DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 07/22/2026 has been entered.
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.
Claims 10 - 12, 15, 16, 18, 25, 28, and 30 are rejected under 35 U.S.C. 103 as being unpatentable over Evans et al (US20120114612A1, hereinafter “Evans”) in view of Zitvogel et al (US10765710B2, hereinafter “Zitvogel”).
Evans teaches different strains of poxviruses, including vaccinia virus, in oncolytic virotherapy (Abstract). Evans teaches that the vaccinia virus can have functionally inactivated thymidine kinase (TK) and/or vaccinia virus growth factor (VGF) genes (claim 16). Evans teaches that the oncolytic composition can be comprised of both vaccinia virus and hydroxyurea (¶0014, claim 33). Evans teaches the vaccinia virus replicates in neoplastic disorder cells that have increased ribonucleotide reductase (RR) levels, inducing death (¶0006,0104). Evan teaches that hydroxyurea is a chemotherapeutic that is used to treat a wide variety of cancers by targeting RR (¶0104, 0122). Evans also teaches administration regimens for vaccinia virus and hydroxyurea (claim 33).
Regarding claim 10, Evans teaches administering vaccinia virus and hydroxyurea to an individual having lung cancer, wherein the vaccinia virus is a recombinant vaccinia virus in which TK and VGF genes are functionally inactivated (¶0014, 0016, claim 33).
While Evans does teach non-functional TK and VGF genes, Evans does not explicitly teach deleted TK and VGF genes, although both deletion and functional inactivation would result in the absence of TK and VGF activity.
However, Zitvogel teaches a method for treating cancer (Page 24, Col. 27, 61 - 67), comprising: administering a pharmaceutical composition comprising a vaccinia virus and an immune checkpoint modulator coupled to a 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 10, Zitvogel teaches 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, Evans teaches the vaccinia virus and hydroxyurea are administered with a regiment where vaccinia virus and hydroxyurea are administered in combination sequentially (¶0122, claim 33).
Regarding claim 12, Evans teaches the hydroxyurea is administered after administration of the vaccinia virus (¶0122, claim 33).
Regarding claim 15, 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, 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 18, Zitvogel teaches the vaccinia virus intravenously (Page 23, Col. 25, 45 - 50).
Regarding claim 25, Zitvogel teaches a method for treating cancer, including lung cancer (Page 24, Col. 27, 61 - 67).
Regarding claim 28, Evans teaches the use of the Western Reserve strain (Table 1, footnote 1).
Regarding claim 30, Zitvogel further teaches the vaccinia virus can be modified by inserting a gene encoding a cytosine deaminase (Page 16, Col. 11, 11 - 12).
Evans and Zitvogel 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 administer a vaccinia virus comprised of deleted TK and VGF gene, as taught by Zitvogel, along with hydroxyurea to treat lung cancer, as taught by Evans, 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 TK and VGF gene of the vaccinia virus along with administering hydroxyurea 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.
Claims 14 and 17 are rejected under 35 U.S.C. 103 as being unpatentable over Evans and Zitvogel as applied to claims 10 - 12, 15, 16, 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, 16, 18, 25, 28, and 30 were rendered prima facie obvious by the teachings of Evans and Zitvogel. The references teach the use of a vaccinia virus with a deleted TK and VGF genes that is administered with hydroxyurea. 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).
Regarding claim 17, Bonadonna teaches hydroxyurea is administered intravenously (Abstract).
Evans, Zitvogel, and Bonadonna are considered to be analogous to the claim invention because they are in the same field of treating cancer. Therefore, it would have been prima facie obvious before the effective filing date of the claimed invention to administer a vaccinia virus comprised of deleted TK and VGF gene, as taught by Zitvogel, along with hydroxyurea to treat lung cancer at a dosage of 10 mg/kg/day to 90 mg/kg/day, as taught by Evans and Bonadonna, because doing so would reduce side effects of hydroxyurea. One of ordinary skill in the art would have reasonable expectation of success in using the vaccinia virus in combination with the hydroxyurea to treat lung cancer wherein the dosage 40mg/kg/day oral delivery or 10 mg/kg/day intravenously 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.
Claim 29 is rejected under 35 U.S.C. 103 as being unpatentable over Evans and Zitvogel as applied to claims 10 - 12, 15, 16, 18, 25, 28, and 30 above, and further in view of Thorne et al. (US20160235793A1, hereinafter “Thorne”).
As discussed above, claims 10 - 12, 15, 16, 18, 25, 28, and 30 were rendered prima facie obvious by the teachings of Evans and Zitvogel. The references teach the use of a vaccinia virus with a deleted TK and VGF genes that is administered with hydroxyurea. The reference fails to teach vaccinia virus comprising a further deletion of the A56R gene.
However, Thorne teaches oncolytic vaccinia viruses which have been modified to promote anti-tumor immunity, reduce host immunity, and/or antibody response against the virus (Abstract). Thorne teaches that vaccinia virus expressing GM-CSF boost host lymphocytes and destroy tumor cells through selective replication leading to directly to cell lysis (¶0004).
Regarding claim 29, Thorne teaches a vaccinia virus comprising of a deleted A56R gene in vaccinia virus to increase viral spread and activity (Page 57, Para. 0061).
Evans, Zitvogel, and Thorne are 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 Evans and 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.
Double Patenting
A rejection based on double patenting of the “same invention” type finds its support in the language of 35 U.S.C. 101 which states that “whoever invents or discovers any new and useful process... may obtain a patent therefor...” (Emphasis added). Thus, the term “same invention,” in this context, means an invention drawn to identical subject matter. See Miller v. Eagle Mfg. Co., 151 U.S. 186 (1894); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Ockert, 245 F.2d 467, 114 USPQ 330 (CCPA 1957).
A statutory type (35 U.S.C. 101) double patenting rejection can be overcome by canceling or amending the claims that are directed to the same invention so they are no longer coextensive in scope. The filing of a terminal disclaimer cannot overcome a double patenting rejection based upon 35 U.S.C. 101.
Claims 10 – 12, 14 – 18, and 25 are provisionally rejected under 35 U.S.C. 101 as claiming the same invention as that of claims 9, 14, 16 – 18, and 22 of copending Application No. 16/976,125 (reference application). This is a provisional statutory double patenting rejection since the claims directed to the same invention have not in fact been patented.
Regarding claims 10, 14, and 15, claim 9 of copending Application No. ‘125 discloses a method of treating cancer in a subject by administering a recombinant vaccinia virus, comprised of a deletion of the TK gene and insertion of HSV-TK, and hydroxyurea wherein the dose of the vaccinia virus is 1 x 105 pfu to 1 x 1010 pfu and wherein the hydroxyurea is administered at a dose of 10/mg/kg/day to 90/mg/kg/day.
Regarding claims 11 and 12, claim 14 of copending Application No. ‘125 discloses the sequential administration of a recombinant vaccinia virus and hydroxyurea wherein the hydroxyurea- containing composition is administered at least once before, during, or after administration of the oncolytic virus-containing composition.
Regarding claim 16, claim 16 of copending Application No. ‘125 discloses the administration of the vaccinia virus composition is administered to the subject at intervals of 7 to 30 days.
Regarding claim 17, claim 22 of copending Application No. ‘125 discloses administration of hydroxyurea composition is administered intratumorally, intraperitoneally, or intravenously.
Regarding claim 18, claim 18 of copending Application No. ‘125 discloses administration of the vaccinia virus composition is administered intratumorally, intraperitoneally, or intravenously.
Regarding claim 25, claim 17 of copending Application No. ‘125 discloses the treatment of cancer wherein the cancer is any one selected from the group consisting of lung cancer, colorectal cancer, prostate cancer, thyroid cancer, breast cancer, brain cancer, head and neck cancer, esophageal cancer, skin cancer, thymic pressure, gastric cancer, colon cancer, liver cancer, ovarian cancer, uterine cancer, bladder cancer, rectal cancer, gallbladder cancer, biliary cancer, pancreatic cancer, and combinations thereof.
Response to Arguments
1) Applicant states that Zitvogel does not teach administration of hydroxyurea
Claim 10 as submitted on 02/20/2026 recited “a first pharmaceutical composition comprising a vaccinia virus and a second composition comprising hydroxyurea.” As discussed previously and above, Zitvogel teaches the administration of a vaccinia virus and a hydroxyurea coupled with immune checkpoint modulators to treat lung cancer. The amendments now require administration of hydroxyurea itself in combination with a recombinant vaccinia virus. In view of the amendments, the Examiner now details the teachings of Evans which teaches the use of a recombinant vaccinia virus in combination with hydroxyurea. Therefore, the claimed invention is rendered prima facie oblivious by the teachings of Evans and Zitvogel.
2) Applicant states Bonadonna does not suggest the claimed combination
As discussed previously and above, Bonadonna teaches the use of hydroxyurea as a monotherapy and teaches the dosages for treating lung cancer. Bonadonna does not disclose a recombinant vaccinia virus or co-administration of hydroxyurea with a vaccinia virus.
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). The use of hydroxyurea to treat lung cancer is known as taught by Evans, Zitvogel, and Bonadonna. Zitvogel teaches the use of a recombinant vaccinia virus administered with an immune checkpoint inhibitor coupled to hydroxyurea to treat lung cancer. Evans teaches the use of a recombinant vaccinia virus administered with hydroxyurea alone to treat lung cancer. Furthermore, Evans and Zitvogel teach vaccinia virus without functioning TK and VGF genes either through mutation or deletion. Therefore, the prior art teaches both hydroxyurea and vaccinia virus as treatments for lung cancer. The idea of combining them flows logically from there having been individually taught in the prior art.
3) Applicant states Boucher does not remedy the deficiencies of Zitvogel and Bonadonna nor teach HSVtk-related mutations.
Boucher is not relied upon for any of the claims under consideration.
4) Applicant state Thorne merely discloses Vaccinia Virus engineering
As discussed previously and above, Thorne teaches A56R is a modification of vaccinia virus that enhances viral spread and activity. Furthermore, as discussed above, 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). One of ordinary skill in the art would be motivated to adminster a vaccinia virus comprised of TK, VGF, and A56R deletion, as taught by Thorne, with hydroxyurea, as taught by Evans and Zitvogel, because doing so would increase viral spread and activity thereby more effectively targeting cancerous cells.
5) The applicant states the proposed combination is based on hindsight reconstruction
In response to applicant's argument that the examiner's conclusion of obviousness is based upon improper hindsight reasoning, it must be recognized that any judgment on obviousness is in a sense necessarily a reconstruction based upon hindsight reasoning. But so long as it takes into account only knowledge which was within the level of ordinary skill at the time the claimed invention was made, and does not include knowledge gleaned only from the applicant's disclosure, such a reconstruction is proper. See In re McLaughlin, 443 F.2d 1392, 170 USPQ 209 (CCPA 1971).
Evans, Zitvogel, Bonadonna, and Thorne are considered to be analogous to the claim invention because they are in the same field of treating cancer. Evans and Thorne alone teach compositions comprised of vaccinia virus and hydroxyurea to treat cancer. One of ordinary skill at the time the claimed invention was made would combine the teachings of Evans and Zitvogel with Bonadonna as Bonadonna teaches effective dosages of hydroxyurea to treat lung cancer. One of ordinary skill at the time the claimed invention was made would combine the teachings of Evans and Zitvogel with Thorne as Thorne teaches improvements by deleting A56R in a base vaccinia virus comprised of TK and VGF to improve viral spread and activity. The prior art rendered the claimed invention prima facie obvious.
Conclusion
NO CLAIMS ARE ALLOWED
The prior art made of record and not relied upon is considered pertinent to applicant’s disclosure:
Veale, D., et al. "Phase 1 study of high-dose hydroxyurea in lung cancer." Cancer chemotherapy and pharmacology 21.1 (1988): 53-56.
Mackett, Michael, Geoffrey L. Smith, and Bernard Moss. "Vaccinia virus: a selectable eukaryotic cloning and expression vector." Proceedings of the National Academy of Sciences 79.23 (1982): 7415-7419.
Panicali, Dennis, and Enzo Paoletti. "Construction of poxviruses as cloning vectors: insertion of the thymidine kinase gene from herpes simplex virus into the DNA of infectious vaccinia virus." Proceedings of the National Academy of Sciences 79.16 (1982): 4927-4931.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Danyal H Alam whose telephone number is (571)272-1102. The examiner can normally be reached M - F 9am - 5pm.
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/DANYAL HASSAN ALAM/Examiner, Art Unit 1672
/THOMAS J. VISONE/Supervisory Patent Examiner, Art Unit 1672
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