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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 2/13/26 has been entered.
Election/Restrictions
Applicant’s election without traverse of the required species in the reply filed on 5/18/2022 is acknowledged.
Claims 12-19 and 22 are examined on the merits.
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.
(Prior Rejection Maintained and extended to new limitations) Claim(s) 12-19 and 22 are rejected under 35 U.S.C. 102a1 as being anticipated by Voellmy and Bloom (WO/16/030392).
A method of immunization of a subject, the method of immunization comprising
(a) administering to an inoculation site region in the body of the subject a composition comprising an effective amount of a replication-competent controlled herpesvirus which is a recombinant virus in which one or more replication-essential genes have been placed under the control of a gene switch that is inserted in the genome of the recombinant virus and that can be activated deliberately, and
(b) exposing the inoculation site region of the mammalian subject to a localized activation treatment that activates the recombinant virus to undergo a round of replication in the inoculation site region,
wherein the replication-competent controlled herpesvirus carries an expressible gene for all or part of a hemagglutinin or all or part of a neuraminidase of an influenza virus strain that differs genetically from an influenza virus strain circulating at the time of immunization, the influenza virus strain circulating at the time of immunization defined as an influenza virus strain identified by competent regulatory bodies or institutions engaged by such regulatory bodies that are concerned with the identification of virus strains to be targeted by the next seasonal vaccine, and wherein the immunization cross-protects the subject against influenza.
Wherein the activation treatment comprises administering an activating heat dose to the inoculation site region.
Wherein the replication-competent controlled herpesvirus is a recombinant herpesvirus that comprises an inserted gene encoding a small-molecule regulator-activated transactivator which gene is functionally linked to a nucleic acid sequence that acts as a heat shock promoter as well as a transactivator-responsive promoter, and one or more transactivator-responsive promoters that are functionally linked to the one or more replication-essential genes.
Wherein the replication-competent controlled herpesvirus is a recombinant HSV-1 or HSV-2 and the replication-essential viral genes that are functionally linked to transactivator-responsive promoters include at least all copies of the ICP4 gene or the ICP8 gene.
Wherein the small-molecule regulator-activated transactivator contains a truncated ligand-binding domain from a progesterone receptor and is activated by a progesterone receptor antagonist that iscapable of interacting with the ligand-binding domain and activating the transactivator.
Wherein the replication-competent controlled herpesvirus is a recombinant virus selected from the group consisting of an HSV-1, an HSV-2, a varicella zoster virus and a cytomegalovirus.
Wherein the replication-competent controlled herpesvirus is a recombinant herpesvirus that comprises an inserted gene encoding a transactivator activated by a small-molecule regulator, wherein the gene encoding the transactivator is functionally linked to a nucleic acid that acts as a heat shock promoter, and one or more transactivator-responsive promoters that are functionally linked to one or more replication-essential genes.
Wherein the replication-competent controlled herpesvirus is a recombinant herpesvirus that comprises an inserted gene encoding a small-molecule regulator-activated transactivator wherein the gene encoding the transactivator is functionally linked to a nucleic acid that acts as a constitutively active promoter or a transactivator-responsive promoter, a first replication-essential gene of the replication-competent controlled herpesvirus that is functionally linked to a promoter activated by heat and a second replication- essential gene of the replication-competent controlled herpesvirus that is functionally linked to a transactivator-responsive promoter.
Wherein the replication-competent controlled herpesvirus carries an expressible gene for an antigen of an influenza virus strain that differs in clade from the influenza virus strain against which the immunization is directed.
Wherein the replication-competent controlled herpesvirus carries an expressible gene for an antigen of an influenza virus strain that differs in subtype from the influenza virus strain against which the immunization is directed.
Wherein the inoculation site region is a cutaneous or subcutaneous region on the trunk or on an extremity of the mammalian subject.
Wherein the expressible gene for an antigen of an influenza virus strain is a gene or gene fragment encoding all or part of a hemagglutinin.
The prior art
Voellmy and Bloom teach the generation of a recombinant HSV virus that contains antiprogestin and heat activated gene regulation mechanism. [see page 26] These mechanisms control the expression of a heterologous gene, such as an influenza HA protein. [see page 3 and page 10, lines 32-34] They teach that influenza viruses undergo regular antigenic changes and as a result, the administration of their recombinant HSV expressing an influenza HA protein would achieve the immunization against a different influenza virus strain. [see page 3, lines 15-20 and page 10, lines 30-34] Voellmy and Bloom also teach “…because of the error-prone mode of replication and selection in the host, influenza A and B viruses undergo gradual antigenic change in their two surface antigens, the HA and NA proteins. This phenomenon known as antigenic drift necessitates continuous vigilance and yearly review/update of strains used for vaccine production. Pandemics result from antigenic shift, i.e., introduction into the human population of a novel influenza A virus containing either only a novel HA subtype or both novel HA and NA subtypes.” The yearly review/update of strains used for vaccine production would be conducted “…by competent regulatory bodies or institutions engaged by such regulatory bodies that are concerned with the identification of virus strains to be targeted by the next seasonal vaccine…”. [see page 3, lines 17-23]
Voellmy and Bloom also teach the operational linkage of the ICP8 gene with different promoters, such as a heat shock protein. [see page 12, lines 8-19] At the inoculation site, the heat and small-molecule regulator-activated herpesvirus can be activated a by a heat dose. [see page 16, lines 15-26] The inoculation can occur at the trunk or other extremities via the cutaneous or subcutaneous route. [see page 16, lines 27-33] Voellmy and Bloom also teach that the herpesvirus can be a HSV-1. [see page 32, lines 21-28]
Therefore, Voellmy and Bloom anticipate the instant invention.
Response to arguments:
Applicant’s arguments have been considered, but are not persuasive.
In response to applicant’s amendment of: “that differs genetically from an influenza virus strain circulating at the time of immunization, the influenza virus strain circulating at the time of immunization defined as an influenza virus strain identified by competent regulatory bodies or institutions engaged by such regulatory bodies that are concerned with the identification of virus strains to be targeted by the next seasonal vaccine” Voellmy and Bloom teach on page 3: “because of the error-prone mode of replication and selection in the host, influenza A and B viruses undergo gradual antigenic change in their two surface antigens, the HA and NA proteins. This phenomenon known as antigenic drift necessitates continuous vigilance and yearly review/update of strains used for vaccine production. Pandemics result from antigenic shift, i.e., introduction into the human population of a novel influenza A virus containing either only a novel HA subtype or both novel HA and NA subtypes.”
Therefore, since Voellmy and Bloom teach that yearly review and update of strains used for vaccine production, they teach that a competent regulatory body should decide which influenza viruses should be selected for the upcoming seasonal influenza vaccine. An example of a competent regulatory bodies concerned with identifying influenza virus strains to be targeted by the next seasonal vaccine are the Food and Drug Administration of the United States of America. In 2014 (prior to the earliest priority date of Voellmy and Bloom), the Food and Drug Administration met on February 18, 2014 to decide which influenza virus should be included in the upcoming seasonal influenza vaccine. [see attached Influenza Virus Vaccine for the 2014-2015 Season NPL document]
As stated in the most recent Office action and reiterated here, Voellmy and Bloom state on page 3, lines 15-21 [All known HA and NA subtypes could be isolated from wild aquatic birds, which constitute a natural reservoir and a source of genes for pandemic A-type viruses. Because of the error-prone mode of replication and selection in the host, influenza A and B viruses undergo gradual antigenic change in their two surface antigens, the HA and NA proteins. This phenomenon known as antigenic drift necessitates continuous vigilance and yearly review/update of strains used for vaccine production. On page 4, lines 13-15: [Of particular interest is a study on young children that was carried on over two seasons in both of which there was a good match between vaccine and circulating strains. Also, while the selected strains of influenza A and B viruses mimic circulating strains of influenza, these selected strains would also be different compared to circulating subtypes or influenza viruses classified in other clades. More specifically, while the classic subtypes of a seasonal vaccine are Influenza A H1N1 and H3N2 and an influenza B virus, other subtypes of influenza viruses would be “prevalent” at the time of immunization. Furthermore, based on the structural requirements of the claims recombinant HSV, the HSV of Voellmy and Bloom presently teach that influenza HA proteins can be expressed by their replication-competent controlled herpesvirus (see page 10, lines 30-34) and the long history of influenza viruses that are used for producing influenza vaccines. [see pages 3-4] Voellmy and Bloom are the same and therefore would achieve the cross-protection of another prevalent influenza virus. Lastly, the Bloom et al. Vaccines publication from 2024 (referenced by applicant in a prior response) establishes that the seasonal influenza vaccines containing H1N1 can inherently cross-protect against another subtype (H3N2).
Therefore, the teachings of Voellmy and Bloom anticipate instant 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 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 USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The 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/process/file/efs/guidance/eTD-info-I.jsp.
(Prior Rejection maintained) Claims 12-19 and 22 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of U.S. Patent No. 10,478,486 in view of Voellmy and Bloom (WO/16/030392).
Although the claims at issue are not identical, they are not patentably distinct from each other because the patented invention is also drawn to a method of administering to an inoculation site region in the body of the mammalian subject a composition comprising an effective amount of a replication- competent controlled herpesvirus which is a recombinant virus in which one or more replication- essential genes have been placed under the control of a gene switch that is inserted in the genome of the recombinant virus and that can be activated deliberately, and (b) exposing the inoculation site region of the mammalian subject to a localized activation treatment that activates the recombinant virus to undergo a round of replication in the inoculation site region, wherein the replication-competent controlled herpesvirus carries an expressible gene for an antigen of a historical influenza virus. While the patented method does not require using an influenza antigen is from an historical influenza virus, the additional teachings of Voellmy and Bloom (see below) cure this deficiency.
Response to arguments:
Applicant’s response does not overcome the Obviousness Type Double Rejection. As established above, the patented invention in view of the additional teachings of Voellmy and Bloom render obvious the instant invention.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to BENJAMIN P BLUMEL whose telephone number is (571)272-4960. The examiner can normally be reached M-F 8-5 EST.
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/BENJAMIN P BLUMEL/Primary Examiner, Art Unit 1671