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 .
Status of Application/Amendments/Claims
Applicant’s response filed on 2/23/2026 has been considered. Claims 51-60 are newly added. Claims 32-60 are pending. Claims 32-49 are currently withdrawn without traverse from further consideration pursuant to 37 CFR 1.142 (b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Claims 50-60 are the subject of the present Official action. The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Priority
Applicant’s claim for the benefit of a prior-filed application KR10-2020-0035174 and 371 of PCT/KR2021/003488 filed on 3/23/2020 and 3/22/2021, respectively, under 35 U.S.C 119(e) or under 35 U.S.C 120, 121 or 365(c) is acknowledged.
Accordingly, the effective priority date of the instant application is granted as 3/23/3020
Withdrawn Rejections & Objections
The objection to claim 50 has been withdrawn in light of applicants claim amendments which import all the limitations from claim 32 into independent claim 50.
The 35 U.S.C. 103 rejection of claim 50 as being obvious over Sugio in view of Choi has been withdrawn in light of applicants claim amendments deleting the mRNA of AR as a target and limiting to STAT3.
Response to Applicants Arguments
Applicant points to claim amendments which delete the AR alternative and limits the expression cassette to simultaneously inhibiting mTOR and STAT3. Applicant argues that the cited references do not disclose or suggest this feature. Applicant points to experimental data presented in the specification to argue that the simultaneous suppression of mTOR and STAT3 protein expression in bladder cancer cell lines leads to superior antitumor efficacy.
This argument has been fully considered, but is not found persuasive since the newly applied rejections make obvious this new limitation by arguing that it would have been prima facie obvious to one of ordinary skill in the art to modify the double-stranded bispecific siRNA targeting mTOR described by Choi and use simple substitution to target STAT3 rather than AR as described by Santoni in the oncolytic adenovirus described by Sugio.
New 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 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.
Claims 50-53 and 56-60 are rejected under 35 U.S.C. 103 as being unpatentable over Sugio et al. "Enhanced safety profiles of the telomerase-specific replication-competent adenovirus by incorporation of normal cell-specific microRNA-targeted sequences." Clinical Cancer Research 17.9 (2011): 2807-2818 (hereinafter Sugio, reference of record) in view of Choi et al. KR20190009947A, published 1/30/2019 (hereinafter Choi, reference of record) and Santoni et al. "Role of STAT3 pathway in genitourinary tumors." Future science OA 1.3 (2015): FSO15 (hereinafter Santoni). This rejection is newly applied to address applicants claim amendments filed on 2/23/2026.
Claim 50: Sugio describes a method of inhibiting the growth of a tumor and treating cancer using an oncolytic adenovirus (Ad) comprising a human telomerase promoter (hTERT) and an expression cassette containing a first and second nucleotide sequence miR-122a and miR-199a (Sugio, abstract, Fig 5A shown below). In particular, Sugio found that the use of an oncolytic Ad and tumor-specific promoter like hTERT allowed for specific expression in cancer cells with high therapeutic efficacy (Sugio, abstract and intro para 1).
PNG
media_image1.png
160
494
media_image1.png
Greyscale
Claims 51-52: Sugio describes the hTERT promoter being operably linked with E1A and E1B of an endogenous gene of an oncolytic Ad with an IRES (pg 2809, col 1 and Fig 5).
Claim 53: Sugio describes an expression cassette which is regulated by a U6 promoter (Sugio, pg 2809 col 1).
Although Sugio describes an Ad vector which contains a bispecific miR construct under the control of a hTERT promoter, Sugio does not describe a bispecific siRNA or shRNA targeting the mRNA of mTOR and mRNA of STAT3.
Claim 50: However, such bispecific shRNA constructs targeting the mRNA of mTOR were known in the prior art as shown by Choi. Choi describes a double-stranded bispecific siRNA nucleic acid molecule that simultaneously inhibits the expression of mTOR and AR genes as an anticancer therapy (Choi, para 6, 8, 13 and claim 1). Choi describes how both mTOR and AR can be related to uncontrolled cell growth and proliferation and the advantages of targeting both simultaneously as an anticancer therapy (Choi, para 6, and 13). Choi provides alternative embodiments to the use of adenoviral vectors for delivering the bispecific nucleic acid molecule (Choi, para 31).
Claim 56: Choi describes expression of the bispecific construct as a single shRNA molecule (Choi, fig 1).
Claims 59-60: Choi describes the further administration of anticancer agents like cisplatin which provide synergistic anticancer activity (Choi, claim 13 pg 2).
Neither Choi nor Sugio describe a bispecific shRNA construct targeting the mRNA of mTOR and STAT3 as described in newly amended claim 50.
Claim 50: Santoni describes the important role of the STAT3 pathway in genitourinary tumors and describes its role in acting as a transcription factor for promoting tumor invasion (Santoni, pg 2 col 1). Santoni identifies STAT3 as an important and therapeutically relevant target for treating genitourinary tumors like bladder cancer (Santoni, Fig 1).
Claims 57 and 58: Santoni describes how STAT3 is overexpressed in many genitourinary tumors and bladder cancer types (Santoni, Fig 1).
It would have been prima facie obvious to one of ordinary skill in the art to modify the double-stranded bispecific siRNA targeting mTOR described by Choi and use simple substitution to target STAT3 rather than AR as described by Santoni in the oncolytic adenovirus described by Sugio. It would have been a matter of simple substitution of one known element for another to target the mRNA of STAT3 rather than AR using routine and commonly known techniques of molecular biology. One would have been motivated to make this substitution since both mTOR and STAT3 are oncogenes associated with cell growth and proliferation and are known targets for anticancer therapy especially in bladder cancers. One would have a reasonable expectation of success given that the oncolytic STAT3 and tumor-specific promoter like hTERT used by Sugio allow for specific expression in bladder cancer cells with high therapeutic efficacy. Accordingly, in the absence of evidence to the contrary, one of ordinary skill in the art would have considered claims 50-53 and 56-60 to have been prima facie obvious to at the time the invention was made.
Claims 50-60 are rejected under 35 U.S.C. 103 as being unpatentable over Sugio et al. "Enhanced safety profiles of the telomerase-specific replication-competent adenovirus by incorporation of normal cell-specific microRNA-targeted sequences." Clinical Cancer Research 17.9 (2011): 2807-2818 (hereinafter Sugio, reference of record) in view of Choi et al. KR20190009947A, published 1/30/2019 (hereinafter Choi, reference of record) and Santoni et al. "Role of STAT3 pathway in genitourinary tumors." Future science OA 1.3 (2015): FSO15 (hereinafter Santoni) as applied to claims 50-53 and 56-60 in further view of Shenk. "Delivery systems for gene therapy: the adenovirus." Stem Cell Biology and Gene Therapy (1998): 161-178 (hereinafter Shek). This rejection is newly applied to address applicants claim amendments filed on 2/23/2026.
A description of Sugio, Choi and Santoni can be found above with respect to claims 50-53 and 56-60. The collection of cited art is silent with respect to the specific adenovirus serotypes from group C and type 5 since Sugio only generically recites the use of adenovirus.
Claims 54 and 55: However, both group C adenovirus and type 5 adenovirus are routinely used gene therapy vectors and have advantages in their ability to propagate rapidly and hold large therapeutic payloads, which is particularly relevant for the large bispecific shRNA construct being delivered (Shenk, pg 162)
It would have been prima facie obvious to one of ordinary skill in the art to select a group C or type 5 adenovirus serotype given the generic adenovirus disclosure of Sugio. It would have been a matter of combining prior art elements according to known methods to yield predictable results for one of ordinary skill in the art to select either the group C or type 5 adenovirus serotype. One would have been motivated to make this selection given their ability to propagate rapidly and hold large therapeutic payloads, which is particularly relevant for the large bispecific shRNA construct being delivered (Shenk, pg 162). One would have a reasonable expectation of success given that these are well characterized adenovirus serotypes which could accommodate large cargo like a bispecific shRNA. Accordingly, in the absence of evidence to the contrary, one of ordinary skill in the art would have considered the claimed invention to have been prima facie obvious to at the time the invention was made.
Conclusion
No claims 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 extension fee 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 ALEXANDER NICOL whose telephone number is (571)272-6383. The examiner can normally be reached on M-F 8-5 EST.
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, Maria Leavitt can be reached on (571)272-1085. 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 https://ppair-my.uspto.gov/pair/PrivatePair. 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.
Alexander Nicol
Patent Examiner
Art Unit 1634
/ALEXANDER W NICOL/Examiner, Art Unit 1634
/FEREYDOUN G SAJJADI/Supervisory Patent Examiner, Art Unit 1699
Prosecution Insights