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 .
Status of Claims
Claims 1-8 and 10-19 are currently pending. Claims 17-19 are new. Claim 9 is cancelled.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 02/12/2026 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner.
Drawings
The objections are withdrawn following Applicant’s amendments to the specification.
Specification
The objections are withdrawn following Applicant’s amendments to the specification.
WITHDRAWN REJECTIONS
Claim Rejections - 35 USC § 103
Claims 1-3, 7, and 10-16 is/are rejected under 35 U.S.C. 103 as being unpatentable over Campadelli (US20190336551A1; Published Nov 7, 2019; Hereinafter “Campadelli;” See PTO-892) in view of Kuroda et al (BMC Biotechnol. 2006 Sep 22; hereinafter "Kuroda;" See IDS filed 02/06/2023), further as evidenced by Warming et al (Nucleic Acids Res. 2005 Feb 24; hereinafter "Warming;" See PTO-892).
Claims 4-6 are rejected under 35 U.S.C. 103 as being unpatentable over Campadelli (US20190336551A1; Published Nov 7, 2019; Hereinafter “Campadelli;” See PTO-892) in view of Kuroda et al (BMC Biotechnol. 2006 Sep 22; hereinafter "Kuroda;" See IDS filed 02/06/2023) as applied to claims 1-3, 7 and 10-16 above and further in view of Marimoto et al (Microbiol Immunol. 2009 Mar; hereinafter "Marimoto;" See IDS filed 02/06/2023).
Claim 8 is rejected under 35 U.S.C. 103 as being unpatentable over Campadelli (US20190336551A1; Published Nov 7, 2019; Hereinafter “Campadelli;” See PTO-892) in view of Kuroda et al (BMC Biotechnol. 2006 Sep 22; hereinafter "Kuroda;" See IDS filed 02/06/2023) as applied to claims 1-3, 7 and 10-16 above and further in view of Grzesik et al (J Virol Methods. 2018 Nov; hereinafter "Grzesik;" See PTO-892).
The rejections have been withdrawn following claim amendments. New rejections are set forth below.
NEW REJECTIONS NECESSITATED BY AMENDMENTS
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1-7, and 10-19 are rejected under 35 U.S.C. 103 as being unpatentable over Campadelli (US20190336551A1; Published Nov 7, 2019; Hereinafter “Campadelli;” See PTO-892 of 08/25/2025) in view of and Morimoto et al (Microbiol Immunol. 2009 Mar; hereinafter "Morimoto;" See IDS filed 02/06/2023) and Logvinoff et al (Virology. 2000 Feb 1; hereinafter "Logvinoff;" See PTO-892); further as evidenced by Warming et al (Nucleic Acids Res. 2005 Feb 24; hereinafter "Warming;" See PTO-892 of 08/25/2025).
Regarding claims 1-3: Campadelli (US20190336551A1; Published Nov 7, 2019; Hereinafter “Campadelli;” See PTO-892) taught a pharmaceutical composition comprising the herpesvirus, the herpesvirus for use in the treatment of a tumor, infection, degenerative disorder or senescence-associated disease. Campadelli taught insertion of a BAC between UL3 and UL4 (First and second viral proteins). Campadelli taught insertion of BAC plasmid sequences into the HSV genome to generate a recombinant HSV BAC that can be propagated and genetically manipulated in bacteria using recombineering techniques, followed by reconstitution of infectious virus upon transfection into mammalian cells.
Further, Morimoto was directed to finding intergenic regions in HSV that are amenable for transgene insertion. (See Morimoto Abstract). Morimoto indicated that “we present data showing that insertion
of a reporter gene expression cassette into the intergenic regions between HSV-1 UL3 and UL4, UL50 and UL51, and Us1 and Us2 and between HSV-2 UL3 and UL4, and UL50 and UL51 had no effect, relative to wild-type virus, on virus growth in cell culture or virulence in mice following intracerebral inoculation. These results indicate that insertion of foreign genes into the HSV-1 and HSV-2 intergenic regions examined in this study has no or minimal effect on the properties of these parental viruses. In addition to these HSV-1 and HSV-2 intergenic regions, each of the viruses has 10 other intergenic regions with the same structure (Fig. 1a); namely, the intergenic regions between UL7 and UL8, UL10 and UL11, UL15 and UL18, UL21 and UL22, UL26 and UL27, UL35 and UL36, UL40 and UL41, UL45 and UL46, UL55 and UL56, and Us9 and Us10: (See Morimoto, p. 159, col. 2 last para). As such Morimoto identified several intergenic regions that are suitable for transgene insertion.
It is noted that combination of Campadelli and Morimoto did not teach or suggest insertion of additional recombination sites between two other adjacent viral proteins. However, it is submitted that use of recombination sites are commonly used tools of integration of transgenes into a desired vector (such as HSV). For example, Logvinoff taught that “[t]he prokaryotic Cre-loxP recombination system is a powerful tool that enables in vitro and in vivo site-specific manipulations of the genome of eukaryotic cells as well as of DNA viruses and their derived vectors,” and taught that they “have used this system to induce an irreversible switch in the expression of a viral complex transcription unit encoding two different open reading frames and allowing consecutive expression of two reporter genes. “ (See Logvinoff Abstract). As such, Logvinoff expressly taught that prokaryotic Cre/loxP recombination system is a routine and powerful tool for inserting one or more genes into HSV genomes and derived vectors. A person of ordinary skill in the art have been motivated to insert recombination sites at permissive intergenic loci identified by Morimoto in the Campadelli HSV BAC construct to generate modular recombinant HSV vectors. It would have been predictable that such insertions would not disrupt viral replication or BAC functionality. As such the claimed composition is obvious to one of ordinary skill in the art.
Regarding claims 4-6 and 17-18: Morimoto taught that HSV-1 and HSV-2 have “10 other intergenic regions with the same structure the intergenic regions between UL7 and UL8, UL10 and UL11, UL15 and UL18, UL21 and UL22, UL26 and UL27, UL35 and UL36, UL40 and UL41, UL45 and UL46, UL55 and UL56, and Us9 and Us10. Since insertion of a foreign gene(s) into these intergenic regions should not disrupt any viral genes or affect any transcription units near the insertion site, these 10 intergenic regions should also be useful as insertion sites for foreign gene(s).” (See Morimoto, p. 159, col. 2, last para). A person of ordinary skill, in reading Morimoto and Campadelli, would have recognized the desirability of expressing multiple transgenes in HSV vectors and to identify sites where transgenes can be cloned. Morimoto taught a finite number of sites for cloning of transgenes in HSV vectors. (See Morimoto, p. 159, col. 2, last para). Thus, it would have been obvious to a person of ordinary skill in the art to try UL10 and UL11 and UL55 and UL56 as potential sites for cloning transgenes and insertion of recombination sites. It has been held that "a person with ordinary skill has good reason to pursue the known options within his or her technical grasp. If this leads to the anticipated success, it is likely the product not of innovation but of ordinary skill and common sense." See KSR International Co. v Teleflex, Inc. 82 USPQ2d 1385 at 1390.
It is also noted that intergenic regions of UL10 and UL11 and US55 and UL56 are defined by adjacent genes arranged in convergent (tail-to-tail orientation), such that insertion between them does not disrupt coding sequences or transcriptional units, as required by claims 4, 5 and 17-18.
It is also noted that a person of ordinary skill would have been motivated to introduce a recombination site at the UL10/UL11 intergenic region and a second recombination site at UL55/UL56 in addition to the BAC insertion at UL3/UL4 intergenic region in order to provide modular transgene integration capability with a reasonable expectation of success based on Morimoto’s demonstration that such loci tolerate insertion, as required by claims 6 and 18.
Regarding claim 7: Campadelli taught use of pBleoBAC11 as the bacterial artificial chromosome. (See Campadelli Example 1)
Regarding claims 10-13 and 19: Campadelli taught “Construction of HSV recombinants expressing genetically modified gBs carrying a single chain antibody (scFv) directed to HER2“ (See Campadelli, Example 1) using galk recombineering, which is done in E. coli, as required by claim 12. (See evidence in Warming). Morimoto taught that oncolytic viruses armed with “transgenes, such as those encoding immunomodulatory factors inducing anti-tumor immunity and anti-angiogenic factors” (See Morimoto p. 155, col. 2, first para) can be used as therapeutics. Immunomodulatory factors inducing anti-tumor immunity and anti-angiogenic factors read on at least one protein of claim 13 and immunomodulating agents of claim 19. Further, as pointed out above, use of recombination sites are commonly used tools of integration of transgenes into a desired vector (such as HSV). As such as explained above, it would have been routine for a person of ordinary skill in the art to insert recombination sites at permissive intergenic loci identified by Morimoto in the Campadelli HSV BAC construct to generate modular recombinant HSV vectors and insert transgenes into the recombination sites as taught by Logvinoff, as required by claim 11.
Regarding claims 14-16: [0088] of Campadelli taught that “the recombinant herpesvirus of the present invention may be a combined oncolytic and immunotherapeutic virus.”
Claim 8 is rejected under 35 U.S.C. 103 as being unpatentable over Campadelli (US20190336551A1; Published Nov 7, 2019; Hereinafter “Campadelli;” See PTO-892 of 08/25/2025) in view of Morimoto et al (Microbiol Immunol. 2009 Mar; hereinafter "Morimoto;" See IDS filed 02/06/2023) and Logvinoff et al (Virology. 2000 Feb 1; hereinafter "Logvinoff;" See PTO-892) as applied to claims 1-7, and 10-19 above and further in view of Grzesik et al (J Virol Methods. 2018 Nov; hereinafter "Grzesik;" See PTO-892 of 08/25/2025).
Regarding claim 8: Campadelli taught that the pBleoBAC11 vector is flanked by loxP sites. As taught by Grzesik, “One of the most frequently used methods is the utilization of the Cre enzyme to excise the BAC sequence, provided that it is bounded by loxP recognition sites.” (See Grzesik p. 2, para 2). One of ordinary skill in the art would be motivated to use the system taught by Campadelli to use loxP to create the HSV-Bac shuttle vector and effectively remove the BAC after transfection into mammalian cells as taught by Gresik.
Conclusion
No claim is free of art.
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 JAGAMYA VIJAYARAGHAVAN whose telephone number is (703)756-5934. The examiner can normally be reached 9:00a-5:00p.
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/JAGAMYA NMN VIJAYARAGHAVAN/ Examiner, Art Unit 1633
/EVELYN Y PYLA/Primary Examiner, Art Unit 1633