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 .
DETAILED ACTION
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 01/21/2026 has been entered.
Disposition of Claims
Claims 1-2, 4-7, 9-16, and 18-19 remain pending. Amendments to claims 1, 6, and 15 are acknowledged and entered. Claims 3, 8, and 17 remain cancelled. Claims 1-2, 4-7, 9-16, and 18-19 will be examined on their merits.
Examiner’s Note
All paragraph numbers (¶) throughout this office action, unless otherwise noted, are from the US PGPub of this application US20230242887A1, Published 08/03/2023. Amendments to the specification presented on 01/25/2024 are acknowledged and entered.
Response to Arguments
Applicant's arguments filed 01/21/2026 regarding the previous Office action dated 10/21/2025 have been fully considered. If they have been found to be persuasive, the objection/rejection has been withdrawn below. Likewise, if a rejection/objection has not been recited, said rejection/objection has been withdrawn. If the arguments have not been found to be persuasive, or if there are arguments presented over art that has been utilized in withdrawn rejections but utilized in new rejections, the arguments will be addressed fully with the objection/rejection below.
Claim Interpretation
The claims in this application are given their broadest reasonable interpretation using the plain meaning of the claim language in light of the specification as it would be understood by one of ordinary skill in the art.
Claim 1 is drawn to an oncolytic herpes simplex virus-1 (oHSV-1) vector comprising a heterologous, human E-cadherin gene and an HSV IE4/5 promoter, wherein the heterologous, human E-cadherin (CDH1, E-cad) gene is immediately adjacent to the HSV IE4/5 promoter, and wherein the heterologous, human E-cadherin gene is driven by the HSV IE4/5 promoter.
Further limitations on the viral vector of claim 1 are wherein the HSV IE4/5 promoter is selectively active during HSV replication (claim 2); wherein the oHSV-1 further comprises an ICP 6-inactivating mutation or deletion (claim 4); and wherein the oHSV-1 further comprises a gamma (y) 34.5 inactivating mutation or deletion (claim 5).
Claim 6 is drawn to a method for treating a subject having a tumor, the method comprising: administering to a subject in need thereof a therapeutic amount of an oncolytic herpes simplex virus-1 (oHSV-1) comprising a heterologous, human E-cadherin gene and an HSV IE 4/5 promoter, wherein the heterologous, human E-cadherin (CDH1, E-cad) gene is immediately adjacent to the HSV IE4/5 promoter, and wherein the heterologous, human E-cadherin gene is driven by the HSV IE4/5 promoter.
Further limitations on the method of claim 6 are wherein the HSV IE4/5 promoter is selectively active during HSV replication (claim 7); wherein the oHSV-1 further comprises an ICP 6-inactivating mutation or deletion (claim 9); wherein the oHSV-1 further comprises a gamma (y) 34.5 inactivating mutation or deletion (claim 10); wherein the tumor is a solid tumor (claim 11), wherein the solid tumor is a glioblastoma, an ovarian tumor or a breast tumor (claim 12); and wherein the subject is a mammal (claim 13), wherein the mammal is a human (claim 14).
Claim 15 is drawn to a pharmaceutical composition comprising an oncolytic HSV-1 (oHSV-1) and a pharmaceutically acceptable carrier or diluent, wherein the oHSV-1 comprises a heterologous, human E-cadherin gene and an HSV IE4/5 promoter, wherein the heterologous, human E-cadherin (CDH1, E-cad) gene is immediately adjacent to the HSV IE4/5 promoter, and wherein the heterologous, human E-cadherin gene is driven by the HSV IE4/5 promoter.
Further limitations on the pharmaceutical composition of claim 15 are wherein the HSV IE4/5 promoter is selectively active during HSV replication (claim 16); wherein the oHSV-1 further comprises an ICP 6-inactivating mutation or deletion (claim 18); and wherein the oHSV-1 further comprises a gamma (y) 34.5 inactivating mutation or deletion (claim 19).
Claim Rejections - 35 USC § 112(a); First Paragraph
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.
(New rejection – necessitated by amendment.) Claims 1, 6, and 15, and dependent claims 2, 4-5, 7, 9-14, 16, and 18-19 thereof 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.
The term “immediately adjacent” as recited in claims 1, 6, and 15 are not supported by the original disclosure or claim as filed.
Applicant’s amendment, filed 01/21/2026, directs to support to paragraphs [0015][0063][0094] of the specification, along with Fig. 1A, and asserts that no new matter has been added.
However, the specification as filed does not provide sufficient written description of the above-mentioned limitations. The specification does not provide sufficient support for a heterologous transgene that is “immediately adjacent” to the IE4/5 promoter. Under broadest reasonable interpretation, “immediately adjacent” could be construed as 5’ or 3’ to the IE4/5 promoter, but it is unclear as to the metes and bounds as to what is, and what is not “immediately adjacent”. The specification specifically discloses a cartoon drawing of a IE4/5 promoter upstream of a E-cadherin gene, and at ¶[0083] notes the engineering of the oHSV was performed with the fHsvQuik-1 system and that SEQ ID NO: 1 (encoding human CDH1) was cloned into the plasmid “following the HSVIE4/5 promoter”. No sequences for the overall resulting oHSV or region of the oHSV comprising the CDH1 transgene were provided, so it is unclear if the sequence of the IE4/5 promoter is followed immediately downstream by the CDH1 transgene sequence, or if there is intervening sequence between. Therefore, the claims represent a departure from the specification and claims as originally filed, as no specific definition of what is, or what is not, “immediately adjacent” has been provided in the original specification. Additionally, from Applicant’s arguments, they appear to be attempting to narrowly define this limitation (p. 2 of “Remarks”) as the IE4/5 promoter sequence is then immediately followed by the CDH1 with no intervening sequence. However, as the art is apprised (See ¶[0085-0091] of Kaur), there can be additional elements, promoter/transgene arrangements, and non-coding sequences that are within the region that allow for the heterologous transgene to be “operably expressed” from said promoter, and that a skilled artisan would take the disclosure of Kaur to read upon “immediately adjacent” to the IE4/5 promoter, even though it may have additional intervening sequence.
Applicant’s reliance on the generic disclosure (Fig. 1 cartoon, ¶[0015][0063][0094]) does not provide sufficient direction and guidance to the features currently claimed (immediate adjacency of the CDH1 transgene). The instant claims now recite limitations that were not clearly disclosed in the original specification as filed, and now change the scope of the instant disclosure as filed.
Such limitations recited in the present claims, which did not appear in the original specification as filed, introduce new concepts and violate the description requirement of the first paragraph of 35 U.S.C. §112. Applicant is required to cancel the new matter in the response to this Office Action. Alternatively, applicant is invited to provide sufficient written support for the “limitations” indicated above. See MPEP §714.02, §2163.05-06 and §2173.05(i).
Claim Rejections - 35 USC § 103
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
(Rejection maintained.) Claims 1-2, 4-7, 9-16, and 18-19 remain rejected under 35 U.S.C. 103 as being unpatentable over Kaur et. al. (US20130316447A1, Pub. 11/28/2013; hereafter “Kaur”) in view of
Garcia-Rodriguez et. al. (Garcia-Rodríguez L, et. al. Gene Ther. 2011 Jan;18(1):73-81. Epub 2010 Aug 19.; hereafter “Garcia-Rodriguez”);
Corbel et. al. (US20190263899A1; Priority 11/14/2016; CITED ART OF RECORD; hereafter “Corbel”); and
Dewhurst et. al. (US20100316609A1; Pub. 12/16/2010; hereafter “Dewhurst”.)
The analysis of the prior art has been set forth in previous Office actions and will not be repeated herein.
Response to Arguments
Applicant's arguments filed 01/21/2026 have been fully considered but they are not persuasive.
Applicant argues that with the amendments to claims 1, 6, and 15, that it was clarified that the heterologous human E-cadherin gene is immediately adjacent to the HSV IE4/5 promoter and is driven by said promoter, and therefore overcomes the noted art as none of the art teaches or suggests this specific arrangement. However, as noted supra, this newly presented limitation of “immediately adjacent” is new matter.
Even if in arguendo there were support for the limitation “immediately adjacent”, Kaur reasonably teaches this specific placement for heterologous genes under operable control of the IE4/5 promoter (Fig. 2) and notes the placement in the oHSV is that the native HSV immediate early IE4/5 promoter is operably linked to a therapeutic transgene (¶[0016-0017][0019][0021-0022][0024-0026]). As shown in Fig. 2 of Kaur, the IE4/5 promoter is immediately adjacent/upstream to the heterologous transgene, vasculostatin, and Figs. 4-5 confirm said oHSV expresses said heterologous transgene. Kaur teaches the IE4/5 promoter is preferred to the constitutively active cytomegalovirus (CMV) promoter, as it is better for GBM therapy because the IE4/5 promoter (SEQ ID NO: 5) drives the expression of the transgene to levels unseen with a CMV promoter (¶[0048]). Kaur notes the definition of “operably linked” at ¶[0066] in that the elements are “functionally connected and are able to interact with each other”. Kaur notes at ¶[0088] that “The promoter comprises a DNA regulatory sequence, wherein the regulatory sequence is derived from a gene, which is capable of binding RNA polymerase and initiating transcription of a downstream (3′-direction) coding sequence.” Kaur then goes further at ¶[0089] to state that “To bring a coding sequence “under the control of” a promoter, one positions the 5′ end of the transcription initiation site of the transcriptional reading frame “downstream” of (i.e., 3′ of) the chosen promoter. The “upstream” promoter stimulates transcription of the DNA and promotes expression of the encoded RNA.” Kaur notes the spacing between the promoter and nucleic acid elements can be flexible, so long as the promoter function is preserved (¶[0090]).
Therefore, Applicant’s arguments that the limitation of the E-cadherin gene being “immediately adjacent” to the IE4/5 promoter are not persuasive, and the rejection has been maintained.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to RACHEL B GILL whose telephone number is (571)272-3129. The examiner can normally be reached on M to F 8:00 AM to 5:00 PM Eastern.
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/RACHEL B GILL/Primary Examiner, Art Unit 1671