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. Application Status The preliminary amendment filed on 12/20/2023 is acknowledged. Claims 1-18 are currently pending and under consideration. Information Disclosure Statement The information disclosure statement filed on 4/16/2024 is acknowledged and has been considered except where lined through. Specification It is noted that there are multiple uses of trade marks within the specification. For example, the use of the term Carbopol TM 9000 or Eucerin®, which is a trade name or a mark used in commerce, has been noted in this application. The term should be accompanied by the generic terminology; furthermore the term should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term . Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks. The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code. Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01. Claim Objections Claims 10 and 17 are objected to because of the following informalities: Regarding claim 10, claim 10 recites the phrase “weight ratio weight ratio”. It is suggested that Applicants delete one occurrence of “weight ratio”. Regarding claim 17, claim 17 recites “a 5 skin penetration enhancer”. A review of the specification does not point out the significance of “5” and the state of the art does not indicate what a “5” skin penetration enhancer is. As such, “5” appears to be a typo and will not be given any weight. Claim 5 is objected to under 37 CFR 1.75 as being a substantial duplicate of claim 6. When two claims in an application are duplicates or else are so close in content that they both cover the same thing, despite a slight difference in wording, it is proper after allowing one claim to object to the other as being a substantial duplicate of the allowed claim. See MPEP § 608.01(m). Appropriate correction is required. Claim Rejections - 35 USC § 101 35 U.S.C. 101 reads as follows: Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title. Claims 1-18 are rejected under 35 U.S.C. 101 because the claimed invention is not directed to patent eligible subject matter. Based upon an analysis with respect to the claim as a whole, claim(s) 1-18 do not recite something significantly different than a judicial exception. The analysis has been conducted in accordance with the most recent 2014 Interim Guidelines for Subject Matter Eligibility, published by USPTO in the Federal Register on 12/16/2014, http://www.gpo.gov/fdsys/pkg/FR-2014-12-16/pdf/2014-29414.pdf . See information about the Interim Guidelines at http://www.uspto.gov/patents/law/exam/interim_guidance_subject_matter_eligibility.jsp . Based upon an analysis with respect to the claims as a whole, Claims 1-18 directed to a judicial exception (i.e., law of nature, a natural phenomenon, or an abstract idea) without significantly more. Claims 1-18 recite compositions comprising combinations of natural products and as such are directed towards a law of nature and a natural phenomenon. The claimed composition does not have markedly different characteristics from what occurs in nature, and are a “product of nature” exception. Further, the claims do not include any additional elements that are sufficient to amount to significantly more than the judicial exceptions. The rationale for this determination is explained below: Step 1: Is the claim to a process, machine, manufacture or composition of matter ? The elected subject matter, within the scope of the instant claims is construed as a composition comprising (a) an effective amount of a von HippelLindau protein inhibitor selected from meisoindigo , tanshinone IIA, 7-hydroxyflavone, dicumarol,flavone , tab ersonine , danthron, and equol and (b) an effective amount of a PHD2/EGLNI protein inhibitor selected from glabridin , puerarin,wedelolactone , phlorizin : RRR-alpha-tocopherol, docosahexaenoic acid (DHA), arachidonic acid (ARA), Vitamin C, gamma-tocopherol and carotenoids OR a composition comprising an ARG-383 targeting component selected from flavone, echinatin , danthron, eriodictyol , caffeic acid phenethyl ester, myricetin and xanthotoxol and a HIS-3 13 targeting component selected from puerarin , glabridin , wedelolactone, meisoindigo , sophoricoside, isovitexin , and phiorizin . So the answer to Step 1 is: Yes , the claims are drawn to a composition of matter. Step 2A: Is the claim directed to a law of nature, a natural phenomenon, or an abstract idea ? The claimed subject matter appears to describe the mixture of at least two natural products wherein the natural products include but are not limited to: meisoindigo , tanshinone IIA, 7-hydroxyflavone, dicumarol,flavone , tab ersonine , danthron, and equol ; and glabridin , puerarin,wedelolactone , phlorizin : RRR-alpha-tocopherol, docosahexaenoic acid (DHA), arachidonic acid (ARA), Vitamin C, gamma-tocopherol and carotenoids ; f lavone, echinatin , danthron, eriodictyol , caffeic acid phenethyl ester, myricetin and xanthotoxol ; and puerarin , glabridin , wedelolactone, meisoindigo , sophoricoside, isovitexin , and phiorizin : RRR-alpha-tocopherol, docosahexaenoic acid (DHA), arachidonic acid (ARA), Vitamin C, gamma-tocopherol and carotenoids. Because each compound is naturally occurring, their combination together in a composition is considered a “product of nature,” which falls within each of the categories: “laws of nature” and “natural phenomena”. Thus, the claims are drawn to judicially recognized exceptions. See p74623, left column, of the Federal Registry notice : …Courts have held that naturally occurring products and some man-made products that are essentially no different from a naturally occurring product are ‘‘products of nature’’ that fall under the laws of nature or natural phenomena exception. (Section I (3); pp. 74622-4, of the Federal Registry notice discusses Natural Products.). The next question within step 2A is: does the nature based product show “markedly different characteristics” from any naturally occurring counterpart(s) in their natural state, based on structure, function and/or properties ? Claims 1-18 recite a composition comprising natural products in a single formulation. Relative to this composition, there is no naturally occurring counterpart to the claimed composition, having all these compounds present in the same combination. In this case, the combination is compared to the individual components as they occur in their natural state. See p. 74623 of the Federal registry notice, middle column: “ The markedly different characteristics analysis compares the nature-based product limitation to its naturally occurring counterpart in its natural state. When there is no naturally occurring counterpart to the nature based product, the comparison should be made to the closest naturally occurring counterpart. In the case of a nature-based combination, the closest counterpart may be the individual nature-based components that form the combination, i.e., the characteristics of the claimed nature-based combination are compared to the characteristics of the components in their natural state ”. Establishment of a marked difference cannot be based on some inherent or innate characteristic of the naturally occurring counterpart. See p. 74623, footnote 28: “ To show a marked difference, a characteristic must be changed as compared to nature, and cannot be an inherent or innate characteristic of the naturally occurring counterpart. Funk Bros. Seed Co. v. Kalo Inoculant Co., 333 U.S. 127, 130 (1948) (‘‘[The inventor did] not create a state of inhibition or of non-inhibition in the bacteria. Their qualities are the work of nature. Those qualities are of course not patentable.’’); In re Marden, 47 F.2d 958 (CCPA 1931) (eligibility of a claim to ductile vanadium held ineligible, because the ‘‘ductility or malleability of vanadium is . . . one of its inherent characteristics and not a characteristic given to it by virtue of a new combination with other materials or which characteristic is brought about by some chemical reaction or agency which changes its inherent characteristics’’). Further, a difference in a characteristic that came about or was produced independently of any effort or influence by applicant cannot show a marked difference. Roslin, 750 F.3d at 1338 (Because ‘‘any phenotypic differences came about or were produced ‘quite independently of any effort of the patentee ’ ’ ’ and were ‘‘uninfluenced by Roslin’s efforts’’, they ‘‘do not confer eligibility on their claimed subject matter’’ (quoting Funk Bros. )). In the instant case, there seems to be no indication in the specification that the combination of all of the above natural products has any characteristics (structural, functional or other properties) that are different from the naturally occurring compounds, individually. Thus the composition does not have markedly different characteristics from what occurs in nature, and is a “product of nature exception”. So the answer to Step 2A is: Yes , the claims are drawn to a natural composition. Step 2B: Does the claim recite additional elements that amount to significantly more than the judicial exemption ? The claims recite that the compositions can further comprise a carrier selected from a variety of oil or a skin penetration enhancer. However, the carriers include, but not limited to, corn oil, mineral oil, vegetable oil, sesame oil and olive oil and a skin penetration enhancer could include water . Accordingly, since the claim does not include any additional features that could add “significant more” to the exception the answer to Step B is: No , the claims do not recite additional elements that amount significantly more than the judicial exception. The claims do not qualify as eligible subject matter, and are properly rejected under 35 U.S.C. § 101. 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. Claim(s) 1 and 17 is/are rejected under 35 U.S.C. 102 (a)(1) as being anticipated by Tashiro and Pater (US5589182, 1996-12-31) as evidenced by Yasumoto et al. ( Journal of Drug Delivery Science and Technology 2025; 112: 107226 ) . Tashiro and Pater teach a pharmaceutical composition for the treatment of a cardiovascular disease or cerebrovascular disease comprising a mixture of aqueous extracts including, but not limited to, the root tissue of the plant Pueraria pseudo- hirsula containing flavon , puerarin and daidzein (Claim 1 of the patent, (l.)). While Tashiro and Pater do not specifically teach that water e.g. aqueous, is a penetration enhancer, as evidenced by Yasumoto et al. water is the ideal, naturally occurring penetration enhancer (page 1, 2 nd column, 1 st full paragraph). As such, the claim limitation appears to be met. Claim Rejections - 35 USC § 103 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 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. Claim (s) 1-15 and 18 is/are rejected under 35 U.S.C. 103 as being unpatentable over Chang and Cheng (US20170273938A1, 2017-11-28) in view of Shangrao Normal University (CN110665052A, 2020-01-10, google English Translation provided) . Chang and Cheng teach a wound healing composition comprising a flavonoid, specifically flavone, wherein the composition further comprises a pharmaceutically acceptable carrier (paragraph 0024-0025). Moreover, Chang and Cheng teach that the pharmaceutical composition is prepared as an external medicament, a cosmetic or a pharmaceutical, wherein the composition further comprises an additional therapeutic agent (paragraphs 0026-0027). Chang and Cheng further teach a composition comprising 0.5% cirsimaritin a derivative of flavone (paragraph 0037) Chang and Cheng do not specifically that the additional therapeutic agent is puerarin or the various weight ratio’s as claimed. Shangrao Normal University teach a peurarin hydrogel wou n d excipient, wherein puerarin is used for wound healing materials (abstract). Shangrao Normal University further provides application of 2% puerarin hydrogel, 4% puerarin hydrogel and 4% puerarin hydrogel (see Test Example 1 Mice Wound Healing Test) . It would have been prima facie obvious to one of ordinary skill in the art, prior to the effective filing date of the instantly claimed invention, to modify the composition taught by Chang and Cheng to include puerarin in view of the teachings of Shangrao Normal University. One of ordinary skill in the art would have been motivated to make such a modification, with a reasonable expectation of success, because: -Chang and Cheng teaching using flavonoids such as flavone for wound healing and - Shangrao Normal University teaches using peurarin for would healing. "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.... [T]he 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) (citations omitted) Moreover, it would have been prima facie obvious to one of ordinary skill in the art, prior to the effective filing date of the instantly claimed invention, to modify the composition so as to optimize the weight ratios of flavone and puerarin for wound healing. One of ordinary skill in the art would have been motivated to make such a modification, with a reasonable expectation of success, because: Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller , 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955) Claim (s) 16 is/are rejected under 35 U.S.C. 103 as being unpatentable over Chang and Cheng (US20170273938A1, 2017-11-28) in view of Shangrao Normal University (CN110665052A, 2020-01-10, google English Translation provided), as applied above to claims 1-15 and 18, in further view of Poljsak et al. ( Pytotherapy Research 2020; 34:254-269) . The combination of Chang and Cheng and Shangrao Normal University have been described above and is incorporated herein. In short, the combination teaches a pharmaceutical composition for wound healing comprising flavone and puerarin and a pharmaceutically acceptable carrier. The combination does not teach that the carrier is a vegetable oil or coconut oil . Poljsak et al. reviews in vitro and in vivo studies using numerous vegetable butters and oils including coconut oil in the treatment of skin wounds (Abstract). For example, Poljsak et al. teach that applying cold-pressed coconut oil to skin wounds in young rats once a day for 10 days resulted in faster epitherlization , which in turn resulted in faster wound healing than was observed in the untreated wounds of a control group (page 255, 2 nd column, 3.1). It would have been prima facie obvious to one of ordinary skill in the art, prior to the effective filing date of the instantly claimed invention, to modify the composition taught by the combination to include coconut oil in view of the teachings of Poljsak et al. One of ordinary skill in the art would have been motivated to make such a modification, with a reasonable expectation of success, because: - Poljsak et al. teach that many vegetable butter and oils, including coconut oil, offer wound healing benefits. Claim (s) 17 is/are rejected under 35 U.S.C. 103 as being unpatentable over Chang and Cheng (US20170273938A1, 2017-11-28) in view of Shangrao Normal University (CN110665052A, 2020-01-10, google English Translation provided), as applied above to claims 1-15 and 18, in further view of Williams and Barry (Advanced Drug Delivery Reviews 2004; 56:603-618) . The combination of Chang and Cheng and Shangrao Normal University have been described above and is incorporated herein. In short, the combination teaches a pharmaceutical composition for wound healing comprising flavone and puerarin and a pharmaceutically acceptable carrier. The combination does not teach that the composition further comprises a skin penetration enhancer.. Willams and Barry teach that the human skin is a remarkably efficient barrier, designed to keep “our insides in and the outsides out”, which causes difficulties for transdermal delivery of therapeutic agents (page 604, Introduction). Willams and Barry teach that one of the long-standing approaches to increase the range of drugs that can be delivered via this route has been to use penetration enhancers (page 604, Introduction). It would have been prima facie obvious to one of ordinary skill in the art, prior to the effective filing date of the instantly claimed invention, to modify the composition taught by the combination to include a skin penetration enhancer in view of the teachings of Williams and Barry . One of ordinary skill in the art would have been motivated to make such a modification, with a reasonable expectation of success, because: - Williams and Barry teach that the use of penetration enhancers is a long standing approach to overcome difficulties of the human skin in the transdermal delivery of therapeutic agents. Conclusion Therefore, No claim is allowed. 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