DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application is being examined under the pre-AIA first to invent provisions.
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 12/8/2025 has been entered.
Claims 1-9, 11-12, and 16-20, of record 12/8/2025, are pending and subject to prosecution. Claim 8 is amended.
Declaration by Karen Aboody and Maciej Lesniak under 37 CFR 1.132
A declaration under 37 CFR 1.132, of record 12/8/2025 (originally filed in application 14/852378), was filed to disqualify the prior art reference Thaci et al. as being conceived solely by and derived from the work of Karen Aboody and Maciej Lesniak, co-inventors of the instant application.
The declaration is effective to remove the reference Thaci et al. as prior art.
Status of Prior Rejections/Response to Arguments
RE: Rejection of claims 1-9, 11-12, and 16-20 under pre-AIA 35 U.S.C. 103(a) over Tyler et al. (Gene Therapy, 2009) in view of Ulasov et al. (British Journal of Cancer, 2009) and Thaci et al. (Cancer Gene Therapy, 2012):
The declaration under 37 CFR 1.132 is effective to obviate the rejection. Thaci et al. was required by the rejection for teaching the neural stem cell line HB1.F3-CD as a carrier for the CRAd-S-pk7 adenovirus. The rejection is withdrawn.
RE: Rejection of claims 1-9, 11-12, and 16-20 on the ground of nonstatutory double patenting over claims 3-9 and 12-13 of U.S. Patent No. 10238699:
Applicants are reminded that 37 CFR 1.111 requires that replies by applicant or patent owner must reply to every ground of objection and rejection in the prior Office Action. Only objections or requirements as to form not necessary to further consideration of the claims may be requested to be held in abeyance until allowable subject matter is indicated. Non-statutory double patenting rejections may not be held in abeyance. See MPEP 714.02. Applicants did not traverse the NSDP rejection. The rejection is maintained.
RE: Rejection of claims 1, 3-6, 11, and 16-18 on the ground of nonstatutory double patenting over claims 1, 3-4, 6, and 10-12 of U.S. Patent No. 10709745:
The applicant asserts that the instant claims, being directed to methods, do not embrace the issued patent claims, which are directed to pharmaceutical compositions (Applicant Remarks, page 13-14). The applicant asserts that the patented compositions and instant claimed methods are distinct, per MPEP 806.05(h) (Applicant Remarks, page 14-15).
These arguments are not found persuasive. The instant application is a continuation of parent application 16/361100 (US patent 10709745), which was not subject to restriction. A finding of independent and distinct subject matter is made by the Office in the form of a restriction requirement, and such a finding had not been made in the parent application. Further, the test for distinct inventions cited by the applicant applies only to inventions in a single given application for the purpose of restriction.
The instant claims are not patentably distinct because the doctrine of double patenting covers not only the invention in the patent but also any modifications or variants that would have been obvious to one of ordinary skill in the art. See MPEP 804. Patented claim 1 recites “[a] pharmaceutical composition for treating cancer, comprising a tropic cell that carries a modified oncolytic virus, wherein the virus comprises a tumor selective promoter element and/or a capsid protein that binds a tumor-specific cell surface molecule, and wherein the tropic cell is a stem cell from a neural stem cell line HB1.F3-CD” (emphasis added). The claim thus renders obvious a method of treating cancer by administration of the virus-laden cell, as one of ordinary skill in the art would understand that a pharmaceutical composition is inherently intended to be used as a pharmaceutical, i.e., administered to a subject. Because one of ordinary skill would also understand that an oncolytic virus selectively infects and kills cancer cells via lysis, administration of the composition would encompass killing of the tumor cells to which they are directed. The patented claims therefore render obvious the instant claims.
The rejection is maintained.
Maintained Rejections
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1-9, 11-12, and 16-20 remain rejected on the ground of nonstatutory double patenting as being unpatentable over claims 3-9 and 12-13 of U.S. Patent No. 10238699. Although the claims at issue are not identical, they are not patentably distinct from each other because of the following reasons.
Regarding claims 1 and 12: Patented claim 12 is directed to a method of treating cancer (which reads on “killing a tumor cell”) comprising administering, to a subject, a therapeutically effective amount of a pharmaceutical composition which comprises a tropic cell that carries a modified oncolytic virus, wherein the virus comprises a tumor selective promoter element and/or a capsid protein that binds a tumor-specific cell surface molecule, and wherein the tropic cell is a stem cell from a neural stem cell line HB1.F3-CD, and further administering one or more therapeutic agent comprising temozolomide, radiotherapy, or both. The method of patented claim 12 anticipates instant claims 1 and 12.
Regarding claims 3 and 16: Following the discussion of instant claims 1 and 12, patented claim 12 does not teach the modified oncolytic virus as a modified conditionally replicating adenovirus, however, patented claim 13 does teach a modified conditionally replicating adenovirus. It would have been obvious to one having ordinary skill in the art prior to the effective filing date of the claimed invention to modify the method of patented claim 12 to comprise a modified conditionally replicating adenovirus. One would be motivated to do so for improving the safety and efficacy of cancer treatment, and such a modification could be readily made. Patented claims 12-13 render obvious instant claims 3 and 16.
Regarding claims 4 and 17: Following the discussion of instant claims 1 and 12, patented claim 12 does not teach the tumor selective promoter element as a survivin promoter, a cyclooxygenase-2 promoter, prostate specific antigen promoter, a CXCR4 promoter, or a STAT3 promoter. However, patented claim 3 is directed to a method of killing a tumor cell with a modified oncolytic virus comprising a survivin promoter, a cyclooxygenase-2 promoter, prostate specific antigen promoter, a CXCR4 promoter, or a STAT3 promoter as the tumor selective promoter element. It would have been obvious to one having ordinary skill in the art prior to the effective filing date of the claimed invention to modify the method of patented claim 12 to comprise a virus having one of the promoters of patented claim 3 in order to promote viral replication in cancer cells alone. Such a modification could be readily made. Patented claims 3 and 12 render obvious instant claims 4 and 17.
Regarding claims 5 and 18: Following the discussion of instant claims 1 and 12, patented claim 12 does not teach the capsid fiber as a fiber, penton, or hexon protein, however, patented claim 4 is directed to a method of killing a tumor cell with a modified oncolytic virus comprising a fiber, penton, or hexon capsid protein for binding a tumor-specific molecule. It would have been obvious to one having ordinary skill in the art prior to the effective filing date of the claimed invention to modify the method of patented claim 12 to comprise an oncolytic virus having the tumor-specific fiber, penton, or hexon capsid protein of patented claim 4. One would be motivated to do so for optimal targeting of tumor cells, and such a modification could be readily made. Patented claims 4 and 12 render obvious instant claims 5 and 18.
Regarding claim 6: Following the discussion of instant claims 1, 5, and 12, patented claims 4 and 12 do not teach a particular tumor-specific cell surface molecule, however, patented claim 5 is directed to a method of patented claim 4 wherein the tumor-specific molecule is an integrin, an EGF receptor family member, a proteoglycan, a disialoganglioside, B7-H3, CA-125, EpCAM, VEGFR1, VEGFR2, CEA, a tumor associated glycoprotein, CD19, CD20, CD22, CD30, CD33, CD40, CD44, CD52, CD74, CD152, MUC1, a tumor necrosis factor receptor, an insulin-like growth factor receptor, folate receptor a, transmembrane glycoprotein NMB, a C-C chemokine receptor, PSMA, recepteur d′origine nantais (RON) receptor, or CTLA-4. It would have been obvious to one having ordinary skill in the art prior to the effective filing date of the claimed invention to modify the method of patented claim 12 to comprise an oncolytic virus capable of binding one of the antigens of patented claim 5. One would be motivated to do so for optimal targeting of tumor cells, and such a modification could be readily made. Patented claims 4-5 and 12 render obvious instant claim 6.
Regarding claim 7: Following the discussion of instant claims 1 and 12, patented claim 12 does not teach a specific tumor cell type, however, patented claim 6 is directed to a method of killing a tumor cell with a modified oncolytic virus wherein the tumor cell is part of a brain tumor, breast tumor, bone tumor, bladder tumor, tumor of the urinary tract, carcinoma, cervical tumor, colon tumor, esophageal tumor, gastric tumor, head and neck tumor, hepatocellular tumor, liver tumor, lung tumor, lymphoma and leukemia, melanoma, ovarian tumor, pancreatic tumor, pituitary tumor, prostate tumor, rectal tumor, renal tumor, sarcoma, testicular tumor, thyroid tumor, or uterine tumor. It would have been obvious to one having ordinary skill in the art prior to the effective filing date of the claimed invention to modify the method of patented claim 12 to comprise targeting of any of the tumor cells of patented claim 6. One would be motivated to do so for targeting of cells in specific tumor types, and such a modification could be readily made. Patented claims 6 and 12 render obvious instant claim 7.
Regarding claims 8 and 19: Patented claim 7 is directed to a method of killing a brain tumor cell comprising contacting the brain tumor cell with a neural stem cell that carries a modified conditionally replicating adenovirus which comprises a tumor selective promoter element and/or a fiber protein that binds heparan sulfate proteoglycans, wherein the neural stem cell is from a neural stem cell line HB1.F3-CD, but does not teach the further use of one or more therapeutic agents. Patented claim 12 is directed to a method of treating cancer comprising administering to a subject a therapeutically effective amount of a pharmaceutical composition which comprises a tropic cell that carries a modified oncolytic virus and administering one or more therapeutic agent comprising temozolomide, radiotherapy, or both. It would have been obvious to one having ordinary skill in the art prior to the effective filing date of the claimed invention to modify the method of patented claim 7 to further comprise administration of temozolomide and/or radiotherapy, per patented claim 12, in order to increase anti-cancer effects. There would be a reasonable expectation of success in doing so because the virus-bearing neural stem cell line could be readily administered along with an additional therapy. Patented claims 7 and 12 render obvious instant claims 8 and 19.
Regarding claims 2, 9, and 20: Following the discussion of instant claims 1, 8, 12, and 19, patented claims 7 and 12 do not teach the tumor cell as a glioma, however, patented claim 8 is directed to the method of patented claim 7 wherein the brain tumor cell is a glioma cell. It would have been obvious to one having ordinary skill in the art prior to the effective filing date of the claimed invention to modify the method of patented claims 1, 7, and 12 to comprise targeting of a glioma cell, per patented claim 8. One would be motivated to make this modification in order to target a specific invasive and difficult-to-treat type of brain tumor. There would be a reasonable expectation of success in doing so because the modified method could be readily applied to the treatment of gliomas. Patented claims 1, 7-8, and 12 render obvious instant claims 2, 9, and 20.
Regarding claim 11: Following the discussion of instant claim 8, patented claims 7 and 12 do not teach the tumor-selective promoter as a survivin promoter, however, patented claim 9 is drawn to the composition of patented claim 7 wherein the promoter is a survivin promoter. It would have been obvious to one having ordinary skill in the art to modify the method of patented claims 7 and 12 to further comprise a survivin promoter, per patented claim 9. One would be motivated to make this modification for viral proliferation specifically in solid tumors. A survivin promoter could be readily used as the tumor-specific promoter of patented claims 7 and 12. Patented claims 7, 9, and 12 render obvious instant claim 11.
Claims 1, 3-6, 11, and 16-18 remain rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 3-4, 6, and 10-12 of U.S. Patent No. 10709745. Although the claims at issue are not identical, they are not patentably distinct from each other because of the following reasons.
Regarding claim 1: Patented claim 1 is directed to a pharmaceutical composition for treating cancer, comprising a tropic cell that carries a modified oncolytic virus, wherein the virus comprises a tumor selective promoter element and/or a capsid protein that binds a tumor-specific cell surface molecule, and wherein the tropic cell is a stem cell from a neural stem cell line HB1.F3-CD (which reads on “a neural stem cell”). It has been held that a claim to a method of using a composition is not patentably distinct from an earlier claim to the identical composition in a patent disclosing the identical use. See Pfizer, 518 F.3d at 1363; Geneva, 349 F.3d at 1385-86, and Sun Pharmaceutical Industries v. Eli Lilly and Co., 611 F. 3d 1381, 1387 (CAFC 2010). See MPEP 804(II)(B)(1).
Patented claim 1 does not teach the further use of radiotherapy or temozolomide, however, patented claim 3 is drawn to the pharmaceutical composition of claim 1 wherein one or more additional therapeutic agents comprise a chemotherapeutic agent, a radioisotope (which reads on “radiotherapy”), a therapeutic antibody, or a toxin, and patented claim 4 is drawn to the claim 3 composition wherein the chemotherapeutic agent is temozolomide. It would have been obvious to one having ordinary skill in the art prior to the effective filing date of the claimed invention to modify the composition of patented claim 1 to further comprise both a radioisotope and temozolomide. One would be motivated to make this modification to increase the efficacy of the cancer treatment. There would be a reasonable expectation of success in doing so because patented claims 3-4 indicate that such a combination would be feasible. Patented claims 1 and 3-4 render obvious instant claim 1.
Regarding claims 3 and 16: Following the discussion of instant claim 1, patented claims 1 and 3-4 do not teach the virus as an adenovirus. Patented claim 6 is drawn to the composition of patented claim 1 wherein the modified oncolytic virus is a conditionally replicating adenovirus. It would have been obvious to one having ordinary skill in the art prior to the effective filing date of the claimed invention to modify the composition of patented claims 1 and 3-4 to comprise a modified conditionally replicating adenovirus. One would be motivated to do so for improving the safety and efficacy of cancer treatment, and such a modification could be readily made. Patented claims 1, 3-4, and 6 render obvious instant claims 3 and 16.
Regarding claims 4 and 17: Following the discussion of instant claim 1, patented claims 1 and 3-4 do not teach a particular tumor-selective promoter. Patented claim 10 is drawn to the composition of patented claim 1 wherein the tumor-selective promoter element is a survivin promoter, a cyclooxygenase-2 promoter, prostate specific antigen promoter, a CXCR4 promoter, or a STAT3 promoter. It would have been obvious to one having ordinary skill in the art prior to the effective filing date of the claimed invention to modify the composition of patented claims 1 and 3-4 to comprise a virus having one of the promoters of patented claim 10 in order to promote viral replication in cancer cells alone. Such a modification could be readily made. Patented claims 1, 3-4, and 10 render obvious instant claims 4, and 17.
Regarding claims 5 and 18: Following the discussion of instant claim 1, patented claims 1 and 3-4 do not teach the capsid fiber as a fiber, penton, or hexon protein, however, patented claim 12 is directed to the composition of patented claim 1 with a modified oncolytic virus comprising a fiber, penton, or hexon capsid protein for binding a tumor-specific molecule. It would have been obvious to one having ordinary skill in the art prior to the effective filing date of the claimed invention to modify the composition of patented claims 1 and 3-4 to comprise an oncolytic virus having the tumor-specific fiber, penton, or hexon capsid protein of patented claim 12. One would be motivated to do so for optimal targeting of tumor cells, and such a modification could be readily made. Patented claims 1, 3-4, and 12 render obvious instant claims 5 and 18.
Regarding claim 6: Following the discussion of instant claims 1-2 and 5, patented claims 1 and 3-4 do not teach a particular tumor-specific cell surface molecule, however, patented claim 11 is directed to the composition of patented claim 1 wherein the tumor-specific molecule is an integrin, an EGF receptor family member, a proteoglycan, a disialoganglioside, B7-H3, CA-125, EpCAM, VEGFR1, VEGFR2, CEA, a tumor associated glycoprotein, CD19, CD20, CD22, CD30, CD33, CD40, CD44, CD52, CD74, CD152, MUC1, a tumor necrosis factor receptor, an insulin-like growth factor receptor, folate receptor a, transmembrane glycoprotein NMB, a C-C chemokine receptor, PSMA, recepteur d′origine nantais (RON) receptor, or CTLA-4. It would have been obvious to one having ordinary skill in the art prior to the effective filing date of the claimed invention to modify the composition of patented claims 1 and 3-4 to comprise an oncolytic virus capable of binding one of the antigens of patented claim 11. One would be motivated to do so for optimal targeting of tumor cells, and such a modification could be readily made. Patented claims 1, 3-4, and 11 render obvious instant claim 6.
Regarding claim 11: Following the discussion of instant claim 8, patented claims 1 and 3-4 do not teach the tumor-selective promoter as a survivin promoter, however, patented claim 10 is drawn to the composition of patented claim 1 wherein the promoter can be a survivin promoter. It would have been obvious to one having ordinary skill in the art to modify the composition of patented claims 1 and 3-4 to further comprise a survivin promoter, per patented claim 10. One would be motivated to make this modification for viral proliferation specifically in solid tumors. A survivin promoter could be readily used as the tumor-specific promoter of patented claims 1 and 3-4. Patented claims 1, 3-4, and 10 render obvious instant claim 11.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JENNIFER S SPENCE, whose telephone number is 571-272-8590. The examiner can normally be reached M-F 8:30-5:30.
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/J.S.S./Examiner, Art Unit 1633
/CHRISTOPHER M BABIC/Supervisory Patent Examiner, Art Unit 1633