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 .
Claims 16, 21-24, 26-36 are pending in the application. Claims 26-34 are withdrawn. Claims 16, 21-24, 35 and 36 are currently under examination.
This office action is in response to the amendment filed on 8/20/2020.
All previous rejection not reiterated in this office action are withdrawn.
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 16, 21-24 and 35 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 16), and the virus vector has been modified to place critical genes for replication under the control of a tumor specific promoter (claim 22), and PTEN gene linked to a constitutive promoter (claim 24) .
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]). 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 claim 16, 21 and claim 35 would have been prima facie obvious to an ordinary skilled in the art at the time the application was filed.
Regarding claim 22, 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 23, Durden teaches the expression of PTEN is under inducible promoter that respond to muristirone (col.6, lines 62-65).
Regarding claim 24, 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.
Response to Arguments
Applicant argues that combined teaching from prior art does not teach each and every element of the claimed invention.
This argument is not persuasive for reasons discussed in the above rewritten rejection addressing specifically to amended claim 16 and dependent claims thereof.
Applicant argues that the ability of an oncolytic virus to spread and replicate within a tumor cell is critical to its therapeutic modality, a POSITA would consider whether a transgene payload to be delivered by an oncolytic HSV would impair the ability of the oncolytic virus to infect and replicate in a subject. Applicant argues that the ability of an oncolytic virus to spread and replicate within a tumor cell is critical to its therapeutic modality, a POSITA would consider whether a transgene payload to be delivered by an oncolytic HSV would impair the ability of the oncolytic virus to infect and replicate in a subject. Applicant asserts that the art at the filing date indicated that restoration of PTEN expression in PTEN deficient tumor cells drives an anti-viral response to oncolytic viruses and diminish the ability of an oncolytic virus to infect and replicate in tumor cells before being immune-neutralized. Applicant cites Matveeva in support of this point. Applicant asserts that Matveeva is pointing to a number of different studies using different viruses, and point out how diverse genes involved in the interferon pathway and affecting viral infection/replication have been observed across a wide range of viruses in various studies.
The above argument has been considered but deemed unpersuasive. While the teaching from Matveeva establishes the relationship between PTEN and antiviral innate immunity, none of the reference teaches that viral vectors having HSV-1 backbone would not be able to deliver a transgene into tumor cells. In fact, as discussed in the rejection above, Martuza specifically teaches oncolytic vectors that targeting tumor to deliver anti-oncogenic genes, wherein said HSV lacks expression of certain genes including UL56 and ICP34.5. Therefore, for reasons discussed in the previous office action and set forth above, this rejection is still considered proper and maintained.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 35 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends. Claim 35 recites the expression cassette encodes PTEN-Long, which is already recited in claim 16. Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements. This is a new ground of rejection necessitated by amendment.
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claim 16, 21-24, 35 and 36 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention. This is a new matter rejection.
Newly amended claim 16 recites oncolytic HSV lacks functional ICP35.5 expression. Applicant states that the support to claim 16 can be found in the specification at page 8, lines 21-24. However, there is no teaching in this section referring to HSV lacking ICP35.5 expression. In fact, there is no teaching from the entire specification referring to HSV lacking ICP35.5 expression. Since this limitation is introduced after filing of the original specification, it constitutes new matter. Dependent claims 21-24 35 and 36 are rejected for same reason because they all contain this limitation. Moreover, claim 36 recites “the HSV comprises a null mutation in a gene encoding ICP34.5,” which is in addition to the HSV lacks UL56 or ICP35.5 recited in claim 16. However, there is no teaching from the entire specification describes a HSV comprises this specific double knockout of UL56 and ICP34.5. Since this limitation is introduced after filing of the original specification, it constitutes new matter.
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.
Claim 16, 21-24 and 35 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1-3 and 5-7 of copending Application No. 16/321,777 (reference application), in view of Martuza
Claims 1-3, 5-7 of ‘777 application recites a recombinant oncolytic HSV comprising a HSV-1 backbone and a mammalian PTEN long gene, which overlaps in scope with the currently claimed HSV in claims 16, 21-24 and 35 (target tumor cells, tissue specific, constitutive and inducible promoter), except that the presence of a UL56 deletion.
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 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 teaching of Martuza. The ordinary skilled in the art would be motivated to use the modified HSV-1 to deliver the PTEN-Long rendered obvious 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]), wherein such HSV vector including the modified vector lacking UL56 expression (paragraph [0061]). Therefore, the claimed invention of claim 16, 21-24 and claim 35 would have been prima facie obvious to an ordinary skilled in the art at the time the application was filed in view of claims 1-3 and 5-7 of ‘777 application and the teaching from Martuza.
This is a provisional nonstatutory double patenting rejection.
Conclusion
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 CELINE X QIAN whose telephone number is (571)272-0777. The examiner can normally be reached M-F (8-4:00).
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/CELINE X QIAN/Primary Examiner, Art Unit 1637
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