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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 8/22/2025 has been entered.
All previous rejection not reiterated in this office action are withdrawn.
Claims 1-3, 5-19 are pending in the application. Claims 8-15 are withdrawn. Claims 1-3, 5-7, 16-19 are currently under examination.
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.
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 1-3, 5-7, 17 and 18 is/are rejected under 35 U.S.C. 103 as being unpatentable over Durden (US 6,777,439, IDS) and Parsons (US 9017981, cited previously), in view of Martuza (US 2009/0285860). This rejection is rewritten to address the amendment.
Durden teaches a nucleic acid encoding a PTEN (Col.13, lines 60-61, and 66, Col.14, lines 21-25). Durden teaches the nucleic acid encodes a PTEN from human origin (Col.14, lines 23-24). Durden teaches a variety of vectors may be used to deliver said PTEN nucleic acid to a target cell, wherein the vectors includes viruses such as SV40, vaccinia virus, herpes viruses HSV and EBV, retroviruses (col.23, liens 15-20). Durden also teach PTEN is a pivotal signaling molecule which modulates a wide variety of cellular processes, and mutations in PTEN have been associated with malignant progression of brain tumors (col.2, lines 26-29). Durden teaches delivering native PTEN encoding nucleic acid to cancer cells to treating cancer associated with PTEN mutation (col.2, lines 34-40). Durden demonstrates glioblastoma U87MG cells engineered to stably express PTEN sensitizes the cells to chemotherapeutic agents (example 5, lines 64).
However, Durden does not teach the PTEN gene is PTEN-long gene, and HSV lacks functional UL56 protein (claim 1), and the virus vector has been modified to place critical genes for replication under the control of a tumor specific promoter (claim 3).
Parson teaches a PTEN-long, which is a differentially translated PTEN that contains a N-terminal signal peptide and secreted extracellularly (col.3, lines 23-26). Parson teaches expression vectors comprising nucleic acid encoding PTEN-long (col.4, lines 44-54). Parson teaches injection of PTEN-long to the mouse xenografts U87 model showed inhibition of angiogenesis compared to PTEN, suggesting PTEN-long affects the tumor environment (col.21, lines 20-26). Parson teaches PTEN-long is a novel antitumor compound that is normally present in human serum, which has anti-angiogenic and pro-apoptotic properties (col. 22, lines 49-51).
Martuza et al. teach cancer immunotherapy that comprises oncolytic virus compositions, wherein the preferred oncolytic virus comprises HSV1 that do not express functional ICP34.5, and/or other genes including UL56 (paragraph [0061], lines 1-4, and lines line 17). Martuza et al. teach said oHSV can include exogenous nucleic acid, serving as oncolytic virus vector, preferably encodes an anti-oncogenic or oncolytic gene product, and the gene product inhibits growth or replication of only the cell infected by virus (paragraph [0060]).
It would have been obvious to an ordinary skilled in the art that the PTEN variant, PTEN long has tumor suppressive action in a mouse model of glioblastoma based on the teaching from Parson. The ordinary skilled in the art reading Durden would be motivated to use PTEN-Long to further testing the specific form of PTEN’s ability to treat cancer because Parson teaches PTEN-long is an antitumor compound. It would have been obvious to an ordinary skilled in the art that the oncolytic vectors may be used to deliver PTEN long may be modified to knockout specific genes such as ICP34.5 and/or UL56 to target specific cancer based on combined teaching of Durden, Parson and Martuza. The ordinary skilled in the art would be motivated to use the modified HSV-1 to deliver the PTEN-Long rendered obvious by Durden and Parson because Martuza specifically teaches oncolytic vector that encoding anti-oncogenic gene product that inhibits growth or replication of only the cell infected by virus (paragraph [0060]). It would have been obvious to an ordinary skilled in the art to use tissue specific promoter to direct the expression of PTEN-Long depending on the type of tissue the tumor originates. The ordinary skilled in the art would have reasonable expectation of success following teaching from Durden, Parson and Martuza to make a recombinant virus such as NV1020 (with UL56 deletion) with PTEN-Long inserted into said vector. Therefore, the claimed invention of claims 1, 2 and 5 would have been prima facie obvious to an ordinary skilled in the art at the time the application was filed.
Regarding claim 3, Martuza teaches the main transcriptional unit of an HSV may be placed under transcriptional control of tumor growth factor-beta promoter, because it is known that certain tumor cells overexpress TGF-beta, relative to non-tumor cells of the same type (paragraph [00063]), which meets the limitation of tumor specific promoter.
Regarding claim 6, Durden teaches the expression of PTEN is under inducible promoter that respond to muristirone (col.6, lines 62-65).
Regarding claim 7, Durden discloses the U87MG cells are transfected with PTEN gene under constitutive or muristirone induced conditions (col. 40, lines 45-49), which meets the limitation of PTEN gene operably linked to constitutive or inducible promoter.
Regarding claims 17 and 18, the PTEN-L gene taught by Parson comprises nucleic acid sequence having 99.9% identical to SEQ ID NO: 1 (see attached alignment). Since the specification does not disclose any amino acid sequence that is encoded by SEQ ID NO:1, nor does the specification teach any modification to PTEN-L gene, the PTEN-L gene taught by Parson meets the claimed limitation of both claims.
Claim(s) 16 and 19 is/are rejected under 35 U.S.C. 103 as being unpatentable over Durden, Martuza and Parson, as applied to claim 1 above, and further in view of Kaur (US20100272686).
The teaching from Durden, Martuza and Parson has been discussed above. However, they do not teach the oncolytic virus being HSVQ (19) or HSV-P10 (16).
Kaur teaches generation of oncolytic virus capable of killing target cells, wherein the oncolytic virus is armed or encodes a therapeutic polypeptide (abstract). Kaur teaches using HSVQuick methodology to produce oncolytic virus expressing a heterologous polypeptide, wherein the entire HSV-1 genome lacking a functional ICP6 gene and deleted in both copies of the gamma 34.5 gene (paragraph [0107]). Kaur teaches such modifications allows the virus to replicate selectively in cancer cells (paragraph [0107]).
It would have been obvious to an ordinary skilled in the art to use HSVQ as oncolytic virus to express PTEN-Long gene because Kaur already demonstrates that HSVQ can target and replicate in tumor cells and expressing heterologous protein. The ordinary skilled in the art would thus be motivated to use said recombinant oncolytic HSV to express PTEN-Long. The specification teaches HSV-P10 is a HSV-1 with doubly deleted gamma 34.5 and insertional mutation in viral ICP6, including GFP and PTEN-Long expression vectors. As such, the resultant recombination HSV that comprises PTEN-Long and HSVQ meets the structural limitation of HSV-P10. Therefore, the claimed invention of claims 16 and 19 would have been prima facie obvious to an ordinary skilled in the art at the time of filing in view of combined teaching from Durden, Martuza, Parson and Kaur.
Response to Arguments
Applicant’s arguments are directed to prior cited references, Durden and Kambara. Since the above rejection has been rewritten to address the amended claims, and uses different combination of references, the arguments are considered moot.
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 filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual 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/apply/applying-online/eterminal-disclaimer.
Claims 1-3, 5-7, 16-19 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 16, 21-24, 35 and 36 of copending Application No. 18151,195, in view of Kaur.
Claims 16, 21-24, 35 and 36 of ‘195 application recites a recombinant HSV comprising an expression cassette encoding PTEN-Long, which overlaps in scope with the currently claimed HSV in claims 1-3, 5-7, 16-19 (target tumor cells, tissue specific, constitutive and inducible promoter), except that the HSV comprises HSV-1 backbone, HSVQ, HSV-P10.
Kaur teaches generation of oncolytic virus capable of killing target cells, wherein the oncolytic virus is armed or encodes a therapeutic polypeptide (abstract). Kaur teaches using HSVQuick methodology to produce oncolytic virus expressing a heterologous polypeptide, wherein the entire HSV-1 genome lacking a functional ICP6 gene and deleted in both copies of the gamma 34.5 gene (paragraph [0107]). Kaur teaches such modifications allows the virus to replicate selectively in cancer cells (paragraph [0107]).
It would have been obvious to an ordinary skilled in the art to use HSVQ as oncolytic virus to express PTEN-Long gene because Kaur already demonstrates that HSVQ (which comprises HSV-1 backbone) can target and replicate in tumor cells and expressing heterologous protein. The ordinary skilled in the art would thus be motivated to use said recombinant oncolytic HSV to express PTEN-Long. The specification teaches HSV-P10 is a HSV-1 with doubly deleted gamma 34.5 and insertional mutation in viral ICP6, including GFP and PTEN-Long expression vectors. As such, the resultant recombination HSV that comprises PTEN-Long and HSVQ meets the structural limitation of HSV-P10.
This is a provisional nonstatutory double patenting rejection.
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/CELINE X QIAN/Primary Examiner, Art Unit 1637