ph.D., may be reached at (571) 272-0763.
To aid in correlating any papers for this application, all further correspondence regarding this application should be directed to Group Art Unit 1631; Central Fax No. (571) 273-8300.
Any inquiry of a general nature or relating to the status of this application or proceeding should be directed to (571) 272-0547.
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/QUANG NGUYEN/Primary Examiner, Art Unit 1631
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