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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 10/31/2025 has been entered. Applicant's response filed on 10/31/2025 has been received and entered into the case.
Declaration under 37 CFR 1.132
The declaration under 37 CFR 1.132 filed by Dr. Stephen Thorne on 10/31/2025 is insufficient to overcome the rejection of instant claims based upon 35 U.S.C 103 as set forth in the last Office action.
Claim Status
Claims 212, 219-223 and 225-244 are pending.
Claims 219, 223, 232 and 240-241 have been withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to non-elected inventions, there being no allowable generic or linking claim. Elections were made without traverse on 03/31/2023 and 06/26/2024.
Claims 212, 220-222, 225-231, 233-239 and 242-244 are considered on the merits.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 10/31/2025 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner. The corresponding signed and initialed PTO form 1449 has been mailed with this action.
Maintained 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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
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 230, 220, 225-229, 234, 236-237, 242 and 244 stand rejected under 35 U.S.C. 103 as being unpatentable over Thorne (US PGPub 2016/0235793 A1, published 08/18/2016. Cited in IDS 06/04/2021) in view of Gaston et al (PLoS ONE. 2013; 8(11): e81768. P. 1-13. Cited in IDS 06/28/2022).
With respect to independent claim 230, Thorne teaches an oncolytic vaccinia virus that have been modified to promote anti-tumor immunity and/or to reduce host immunity and antibody response against the virus that can be used in the treatment of cancers (abstract), thus teaches the preamble an oncolytic virus and the limitation the oncolytic virus comprising a modified viral genome in claim 230.
In regard to the oncolytic virus, Thorne teaches in Examples 1-7 an oncolytic virus, specifically a Western Reserve vaccinia virus that belongs to poxvirus (thus teaches claims 226, 227 and 228), comprising a deletion of the thymidine kinase gene (TK-) (thus teaches claims 229 and 234). Thorne teaches the oncolytic virus is modified in the viral genome to delete various viral genes to promote anti-tumor immunity and to reduce host immunity against the virus (abstract). Specifically in Example 7, Thorne teaches the virus comprises an enveloped extracellular form (EEV)-enhancing point mutation in the A34R viral gene that increases activity and spread (p. 16, right col, para 13, also see Fig 29), thus teaches claims 220 and 225.
In regard to exogenous nucleic acids encoding cytokines, Thorne teaches that “VV is modified to include one or more nucleic acids encoding a peptide or protein which promotes a T cell response…which can promote the expression of one or more proinflammatory cytokines…can include …IL-12, IL-15, IL-18, … IFN-γ” ([0054]) and “the nucleic acid may encode GM-CSF, IL-12, IFN-γ or IL-18” and “more than one such nucleic acid may be incorporated into VV” ([0057]), thus suggests the oncolytic virus comprises more than one exogenous nucleic acids encoding separate proteins (such as cytokines GM-CSF, IL-12, IFN-γ or IL-18, see [0057]), encompassing the claimed a first cytokine, a second cytokine and a third cytokine in claim 230 and claim 242. Since Thorne teaches the encoded protein promotes expression of cytokine IL-15 (see [0054] above), one of ordinary skill in the art would have immediately acknowledged that the most direct approach to promote IL-15 expression would be that the virus is modified to include a nuclei acid encoding IL-15 itself. Thus, one of ordinary skill in the art would have appreciated that Thorne has suggested an oncolytic virus comprising an exogenous nucleic acid that codes for a first cytokine wherein the first cytokine is IL-15, and an exogenous nucleic acid that codes for a second cytokine in claim 230, and an exogenous nucleic acid that codes for a third cytokine in claim 242. Furthermore, Thorne teaches the one or more peptides or proteins can result in the increased expression of one or more immune activating chemokines (end of [0058]), thus suggests one of the cytokines being a chemokine in claim 244.
Accordingly, it would have been obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the Western Reserve vaccinia virus comprising a deletion of the thymidine kinase gene and a mutation in the A34R gene disclosed by Thorne, by incorporating multiple exogenous nucleic acids that code for a first cytokine, a second cytokine and a third cytokine in which the first cytokine is IL-15 and one cytokine is a chemokine as suggested by Thorne with a reasonable expectation of success. One of ordinary skill in the art would have had a reason to do so in order to promote anti-tumor immunity of the oncolytic virus for cancer treatment, since Thorne teaches vaccinia viruses have been used in clinical trial against multiple types of cancers ([0003], [0004], [0147]), and suggests VV can be modified to include more than one nucleic acids encoding separate peptides or proteins, such as cytokines and chemokines to promote expression of proinflammatory cytokines such as IL-15 to promote immune cell responses (see p. 5-6, para 5.3 and 5.4).
However, Thorne does not specifically teach the oncolytic virus comprises nucleic acids encoding for separate protein expression products, i.e., a second exogenous nucleic acid that codes for IL15-Ra or a functional variant in claim 230, or the functional variants of IL15 and IL15-Ra comprise functional fragments in claims 236-237.
Gaston teaches an oncolytic herpes simplex virus (oHSV) comprising a first exogenous nucleic acid encoding IL15 (transcript variant 1 from InvivoGen) and a second exogenous nucleic acid encoding IL15-Ra (transcript variant 1 from InvivoGen) and the IL15 and IL15-Ra are expressed separately (abstract, p. 2, right col, last para - p. 3, left col, para 1, see Fig 1A), thus teaches an oncolytic virus comprising exogenous nucleic acids that code for separate IL15 and IL15-Ra functional variants in claim 230. Gaston teaches the virus comprising both IL15 and IL15-Ra (J100D) results in enhanced production of IL-15 in infected tumor cells as compared to virus comprising IL15 alone (J100), suggesting that IL15-Ra improves IL15 production (see e.g., abstract and Fig 3). Gaston teaches the IL15 and IL15-Ra expressed by the oncolytic virus form soluble IL-15/IL-15Rα complex, which is bioactive evidenced by being capable of stimulating NK cells to proliferate and reduce the viability of syngeneic GL261 and CT-2A tumor cells (abstract, p. 7, right col - p. 8, left col, para 1, see Fig 4 and Fig 5), thus teaches the functional variant of IL15 comprises a functional fragment in claim 236 and the functional variant of IL15-Ra comprises a functional fragment in claim 237. Gaston teaches “IL-15 produced in the tumor microenvironment can stimulate anti-tumor immune responses that improve survival” (p. 11, left col, para 1) and IL-15Rα “greatly increased the production of IL-15 (Figure 3A). This is likely due to increased stability of IL-15 when in complex with IL-15Rα” (p. 10, left col, para 2).
Therefore, it would have been obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the oncolytic virus comprising multiple nucleic acids encoding for separate cytokines/chemokines as suggested by Thorne, by choosing a functional variant of IL15 comprising a functional fragment and by combining a separate functional variant of IL15-Ra comprising a functional fragment as taught by Gaston with a reasonable expectation of success. Since Thorne suggests the oncolytic virus can be modified to include more than one nucleic acids encoding for separate cytokines/chemokines to promote expression of cytokines such as IL-15 to promote immune cell responses (see p. 5-6, para 5.3 and 5.4), and since Gaston teaches coexpression of IL15 and IL15-Ra greatly increases IL15 production (abstract and Fig 3) and stability (p. 10, left col, para 2), and the soluble functional IL-15/IL-15Rα complex can stimulate T cells and NK cells to proliferate and reduce the viability of syngeneic tumor cells (abstract, p. 7, right col - p. 8, left col, para 1, see Fig 4 and Fig 5), one of ordinary skill in the art would have had a reason to combine IL15 and IL15-Ra of Gaston in the oncolytic virus of Thorne in order to obtain enhanced anti-tumor immunity. Furthermore, since both Thorne and Gaston teach treating glioma (see [0147] of Thorne), there would have been a reasonable expectation of success to make and use the taught modified oncolytic viruses comprising IL15 and IL15-Ra for this purpose.
Hence, the claimed invention as a whole was prima facie obvious to a person of ordinary skill before the effective filing date of the claimed invention in the absence of evidence to the contrary.
Response to Traversal:
Applicant's arguments and Dr. Stephen Thorne’s declaration filed on 10/31/2025 are acknowledged.
Applicant argues that (1) the Office cannot use simply what is not prohibited as a basis for motivation to substitute for what is taught or suggested by the cited publications (regarding examiner’s response mailed on May 2, 2025, at page 30). Thorne does not mention anything about a VV encoding for exogenous IL15, neither does Thorne expressly discloses exogenous expression of a second cytokine. Gaston does not teach or suggest a second cytokine. (Remarks, p. 5-6).
Applicant’s argument has been fully considered but it is not persuasive.
As a first matter, Applicant’s quotation from the prior Office action mailed on May 2, 2025 (at page 30) is from examiner’s response to Applicant’s previous argument that “Thorn explicitly describes exogenous nucleic acids (encoding for other than IL-15) which may, once expressed, result in increased expression of endogenous IL-15” (Applicant's arguments filed on 03/07/2025, p. 6-7). In that response, examiner points out that “Applicant’s argument … is not supported by the reference of Thorn. Nowhere in Thorn explicitly prohibits incorporating an exogenous nucleic acid encoding IL-15 into the virus to result in increased expression of exogenous IL-15.” Therefore, it is clear that the quotation (of what is not prohibited) was not used as a basis for motivation.
Furthermore, although Thorne does not provide a preferred embodiment of an oncolytic virus comprising exogenous nucleic acids encoding a first cytokine IL-15 and a second cytokine, Thorne does teach that the virus comprises nucleic acids encoding proteins that promote expression of cytokines such as IL-15 ([0054]), and that “VV(vaccinia virus) is modified to include one or more nucleic acids” ([0054]) and “more than one such nucleic acid may be incorporated into VV” ([0057]). The MPEP 2123 (I) states that patents are relevant as prior art for all they contain, and that a reference may be relied upon for all that it would have reasonably suggested to one having ordinary skill the art, including nonpreferred embodiments. In instant case, one of ordinary skill in the art would have immediately acknowledged that the most direct approach to promote IL-15 expression would have been that the virus is modified to include a nuclei acid encoding IL-15 itself. One of ordinary skill in the art would have appreciated that Thorne would have suggested that the oncolytic virus comprises more than one exogenous nucleic acids encoding more than one cytokines.
Applicant further argues that (2) there is no reasonable expectation of success because Thorne does not provide a working example showing an oncolytic virus expressing two cytokines and IL15-Ra. Gaston only provides guidance as to expressing two proteins IL15 and IL15-Ra (Remarks, p. 7).
Applicant’s argument has been fully considered but it is not persuasive.
As stated supra, although Thorne does not provide a working example of an oncolytic virus comprising exogenous nucleic acids encoding a first cytokine IL-15 and a second cytokine, Thorne does teach that the virus comprises nucleic acids encoding proteins that promote expression of cytokines such as IL-15 ([0054]), and that “VV(vaccinia virus) is modified to include one or more nucleic acids” ([0054]) and “more than one such nucleic acid may be incorporated into VV” ([0057]). Thus, one of ordinary skill in the art would have immediately acknowledged that the most direct approach to promote IL-15 expression would have been that the virus is modified to include a nuclei acid encoding IL-15 itself. One of ordinary skill in the art would have appreciated that Thorne would have suggested that the oncolytic virus comprises more than one exogenous nucleic acids encoding more than one cytokines. See MPEP 2123 (I). Thus, one of ordinary skill in the art would have had a reasonable expectation of success in combining Gaston’s IL15 and IL15-Ra into Thorne’s oncolytic virus.
Applicant finally argues, and Dr. Thorne declares, that (3) the recitation of increased expression of IL-15 in Thorne is directed to a different technical solution and a person of ordinary skill in the art would not equate a nucleic acid encoding a protein for promoting expression of IL-15 to a nucleic acid encoding a protein directly expressing IL-15. And Thorne does not provide any guidance as to a VV encoding two exogenous cytokines (Remarks, p. 7-8, Declaration, p. 2).
Applicant’s argument and Dr. Thorne’s declaration have been fully considered but they are not persuasive.
As stated supra, Thorne clearly teaches that the virus comprises nucleic acids encoding proteins that promote expression of cytokines such as IL-15 ([0054]). One of ordinary skill in the art would have immediately acknowledged that the most direct approach to promote IL-15 expression would have been that the virus is modified to include a nuclei acid encoding IL-15 itself. Furthermore, Thorne teaches that “VV(vaccinia virus) is modified to include one or more nucleic acids” ([0054]) and “more than one such nucleic acid may be incorporated into VV” ([0057]). Thus, one of ordinary skill in the art would have appreciated that Thorne has suggested that the oncolytic virus comprises more than one exogenous nucleic acids encoding more than one cytokines. See MPEP 2123 (I).
Claims 212 and 221-222 stand rejected under 35 U.S.C. 103 as being unpatentable over Thorne (US PGPub 2016/0235793 A1, published 08/18/2016. Cited in IDS 06/04/2021) in view of Gaston et al (PLoS ONE. 2013; 8(11): e81768. P. 1-13. Cited in IDS 06/28/2022), as applied to claims 226-227 and 230 above, and further in view of Wu et al (Molecular Cancer. 2012, 11:3, p. 1-16. Prior art of record).
Claim 212 is directed to the oncolytic virus further comprising a chemokine receptor or a variant. Claim 221 is directed to the chemokine receptor comprising a CXC receptor. Claim 222 is directed to the chemokine receptor comprising a CXCR3.
However, Thorne and Gaston are silent on the oncolytic virus further comprising a CXCR3 variant.
Wu teaches two CXCR3 variants CXCR3A and CXCR3B and altered expression of the variants regulates cancer cell migration and invasion (title, abstract). Wu teaches “CXCR3A mRNA level was upregulated while CXCR3B mRNA was downregulated in these prostate cancer specimens” (abstract, p. 3, left col, also see Fig 2A-2B) and teaches overexpression of CXCR3B in prostate cancer cells DU-145 inhibits cell motility and invasion (p. 9, left col, para 1, last sentence, and p. 11, right col, last para, see Fig 6D-6E), thus teaches a rational approach to limit prostate cancer invasion and metastasis by overexpressing CXCR3B in prostate cancer cells, which can also apply to other cancers like breast cancer, colon cancer, osteosarcoma and melanoma (p. 13, left col, line 2 and p. 12, right col, end of para 2), related to claims 212 and 221-222.
Therefore, it would have been obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the oncolytic virus expressing an exogenous IL15, an exogenous IL15-Ra and an exogenous second cytokine separately for cancer treatment suggested by Thorne in view of Gaston, by combining a CXCR3B variant in the virus as taught by Wu with a reasonable expectation of success. One of ordinary skill in the art would have had a reason to do so since Thorne teaches that “VV is modified to include one or more nucleic acids encoding a peptide or protein which promotes a T cell response” for treating cancers including prostate cancer, breast cancer, colon cancer, osteosarcoma and melanoma (p. 5, para 5.3, [0054], see Examples 4 and 6 for cancer therapy and [0147] for cancer types), and since Wu teaches overexpression of CXCR3B variant in cancer cells inhibits cell motility and invasion (Wu, p. 11, right col, last para, see Fig 6D-6E), thus combining a CXCR3B variant of Wu would have improved the oncolytic virus of Thorne in view of Gaston to inhibit cancer metastasis. Furthermore, since both Thorne and Wu teach treating prostate cancer, breast cancer, colon cancer, osteosarcoma and melanoma (see above), there would have been a reasonable expectation of success to make and use the taught modified viruses comprising IL15, IL15-Ra and CXCR3B for this purpose.
Hence, the claimed invention as a whole was prima facie obvious to a person of ordinary skill before the effective filing date of the claimed invention in the absence of evidence to the contrary.
Response to Traversal:
Applicant's arguments and Dr. Stephen Thorne’s declaration filed on 10/31/2025 are acknowledged and have been discussed above.
Claim 231 stands rejected under 35 U.S.C. 103 as being unpatentable over Thorne (US PGPub 2016/0235793 A1, published 08/18/2016. Cited in IDS 06/04/2021) in view of Gaston et al (PLoS ONE. 2013; 8(11): e81768. P. 1-13. Cited in IDS 06/28/2022), as applied to claims 226-227 and 230 above, and further in view of Benfield et al (Journal of General Virology. 2013; 94: 1647–1657. Prior art of record).
Claims 231 is directed to an oncolytic virus further comprising a deletion of the viral gene K7R.
As stated supra, Thorne teaches the viral backbone may contain “one or more of the mutations in (including deletion of) a nucleic acid encoding … Bcl-2 like proteins (such as … K7)” ([0049], line 2 and 2nd line from end) that favors “increased induction of a Cytotoxic T-Lymphocyte (CTL) immune response” ([0047]).
However, Thorne and Gaston do not specifically teach the oncolytic virus comprising a deletion of the viral gene K7R.
Benfield teaches a Western Reserve vaccinia virus lacking the K7R gene (vΔK7) induces enhanced T cell and NK cell infiltration in the lung after intranasal infection and have augmented intrapulmonary cytosis (abstract, p. 1650, left col, last para and p. 1651, both cols, also see Figs 6-7), thus teaches “loss of K7 induced a more robust Th1-cell-mediated immune response” (p. 1653, right col, para 2).
Therefore it would have been obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the oncolytic virus comprising mutations in viral genome for cancer treatment suggested by Thorne in view of Gaston, by choosing a deletion of the viral gene K7R as taught by Thorne and Benfield with a reasonable expectation of success. One of ordinary skill in the art would have had a reason to do so since Thorne teaches the viral backbone may contain “one or more of the mutations in (including deletion of) a nucleic acid encoding … Bcl-2 like proteins (such as … K7)” ([0049], line 2 and 2nd line from end) that favors “increased induction of a Cytotoxic T-Lymphocyte (CTL) immune response” ([0047]), and since Benfield reduces to practice the oncolytic virus lacking the K7R gene (vΔK7) induces enhanced T cell and NK cell infiltration in the lung after intranasal infection and has augmented intrapulmonary cytosis (abstract, p. 1650, left col, last para and p. 1651, both cols, also see Figs 6-7) with “a more robust Th1-cell-mediated immune response” (p. 1653, right col, para 2), thus the deletion of K7R gene practiced by Benfield would have improved the oncolytic virus of Thorne in view of Gaston to induce more robust cytotoxic immune response for cancer treatment.
Hence, the claimed invention as a whole was prima facie obvious to a person of ordinary skill before the effective filing date of the claimed invention in the absence of evidence to the contrary.
Response to Traversal:
Applicant's arguments and Dr. Stephen Thorne’s declaration filed on 10/31/2025 are acknowledged and have been discussed above.
Claims 233 and 235 stand rejected under 35 U.S.C. 103 as being unpatentable over Thorne (US PGPub 2016/0235793 A1, published 08/18/2016. Cited in IDS 06/04/2021) in view of Gaston et al (PLoS ONE. 2013; 8(11): e81768. P. 1-13. Cited in IDS 06/28/2022), as applied to claims 226-227, 229, 230 and 234 above, and further in view of Ho et al (WO 2018/058258 A1, filed October 2, 2017. Prior art of record).
Claims 233 and 235 are directed to the oncolytic virus further comprising a deletion of the A52R gene.
As stated supra, Thorne teaches the viral backbone may contain one or more of the mutations in (including deletion of) viral genes ([0049]) that favors “increased induction of a Cytotoxic T-Lymphocyte (CTL) immune response” ([0047]).
However, Thorne and Gaston do not teach the oncolytic virus further comprising a deletion of the viral gene A52R.
Ho teaches an oncolytic vaccinia virus comprising one or more inactivated immunomodulatory gene including A52R and further comprising inactivated thymidine kinase gene in cancer therapy (abstract). Ho teaches “the best performer, ΔA52R VV, demonstrated consistently significant advantage in viral spread in all cell lines” ([00167]) and “out of all the tested viruses, ΔA52R VV could spread most efficiently in both MC38 and DLD-1 spheroids” ([00171]), and ΔA52R VV has shown tumor selective replication but not in normal tissue as recited “impressively, ΔA52R VV was undetectable in the bowel, spleen, liver, heart, and brain” ([00182]), and has shown enhance immune cell infiltration in tumors as recited “the percent F4/80 staining in MC38 tumours treated with ΔA52R VV was at least 3x times higher than both mock- and vvDD-treated tumours” (p. 42, para 1).
Therefore it would have been obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the oncolytic virus comprising mutations in viral genome including deleted TK gene for cancer treatment suggested by Thorne in view of Gaston, by combining a deletion of the viral gene A52R as taught by Ho with a reasonable expectation of success. One of ordinary skill in the art would have had a reason to do so since Thorne teaches the viral backbone may contain one or more of the mutations in (including deletion of) viral genes ([0049]) that favors “increased induction of a Cytotoxic T-Lymphocyte (CTL) immune response” ([0047]), and since Ho teaches the vaccinia virus lacking the A52R gene (ΔA52R VV) has significant advantage in viral spread in tumors ([00167], [00171]) with tumor selective replication ([00182]) and enhanced immune cell infiltration in tumors (p. 42, para 1), thus combining the deletion of A52R gene taught by Ho would have improved the oncolytic virus of Thorne in view of Gaston with increased viral spread and tumor selective replication and enhanced immune cell infiltration in tumors for cancer treatment.
Hence, the claimed invention as a whole was prima facie obvious to a person of ordinary skill before the effective filing date of the claimed invention in the absence of evidence to the contrary.
Response to Traversal:
Applicant's arguments and Dr. Stephen Thorne’s declaration filed on 10/31/2025 are acknowledged and have been discussed above.
Claims 238-239 stand rejected under 35 U.S.C. 103 as being unpatentable over Thorne (US PGPub 2016/0235793 A1, published 08/18/2016. Cited in IDS 06/04/2021) in view of Gaston et al (PLoS ONE. 2013; 8(11): e81768. P. 1-13. Cited in IDS 06/28/2022), as applied to claim 230 above, and further in view of Liu et al (Oncoimmunology. 2016; 5(3):e1091554, p. 1-10. Prior art of record).
Claims 238-239 are directed to the second cytokine being ITAC.
However, Thorne and Gaston are silent on the second cytokine being ITAC.
Liu teaches an oncolytic vaccinia virus (vvDD, the same strain used by Thorne) armed with the chemokine CXCL11 (also known as ITAC, abstract), thus teaches an oncolytic virus comprising an ITAC in claims 238-239. Liu teaches intratumoral expression of CXCL11 promotes local trafficking of T cells and NK cells and elicits systemic immunity to cancer-associated antigens, thus provides a rationale for expressing CXCL11 to enhance the therapeutic efficacy of oncolytic viruses (abstract, see Figs 2-5).
Therefore it would have been obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the oncolytic virus comprising a second cytokine being a chemokine for cancer treatment suggested by Thorne in view of Gaston, by choosing ITAC as the second cytokine as taught by Liu with a reasonable expectation of success. Since Thorne suggests VV can be modified to include more than one nucleic acids encoding for separate peptides or proteins, such as chemokines to promote immune cell responses (see p. 5-6, para 5.3 and 5.4), and since Liu teaches intratumoral expression of CXCL11 promotes local trafficking of T cells and NK cells and elicits systemic immunity to cancer-associated antigens, thus enhances the therapeutic efficacy of oncolytic viruses (abstract, see Figs 2-5), one of ordinary skill in the art would have had a reason to choose ITAC (CXCL11) as taught by Liu in the oncolytic virus of Thorne in view of Gaston in order to promote immune cell responses and to enhance the therapeutic efficacy of oncolytic viruses (Liu, abstract).
Hence, the claimed invention as a whole was prima facie obvious to a person of ordinary skill before the effective filing date of the claimed invention in the absence of evidence to the contrary.
Response to Traversal:
Applicant's arguments and Dr. Stephen Thorne’s declaration filed on 10/31/2025 are acknowledged and have been discussed above.
Claim 243 stands rejected under 35 U.S.C. 103 as being unpatentable over Thorne (US PGPub 2016/0235793 A1, published 08/18/2016. Cited in IDS 06/04/2021) in view of Gaston et al (PLoS ONE. 2013; 8(11): e81768. P. 1-13. Cited in IDS 06/28/2022), as applied to claims 230 and 242 above, and further in view of Liu et al (Oncoimmunology. 2016; 5(3):e1091554, p. 1-10. Prior art of record) and Tang et al (Cancer Cell, 2016; 29: 285–296. Prior art of record).
Claim 243 is directed to the second cytokine being ITAC and the third cytokine being LIGHT.
However, Thorne and Gaston are silent on the second cytokine being ITAC and the third cytokine being LIGHT.
Regarding the second cytokine being ITAC, Liu teaches an oncolytic vaccinia virus (vvDD, the same strain used by Thorne) armed with the chemokine CXCL11 (also known as ITAC, abstract). Liu teaches intratumoral expression of CXCL11 promotes local trafficking of T cells and NK cells and elicits systemic immunity to cancer-associated antigens, thus provides a rationale for expressing CXCL11 to enhance the therapeutic efficacy of oncolytic viruses (abstract, see Figs 2-5).
Regarding the third cytokine being LIGHT, Tang teaches the TNF superfamily member LIGHT is targeted to the surface of tumor cells by anti-EGFR antibody-guided tumor targeting (see graphic abstract and Fig 3D). Tang teaches targeting tumors with LIGHT increases T cell infiltration into tumor microenvironment and overcomes tumor resistance to checkpoint blockade, indicating that targeting tumor with LIGHT is a potent strategy to increase the responses to checkpoint blockades and other immunotherapies in non-T cell-inflamed tumors (Summary, Significance in p. 285, see Figs 4 and 6).
Therefore it would have been obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the oncolytic virus comprising multiple cytokines for cancer treatment suggested by Thorne in view of Gaston, by choosing ITAC as the second cytokine and LIGHT as the third cytokine as taught by Liu and Tang with a reasonable expectation of success. Since Thorne suggests VV can be modified to include more than one nucleic acids encoding for separate cytokines and chemokines to promote immune cell responses (see p. 5-6, para 5.3 and 5.4), and since Liu teaches intratumoral expression of CXCL11 promotes local trafficking of T cells and NK cells and elicits systemic immunity to cancer-associated antigens thus enhances the therapeutic efficacy of oncolytic viruses (abstract, see Figs 2-5), and Tang teaches targeting tumors with LIGHT increases T cell infiltration into tumor microenvironment and overcomes tumor resistance to checkpoint blockade, indicating that targeting tumor with LIGHT is a potent strategy to increase the responses to checkpoint blockades and other immunotherapies in non-T cell-inflamed tumors (Summary, Significance in p. 285, see Figs 4 and 6), one of ordinary skill in the art would have had a reason to choose ITAC (CXCL11) and LIGHT as taught by Liu and Tang in the oncolytic virus of Thorne in view of Gaston in order to promote local infiltration of immune cells in the tumor microenvironment and elicit systemic immunity to cancer-associated antigens to enhance the therapeutic efficacy of oncolytic viruses for cancer treatment (Thorne [0006]).
Hence, the claimed invention as a whole was prima facie obvious to a person of ordinary skill before the effective filing date of the claimed invention in the absence of evidence to the contrary.
Response to Traversal:
Applicant's arguments and Dr. Stephen Thorne’s declaration filed on 10/31/2025 are acknowledged and have been discussed above.
Maintained Double Patenting Rejections
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 USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The 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/process/file/efs/guidance/eTD-info-I.jsp.
Claims 212, 220-222, 225-231, 233-239 and 242-244 stand rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-10 and 12-24 of US Patent No. 12,036,257 B2 in view of Gaston et al (PLoS ONE. 2013; 8(11): e81768. P. 1-13. Cited in IDS 06/28/2022), Liu et al (Oncoimmunology. 2016; 5(3):e1091554, p. 1-10. Prior art of record) and Tang et al (Cancer Cell, 2016; 29: 285-296. Prior art of record). Although the claims at issue are not identical, they are not patentably distinct from each other.
The subject matter claimed in the instant application is disclosed in the cited patent as follows: the oncolytic virus comprising exogenous nucleic acids of cited patent makes obvious the oncolytic virus comprising exogenous nucleic acids of instant application.
Patented claims recite a vaccinia virus comprising a chemokine receptor CXCR3 and genetic modifications in the viral genome comprising a deletion of A52R gene, a deletion of thymidine kinase gene and a deletion of K7R gene, and comprising at least one of an exogenous nucleic acid that codes for a cytokine or an exogenous nucleic acid that codes for a chemokine.
However, patented claims do not recite separate nucleic acids encoding IL15, IL15Ra, ITAC and LIGHT.
Gaston teaches an oncolytic herpes simplex virus (oHSV) comprising a first exogenous nucleic acid encoding IL15 and a second exogenous nucleic acid encoding IL15Ra and the IL15 and IL15Ra are expressed separately (title, abstract, p. 2, right col, last para - p. 3, left col, para 1, see Fig 1A). Gaston teaches the IL15 and IL15Ra expressed by the oncolytic virus can form soluble IL-15/IL-15Rα complex, which is bioactive evidenced by being capable of stimulating NK cells to proliferate and reduce the viability of syngeneic GL261 and CT-2A tumor cells (abstract, p. 7, right col - p. 8, left col, para 1, see Fig 4 and Fig 5).
Regarding the second cytokine being ITAC, Liu teaches an oncolytic vaccinia virus (vvDD, the same strain used by Thorne) armed with the chemokine CXCL11 (also known as ITAC, abstract), thus teaches an oncolytic virus comprising an ITAC. Liu teaches intratumoral expression of CXCL11 promotes local trafficking of T cells and NK cells and elicits systemic immunity to cancer-associated antigens, thus provides a rationale for expressing CXCL11 to enhance the therapeutic efficacy of oncolytic viruses (abstract, see Figs 2-5).
Regarding the third cytokine being LIGHT, Tang teaches the TNF superfamily member LIGHT is targeted to the surface of tumor cells by anti-EGFR antibody-guided tumor targeting (see graphic abstract and Fig 3D). Tang teaches targeting tumors with LIGHT increases T cell infiltration into tumor microenvironment and overcomes tumor resistance to checkpoint blockade, indicating that targeting tumor with LIGHT is a potent strategy to increase the responses to checkpoint blockades and other immunotherapies in non-T cell-inflamed tumors (Summary, Significance in p. 285, see Figs 4 and 6).
Therefore it would have been obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the oncolytic virus comprising exogenous nucleic acids of cited patent, and have combined separate nucleic acids encoding IL15 and IL15Ra taught by Gaston, an ITAC taught by Liu and a LIGHT taught by Tang with a reasonable expectation of success. One of ordinary skill in the art would have had a reason to do so since Gaston teaches the IL15 and IL15Ra expressed by the oncolytic virus can form soluble IL-15/IL-15Rα complex, which is bioactive and can stimulate NK cells to proliferate and reduce the viability of syngeneic GL261 and CT-2A tumor cells (abstract, p. 7, right col - p. 8, left col, para 1, see Fig 4 and Fig 5), Liu teaches intratumoral expression of CXCL11 promotes local trafficking of T cells and NK cells and elicits systemic immunity to cancer-associated antigens thus enhances the therapeutic efficacy of oncolytic viruses (abstract, see Figs 2-5), and Tang teaches targeting tumors with LIGHT increases T cell infiltration into tumor microenvironment and overcomes tumor resistance to checkpoint blockade, indicating that targeting tumor with LIGHT is a potent strategy to increase the responses to checkpoint blockades and other immunotherapies in non-T cell-inflamed tumors (Summary, Significance in p. 285, see Figs 4 and 6), thus the separate nucleic acids encoding IL15 and IL15-Ra taught by Gaston, an ITAC taught by Liu and a LIGHT taught by Tang would have improved the vaccinia virus of cited patent with enhanced anti-tumor immunity.
Since the instant application claims are obvious over cited patented claims, in view of Gaston, Liu and Tang, said claims are not patentably distinct.
Response to Traversal:
Applicant's arguments and Dr. Stephen Thorne’s declaration filed on 10/31/2025 are acknowledged.
Applicant argues that a terminal disclaimer over US Patent No. 12,036,257 B2 has been submitted therefore the rejection is no longer relevant (Remarks, p. 10).
Applicant’s argument has been fully considered but it is not persuasive because a terminal disclaimer over the US Patent No. 12,036,257 B2 has not been found.
Claims 212, 220-222, 225-231, 233-239 and 242-244 stand rejected on the ground of nonstatutory double patenting as being unpatentable over claims of US Patent No. 12,403,165 (patented from Application No. 18/105,374 to Thorne). Although the claims at issue are not identical, they are not patentably distinct from each other.
The subject matter claimed in the instant application is disclosed in the copending application as follows: the oncolytic virus comprising exogenous nucleic acids of cited application anticipates the oncolytic virus comprising exogenous nucleic acids of instant application.
Patent claims recite a modified Western Reserve vaccinia virus comprising a chemokine receptor CCR2 and genetic modifications in the viral genome comprising a deletion of A52R gene, a deletion of thymidine kinase gene, a deletion of K7R gene, and exogenous nucleic acids coding for a combination of IL15, IL15Ralpha, ITAC and LIGHT.
It is clear that elements of the cited application claims are to be found in instant claims. The difference between the cited application claims and the instant claims lies in the fact that the cited application claims are much more specific. Thus the invention of said claims of the cited application are in effect “species” of the “generic” invention of the instant claim. It has been held that the generic invention is “anticipated” by the “species”. See In re Goodman, 29 USPQ2d 2010 (Fed. Cir. 1993).
Since the instant application claims are anticipated by cited patent claims, said claims are not patentably distinct.
Response to Traversal:
Applicant's arguments and Dr. Stephen Thorne’s declaration filed on 10/31/2025 are acknowledged.
Applicant argues that the instant application has an earlier patent term filing date than that of copending Application 18/105,374, thus the rejection should be withdrawn (Remarks, p. 10-11).
Applicant’s argument has been fully considered but it is not persuasive therefore the rejections are maintained. Applicant is reminded that a complete response to a nonstatutory double patenting (NSDP) rejection is either a reply by applicant showing that the claims subject to the rejection are patentably distinct from the reference claims, or the filing of a terminal disclaimer. Such a response is required even when the nonstatutory double patenting rejection is provisional. See MPEP 804.I.B.1.
Claims 212, 220-222, 225-231, 233-239 and 242-244 stand rejected on the ground of nonstatutory double patenting as being unpatentable over claims of US Patent No. 12,472,217 (patented from copending Application No. 17/575,787), in view of Gaston et al (PLoS ONE. 2013; 8(11): e81768. P. 1-13. Cited in IDS 06/28/2022) and Liu et al (Oncoimmunology. 2016; 5(3):e1091554, p. 1-10. Prior art of record). Although the claims at issue are not identical, they are not patentably distinct from each other.
The subject matter claimed in the instant application is disclosed in the copending application as follows: the oncolytic virus comprising exogenous nucleic acids of cited application makes obvious the oncolytic virus comprising exogenous nucleic acids of instant application.
Patent claims recite a Western Reserve vaccinia virus comprising a chemokine receptor CXCR3 and genetic modifications in the viral genome comprising a deletion of A52R gene, a deletion of thymidine kinase gene and a deletion of K7R gene and an exogenous nucleic acid that codes for at least LIGHT.
However, patent claims do not recite separate nucleic acids encoding IL15 and IL15Ra in claim 230 and an ITAC in claims 238-239.
Gaston teaches an oncolytic herpes simplex virus (oHSV) comprising a first exogenous nucleic acid encoding IL15 and a second exogenous nucleic acid encoding IL15Ra and the IL15 and IL15Ra are expressed separately (title, abstract, p. 2, right col, last para - p. 3, left col, para 1, see Fig 1A). Gaston teaches the IL15 and IL15Ra expressed by the oncolytic virus can form soluble IL-15/IL-15Rα complex, which is bioactive evidenced by being capable of stimulating NK cells to proliferate and reduce the viability of syngeneic GL261 and CT-2A tumor cells (abstract, p. 7, right col - p. 8, left col, para 1, see Fig 4 and Fig 5).
Liu teaches an oncolytic vaccinia virus armed with the chemokine CXCL11 (also known as ITAC, abstract), thus teaches an oncolytic virus comprising an ITAC. Liu teaches intratumoral expression of CXCL11 promotes local trafficking of T cells and NK cells and elicits systemic immunity to cancer-associated antigens, thus provides a rationale for expressing CXCL11 to enhance the therapeutic efficacy of oncolytic viruses (abstract, see Figs 2-5).
Therefore it would have been obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the oncolytic virus comprising exogenous nucleic acids of cited patent, and have combined separate nucleic acids encoding IL15, IL15Ra and ITAC taught by Gaston and Liu with a reasonable expectation of success. One of ordinary skill in the art would have had a reason to do so since Gaston teaches the IL15 and IL15Ra expressed by the oncolytic virus can form soluble IL-15/IL-15Rα complex, which is bioactive and can stimulate NK cells to proliferate and reduce the viability of syngeneic GL261 and CT-2A tumor cells (abstract, p. 7, right col - p. 8, left col, para 1, see Fig 4 and Fig 5), and Liu teaches CXCL11 in the oncolytic virus promotes local trafficking of T cells and NK cells and elicits systemic immunity to cancer-associated antigens, thus provides a rationale for expressing CXCL11 to enhance the therapeutic efficacy of oncolytic viruses (abstract, see Figs 2-5), thus the separate nucleic acids encoding IL15, IL15-Ra taught by Gaston and an ITAC taught by Liu would have improved the vaccinia virus of cited patent with enhanced anti-tumor immunity.
Since the instant application claims are obvious over cited patent claims, in view of Gaston and Liu, said claims are not patentably distinct.
Response to Traversal:
Applicant's arguments and Dr. Stephen Thorne’s declaration filed on 10/31/2025 are acknowledged.
Applicant argues that a terminal disclaimer over copending application has been submitted therefore the rejection is no longer relevant (Remarks, p. 11).
Applicant’s argument has been fully considered but it is not persuasive because a terminal disclaimer over the copending application has not been found.
Claims 212, 220-222, 225-231, 233-239 and 242-244 stand rejected on the ground of nonstatutory double patenting as being unpatentable over claims of US Patent No. 12,318,419 (patented from copending Application No. 17/498,158), in view of Gaston et al (PLoS ONE. 2013; 8(11): e81768. P. 1-13. Cited in IDS 06/28/2022), Liu et al (Oncoimmunology. 2016; 5(3):e1091554, p. 1-10. Prior art of record) and Tang et al (Cancer Cell, 2016; 29: 285-296. Prior art of record). Although the claims at issue are not identical, they are not patentably distinct from each other.
Patent claims recite a method of using vaccinia virus for treatment of cancer, the virus comprising a chemokine receptor CXCR3 and genome modifications comprising a deletion of A52R gene, a deletion of thymidine kinase gene and a deletion of K7R gene.
However, copending claims recite an obvious use of the oncolytic virus and do not recite separate nucleic acids encoding IL15, IL15Ra, ITAC or LIGHT.
Gaston teaches an oncolytic herpes simplex virus (oHSV) comprising a first exogenous nucleic acid encoding IL15 and a second exogenous nucleic acid encoding IL15Ra and the IL15 and IL15Ra are expressed separately (title, abstract, p. 2, right col, last para - p. 3, left col, para 1, see Fig 1A). Gaston teaches the IL15 and IL15Ra expressed by the oncolytic virus can form soluble IL-15/IL-15Rα complex, which is bioactive evidenced by being capable of stimulating NK cells to proliferate and reduce the viability of syngeneic GL261 and CT-2A tumor cells (abstract, p. 7, right col - p. 8, left col, para 1, see Fig 4 and Fig 5).
Liu teaches an oncolytic vaccinia virus (vvDD, the same strain used by Thorne) armed with the chemokine CXCL11 (also known as ITAC, abstract), thus teaches an oncolytic virus comprising an ITAC. Liu teaches intratumoral expression of CXCL11 promotes local trafficking of T cells and NK cells and elicits systemic immunity to cancer-associated antigens, thus provides a rationale for expressing CXCL11 to enhance the therapeutic efficacy of oncolytic viruses (abstract, see Figs 2-5).
Tang teaches the TNF superfamily member LIGHT is targeted to the surface of tumor cells by anti-EGFR antibody-guided tumor targeting (see graphic abstract and Fig 3D). Tang teaches targeting tumors with LIGHT increases T cell infiltration into tumor microenvironment and overcomes tumor resistance to checkpoint blockade, indicating that targeting tumor with LIGHT is a potent strategy to increase the responses to checkpoint blockades and other immunotherapies in non-T cell-inflamed tumors (Summary, Significance in p. 285, see Figs 4 and 6).
Therefore it would have been obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the oncolytic virus comprising exogenous nucleic acids of cited patent, and have combined separate nucleic acids encoding IL15 and IL15Ra taught by Gaston, an ITAC taught by Liu and a LIGHT taught by Tang with a reasonable expectation of success. One of ordinary skill in the art would have had a reason to do so since Gaston teaches the IL15 and IL15Ra expressed by the oncolytic virus can form soluble IL-15/IL-15Rα complex, which is bioactive and can stimulate NK cells to proliferate and reduce the viability of syngeneic GL261 and CT-2A tumor cells (abstract, p. 7, right col - p. 8, left col, para 1, see Fig 4 and Fig 5), Liu teaches intratumoral expression of CXCL11 promotes local trafficking of T cells and NK cells and elicits systemic immunity to cancer-associated antigens thus enhances the therapeutic efficacy of oncolytic viruses (abstract, see Figs 2-5), and Tang teaches targeting tumors with LIGHT increases T cell infiltration into tumor microenvironment and overcomes tumor resistance to checkpoint blockade, indicating that targeting tumor with LIGHT is a potent strategy to increase the responses to checkpoint blockades and other immunotherapies in non-T cell-inflamed tumors (Summary, Significance in p. 285, see Figs 4 and 6), thus the separate nucleic acids encoding IL15 and IL15-Ra taught by Gaston, an ITAC taught by Liu and a LIGHT taught by Tang would have improved the vaccinia virus of cited application with enhanced anti-tumor immunity.
Since the instant application claims are obvious over cited patent claims, in view of Gaston, Liu and Tang, said claims are not patentably distinct.
Response to Traversal:
Applicant's arguments and Dr. Stephen Thorne’s declaration filed on 10/31/2025 are acknowledged.
Applicant argues that a terminal disclaimer over copending application has been submitted therefore the rejection is no longer relevant (Remarks, p. 11).
Applicant’s argument has been fully considered but it is not persuasive because a terminal disclaimer over the copending application has not been found.
Claims 212, 220-222, 225-231, 233-239 and 242-244 stand rejected on the ground of nonstatutory double patenting as being unpatentable over claims of US Patent No. 12,226,440 (patented from copending Application No. 17/513,034), in view of Gaston et al (PLoS ONE. 2013; 8(11): e81768. Cited in IDS 06/28/2022), Liu et al (Oncoimmunology. 2016; 5(3):e1091554, p. 1-10. Prior art of record) and Tang et al (Cancer Cell, 2016; 29: 285–296. Prior art of record). Although the claims at issue are not identical, they are not patentably distinct from each other.
Patent claims recite a vaccinia virus comprising a chemokine receptor CXCR3 and genetic modifications in the viral genome comprising a deletion of A52R gene, a deletion of thymidine kinase gene and a deletion of K7R gene.
However, copending claims recite an obvious use of the oncolytic virus and do not recite separate nucleic acids encoding IL15, IL15Ra, ITAC or LIGHT.
Gaston teaches an oncolytic herpes simplex virus (oHSV) comprising a first exogenous nucleic acid encoding IL15 and a second exogenous nucleic acid encoding IL15Ra and the IL15 and IL15Ra are expressed separately (title, abstract, p. 2, right col, last para - p. 3, left col, para 1, see Fig 1A). Gaston teaches the IL15 and IL15Ra expressed by the oncolytic virus can form soluble IL-15/IL-15Rα complex, which is bioactive evidenced by being capable of stimulating NK cells to proliferate and reduce the viability of syngeneic GL261 and CT-2A tumor cells (abstract, p. 7, right col - p. 8, left col, para 1, see Fig 4 and Fig 5).
Liu teaches an oncolytic vaccinia virus (vvDD, the same strain used by Thorne) armed with the chemokine CXCL11 (also known as ITAC, abstract), thus teaches an oncolytic virus comprising an ITAC. Liu teaches intratumoral expression of CXCL11 promotes local trafficking of T cells and NK cells and elicits systemic immunity to cancer-associated antigens, thus provides a rationale for expressing CXCL11 to enhance the therapeutic efficacy of oncolytic viruses (abstract, see Figs 2-5).
Tang teaches the TNF superfamily member LIGHT is targeted to the surface of tumor cells by anti-EGFR antibody-guided tumor targeting (see graphic abstract and Fig 3D). Tang teaches targeting tumors with LIGHT increases T cell infiltration into tumor microenvironment and overcomes tumor resistance to checkpoint blockade, indicating that targeting tumor with LIGHT is a potent strategy to increase the responses to checkpoint blockades and other immunotherapies in non-T cell-inflamed tumors (Summary, Significance in p. 285, see Figs 4 and 6).
Therefore it would have been obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the oncolytic virus comprising exogenous nucleic acids of cited patent, and have combined separate nucleic acids encoding IL15 and IL15Ra taught by Gaston, an ITAC taught by Liu and a LIGHT taught by Tang with a reasonable expectation of success. One of ordinary skill in the art would have had a reason to do so since Gaston teaches the IL15 and IL15Ra expressed by the oncolytic virus can form soluble IL-15/IL-15Rα complex, which is bioactive and can stimulate NK cells to proliferate and reduce the viability of syngeneic GL261 and CT-2A tumor cells (abstract, p. 7, right col - p. 8, left col, para 1, see Fig 4 and Fig 5), Liu teaches intratumoral expression of CXCL11 promotes local trafficking of T cells and NK cells and elicits systemic immunity to cancer-associated antigens thus enhances the therapeutic efficacy of oncolytic viruses (abstract, see Figs 2-5), and Tang teaches targeting tumors with LIGHT increases T cell infiltration into tumor microenvironment and overcomes tumor resistance to checkpoint blockade, indicating that targeting tumor with LIGHT is a potent strategy to increase the responses to checkpoint blockades and other immunotherapies in non-T cell-inflamed tumors (Summary, Significance in p. 285, see Figs 4 and 6), thus the separate nucleic acids encoding IL15 and IL15-Ra taught by Gaston, an ITAC taught by Liu and a LIGHT taught by Tang would have improved the vaccinia virus of cited application with enhanced anti-tumor immunity.
Since the instant application claims are obvious over cited patent claims, in view of Gaston, Liu and Tang, said claims are not patentably distinct.
Response to Traversal:
Applicant's arguments and Dr. Stephen Thorne’s declaration filed on 10/31/2025 are acknowledged.
Applicant argues that a terminal disclaimer over copending application has been submitted therefore the rejection is no longer relevant (Remarks, p. 11).
Applicant’s argument has been fully considered but it is not persuasive because a terminal disclaimer over the copending application has not been found.
Conclusion
No claims are allowed.
Examiner Contact Information
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Jianjian Zhu whose telephone number is (571)272-0956. The examiner can normally be reached M - F 8:30AM - 4PM (EST).
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/JIANJIAN ZHU/Examiner, Art Unit 1631
/JAMES D SCHULTZ/ Supervisory Patent Examiner, Art Unit 1631