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 .
Response to Amendment
The Amendment filed 02/20/2026 in which claims 10 and 29 were amended has been entered. Claims 1 – 6, 8 – 9, 13, and 26 – 7 were previously withdrawn.
Claims 10 – 12, 14 – 18, 25, and 28 – 30 are under examination on the merits.
Nucleotide and/or Amino Acid Sequence Disclosures
(Previous objection, withdrawn) Applicant’s substitute specification and sequence listing submitted on 02/20/2026 have overcome the objection previously set forth in the Non-Final Office Action mailed 11/20/2025.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
(Previous rejection, withdrawn as to claims 10 and 29) Claims 10 and 29 were rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Applicant’s amendments to claim 10 and 29 have overcome previous rejections to those claims.
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.
(Previous rejection, maintained as necessitated by amendment as to claims 10 - 12, 15 - 18, 25, 28, and 30, expanded as to claims 10 - 12, 15 - 18, 25, 28, and 30) Claims 10 - 12, 15 - 18, 25, 28, and 30 are rejected under 35 U.S.C. 103 as being unpatentable over Zitvogel.
See claims 10 - 12, 15 - 18, 25, 28, and 30 as submitted on 02/20/2026.
Regarding claim 10, as previously indicated, Zitvogel teaches a method for treating cancer (Page 24, Col. 27, 61 - 67), comprising: administering a pharmaceutical composition comprising a vaccinia virus and hydroxyurea to an individual having cancer (Page 11, Col. 1, 23 - 26; Page 22, Col. 21, 21 - 33), where the vaccinia virus is a recombinant vaccinia virus in which thymidine kinase gene is deleted and vaccinia growth factor (VGF) gene is deleted (Page 11, Col. 2, line 45 - 50).
Regarding claim 11, it is noted that no amendments were introduced to claim 11 in the amendment filed on 02/20/2026. As previously explained, Zitvogel teaches the vaccinia virus and the hydroxyurea are administered with a regiment where vaccinia virus and hydroxyurea are administered in combination sequentially (Page 23, Col. 26, 4 - 9).
Regarding claim 12, it is noted that no amendments were introduced to claim 12 in the amendment filed on 02/20/2026. As previously explained, Zitvogel teaches the hydroxyurea is administered after administration of the vaccinia virus (Page 23, Col. 26, 4 - 9).
Regarding claim 15, it is noted that no amendments were introduced to claim 15 in the amendment filed on 02/20/2026. As previously explained, Zitvogel teaches the vaccinia virus is administered at a dose of 1x105 pfu to 1x1010 pfu (Page 23, Col. 25, 11 - 20).
Regarding claim 16, it is noted that no amendments were introduced to claim 16 in the amendment filed on 02/20/2026. As previously explained, Zitvogel teaches that the vaccinia virus is preferably administered at intervals starting from 7 days to 21 days (Page 23, Col. 26, 27 - 30).
Regarding claim 17, it is noted that no amendments were introduced to claim 17 in the amendment filed on 02/20/2026. As previously explained, Zitvogel teaches an immune checkpoint modulator coupled to hydroxyurea is administered intravenously (Page 23, Col. 25, 45 - 50).
Regarding claim 18, it is noted that no amendments were introduced to claim 18 in the amendment filed on 02/20/2026. As previously explained, Zitvogel teaches the vaccinia virus intravenously (Page 23, Col. 25, 45 - 50).
Regarding claim 25, it is noted that no amendments were introduced to claim 25 in the amendment filed on 02/20/2026. As previously explained, Zitvogel teaches a method for treating cancer, including lung cancer (Page 24, Col. 27, 61 - 67).
Regarding claim 28, it is noted that no amendments were introduced to claim 25 in the amendment filed on 02/20/2026. As previously explained, Zitvogel teaches the use of the Western Reserve strain (Page 15, Col. 9, 15 - 17).
Regarding claim 30, it is noted that no amendments were introduced to claim 30 in the amendment filed on 02/20/2026. As previously explained, Zitvogel further teaches the vaccinia virus can be modified by inserting a gene encoding a cytosine deaminase (Page 16, Col. 11, 11 - 12).
In view of the foregoing, all the claimed limitations are found in one reference and are taught to be optional variations to a ‘base’ method they exemplify. As such, the claimed method is within the scope of Zitvogel, and thus Zitvogel renders the method prima facie obvious. The rationale to support this conclusion of obviousness is that Zitvogel provides a teaching, suggestion, and motivation to substitute different variables disclosed within the reference. Furthermore, there is no evidence on the record that indicates that the claimed supplement exhibits any unexpected results compared to the prior art.
Accordingly, the claimed invention was prima facie obvious to one of ordinary skill in the art at the time of filing especially in the absence of evidence to the contrary.
(Previous rejection, maintained as necessitated by amendment as to claims 29) Claim 29, as previously indicated, is rejected under 35 U.S.C. 103 as being unpatentable over Zitvogel as applied to claims 10 - 12, 15 - 18, 25, 28, and 30 above, and further in view of Thorne et al. (US20160235793A1, hereinafter “Thorne”).
As discussed above, claims 10 - 12, 15 - 18, 25, 28, and 30 were rendered prima facie obvious by the teachings of Zitvogel.
The reference fails to teach the method of claim 29, wherein the at least one gene from the wild-type vaccinia virus is obtained by deleting further any one selected from the group consisting of F13.5L gene, F14.5 gene, A56R gene, B18R gene, or combinations thereof.
However, Thorne teaches deleting the A56R gene in vaccinia virus to increase viral spread and activity (Page 57, Para. 0061).
Zitvogel and Thorne are both considered to be analogous to the claim invention because they are in the same field of treating cancer through oncolytic viruses. Therefore, it would have been prima facie obvious before the effective filing date of the claimed invention to utilize the art-recognized method to modify vaccinia virus by deleting the A56R gene to treat cancer as taught by Thorne in the method taught by Zitvogel because doing so would advantageously increase viral spread and activity, thereby increasing probability of affecting cancerous cells. One of ordinary skill in the art would have reasonable expectation of success in deleting the A56R gene of the vaccinia virus to increase efficacy of cancer treatment given that this method is well known, has been successfully demonstrated, and commonly used in the prior art.
Accordingly, the claimed invention was prima facie obvious to one of ordinary skill in the art at the time of filing especially in the absence of evidence to the contrary.
(Previous rejection, maintained as necessitated by amendment as to claims 14) Claim 14, as previously indicated, is rejected under 35 U.S.C. 103 as being unpatentable over Zitvogel as applied to claims 10 - 12, 15 - 18, 25, 28, and 30 above, and further in view of Bonadonna et al. (Tumori Journal, 1967, hereinafter “Bonadonna”).
As discussed above, claims 10 - 12, 15 - 18, 25, 28, and 30 were rendered prima facie obvious by the teachings of Zitvogel. The reference fails to teach the method of claim 14, where hydroxyurea is administered at a dosage of 10/mg/kg/day to 90 mg/kg/day. However, Bonadonna teaches a standalone treatment of hydroxyurea to treat lung cancer using 40mg/kg/day oral delivery or 10 mg/kg/day intravenously (Abstract).
It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... The idea of combining them flows logically from their having been individually taught in the prior art. In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980). Zitvogel teaches the use of a vaccinia virus in conjunction with an immune checkpoint modulator coupled to hydroxyurea at a dose of 0.01 mg/kg to 50 mg/kg to treat lung cancer while Bonadonna teaches the use of hydroxyurea alone to treat lung cancer. The use of these two inventions in combination to treat lung cancer flows logically. Therefore, one of ordinary skill in the art would have reasonable expectation of success in using the vaccinia virus in combination with the hydroxyurea without a conjugated immune checkpoint modulator to treat lung cancer given that this method is well known, has been successfully demonstrated, and commonly used in the prior art. And indeed, the combination of using an oncolytic virus to deliver the HSV-TK gene in combination with hydroxyurea to treat cancer (Boucher et al. Gene Therapy, 2002) has been shown to be effective before the effective filing date of the claimed invention. Furthermore, there is no evidence on the record that indicates that the claimed supplement exhibits any unexpected results compared to the prior art.
Accordingly, the claimed invention was prima facie obvious to one of ordinary skill in the art at the time of filing especially in the absence of evidence to the contrary.
Response to Arguments
Applicant's arguments filed 02/20/2026 have been fully considered but they are not persuasive.
Applicant argues on pages 8 of Remarks: That Zitovgel does not teach use of vaccinia virus before administration of HU and that Zitvogel teaches only a vaccinia virus administered in combination with an immune checkpoint modulator coupled to HU.
In response: This is not persuasive because as explained above and previously, regarding claim 10, Zitvogel teaches administration of a vaccinia virus together with an immune checkpoint modulator that can be coupled to HU (column 1, lines 23-26; column 21, lines 21-33; and column 2, lines 45-50). Claim 10 uses the transitional term “comprising” which is open ended and therefore HU only needs to be included to satisfy the claim. The broadest reasonable interpretation of “a second composition comprising hydroxyurea” includes both free HU as well as a HU coupled with immune checkpoint modulator, i.e., both reasonably comprise HU. Zitvogel also teaches that the vaccinia virus and HU can be administered sequentially as previously discussed (Col. 26, 4 – 9).
Applicant argues on pages 8 of Remarks: That while Bonadonna discloses administration of HU alone, HU produces no definite change in the basic course of lung cancer and further describes adverse effects and, accordingly, one of ordinary skill in the art would not have been motivated to administer HU alone for cancer treatment.
In response: Bonadonna teaches “a significant number of improvements
(9 out of 27 patients) in lung cancer” (Discussion, Table 3). Bonadonna also teaches that the effects of hydroxyurea on advanced lung cancer “is not inferior to conventional treatment with alkylating agents (16, 37) which overall produce regressions in approximately 30% of cases and that the drug administered at a dose of 100 mg/kg every other day intravenously deserves further testing on a larger case series” (Discussion). Bonadonna teaches “[t]he administration of hydroxyurea in advanced lung cancer at a dose of 100 mg/kg every other day intravenously deserves more extensive testing.”
Both Zitvogel and Bonadonna teach method of treating lung cancer. Zitvogel teaches that a combinatorial treatment of a vaccinia virus with an immune modulator coupled to HU while Bonadonna teaches that HU alone can be used to treat lung cancer. Therefore, it would have been prima facie obvious to a person of ordinary skill in the art to combine the teachings of Zitvogel and Bonadonna to increase the chances of successfully treating lung cancer because doing so would allow specific titration of dosages of the vaccinia virus and the HU.
Taken together, Bonadonna provides a clear teaching, suggestion, and motivation to utilize HU as a treatment for lung cancer.
Applicant argues on pages 8 and 9 of Remarks: Applicant states that “Boucher employs a retrovirus and evaluates anticancer effects resulting from administration of not only HU but also GCV.”
In response: The use of vaccinia virus along with an immune checkpoint inhibitor coupled to HU as well as the stand-alone usage of HU is known in the art as taught by Bonadonna and Zitvogel (discussed previously and above). Furthermore, Boucher established that 1) Retrovirus delivered HSVtk gene in combination with GCV is effective in killing tumor cells (Section: Introduction ¶1) and that 2) HU enhances the desired destruction of tumor cells (Figure 3). It would have been obvious to one of ordinary skill in the art to increase the chances and avenues of successful cancer treatment by targeting multiple pathways such as those affected by HU, those affected by vaccinia virus activity, and those caused specifically by the activity of HSVtk. Therefore, it would have been obvious to one of ordinary skill in the art to not only use vaccinia virus with HU but to also include the HSVtk gene because doing so allows other avenues of tumor destruction. As discussed above and previously, it is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... The idea of combining them flows logically from their having been individually taught in the prior art. In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980).
Applicant argues on pages 8 and 9 of Remarks: Applicant states that “Thorne merely discloses a VV having mutation/deletion of A56R and provides no teaching regarding HU… neither Throne nor Boucher discloses or suggests any therapeutic effect resulting from co-administration of VV and HU.”
In response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986).
The use of vaccinia virus along with an immune checkpoint inhibitor coupled to HU as well as the stand-alone usage of HU is known in the art as taught by Bonadonna and Zitvogel (discussed previously and above). Thorne explicitly states A56R is a modification to vaccinia virus that enhance viral spread and activity (¶61). As discussed above and previously, Boucher teaches the advantages of including HSVtk gene to an oncolytic virus. Therefore, it would have been obvious to one of ordinary skill in the art to not only use vaccinia virus with HU but to also include the HSVtk gene and/or mutation/deletion of A56R because doing so allows other avenues of tumor destruction as well as increase viral spread and activity.
Conclusion
NO CLAIMS ARE ALLOWED
Prior art not discussed but pertinent to the application:
Saban et al. (Cancer Chemother Pharma, 2009)
Veale et al. (Cancer Chemother Pharmacol, 1988)
THIS ACTION IS MADE FINAL. 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.
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/DANYAL HASSAN ALAM/Examiner, Art Unit 1672
/THOMAS J. VISONE/Supervisory Patent Examiner, Art Unit 1672