DETAILED ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA . The submission filed on 05/24/2023 has been entered. Claims 1-32 are pending in this application. Claims 1-14 and 20-32 are withdrawn. Claims 15-19 are currently under examination.
Priority
This is US Application No. 18/323,032 filed on 05/24/2023 and claims benefit of US PRO 63/345,702 filed on 05/25/2022.
Election/Restrictions
Applicant's election with traverse of Group II invention (claims 15-19) and species (a. a combination of 12 purified compounds: quercetin, luteolin, kaempferol, catechin, ß-carotene, formononetin, wogonin, paeoniflorin qt., betulinic acid (mairin), isoamebrin 4, ß-sitosterol and indirubin; and b. a combination of (i) oral, (ii) cream, and (iii) powder forms of a composition) in the reply filed on 02/09/2026 is acknowledged. The traversal is on the ground(s) that “Group II claims are directed to a pharmaceutical composition formulation comprising the same active compounds as recited in Group I claims… Group III claims are directed to a method of using the pharmaceutical composition of Group I, and Group IV claims are directed to the method of treating eczema in a subject using a pharmaceutical composition formulation of Group IL Therefore, Groups I-IV are all related to each other as different aspects of a single invention and are not "independent and distinct"… it is believed that search and consideration of all four groups would not impose a serious burden” (p. 3, last para.; p. 4, para. 1 to 2). This is not found persuasive because " Inventions I/III and II/IV are related as product and process of use. The inventions can be shown to be distinct if either or both of the following can be shown: (1) the process for using the product as claimed can be practiced with another materially different product or (2) the product as claimed can be used in a materially different process of using that product. See MPEP § 806.05(h)… Inventions I/II, I/IV, II/III, and III/IV are unrelated. Inventions are unrelated if it can be shown that they are not disclosed as capable of use together and they have different designs, modes of operation, and effects (MPEP § 802.01 and § 806.06)… Restriction for examination purposes as indicated is proper because all the inventions listed in this action are independent or distinct for the reasons given above and there would be a serious search and/or examination burden if restriction were not required because one or more of the following reasons apply:
• The inventions have acquired a separate status in the art in view of their different classification.
• The inventions require a different field of search (e.g., searching different classes/subclasses or electronic resources, or employing different search strategies or search queries)”, as set forth on pages 3 to 4 of the Restriction/Election Requirement mailed on 12/09/2025.
Claims 1-14 and 20-32 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention or species, there being no allowable generic or linking claim. Thus, claims 15-19 are currently under examination.
The requirement is still deemed proper and is therefore made FINAL.
Claim Objections
Claims 15 and 17 are objected to because of the following informalities: In claim 15, insert the missing conjunction “and” immediately before the recitation “formulated” (lines 2, 4, and 5, a total of 3 occurrences) because the purified compound, not Table 1, is formulated. In claim 17, insert the synonymous term ”(cianidanol)” immediately after the recitation “catechin” because Table 1 disclosed the synonymous term; change the misspelled “isoarnebrin 4” (line 4) to “isoarnebin 4 (shikonin)” because Table 1 disclosed the synonymous shikonin; and delete the redundant “sitosterol” (5th compound in line 4), which has the same structure and molecular weight as “ß-sitosterol” in Table 1. Appropriate correction is required.
Claim Rejections - 35 USC § 112
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 15-19 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. Claims 17-19 depend from claim 15.
Claims 15 and 16 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being incomplete for omitting essential structural cooperative relationships of elements, such omission amounting to a gap between the necessary structural connections. See MPEP § 2172.01. The omitted structural cooperative relationships are: Claim 15 recites “A pharmaceutical composition… formulated for oral administration… formulated as a cream, and… formulated as a powder for soak”, which requires a composition formulated for oral administration, as a cream, and as a powder for soak. It is unclear how oral formulation can be a cream or a powder for soak, a cream can be used for oral administration or as a powder for soak, or a powder for soak can be used for oral administration or as a cream. Claim 16 recites “said at least one purified compound comprises” (lines 1 to 2), in which the “comprises” is open-ended and is broader than the preceding closed transitional phrase “selected from” in claim 15. To overcome the rejection, Applicant is advised to insert the phase “form or forms of a” immediately before the recitation “pharmaceutical” (line 1 of claim 15); and to change the recitation “said at least one purified compound comprises” (lines 1 to 2 of claim 16) to “said composition comprises”.
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 15-19 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a natural phenomenon or a product of nature without significantly more. The 2019 Revised Patent Subject Matter Eligibility Guidance (issued January 7, 2019)” (https://www.govinfo.gov/content/pkg/FR-2019-01-07/pdf/2018-28282.pdf) and “October 2019 Update: Subject Matter Eligibility (issued October 17, 2019)” (https://www.uspto.gov/sites/default/files/documents/peg_oct_2019_update.pdf), are followed here. The claim is directed to a statutory category, e.g., a composition of matter (Step 1: YES). The claim is then analyzed in Step 2A (Prong one) to determine whether it is directed to any judicial exception. The claims 15-19 recite a composition comprising at least one purified compound selected from Table 1 (or a combination of or selected from the group consisting of quercetin, luteolin, kaempferol, catechin, ß-carotene, formononetin, wogonin, paeoniflorin qt, betulinic acid (mairin), isoarnebin 4, ß-sitosterol, indirubin, licochalcone B, and stigmasterol), which are products of nature. Accordingly, the claim is directed to at least one exception (Step 2A, prong one: YES). The claim is then analyzed in Step 2A (Prong two) and is determined that this judicial exception is not integrated into a practical application because there is no indication that mixing them in the recited forms (i.e., formulated for oral administration, as a cream, and/or as a powder for soak) changes the structure, function, or other properties of individual purified compound in any marked way. Instead, the individual purified compound retains its naturally occurring structure and properties (e.g., antioxidant or anti-inflammatory activity). Thus, the claimed mixture as a whole does not display markedly different characteristics compared to the closest naturally occurring counterpart. Accordingly, the Step 2A (Prong two) is NO. The claim(s) does/do not include additional elements that are sufficient to amount to significantly more than the judicial exception because prior to applicant’s invention and at the time of filing the application, mixing of recited purified compounds was well-understood, routine and conventional in the field, as evidenced by the reference under the 102 and 103 rejections below. The recitation of different forms (formulated for oral administration, as a cream, and/or as a powder for soak) does not affect this analysis, because it was also well-understood, routine and conventional at the time to obtain different forms, e.g., to achieve commercially acceptable chemical complex for different purposes. Thus, the different forms of recited composition, when recited at this high level of generality, does not meaningfully limit the claim, and the claim as a whole does not amount to significantly more than each “product of nature” by itself (Step 2B: NO). The claim does not qualify as eligible subject matter.
Claim Rejections - 35 USC § 102
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.
(I) Claims 15-19 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Mamouni et al. (Neoplasia 20, 789–799, 2018, hereinafter referred to as Mamouni ‘2018).
With regard to the structural limitations “a form or forms of a pharmaceutical composition comprising at least one purified compound (or a combination of purified compounds) selected from Table 1 (or selected from the group consisting of quercetin, luteolin, and kaempferol) and formulated for oral administration” (claims 15-19):
Mamouni ‘2018 disclosed ProFine, a standardized composition of luteolin, quercetin, and kaempferol as a nutraceutical. Oral administration of ProFine did not exhibit obvious toxicities in mice, and the three ingredients retained their individual pharmacokinetic and bioavailability profiles. ProFine was prepared as a stock solution of 100 mg/ml, containing 24.68 mg/ml luteolin, 26.06 mg/ml quercetin, and 49.35 mg/ml kaempferol in 100% dimethyl sulfoxide (DMSO). The composition of ProFine formulation for oral gavage administration (page 789, Abstract page 790, left col., para. 3).
Thus these teachings of Mamouni ‘2018 anticipate Applicant’s claims 15-19 and carry the same properties or would achieve the intended purposes, including “for treating eczema”, required by claim 1.
(I) Claims 15-19 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Hu et al. (US 2003/0166583, Sep. 4, 2003, hereinafter referred to as Hu ‘583).
With regard to the structural limitations “a form or forms of a pharmaceutical composition comprising at least one purified compound (or a combination of purified compounds) selected from Table 1 (or selected from the group consisting of quercetin, luteolin, kaempferol, catechin, formononetin, wogonin, and paeoniflorin qt) and formulated for oral administration (or as a cream, and/or as a powder)” (claims 15-19):
Hu ‘583 disclosed a composition for inhibiting a dermal cytochrome P450 1A (CYP1A) comprising (-)-Epicatechin, (+)-Catechin, (+)-Epicatechin, (+)-Limonene, 3-Phenylpropyl acetate, α-naphthoflavone (Alpha-NF), Apigenin, Baicalein, Baicalin, Beta-Myrcene, Beta-Naphthoflavone, Catechin, Cineole, Daidzein, Daidzin, Diosmin, Ergosterol, Formononetin, Gallic acid, Genistein, Glycyrrhizin, Glycyrrhizic acid, Hesperetin, Hesperidin, Isoquercitrin, Kaempferol, Lauryl alcohol, Luteolin, Luteolin-7-Glycoside, Narigenin, Narigin, Nordihydroguaiaretic acid, Oleanolic acid, Paeoniflorin, Quercetin, Quercitrin, Rutin, Swertiamarin, Terpineol, Trans-Cinnamaldehyde, Trans-Cinnamic acid, Umbelliferone, Genkwanin, Homoorientin, Isovitexin, Neohesperidin, Wogonin, Capillarisin, Ursolic acid, or the pharmaceutically acceptable salts thereof, or a combination of two or more of the above. The preferred dermal CYP1A inhibitors are kaempferol, luteolin-7-glycoside, terpineol, α-naphthoflavone, ß-naphthoflavone, and hesperetin. The dermal CYP1A inhibitors suppress first-pass effect on dermatological drugs. The “first-pass effect” of drugs refers to the process of drug degradation during a drug's transition from initial ingestion or application to skin to circulation in the blood stream. One example of the “first-pass effect” drug that can be combined with the CYP1A inhibitor is retinoid. A pharmaceutical composition having a retinoid-like compound or compounds as the active ingredient are useful as agents for treating skin-related diseases, including, actinic keratoses, arsenic keratoses, inflammatory and non-inflammatory acne, psoriasis, ichthyoses and other keratinization and hyperproliferative disorders of the skin, eczema, atopic dermatitis (pages 3/12 and 5/12, [0009, 0010, 0015-0017, 0022]). Wogonin can be extracted from the root of Scutellaria baicalensis GEORGI. In addition, the root of Scutellaria baicalenesis GEORGI contains steroids such as ß-sitosterol, campesterol, stigmasterol; and sugars. The dermal CYP1A inhibitors can be applied alone or together with dermatological drug(s) to skin in topical formulations. The formulations suitable for topical administration and suitable for penetration through the skin to the site of where treatment is required, such as liniments, lotions, creams, ointments or pastes. Creams, ointments or pastes are semi-solid formulations and may be made by mixing the CYP1A inhibitors in finely-divided or powdered form, alone, or in solution or suspension in an aqueous or non-aqueous fluid (page 6/12, [0028, 0031, and 0034]). Some compounds achieved the most effective inhibition at concentration of 100 uM. Such compounds include kaempferol (which inhibited about 100% of CYP1A activity), α-naphthoflavone (which inhibited about 99% of CYP1A activity). luteolin-7-glucoside (which inhibited about 97% of CYP1A activity), ß-naphthoflavone (which inhibited about 96% of CYP1A activity), quercetin (which inhibited about 92% of CYP1A activity), luteolin (which inhibited about 90% of CYP1A activity), narigenin (which inhibited about 83% of CYP1A activity) (page 9/12, [0055]).
Thus, these teachings of Hu ‘583 anticipate Applicant’s claims 15-19 because claim 15 recites open-ended “comprising” for the claimed pharmaceutical composition which encompasses additional compounds, not listed in Table 1.
Claim Rejections - 35 USC § 103
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.
Claims 15-19 are rejected under 35 U.S.C. 103 as being unpatentable over Hu et al. (US 2003/0166583, Sep. 4, 2003, hereinafter referred to as Hu ‘583) in view of Pushpangadan et al. (Annals of Phytomedicine 4(1): 17-36, 2015, hereinafter referred to as Pushpan ‘2015). Claims 15-19 are rejected here because they have been rejected by the primary reference under 102 above. Thus, the above disclosure of Hu ‘583 is incorporated in its entirety here.
Hu ‘583 did not explicitly disclose the elected “a combination of 12 purified compounds: quercetin, luteolin, kaempferol, catechin, ß-carotene, formononetin, wogonin, paeoniflorin qt., betulinic acid (mairin), isoamebin 4 (shikonin), ß-sitosterol and indirubin”.
Pushpan ‘2015 disclosed molecular mechanisms through which several phytochemicals may inhibit inflammation. Betulinic acid suppresses NF-κB dependent reporter gene expression and the production of NF-κB regulated gene products such as COX-2 and MMP-9 induced by inflammatory stimuli. Shikonin exerts anti-inflammatory properties, possibly through inhibition of the NF-κB signaling pathway and substantially affects transgenic and/or endogenous expression of TNF-α, GM-CSF and other cytokine genes in mouse skin tissue. Indirubin suppressed NF-κB activation induced by various inflammatory agents (page 17, Abstract; page 26, left col.; page 22, right col.; page 27, left col.).
Thus, it would have been prima facie obvious to one of ordinary skill in the art at the time the invention was filed to combine the CYP1A inhibitors, including quercetin, luteolin, kaempferol, catechin, retinoid (or its precursor ß-carotene), formononetin, wogonin, paeoniflorin, and ß-sitosterol as taught by Hu ‘583 with other phytochemicals, including Betulinic acid, Shikonin, and Indirubin in view of Pushpan ‘2015 to obtain an additive anti-inflammatory effect on skin, including eczema because (a) Hu ‘583 teaches a combination of two or more of the disclosed dermal CYP1A inhibitors, and (b) Pushpan ‘2015 also teaches Betulinic acid, Shikonin, and Indirubin as anti-inflammatory phytochemicals, also suitable for skin application, described above. Thus, one of skill in the art would have a reasonable expectation that by combining the CYP1A inhibitors, including quercetin, luteolin, kaempferol, catechin, retinoid (or its precursor ß-carotene), formononetin, wogonin, paeoniflorin, and ß-sitosterol as taught by Hu ‘583 with other phytochemicals, including Betulinic acid, Shikonin, and Indirubin in view of Pushpan ‘2015 to obtain an additive anti-inflammatory effect on skin, one would achieve Applicant’s claims 15-19 and elected combination of 12 purified compounds. “In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980) (citations omitted) (Claims to a process of preparing a spray-dried detergent by mixing together two conventional spray-dried detergents were held to be prima facie obvious.). See also In re Crockett, 279 F.2d 274, 126 USPQ 186 (CCPA 1960) (Claims directed to a method and material for treating cast iron using a mixture comprising calcium carbide and magnesium oxide were held unpatentable over prior art disclosures that the aforementioned components individually promote the formation of a nodular structure in cast iron.); and Ex parte Quadranti, 25 USPQ2d 1071 (Bd. Pat. App. & Inter. 1992) (mixture of two known herbicides held prima facie obvious)”. See MPEP § 2144.06 [R-01.2024] [I].
Conclusion
No claims are allowed.
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/YIH-HORNG SHIAO/Primary Examiner, Art Unit 1691
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