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 .
Status of Claims
Claims 1-3, 24, 50, 52, 57, 62, 67-69 and 71 are pending and presented for examination.
Priority
This application claims the benefit of the priority of U.S. Provisional Application No. 63/210,405, filed June 14, 2021.
Information Disclosure Statement
The Information Disclosure Statement filed 10/02/2025 has been considered by the Examiner. The submission is in compliance with the provisions of 37 CFR §§ 1.97 and 1.98. Enclosed with this Office Action is a return-copy of the Forms PTO-1449 with the Examiner’s signature and indication of those references that have been considered.
Withdrawn rejection(s)
Claims 1-4, 11, 15, 24, 32, 34, 37, 40, 42, 50, 52, 57, 62, 67-69 and 71 were rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification is enabling for treating or ameliorating glioblastoma cancer, inhibiting the growth of glioblastoma cancer, or increasing the quality of life in a subject having glioblastoma cancer by administering A6.
Claims 1-4, 11, 15, 24, 32, 34, 37, 40, 42, 52, 57, 62, and 67-69 were rejected under 35 U.S.C. 102a1 as being anticipated by Mazzio et al. (US 2006/0035981 A1).
Claim 71 was rejected under 35 U.S.C. 103 as being unpatentable over Mazzio et al. (US B. 2006/0035981 A1) in view of Ding et al. (US 6,011,029 A).
Applicant’s amendment and corresponding reply pertaining to the newly added limitation have overcome the 112a scope of enablement, the anticipation, and the obviousness rejections made of record in the previous Office Action – specifically, the narrowing of the cancer limitation to claims 1, 2 and 3 that requires glioblastoma as the cancer. Therefore, the above rejections are hereby withdrawn.
Claim Rejections - 35 USC § 103
New rejection, necessitated by amendment
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.
A. Claims 1-3, 24, 50, 52, 57, 62, and 67-69 are rejected under 35 U.S.C. 103 as being unpatentable over Mazzio et al. (US 2006/0035981 A1) in view of Baillie et al. (Antioxidants 2018, 7, 115; doi:10.3390/antiox7090115).
Claimed invention
A method of:
treating or alleviating one or more symptoms of glioblastoma in a subject in need thereof, comprising administering intratumorally (Claim 1),
inhibiting the growth of glioblastoma in a subject in need thereof, comprising administering (Claim 2),
increasing the quality of life of a subject in need thereof glioblastoma, comprising administering (Claim 3),
to the subject in need thereof a therapeutically effective amount of:
(i) ascorbic acid, and
(ii) the quinone compound - 2,3-dimethoxy-5-methyl-1,4-benzoquinone
a.k.a. ubiquinone (0) a.k.a. CoQ0 -num]\ i.e.,
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.
Prior art
Mazzio teaches natural non-toxic compositions containing therapeutically effective amounts of actives for treating cancer. See title; abstract; claim 1. An example composition contains Vitamin C (a.k.a. ascorbate) and DMBQ1 (ubiquinone (0) a.k.a. CoQ0).
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. Example 4 at 0044.
The exemplified compositions are used to treat several cancers including brain cancer. See 0045; Claim 23. The composition is administered intratumorally. See 0047; Claim 18. Treatment includes inhibiting cancer growth. See 0024; Fig.3; see also 0048. The compositions of the invention is non-toxic, limits adverse effects and does not cause weight loss associated with known anticancer agents such as taxol. See abstract; 0021; 0026. Thus, indicated reducing symptoms and increasing quality of life (QoL).
While Mazzio teaches natural non-toxic compositions containing therapeutically effective amounts of Vitamin C (a.k.a. ascorbate) and DMBQ (ubiquinone (0) a.k.a. CoQ0) for treating cancer including brain cancer, astrocytomas and gliomas, Mazzio does not expressly teach treating glioblastoma as the brain cancer or glioma.
However, treatment of glioblastoma with a composition comprising ascorbic acid was already practiced. For example, Baillie highlights the benefits of intravenous vitamin C as a supportive therapy for patients with glioblastoma. See Baillie, abstract. Baillie also teaches a small trial of IV vitamin C in combination with standard therapy in glioblastoma patients indicated a trend towards enhanced median survival. See Baillie, p. 1; see also p. 4. Symptoms such as fatigue, dyspnoea, and insomnia were improved with vitamin C treatment. See Baillie, Table 2 at p. 3. Thus, indicated reducing symptoms and increasing quality of life (QoL).
A person of ordinary skill in the art (POSA) would have found it obvious to treat glioblastoma with combination therapy of ascorbic acid (i.e., vitamin C) and 2,3-dimethoxy-5-methyl-1,4-benzoquinone (i.e., ubiquinone (0) a.k.a. CoQ0) because Mazzio teaches vitamin C and CoQ0 are useful for treating brain cancer including gliomas and Baillie teaches vitamin C is effective for treating glioblastoma (an aggressive form of glioma). The POSA would have had a reasonable expectation that the combination of Vitamin C and CoQ0 would provide anticancer efficacy against glioblastoma, given that the combination of Vitamin C and CoQ0 was known to provide anticancer activity against brain cancers such as gliomas and vitamin C alone was known to provide anticancer efficacy against an aggressive form of gliomas, i.e., glioblastoma.
Claim 24 limits claim 1, wherein the ascorbic acid is L-ascorbic acid or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable solvate or hydrate thereof. Mazzio teaches Vitamin C/ascorbate, which indicates the salt form of the L-isomer.
Claim 50 depends from claim 1, wherein the weight ratio of the ascorbic acid to the quinone compound is ranging from about 50, about 100, about 200 or about 400. Although Mazzio does not expressly teach the claimed ratios, Example 4 teaches a composition containing ascorbic acid within a preferred amount of 200-400 mg/day/human and DMBQ (a.k.a. CoQ0) within a broad amount of 0-1000 mg/day/human. Mazzio discloses this combination for suitable in vivo use to provide effective anticancer activity and reduced toxicity. A POSA would have found it obvious to select a weight for each agent within the disclosed overlapping claimed ratio to optimize therapeutic outcomes. Thus, using the disclosed ranges, at 400 mg ascorbic acid and 8, 4, 2, or 1 mg DMBQ, the weight ratio is 50, 100, 200 or 400, respectively.
Therefore, the claimed invention as a whole would have been prima facie obvious at the time the invention application was filed.
Claim 52 and Claim 57 and Claim 62 limit claim 1, wherein the ascorbic acid (Claim 52; Claim 62) or the quinone compound (Claim 57; Claim 62) is administered via direction injection, intracerebral delivery, intracranial delivery, convection-enhanced delivery, or implantation. Mazzio teaches intratumoral deliver. See 0047; Claim 18. The agents are administered together and are exemplified in the same composition. See abstract; Example 4. This also meets the limitations of Claim 67.
Claim 68 and Claim 69 limit claim 1, further comprising administering to the subject in need thereof a therapeutically effective amount of an additional therapeutic anticancer agent. Mazzio further teaches the additional administration of one or more additional chemotherapeutic agents (e.g., adriamycin, busulfan, dacarbazine, flutamide, topotecan, etc.). See abstract; Claim 24. Mazzio further teaches that the composition of Example 4 contains niacin, i.e., an anticancer agent. See 0044.
Response to arguments
Applicant contends that the rejection improperly relies on hindsight and that a POSA would not have had a reasonable expectation of success in treating glioblastoma because oncological drug development is unpredictable and efficacy in one cancer does not necessarily translate to another. However, these arguments do not overcome the prima facie case of obviousness. As outlined in the OA, the rejection does not rely on Mazzio alone to teach treatment of glioblastoma. Rather, Mazzio is used to demonstrate that others already acknowledged compositions comprising ascorbic acid and CoQ0/DMBQ as effective anticancer agents, including brain cancers, specifically gliomas, and further teaches intertumoral administration of such compositions. Baillie teaches that vitamin C has been used been used in glioblastoma patients, including improvement of symptoms and QoL and reported a trend towards enhanced median survival. Therefore, together these references provide a reason to apply the anticancer compositions of Mazzio to glioblastoma with a reasonable expectation of success.
Applicant’s reliance on general statements regarding unpredictability in oncology is not persuasive. Obviousness does not require absolute certainty of success or proof of clinical efficacy, but only a reasonable expectation of success. The fact that glioblastoma is an aggressive or clinically challenging cancer does not negate obviousness where the prior art identifies compositions containing ascorbic acid and CoQ0 are effective for treating gliomas and further identifies glioblastoma as a form of glioma effectively treated with ascorbic acid. These teachings in combination reasonably suggests the use of a composition containing ascorbic acid and CoQ0 for glioblastoma treatment.
Applicant imposes a requirement for experimental proof of the exact claimed method in the prior art, particularly requiring proof of efficacy of intratumoral glioblastoma injection. Such a rigid experimental assessment is not required for obviousness.
B. Claim 71 is rejected under 35 U.S.C. 103 as being unpatentable over Mazzio et al. (US 2006/0035981 A1) view of Baillie et al. (Antioxidants 2018, 7, 115; doi:10.3390/antiox7090115), as applied to claims 1-3, 24, 50, 52, 57, 62, and 67-69 above, taken further in view of Ding et al. (US 6,011,029 A).
Claimed invention
Claim 71 limits claim 68, wherein the additional therapeutic agent is a farnesyltransferase inhibitor (FTI).
Prior art
While the limitations of Claim 68 are met by Mazzio and Baillie as described above, their combination does not expressly teach that the additional anticancer agent of Claim 68 is an FTI.
However, FTIs were already known for effective treatment of cancer. For example, Ding teaches FTIs can be used as therapeutic agents to treat several cancer types including, inter alia, bladder cancer, breast cancer, and colon cancer. See col 1:12-13; See also the paragraph bridging columns 6 and 7. The FTIs interfere with tumor growth. See co. 7:32-36. Ding further teaches working examples of potent FTIs and discusses their use in combination with other anticancer agents. See column 8:~27-36.
A person of ordinary skill in the art (POSA) would have found it obvious to add a known FTI to the CoQ0/ascorbic acid regimen suggested by Mazzio and Baillie because the combination of these references suggests CoQ0/ascorbic acid in combination is effective for treating glioblastoma while Ding teaches FTIs were known to provide therapeutic activity for treating several cancer types. The POSA would have had a reasonable expectation of success in combining these FTI agents of Ding with the CoQ0/ascorbic acid combination disclosed by Mazzio and Baillie based on the separately known activity against cancer. The POSA would have sought to combine the anticancer activity of FTI with CoQ0/ascorbic acid to at least obtain an additive anticancer effect to a subject with cancer.
Therefore, the claimed invention as a whole would have been prima facie obvious at the time the invention application was filed.
Response to arguments
Applicant’s arguments, to the extent they are directed to the present rejection, have been considered but are not persuasive.
Conclusion
No claims are allowed.
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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CHRIS E SIMMONS whose telephone number is (571)272-9065. The examiner can normally be reached M-F: 9:30-6:00p.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, James H. Alstrum-Acevedo can be reached at (571) 272-5548. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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CHRIS E. SIMMONS
Examiner
Art Unit 1622
/CHRIS E SIMMONS/Examiner, Art Unit 1622
/JAMES H ALSTRUM-ACEVEDO/Supervisory Patent Examiner, Art Unit 1622
1 “…2,3-dimethoxy-5-methyl-1,4-benzoquinone (ubiquinone (0)) herein termed “DMBQ"…” See 0026.