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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 October 31, 2025 has been entered.
Priority
The present Application, filed March 21, 2021, claims priority to International Patent Application No. PCT/US2019/051354, filed September 16, 2019, which claims the benefit of U.S. Provisional Patent Application No. 62/731,586, filed September 14, 2018.
Status of the Claims
In the amendment filed October 31, 2025, claim 6 is canceled and new claims 29-36 are added. Claims 1, 3, and 7-8 are amended and claims 2, 4-5, 9-10, 12, 16, and 18-27 were previously canceled. Claims 1, 3, 7-8, 11, 13-15, 17, and 28-36 are currently pending and subject to examination herein.
Response to Amendments/Arguments
The previous rejections are withdrawn. Applicant’s arguments are moot in view of the grounds of rejection presented herein.
Claim Rejections - 35 USC § 112(b) – Newly Applied
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.
Claims 1, 3, 11, 13-15, 17, 28-30 and 32-36 are indefinite:
Claims 1, 3, 11, 13-15, 17, 28-30 and 32-36 are 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.
Claim 1 is indefinite for reciting, “a mitochondrial complex I inhibitor,” and claim 29 is indefinite for reciting “a glucose-6-phosphate dehydrogenase inhibitor,” because a person having ordinary skill in the art could not reasonably determine the metes and bounds of this limitation. The non-patent publication, Inhibition of mitochondrial complex I by various non-steroidal anti-inflammatory drugs and its protection by quercetin via a coenzyme Q-like action, Chem. Biol. Interact., 199, pgs. 18-28 (2012) by Sandoval-Acuña et al. (hereinafter, “Sandoval-Acuña”) describes an investigation of whether various NSAIDs, such as aspirin and ibuprofen are in vitro inhibitors of mitochondrial complex I (Abstract). Sandoval-Acuña teaches that aspirin, for example, does inhibit complex I activity in mitochondria isolated from Caco-2 cells with an IC50 of ~25 µM (Table 1).
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Above: Table 1 of Sandoval-Acuña.
At the same time, and with respect to claim 29, the non-patent publication, Aspirin inhibits glucose‑6‑phosphate dehydrogenase activity in HCT 116 cells through acetylation: Identification of aspirin-acetylated sites, Mol. Med. Rep., 14, pgs. 1726-1732 (2016) by Ai et al. (hereinafter, “Ai”) teaches aspirin is also an inhibitor of G6PD. Ai teaches that exposure of HCT 116 human colorectal cancer cells to aspirin causes acetylation of G6PD, and this is associated with a decrease in its enzyme activity (Abstract). Thus, aspirin, as just one example, can plausibly be considered as an inhibitor of both mitochondrial complex I and G6PD, albeit a relatively weak and obviously a fairly nonspecific one. However, it would be unclear whether an unmentioned yet common compound like acetylsalicylic acid (aspirin) would be considered “a mitochondrial complex I inhibitor” of claim 1, “a glucose-6-phosphate inhibitor” of claim 29, both, or neither. More generally, in the absence of a list of specified compounds, and without any limitations of inhibitory potency, specificity, or mechanism of action, it would not be possible to discern with certainty which compounds constitute either “a mitochondrial complex I inhibitor” of claim 1, “a glucose-6-phosphate inhibitor” of claim 29.
Claims 3, 11, 13-15, 17, and 28 are indefinite for depending from claim 1 without curing the indefiniteness of the base claim. Claims 30 and 32-36 are indefinite for depending from claim 29 without curing the indefiniteness of the base claim. For the purpose of examination against the prior art, “a mitochondrial complex I inhibitor” and “a glucose-6-phosphate inhibitor” will be construed as any compound that has been shown in the art to have any inhibitory activity toward mitochondrial complex I or toward G6PD, respectively.
Claim Rejections-- 35 USC § 103 – Newly Applied
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.
Claims 1, 3, 11, 13-15, 17, 28-30 and 32-36 are unpatentable over Gao2:
The rejection of claims 1, 3, 11, 13-15, 17, 28-30 and 32-36 under 35 U.S.C. 103 as being unpatentable over International Patent Application Publication No. WO2016/049012 to Gao et al. (hereinafter, “Gao2”).
Claim 1 recites a composition comprising (i) a gnetin H (GH) and (ii) a mitochondrial complex I inhibitor. Claim 29 recites a composition comprising (i) a gnetin H (GH) and (ii) a or glucose-6-phosphate dehydrogenase inhibitor.
Gao2 teaches prophylactic compositions that contain cis or trans-gnetin H and methods of using the compositions (Abstract). Gao2 teaches that the composition can further comprise an additional active agent that can be an anti-inflammatory agent (claim 12, pg., 3, lines 8-10), and further teaches that exemplary anti-inflammatory agents include non-steroidal anti-inflammatory drugs (pg. 20, lines 27-31). Given that aspirin is a canonical NSAID, Gao2 thus renders obvious a composition comprising gnetin H (either cis or trans) and aspirin. Because, for the reasons noted above with respect to the rejections for indefiniteness (referencing the teachings of Sandoval-Acuña and Ai) aspiring is understood as both “a mitochondrial complex I inhibitor” of claim 1 and “a glucose-6-phosphate inhibitor” of claim 29, claims 1 and 29 are obvious over Gao2.
With respect to claims 3 and 30, as noted, Gao2 teaches the composition can include trans-gnetin H (Abstract). With respect to claims 11 and 32, Gao2 teaches that the composition can be administered prophylactically in an amount effective to prevent or delay the development of inflammation as brought on by an inflammatory condition such as cancer (pg. 19, line 27 through pg. 20, line 18). With respect to claims 13-14 and 33-34, Gao2 teaches that the composition can be administered to a human. With respect to claims 17 and 36, Gao2 teaches that the composition can be administered by various routes, including oral or various injection administrations (pg. 9, line 30 through pg. 10, line 2).
Claims 15 and 35 recite the methods of claims 11 and 32 wherein the subject lacks functional p53 or has dysfunctional p53, while claim 28 recites the method of claim 11 wherein the subject has functional p53.
Gao2 is applied to claims 15, 28, and 35 as to claims 11 and 32, above. While Gao2 does not expressly discuss dysfunctional or functional p53, Gao2 does teach preclinical testing of a gnetin H composition on THP-1 cells (Abstract). THP-1 cells are known to be TP53 null (lack functional p53). See, for example, the non-patent publication, Therapeutic Targeting of TP53-mutated Acute Myeloid Leukemia by Inhibiting HIF-1α with Echinomycin, Oncogene, 39, pgs. 3015–3027 (2020) by Wang et al. (hereinafter, “Wang”), e.g. at Figure 4. Similarly, Gao2 teaches preclinical testing of a gnetin H composition on A549 cells. A549 cells are known to have wild type p53 (functional p53). See, for example, the non-patent publication, The p53-53BP1-Related Survival of A549 and H1299 Human Lung Cancer Cells after Multifractionated Radiotherapy Demonstrated Different Response to Additional Acute X-ray Exposure, Int. J. Mol. Sci., 21, art. 3342 pgs. 1-21 (2020) by Pustovalova et al. (hereinafter, “Pustovalova”). Neither Wang nor Pustovalova is cited as prior art, but merely to demonstrate the inherent properties of these cells lines as having dysfunctional or functional p53. In view of the preliminary tests on these cell lines having dysfunctional or functional p53, claims 15, 28, and 35 are obvious.
Allowable Subject Matter
Claims 7-8 and 31 are objected to as being dependent upon rejected base claims, but would be allowable if rewritten in independent form including all of the limitations of the base claims and any intervening claims.
Conclusion
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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/ALEXANDER K. SHOWALTER/Examiner, Art Unit 1629
/JEFFREY S LUNDGREN/Supervisory Patent Examiner, Art Unit 1629