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 amendment filed on 7/22/2026 is acknowledged and has been entered. Claims 1-5 and 7-18 are currently pending and under consideration.
Response to Amendment
The Declaration of Dr. Abdulhafez Selim under 37 CFR 1.132 filed on 7/22/2026 is insufficient to overcome the 103 rejections as set forth in the last Office action for the following reasons:
The majority of the Declarants arguments pertain to the ability of the compounds to affect different aspects of the HIF degradation pathway which is not suggested by the prior art. However, the examiner recognizes that “The reason or motivation to modify the reference may often suggest what the inventor has done, but for a different purpose or to solve a different problem. It is not necessary that the prior art suggest the combination to achieve the same advantage or result discovered by applicant. See, e.g., In re Kahn, 441 F.3d 977, 987, 78 USPQ2d 1329, 1336 (Fed. Cir. 2006).” See MPEP 2144. In the instant case, both flavone and puerarin are useful for wound healing. As such, "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)
Rejections Maintained:
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 1-5 and 7-18 remain 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) 1-5 and 7-18 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 1-5 and 7-18 are 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;
flavone, 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 1-5 and 7-18 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.
In response to this rejection, Applicants contend that the pending claims are directed to specific combinations selected for their respective ability to affect different aspects of the hypoxia-inducible factor (HIF) degradation pathway. As such, Applicants contend that the claimed compositions are not merely the use of naturally occurring compounds in isolation, but rather to specifically selected combinations designed to achieve a particular biological effect. For example, Applicants contend that the specification contains experimental evidence demonstrating that the claimed combinations exhibit biological activity not exhibited by the individual constituents (see for example 3).
These arguments have been carefully considered, but are not found persuasive.
In response to Applicants arguments, the Examiner recognizes that a composition comprising at least flavone and puerarin does appear to be found in nature. For example, Tashiro and Pater (US5589182, 1996-12-31, cited in the prior office action) teaches that the root tissue of the plant Pueraria pseudo-hirsula contains both flavon and puerarin, as well as, daidzein. Moreover, Applicants are reminded that the instant claims recite a composition “comprising”, wherein the transitional term "comprising", which is synonymous with "including," "containing," or "characterized by," is inclusive or open-ended and does not exclude additional, unrecited elements or method steps. See, e.g., Mars Inc. v. H.J. Heinz Co., 377 F.3d 1369, 1376, 71 USPQ2d 1837, 1843 (Fed. Cir. 2004).
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 remain 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, 2nd column, 1st full paragraph). As such, the claim limitation appears to be met.
In response to this rejection, Applicants contend that although Tashiro generally discloses complex herbal preparations containing numerous naturally occurring constituents, Tashiro does not identify any disclosed constituent as a VHL protein inhibitor or as a PHD2/EGLN1 protein inhibitor. Moreover, Applicants contend that in addition to not identifying flavone or puerarin as inhibitors of the recited protein target, Tashiro does not disclose any amount of either compound that is effective to inhibit VHL or PHD2/EGLN1.
These arguments have been carefully considered, but are not found persuasive.
In response to these arguments, the Examiner acknowledged and does not dispute Applicants contention that Tashiro does not identify any disclosed constituent as a VHL protein inhibitor or as a PHD2/EGLN1 protein inhibitor. However, as set forth above, the Examiner recognizes that Tashiro does 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. Thus, while Applicants have discovered an unappreciated property of the claimed compounds, the Examiner recognizes that a composition comprising said compounds appears to be known and/or taught. Applicants are reminded that that the instant claims recite a composition “comprising”, wherein the transitional term "comprising", which is synonymous with "including," "containing," or "characterized by," is inclusive or open-ended and does not exclude additional, unrecited elements or method steps. See, e.g., Mars Inc. v. H.J. Heinz Co., 377 F.3d 1369, 1376, 71 USPQ2d 1837, 1843 (Fed. Cir. 2004).
Regarding Applicants arguments pertaining to the effective amount, the Examiner recognizes that the specification teaches that “effective” amount means an amount or dose of active ingredient effective in treating the particular disease, condition or disorder (see Specification, page 6, lines 14-20). As such, “effective amount” does not appear to be limited to an amount of either compound that is effective to inhibit VHL or PHD2/EGLN1. Moreover, Applicants are reminded that the instant claims are drawn to a composition, not a method of treatment. As long as the compositions is capable of performing the asserted use, the composition is 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) 1-5, 7-15 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 wound 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)
In response to the rejection, Applicants do not dispute that the references generally relate to wound healing. However, the majority of Applicants arguments appear to stem from the specifications identification of a specific biological rationale underlying the compositions and the disclosed compounds were selected based on their ability to affect distinct aspects of the HIF degradation pathway which is not taught or suggested by the prior art.
These arguments have been carefully considered, but are not found persuasive.
In response to Applicants arguments, the Examiner acknowledges and does not dispute Applicants contention that neither reference teaches modulation of separate HIF degradation pathways. However, the examiner recognizes that “The reason or motivation to modify the reference may often suggest what the inventor has done, but for a different purpose or to solve a different problem. It is not necessary that the prior art suggest the combination to achieve the same advantage or result discovered by applicant. See, e.g., In re Kahn, 441 F.3d 977, 987, 78 USPQ2d 1329, 1336 (Fed. Cir. 2006).” See MPEP 2144. In the instant case, both flavone and puerarin are useful for wound healing. As such, "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)
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 1-5, 7-15 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, 2nd 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.
In response to the rejection, Applicants assert that the additional references do not remedy the deficiencies of Chang and Shangrao for at least the reasons discussed above.
These arguments have been carefully considered but are not found persuasive for the reasons set forth above and incorporated herein.
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 1-5, 7-15 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..
Williams 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). Williams 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.
In response to the rejection, Applicants assert that the additional references do not remedy the deficiencies of Chang and Shangrao for at least the reasons discussed above.
These arguments have been carefully considered but are not found persuasive for the reasons set forth above and incorporated herein.
Conclusion
Therefore, No claim is 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 BRANDON J FETTEROLF whose telephone number is (571)272-2919. The examiner can normally be reached M-F 6AM-4PM.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Jeffrey S Lundgren can be reached at 571-272-5541. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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BRANDON J. FETTEROLF, PHD
Primary Patent Examiner
Art Unit 1626
/BRANDON J FETTEROLF/Primary Examiner, Art Unit 1626
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