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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 Sep. 25, 2025 has been entered.
DETAILED ACTION
Acknowledgement is hereby made of receipt and entry of the communication filed on Sep. 25, 2025. Claims 1-5, 11-16 and 18-24 are pending and currently examined.
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.
(Previous Rejection – Maintained) Claims 1-5, 10-16 and 18-20 are rejected under 35 U.S.C. 103 as being unpatentable over Zhou et al. (WO 2017/181420 A1, published on Oct. 26, 2017; submitted in IDS filed on Feb. 15, 2022).
This rejection is extended to new claims 21-24.
The base claim 1 is amended to specify that the oHSV is not adsorbed on an antigen-specific lymphocyte. New claims 21-24 further exclude other carrier elements.
Zhou teaches an invention relating to an obligate oHSV vector comprising modified viral DNA genome, a recombinant oHSV-1 construct comprising the obligate oHSV vector and a heterologous nucleic acid sequence encoding an immunostimulatory and/or immunotherapeutic agent, and compositions comprising the recombinant oHSV-l construct that can be used for treating cancers. See Abstract. Zhou teaches that the modification of the oHSV vector comprises a deletion between the promoter of UL56 gene and the promoter of US1 of a wild-type HSV-1 genome such that (i) one copy of all double-copy genes is absent and (ii) sequences required for expression of all existing open reading frames (ORFs) in the viral DNA after the deletion are intact. See [0013].
Figure 2 of Zhou shows schematic representations of oncolytic HSV-1 viruses based on the obligate vectors, which express immunostimulatory and/or immunotherapeutic agents. IMMV502, oHSV-1 expressing human anti-PD-1 scFv and murine IL 12; IMMV504, oHSV-1 expressing murine anti-CTLA-4 scFv and murine IL 12; IMMV503, oHSV-1 expressing human anti-PD-1 scFv and human IL 12; IMMVSOS, oHSV-1 expressing human anti-CTLA-4 scFv and human IL 12; IMMV507, oHSV-1 expressing human anti-CTLA-4 scFv and human anti-PD-1 scFv; IMMV603, oHSV-1 expressing human anti-CTLA-4 scFv, human anti-PD-1 scFv and human IL 12. See [0022]. See below:
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Figure 2 shows that recombinant HSV vector constructs with the region between nt 117005 to 132096 of the HSV genome is deleted and replaced with a heterologous sequence encoding IL-12 or scFv-PD-1. The constructs also contain heterologous sequences encoding ScFv-PD-1 or CTLA4 placed between UL3 and UL4.
Zhou teaches that modified HSV of the invention may be based on HSV-1 selected from strains or any existing HSV isolate including strains F, KOS, and 17, and that the deletion may cause excision of nucleotide positions 117005 to 132096 in the genome of F strain. See claims 4-5.
Zhou teaches a pharmaceutical composition comprising an effective amount of the recombinant oncolytic HSV-1 of any of claim 6 to 25 and a pharmaceutically acceptable carrier (see claim 26), and that the pharmaceutical composition may be formulated for intratumor administration (see claim 27). Zhou further teaches a method of treating or alleviating a cancer comprising administrating an effective amount of the pharmaceutical composition of the invention. See claims 28-32.
Accordingly, Zhou teaches a method for treating cancer in a subject comprising administering to the subject “a modified HSV-1 virus capable of acting as a vector of cellular and or viral genes wherein the modification comprises a deletion between the promoter of UL56 and the promoter of U51 of a wild-type HSV-1 genome such that (i) one copy of all double-copy genes is absent and (ii) sequences required for expression of all existing open reading frames (ORFs) in the viral DNA after the deletion are intact; and a heterologous nucleic acid sequence encoding an immunostimulatory and/or immunotherapeutic agent, wherein the heterologous nucleic acid sequence is stably incorporated into at least the deleted region of the modified HSV-1 genome” (recited in claim 6 of Zhou). Zhou further teaches that the oHSV-1 of the invention encompasses a deletion causing excision of nucleotide positions 117005 to 132096 in the genome of F strain (see claim 5 of Zhou), which is an embodiment of the deletion between the promoter of UL56 and the promoter of U51 of a wild-type HSV-1 genome.
However, Zhou does not directly teach systemic administration of the disclosed oHSV-1 to a subject for treating cancer. Instead, Zhou teaches that oHSVs are usually delivered directly into the tumor mass in which the virus can replicate, and that because it is delivered to the target tissue rather than systemically, there are no side effect characteristics of anti-cancer drugs (see [0002]). This teaching mentions systemic administration, indicating that this administration route is known at the time of the current invention.
It would have been prima facie obvious for one of ordinary skill in the art before the filing date of the current invention to modify the teachings of Zhou to arrive at the invention as currently claimed. E.g., one of skill in the art would have found it obvious to test systemic administration of the oHSV of Zhou when intratumor administration is not effective, or not practical – such as when treating a metastatic cancer. There is a reasonable expectation of success that systemic administration can be done and cancer treatment effect be evaluated.
Response to Applicant’s Arguments
Applicant’s arguments filed on Sep. 25, 2025 have been fully considered and are addressed as follows.
Applicant argues that significant scientific hurdles existed for systemic delivery of oHSV-1, including dilution by circulating fluids, interference by circulating blood components, and potential non-targeted infection (paragraph [0004] in the Background part of the present invention), and that there were several attempts to deliver oHSV systemically. Applicant argues that Kanzaki et al. shows that mice i.v. administered via tail-vein injection with oHSV-1 adsorbed onto lymphocytes (Groups 3 and 4) produced better anti-tumor effect than oHSV-1 only without lymphocyte carrier (Group 6), which is only slightly better than the PBS control (Group 5, Applicant argues that the difference is not significant). Applicant argues that Kanzaki and others evidently teach that oHSV has to be delivered on tumor antigen-specific lymphocytes in order to be effectively systematically administered, and that the status of the art teaches away from not using tumor antigen-specific lymphocytes as carrier to deliver oHSV.
Applicant’s arguments above are not persuasive. Systemic administration of oHSV for cancer treatment are performed regularly, as shown in Kanzaki et al. and other prior art references discussed in the current Specification, done in different formulations or in parallel with the other administration routes, for the purpose of comparison, even though it has been observed that systemic administration of oHSV has disadvantages and hurdles. Therefore, one of skill in the art would have found it obvious to test systemic administration of the oHSV of Zhou et al. for the same reasons as in other prior art studies.
As to the argument of teaching away, a prior art reference that "teaches away" from the claimed invention is a significant factor to be considered in determining obviousness; however, "the nature of the teaching is highly relevant and must be weighed in substance. A known or obvious composition does not become patentable simply because it has been described as somewhat inferior to some other product for the same use." In re Gurley, 27 F.3d 551,554, 31 USPQ2d 1130, 1132 (Fed. Cir. 1994). Here, as indicated above, systemic administration of oHSV in cancer treatment is tested regularly, even though disadvantages or hurdles are known.
Applicant argues that in the claimed invention, the oHSV-1 is not adsorbed on an antigen-specific lymphocyte, and that the examples of the present application had fully demonstrated that a single intravenous injection of such an oHSV-1 can effectively inhibit tumor growth, and that the examples showed that T3011, when systemically administered, maintains its tumor killing activity while not being cleared by the immune system of the host.
Applicant appears to be arguing based on unexpected results. As an initial matter, “the burden of showing unexpected results rests on he who asserts them. Thus it is not enough to show that results are obtained which differ from those obtained in the prior art: that difference must be shown to be an unexpected difference.” In re Klosak, 455 F.2d 1077, 1080 (CCPA 1972) (citation omitted). Moreover, “[i]t is well settled that unexpected results must be established by factual evidence. Mere argument or conclusory statements in the specification does not suffice.” In re De Blauwe, 736 F.2d 699, 705 (Fed. Cir. 1984) (citation omitted). Applicant’s attention is directed to MPEP 716.02(b)-(e) for how unexpected results can be established. E.g., to evaluate if the claimed invention produces unexpected results, one must consider if the results produced by the claimed invention are commensurate in scope with the claims and how the results compare with the closest prior art. See MPEP Section 716.02(d) and (e). Here, the instant specification discloses “Single-Injected Via Tail Intravenous of T3011 Inhibited KYSE30 Tumor Growth”, and “Single-Injected Via Tail Intravenous of T3011 Inhibited HCT116 and ECA109 Tumors Growth”. See [0072] and [0077]. There is not sufficient information for the Office to consider if the results produced by the claimed invention are commensurate in scope with the claims and how the results compare with the closest prior art.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to NIANXIANG (NICK) ZOU whose telephone number is (571)272-2850. The examiner can normally be reached on Monday - Friday, 8:30 am - 5:00 pm, EST. If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, JANET ANDRES, on (571) 272-0867, can be reached. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300. Information regarding the status of an application may be obtained from the Patent Application Information Retrieval (PAIR) system. Status information for published applications may be obtained from either Private PAIR or Public PAIR. Status information for unpublished applications is available through Private PAIR only. For more information about the PAIR system, see http://pair-direct.uspto.gov. Should you have questions on access to the Private PAIR system, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative or access to the automated information system, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/NIANXIANG ZOU/
Primary Examiner, Art Unit 1671