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 and response filed on 5/1/2026 has been received and entered into the case.
Claim 7 has been canceled, claims 11-30 have been withdrawn from consideration as being drawn to non-elected subject matter, and claims 1-6, 8-10 and 31-36 have been considered on the merits. All arguments have been considered.
The claim rejections under 35 USC 112(a) have been withdrawn due to the instant amendment.
The claim rejection under 35 USC 112(b) has been withdrawn due to the instant amendment.
The claim rejections under 35 USC 103 have been withdrawn due to the instant amendment. However, the new rejections under 103 are presented below.
Claim Rejections - 35 USC § 102
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 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.
Claim(s) 1-3, 5, 9-10 and 31-32 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Chowdhury (US2018/0353596 A1; of record) as evidenced by Mossman et al. (WO2009/033278; IDS ref.) and Kim et al. (2019, Cancer Immunol. Res.; of record)
Chowdhury teach a recombinant BoHV-1 designated as UL49.5Δ30-32CT-null/gE-CTΔ/Us9Δ virus (see Fig.3A), and this virus contains deletion at amino acid 30-32 and 80-96 of UL49.5 (Δ30-32 and CT-null) and deletion of cytoplasmic tail of gE (para. 4). Thus, the BoHV-1 of Chowdhury would meet the limitation of claims 1 and 3.
The limitation “at least one of a gI or gE gene deletion” is interpreted under broadest reasonable interpretation such that a partial deletion of the gene would be also encompassed by the limitation as the “deletion” is not particularly limited with “fully” or “partially”, and thus the scope would encompass both “fully” as well as “partially”.
Regarding the BHV-1 is oncolytic virus, the limitation is considered inherent for the BHV-1 as Mossman et al. teach that BHV-1 is an oncolytic virus that infect human tumor cells but not normal human cells (para. 4 and 7). The term “oncolytic” is interpreted as an intended purpose of the claimed product. At the same time, it is an inherent property of BHV-1 according to Mossman et al. Therefore, in the absence of any other structural feature(s) necessary for the virus being oncolytic, it is considered that the BHV-1 mutant taught by Chowdhury would be oncolytic.
Regarding claims 2 and 9-10 directed to the virus expressing a gene encoding an immunomodulatory molecule (claim 2); the immunomodulatory molecule being a chemokine (claim 9); and the immunomodulatory molecule being GM-CSF (claim 10), Chowdhury teach the BHV-1 mutant having UL49.5Δ30-32CT-null further comprising the cassette expressing GM-CSF inserted into a gene (gG deletion site) of the BHV-1(Fig. 22; para. 30). This teaching would meet the limitations of claims 2 and 9-10.
Regarding claim 5, the wherein clause is directed to the property of the claimed mutant BoHV-1 virus (UL49.5Δ30-32CT-null/gE-CTΔ/Us9Δ), as the BoHV-1 mutant taught by Chowdhury is considered identical to the claimed mutant virus, it is expected that the BHV-1 mutant of Wei et al. has identical property as the claimed virus in the absence of any evidence to the contrary. In the absence of any evidence that the term “oncolytic” requires any specific structure of the BoHV-1, it is considered that the BoHV-1 mutant taught by Chowdhury would be oncolytic.
Regarding claim 31, the wherein clause is directed to the property of the immunomodulatory molecule, and the intended result of the molecule when the claimed product is utilized. GM-CSF expressed by the BHV-1 mutant of Chowdhury as discussed above is known to promote antitumor immunity according to Kim et al. (see abstract).
Regarding claim 32, Chowdhury teach carriers such as sterile aqueous or non-aqueous solutions including polyethylene glycol (para. 152 and 162).
Thus, the reference anticipates the claimed invention.
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.
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.
Claim(s) 1, 3-6 and 32 is/are rejected under 35 U.S.C. 103 as being unpatentable over Mossman et al. (supra) in view of Wei et al. (of record) and Kaashoek et al. (supra).
Mossman et al. teach a BHV-1 including derivatives including mutants of BHV is oncolytic for the ability to selectively kill tumor cells (para. 37). Mossman et al. teach BHV may be genetically modified in order to alter specific characteristics by introducing or deleting specific genes within the BHV genome to produce recombinant BHV (para. 25).
Mossman et al. do not teach the mutants of BHV as required by claim 1.
Wei et al. teach that the mutant BHV-1 having UL49.5Δ30-32 CT-null compared to the while type BHV-1 showed that the UL49.5 luminal domain residues 30-32 and CT residues are critical for efficient TAP inhibition and MHC-1 down-regulation functions (Abstract). Thus, the mutant BHV-1 cannot efficiently inhibit TAP (transporter associated with antigen processing) and cannot down-regulate MHC-1 function, indicating that the virus would lyze cancer cells and press antigen presenting of the cancer cells.
It would have been obvious to a person skilled in the art to use the BHV-1 mutant taught by Wei et al. for the purpose of killing tumor cells taught by Mossman et al. because the mutant BHV-1 of Wei et al. cannot evade host immune system due to the deletion of UL49.5 luminal domain residue 30-32 and the deletion of the cytoplasmic tail, and thus, induces the host immune system targeting the tumor cells.
Mossman et al. in view of Wei et al. do not teach the deletion of gI and/or gE gene.
Kasshoeck et al. teach that the deletion of both gI and gE genes in BHV-1 would reduce the immunogenicity to the virus (Abstract). Kasshoeck et al. teach that deletion of gI or gE, or both gI/gE resulted in significantly less virulent than the wt BHV-1 (Abstract).
It would have been obvious to a person skilled in the art to incorporate the gI and/or gE gene deletion into the mutant BHV-1 of Mossman et al. in view of Wei et al. with a reasonable expectation of success. A person of ordinary skilled in the art would have been motivated to do so because Kasshoeck et al. teach that the dual deletion of gI and/or gE from the BHV-1 virus cause less host immune response compared to BHV-1 (wt) and less virulent than using wt BHV-1, and thus, one skilled in the art would delete gI and/or gE genes from the BHV-1 UL49.5Δ30-32ΔCT-null taught by Wei et al. in order to obtain least immunogenic virus for the purpose of killing tumor cells.
Regarding claim 32 directed to the composition comprising the BHV-1 mutant virus and a pharmaceutically acceptable carrier, Mossman et al. teach the composition comprising oncolytic BHV and a pharmaceutically acceptable carrier (p.9, claim 1).
Therefore, the invention as a whole would have been prima facie obvious to a person of ordinary skill before the effective filing date of the claimed invention.
Claim(s) 2, 8-10 and 31 is/are rejected under 35 U.S.C. 103 as being unpatentable over Mossman et al. (supra) in view of Wei et al. (supra) and Kaashoek et al. (supra) as applied to claims 1, 3-6 and 32 above, in view of Ma et al. (2018, BMC Immunology) and Weiss et al. (2015, Braz. J. Med. Biol. Res.; IDS ref.)
Regarding claims 2, 8-10 and 31, Mossman et al. in view of Wei et al. and Kaashoek et al. do not teach that BHV-1 virus genetically modified to express an immunomodulatory molecule that induces an anti-tumor immune response.
Ma et al. teach the use of oncolytic herpes simplex virus in an application of treating cacner, and the oncolytic HSV is engineered to express GM-CSF (see p.6; Table 2; oncovex-csf)
It would have been obvious to a person skilled in the art to engineer the BHV mutant of Mossman et al. in view of Wei et al. and Kasshoek et al. to express GM-CSF useful in treating a cancer as taught by Nakao et al. with a reasonable expectation of success. This teaching would meet claims 9 and 10.
Regarding claim 8 directed to the gene encoding an immunostimulatory molecule being inserted within the gE gene locus or the gI gene locus, Mossman et al. in view of Wei et al. and Kaashoek et al. do not teach the limitation.
Weiss et al. teach a gE gene-deleted BHV-1 and the gE was replaced with the GFP gene (Abstract; Fig. 1).
It would have been obvious to a person skilled in the art to replace the gE gene from BHV-1 of Mossman et al. in view of Wei et al. and Kaashoek et al. and insert a transgene of interest as Weiss et al. show that the gE gene of BHV-1 can be deleted and replaced with a gene of interest (e.g. GFP). Thus, one skilled in the art would insert a therapeutic gene, e.g. GM-CSF taught by Ma et al., in the place of gE gene being deleted from the BHV-1 as the BHV-1 taught by Mossman et al. in view of Wei et al. and Kaashoek et al. is intended for a gene therapy.
Therefore, the invention as a whole would have been prima facie obvious to a person of ordinary skill before the effective filing date of the claimed invention.
Claim(s) 33-36 is/are rejected under 35 U.S.C. 103 as being unpatentable over Mossman et al. in view of Wei et al. and Kaashoek et al. as applied to claims 1, 3-6 and 32 above, further in view of Tsimberidou et al. (2020, Cancer Treatment Review; of record)
Regarding claims 33-36, while Mossman et al. teach that mutant BHV-1 is used for the ability to selectively kill tumor cells (para. 37), however, Mossman et al. do not particularly teach the limitation.
Tsimberidou et al. teach various cancer treatment paradigm including chemotherapy, checkpoint inhibitors, immunotherapy and cellular therapy, e.g. chimeric antigen receptor T-cells (see entire document; Abstract).
Thus, it would have been prima facie obvious to a person skilled in the art to combine the BHV-1 mutant of Mossman et al. in view of Wei et al. and Kaashoek et al. along with various known cancer therapies taught by Tsimberidou et al. for the same purpose with a reasonable expectation of success.
Therefore, the invention as a whole would have been prima facie obvious to a person of ordinary skill before the effective filing date of the claimed invention.
Response to Arguments
Applicant’s arguments with respect to the 112 rejections and the 102 rejections based on Osterrieder and Wei have been fully considered and are persuasive based on the instant amendment. As indicated above, the rejections have been withdrawn accordingly.
Regarding the 102 rejection based on Chowdhury, applicant argued that Chowdhury does not teach double deletion (i.e. UL49.5D30-32DCT and deletion of gI or gE). While Chowdhury does not teach “full” deletion of gI or gE along with UL49.5D30-32DCT, however, Chowdhury teaches “partial” deletion of gE as discussed in the claim rejection. Under the broadest reasonable interpretation, the claimed limitation directed to “gI or gE gene deletion” is interpreted to encompass “partial” deletion. As Chowdhury teaches a partial deletion of gE (deletion of C-terminal portion of gE; gECTD) in the BoHV-1 UL49.5D30-32DCT-null/gECTD/Us9D virus (para. 206-207), the BHV-1 virus contains both deletions as claimed. Applicant is advised to limit the gE gene deletion as “deletion of the entire gE gene”, for example, to obviate the 102 rejection.
Regarding the 103 rejections presented in the previous OA, the rejections have been withdrawn due to the instant amendment. The new 103 rejections presented above cite Mossman et al. as a primary reference and new references (Ma et al. and Weiss et al.). Thus, the arguments against the previous 103 rejections are moot.
Conclusion
No claims are 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 TAEYOON KIM whose telephone number is (571)272-9041. The examiner can normally be reached 9-5 EST Monday-Friday.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, JAMES SCHULTZ can be reached at 571-272-0763. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/TAEYOON KIM/Primary Examiner, Art Unit 1631
Prosecution Insights