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 .
Claims 1-12 have been canceled. Claims 13-28 have been added and under consideration.
Claim Objections
Step i) of claim 1 can be written more simply as ---administering an adenoviral vector encoding thymidine kinase (TK) to a mammal that has a tumor intratumorally at least twice---.
Step ii) of claim 1 can be written more simply as ---administering ganciclovir, acyclovir, valacyclovir, valganciclovir, famiciclovir, or an active analog thereof to the mammal orally or intravenously---. The meaning of a “prodrug” that is “activated by the thymidine kinase” cannot be determined. If this is simply a mechanism of action between the prodrug and TK allowing TK to convert to ganciclovir to ganciclovir monophosphate thereby killing cells, then it does not bear any patentable weight.
Step iii) of claim 1 can be written more clearly as ---administering a monoclonal antibody that binds PD1, PDL1, or CTLA4 to the mammal intravenously---.
The final outcome of the steps in claim 1 should match the preamble, i.e. ---such that tumor burden in the mammal decreases---.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Enablement
Claims 13-28 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for
A method of decreasing tumor burden in a mammal comprising:
i) administering an adenoviral vector encoding thymidine kinase (TK) to a mammal that has a tumor intratumorally;
ii) administering a prodrug to the mammal of step i) orally or intravenously; and
iii) administering a monoclonal antibody that binds CTLA4, PD1, PDL1, or TIM1 to the mammal intravenously such that tumor burden in the mammal decreases,
does not reasonably provide enablement for treating any animal other than a mammal. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention commensurate in scope with these claims.
Adenovirus encoding CD
Kaliberov (Cancer Gene Therapy, 2006, Vol. 13, pg 203-214) administered replication-defective Ad encoding cytosine deaminase (CD) and an antibody that recognizes DR5 to increase cancer cell cytotoxicity (Materials and Methods).
Adenovirus encoding HSVTK
Lee WO 2013/027988 (14/239543) administered Ad-HSVTK and sPD1-Ig to a mammal with a tumor such that tumor burden was treated (Example 2-3).
Sandmair (Human Gene Therapy, Nov. 1, 2000, Vol. 11, No. 6, pg 2197-2205) administered packaging cells that produce replication-defective retroviruses or adenoviruses encoding HSV thymidine kinase (TK) operably linked to a ubiquitous CMV promoter (pg 2198, col. 1, “Retrovirus-packaging cell line”; pg 2198, col. 2, "Adenovirus") into a site of glioma tumor resection in humans followed by intravenous injection of ganciclovir (pg 2200, col. 1, “Operation, gene transfer, and ganciclovir medication”). Decreased tumor burden and increased survival occurred (pg 2202, “Efficacy”).
Immonen (Mol. Therapy, Nov. 2004, Vol. 10, No. 5, pg 967-972) made a replication-defective adenovirus encoding TK operably linked to the CMV promoter made by Sandmair ((pg 971, “HSV-tk adenovirus; reference 7 cited at the end of the paragraph). Injection into a site of glioma resection was performed followed by intravenous injection of GCV (pg 971, col. 2, 1st para). Survival was 81% longer (pg 968, col. 1, “Efficacy”).
Yi (Current Gene Therapy, 2011, Vol. 11, pg 218-228) summarizes various gene therapy protocols utilizing HSV-tk (pg 223, Table 2).
“retroviral vectors expressing HSV-tk have been used in antitumor treatment trials [110-112]. In this case, maximum “bystander effect” is required to kill neighboring uninfected cells as well as infected cells. The results of tumor treatment with HSV-tk expressing retroviral vectors were, however, not fully successful due to low infection efficiency and weak bystander effects” (pg 224, col. 1, 2nd full para).
Yi cites references 110-112:
110. Barzon Gene therapy of thyroid cancer via retrovirally-driven combined expression of human interleukin-2 and herpes simplex virus thymidine kinase. Eur J Endocrinol 2003;148:73-80.
111 Orchard Clinical-scale selection of anti-CD3/CD28-activated T cells after transduction with a retroviral vector expressing herpes simplex virus thymidine kinase and truncated nerve growth factor receptor. Hum Gene Ther 2002;13:979-88.
112 Greco Retrovirus-mediated herpes simplex virus thymidine kinase gene transfer in pancreatic cancer cell lines: an incomplete antitumor effect. Pancreas. 2002;25:e21-9.
Palu (Gene Therapy, 1999, Vol. 6, pg 330-337) made “retroviral producing cells (RVPC)” (pg 330, col. 1) that produce “replication competent retroviral” (pg 331, col. 1, half-way down) vectors encoding thymidine kinase operably linked to the ubiquitous SV40 promoter (pg 330, Fig. 1, caption). These RVPCs and retroviral particles therein were directly injected into glioblastomas (pg 336, col. 1, 2nd full para).
CTLA4 antibody treatment
Jure-Kunkel (8119129) taught:
A method for the treatment of cancer, consisting of the administration to a mammal in need thereof a synergistic, therapeutically effective amount of
(i) an anti-CTLA-4 antibody, in addition to one or more diluents, vehicles, excipients, and/or inactive ingredients, and
(ii) a chemotherapeutic agent, wherein said chemotherapeutic agent is N-(2-chloro-6-methylphenyl)-2-[[6-[4-(2-hydroxyethyl)-1-piperazinyl]-2-methyl-4-pyrimidinyl]amino]-5-thiazolecarboxamide, or a pharmaceutically acceptable salt, solvate, or hydrate thereof, in addition to one or more diluents, vehicles, excipients, and/or inactive ingredients.
PD1 antibody treatment
Lee WO 2013/027988 (14/239543) administered Ad-HSVTK and sPD1-Ig to a mammal with a tumor such that tumor burden was treated (Example 2-3).
PDL1 antibody treatment
Tabernero (Am Soc Clin Oncol Meeting May 31-Jun 4, 2013; Abstract 3622) described MPDL3280A therapy against PD-L1 in colorectal cancer.
Atezolizumab (Tecentriq) is a fully humanised IgG1 (immunoglobulin 1) antibody developed by Roche Genentech. In 2016, the FDA approved atezolizumab for urothelial carcinoma and non-small cell lung cancer.
Avelumab (Bavencio) is a fully human IgG1 antibody developed by Merck Serono and Pfizer. Avelumab is FDA approved for the treatment of metastatic merkel-cell carcinoma. It failed phase III clinical trials for gastric cancer.[20]
Durvalumab (Imfinzi) is a fully human IgG1 antibody developed by AstraZeneca. Durvalumab is FDA approved for the treatment of urothelial carcinoma and unresectable non-small cell lung cancer after chemoradiation.[21]
Brahmer (NEJM, 2012, Vol. 366, No. 26, pg 2455-2465);
Brahmer (Cancer Immunol. Res., July 22, 2013, Vol. 1, No. 2, pg 85-91).
The specification and the art at the time of filing do not correlate treating mammals with a tumor using gene therapy and an antibody to treating any subject as broadly encompassed by claims 1 and 21. Given the lack of guidance in the specification taken with the art at the time of filing, it would have required those of skill undue experimentation to determine how to perform the method as broadly claimed other than
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claims 13-28 are rejected under 35 U.S.C. 102a1 as being anticipated by Lee WO 2013/027988 (14/239543) published on Feb. 28, 2013.
Lee administered Ad-HSVTK, ganciclovir (GCV), and sPD1-Ig to a mammal with a tumor such that tumor burden was treated (Example 2-3). This is equivalent to claims 13 and 21.
Lee taught treating colon, prostate, breast, lung… as required in claim 14, 22 in paragraph 38.
Lee taught using radiation, chemotherapy, and surgery in conjunction with the treatment (para 3 and throughout) as required in claims 15-17, 23-25.
Lee used an antibody that binds PD1 as required in claims 18, 26.
Lee taught using an antibody that binds PDL1 as required in claims 19, 27 (pg 6, last partial paragraph of translation).
Lee taught using an antibody that binds CTLA4 as required in claims 20, 28 (pg 6, last partial paragraph of translation).
Claims 13-28 are rejected under 35 U.S.C. 102a1 as being anticipated by Vanderwalde (10034938).
Vanderwalde taught administering a Herpes simplex virus encoding thymidine kinase (HSV-TK) to a mammal with a tumor along with acyclovir followed by intravenous administration of anti-PD1, anti-PDL1 or anti-CTLA4 antibody such that tumor burden decreases (claim 6; para 7, 9, 17, 41). Acyclovir is an “active analog thereof” in claims 13 and 21. This is equivalent to claims 13 and 21.
Vanderwalde taught treating lung as required in claim 14, 22 in paragraph 2 and 4.
Vanderwalde taught using radiation, chemotherapy, and surgery in conjunction with the treatment (para 5, 6, 65) as required in claims 15-17, 23-25.
Vanderwalde taught using an antibody that binds PD1 as required in claims 18, 26 (claim 1).
Vanderwalde taught using an antibody that binds PDL1 as required in claims 19, 27 (para 7, 9, 41 of Background; para 3, 23, 35, et al. of Description).
Vanderwalde taught using an antibody that binds CTLA4 as required in claims 20, 28 (claim 1).
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 13-28 are rejected on the ground of nonstatutory double patenting as being unpatentable over the claims of U.S. Patent No. 10350275. Although the claims at issue are not identical, they are not patentably distinct from each other because they overlap in scope. The claims in this application could have been claimed in 10350275 and vice versa. The differences are merely a matter of choice and are obvious variants based on the specification.
Conclusion
No claim is allowed.
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Michael C. Wilson
/MICHAEL C WILSON/
Primary Examiner, Art Unit 1638
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