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 .
Response to Arguments
Applicant’s arguments, see Page 2, filed 12/18/2025, with respect to the rejection(s) of claim(s) 31-32, 50, 59-60, 70, 72-73, 92, 123-124, 135-138 and 158-159 under Dischler (US Patent No. 20200054061), Gupta et al. (US Patent No. 8211873), Yook et al. (US 20190343783 A1), Zankl et al. Partial uncoupling of oxidative phosphorylation induces premature senescence in human fibroblasts and yeast mother cells, Free Radical Biology and Medicine, September 2007, Pages 947-958 and Baldoni et al. Anti-senescence compounds: A potential nutraceutical approach to healthy aging, Ageing Research Reviews, September 2018, Pages 14-31, have been fully considered and are persuasive. Therefore, the rejection has been withdrawn.
However, upon further consideration, a new ground(s) of rejection is made in view of Fowler et al. (US 20120225840 A1), Dischler (US Patent No. 20200054061), Gupta et al. (US Patent No. 8211873), Yook et al. (US 20190343783 A1), Pranesh et al. (US 20200397807 A1), Zankl et al. Partial uncoupling of oxidative phosphorylation induces premature senescence in human fibroblasts and yeast mother cells, Free Radical Biology and Medicine, September 2007, Pages 947-958 and Baldoni et al. Anti-senescence compounds: A potential nutraceutical approach to healthy aging, Ageing Research Reviews, September 2018, Pages 14-31.
Applicant has canceled claims 52-53, 58, 66-68, 117, 122 and 158-159. Claims 31-32, 41, 45, 49-50, 54-57, 59-61, 70-73, 92, 112, 118, 120-121, 123-124, 135-138, 143 and 160 is now pending. Claims 31-32, 41, 45, 49-50, 54-57, 59-61, 70-73, 92, 112, 118, 120-121, 123-124, 135-138, 143 and 160 are now evaluated on its merits.
Claim Objections
Applicant is advised that should claim 41 be found allowable, claim 57 will be objected to under 37 CFR 1.75 as being a substantial duplicate thereof. 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).
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 41, 57 and 121 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Claims 41, 57 and 121 are directed to the composition of resveratrol, alpha-lipoic acid, niacinamide, quercetin and EGCG for treatment or alleviation of a senescence-associated disease, disorder or effect, further comprising fluphenazine dihydrochloride. From Applicants specification the above agents are for the process of age-related skin or muscles disorders or diseases. Figure 4, from applicants’ specification shows the effects solely of fluphenazine dihydrochloride administration, which is a known anti-psychotic. Applicant fails to teach an anti-psychotic drug which can potentially be used for dementia patients in a composition with resveratrol, a natural polyphenol antioxidant and niacinamide, a versatile water-soluble vitamin essential for cellular function that strengthens the skin barrier. Thus, applicant has not shown a relation for treating a senescence-associated disease, disorder or effect comprising a combination of the above agents, which are used for skin and skeletal muscle disease or disorders with an antipsychotic agent of fluphenazine dihydrochloride.
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 32 and 70-73, 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.
Regarding claim 32, the phrase “A42548” renders the claim indefinite because it is unclear what chemical name is recognized by the above A42548. The claim nor the specification defines or identifies the chemical name or group associated with A42548.
Regarding claim 70, the phrase "such as" renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
Regarding claim 72, the phrase “etc” renders the claim indefinite because it is unclear the limitations of “etc” associated with senescence-associated effects of ageing.
Claims 70 and 72-73 recites the limitation "a composition according to claim 31 wherein the senescence-associated effects of ageing" in lines 1-2. There is insufficient antecedent basis for this limitation in the claim. Claims 135-137 depends from claim 31, in which the claim’s language fails to recite the limitation of “ageing”.
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.
Claims 31, 92 and 135-138 are rejected under 35 U.S.C. 103 as being unpatentable over Fowler et al. (US 20120225840 A1).
Regarding claims 31, 92 and 135-138, Fowler teaches a method to maintain or increase mitochondrial biogenesis in cardiac muscle, skeletal muscles, and liver tissue comprising administration of hydroxytyrosol in combination with at least one of the compounds selected from the group consisting of resveratrol, niacinamide, alpha-lipoic acid, quercetin and EGCG (relevant to claim 31) (abstract). As taught by Fowler mitochondrial function, thus available energy, decreases with aging (relevant to claim 92) (para. 0079). The administration of the above composition protects the mitochondria against infections, inflammation and chronic degenerative diseases (para. 0056). The composition improves skeletal muscle mass by stimulating anabolic pathways, inhibiting catabolic pathways and accelerating muscle regeneration when damaged (relevant to claims 136-137) and maintain tissue/organ function and prevent tissue/organ failure triggered by mitochondrial dysfunction (para. 0068)
Another aspect of the composition is of a cosmetic dermatological skin care composition which promotes mitochondria well-being and which encourages optimal mitochondrial function in the skin, and thus which boosts the energy metabolism of the skin (relevant to claims 135 and 138) (para. 0106-0108).
Therefore, it would have been obvious to someone of ordinary skill in the art at the time of filling to have combined the agents of resveratrol, niacinamide, alpha-lipoic acid, quercetin and EGCG to treat or alleviate a senescence-associated disease, disorder or effect from the teachings of Fowler. One would have been motivated to do so from the teachings of Fowler of a composition comprising one or more agents from a list which consist of resveratrol, niacinamide, alpha-lipoic acid, quercetin and EGCG to improve skeletal muscle mass. There is a reasonable expectation of combining the agents of resveratrol, niacinamide, alpha-lipoic acid, quercetin and EGCG to treat or alleviate a senescence-associated disease, disorder or effect from the teachings of Fowler.
Claims 49 and 112 are rejected under 35 U.S.C. 103 as being unpatentable over Fowler et al. (US 20120225840 A1) in view of Zankl et al. Partial uncoupling of oxidative phosphorylation induces premature senescence in human fibroblasts and yeast mother cells, Free Radical Biology and Medicine, September 2007, Pages 947-958.
The teachings of Fowler for the above 103 rejection of claims 31, 92 and 135-138 is incorporated herein by reference.
Fowler fails to teach the composition further comprising a mitochondrial uncoupler.
Zankl teaches the mitochondrial theory of aging predicts that mitochondrial dysfunction is a major cause of aging and implies that mitochondrial ROS are key players in the process. Chronic exposure of human fibroblasts to the chemical uncoupler carbonylcyanide p-trifluoromethoxyphenylhydrazone (FCCP) led to a temporary, reversible uncoupling of oxidative phosphorylation. FCCP inhibited cell proliferation in a dose-dependent manner, and a significant proportion of the cells entered premature senescence within 12 days. Additionally similar to human fibroblasts, partial uncoupling of oxidative phosphorylation in yeast cells led to a substantial decrease in the mother-cell-specific life span and a concomitant increase in ROS, indicating that life span shortening by mild mitochondrial uncoupling may represent a mechanism of aging (abstract).
Therefore, it would have been obvious to someone of ordinary skill in the art at the time of filling to have combined a mitochondrial uncoupler with the composition taught by Fowler to treat or alleviate a senescence-associated disease, disorder or effect. One would have been motivated to do so from the teachings of Zankl and Fowler of mitochondrial dysfunction and its effect associated with aging. There is a reasonable expectation of combining a mitochondrial uncoupler with the composition taught by Fowler to treat or alleviate a senescence-associated disease, disorder or effect.
Claims 32, 59-60 and 123-124 are rejected under 35 U.S.C. 103 as being unpatentable over Fowler et al. (US 20120225840 A1) in view of Dischler (US Patent No. 20200054061).
The teachings of Fowler for the above 103 rejection of claims 31, 92 and 135-138 is incorporated herein by reference.
Fowler fails to teach the composition comprising a BCL2/X inhibitor.
Dischler teaches senolytic agents for the treatment of diseases of aging related skin conditions of wrinkles on face, loss of energy (ATP) and improve the memory of those suffering from Alzheimer's and other CNS diseases (abstract, para. 0002, 0012, 0020, 0125). In preferred example 1 Dischler teaches combined agents of Nicotinamide and Resveratrol (Step 203) and in example 2 agents of Apigenin and Resveratrol (Step 203) (relevant to claims 32) (para. 0110, 0114, 0118 and 0120). Dischler additionally teaches the composition comprising administration of at least two agents from a group consisting of: apigenin, fisetin, curcumin, quercetin, resveratrol, dasatinib, navitoclax, piperlongumine, niacin and a butyrate source (relevant to claims 59-60 and 123-124) (claims 10-12).
Therefore, it would have been obvious to someone of ordinary skill in the art at the time of filling to have combined Apigenin and navitoclax to the combination composition taught by Fowler to treat or alleviate a senescence-associated disease, disorder or effect. One would be motivated to do so from the teachings of Fowler and Dischler for the same treatment of a skin condition and increase in energy comprising the same ingredients of quercetin, resveratrol and niacin. Thus, the addition of agents of Apigenin and navitoclax would increase the effectiveness of the composition. There is a reasonable expectation of combining Apigenin and navitoclax to the combination composition taught by Fowler to treat or alleviate a senescence-associated disease, disorder or effect.
Claims 50, 54, 118 and 143 are rejected under 35 U.S.C. 103 as being unpatentable over Fowler et al. (US 20120225840 A1) in view of Gupta et al. (US Patent No. 8211873).
The teachings of Fowler for the above 103 rejection of claims 31, 92 and 135-138 is incorporated herein by reference.
Fowler fails to teach the composition further comprising Magnolol and Honokiol.
Gupta teaches treatment of dermatological disorders that include challenged skin from cancer, diabetes, radiation treatments, chemotherapy, and sun-burn; mitochondrial dysfunction; age spots; acne, loss of cellular antioxidants; skin changes associated with aging including collagen loss, loss of skin pliability, loss of skin suppleness, skin wrinkles and fine lines, oxidation, damage from radiation, damage from free radicals, and damage from UV; dry skin; xerosis; ichthyosis; dandruff; brownish spots; keratoses; melasma; lentigines; liver spots; skin pigmentation including pigmented spots, dark circles under the eyes, darkened skin, and blemishes; oily skin; warts; eczema; pruritic skin; psoriasis; inflammatory dermatoses; topical inflammation; disturbed keratinization; scalp dryness; skin depigmentation, and combinations thereof comprising a chiral-correct mitoprotectant agent, and (ii) an Intra-cellular antioxidant or free-radical neutralizing agent, and (iii) an anti-inflammatory agent, and (iv) a collagen or fibrin boosting agent (relevant to claim 143)(Page 2, 1st para.).
Gupta teaches the anti-inflammatory transparent gel of Example 13, which includes a combination of Magnolol and Honokiol (relevant to claims 50, 54 and 118), antioxidants selected from a lit which includes Resveratrol and Quercetin and collagen and fiber boosting agent selected from a list which consist of niacinamide.
Therefore, it would have been obvious to someone of ordinary skill in the art at the time of filling to have combined Magnolol and Honokiol to the combination composition taught by Fowler to treat or alleviate a senescence-associated disease, disorder or effect. One would be motivated to do so from the teachings of Gupta and Dischler for the same treatment of a skin condition comprising the same ingredients of quercetin, resveratrol and niacinamide. Thus, the addition of agents of Magnolol and Honokiol would increase the effectiveness of the composition. There is a reasonable expectation of combining Apigenin and navitoclax to the combination composition taught by Fowler to treat or alleviate a senescence-associated disease, disorder or effect.
Claims 45, 55, 61 and 160 are rejected under 35 U.S.C. 103 as being unpatentable over Fowler et al. (US 20120225840 A1) in view of Gupta et al. (US Patent No. 8211873), Yook et al. (US 20190343783 A1) and Baldoni et al. Anti-senescence compounds: A potential nutraceutical approach to healthy aging, Ageing Research Reviews, September 2018, Pages 14-31.
The teachings of Fowler and Gupta for the above 103 rejection of claims 31, 50, 54, 92, 118, 135-138 and 143 is incorporated herein by reference.
Fowler and Gupta fail to teach the composition further comprising niclosamide, metformin and associated with osteoarthritis.
Baldoni teaches metformin affects a number of aging-associated pathways such as inflammation, autophagy, cell survival, and protein synthesis. It modulates the expression of receptors for cytokines, insulin, and IGF-1, it activates intracellular AMPK and enhances mTOR inhibition. Additionally, metformin treatment increased lifespan and prevented cancer (relevant to claim 61) (Page 17, second column, 4th para.).
Yook teaches niclosamide of the present invention for treatment or prevention of Axin-GSK3 interaction-related disease, and the Axin-GSK3 interaction-related disease may be familial adenomatosis polyposis (FAP), adenomatous colitis, adenomatous colorectal cancer, Alzheimer, diabetes, rheumatoid arthritis, inflammatory skin disease, osteoarthritis, leukopenia and the like (relevant to claims 55 and 160) (abstract, para. 0037).
Therefore, it would have been obvious to someone of ordinary skill in the art at the time of filling to have administered metformin and niclosamide with the compounds taught by Fowler and Magnolol and Honokiol taught by Gupta for treatment of dermatological disorders caused by aging as well as osteoarthritis. One would have been motivated to do so from the teaching of Baldoni of metformin used for aging inflammation, the teachings of Yook on niclosamide for the treatment of inflammatory skin disease and osteoarthritis and the teachings of Fowler and Gupta on aging associated with skeletal muscles as well as dermatological inflammation. There is a reasonable expectation of success with combining metformin and niclosamide with the agents of Gupta and Fowler to treat aging skin inflammations and osteoarthritis.
Claims 56 and 120 are rejected under 35 U.S.C. 103 as being unpatentable over Fowler et al. (US 20120225840 A1) in view of Gupta et al. (US Patent No. 8211873) and Pranesh et al. (US 20200397807 A1), published 12/24/2024 with a provisional filing date of 06/18/2019.
The teachings of Fowler and Gupta for the above 103 rejection of claims 31, 50, 54, 92, 118, 135-138 and 143 is incorporated herein by reference.
Fowler and Gupta fail to teach the composition further comprising nitazoxanide.
Pranesh teaches therapeutic agents of nicotinamide, mitochondrial uncouplers, nitazoxanide (para. 0030) and honokiol (para. 0314) for the treatment of age related mitochondrial related diseases or disorders (para. 0009).
Therefore, it would have been obvious to someone of ordinary skill in the art at the time of filling to have combined nitazoxanide with the composition taught by Fowler and Magnolol and Honokiol taught by Gupta to treat an age-related condition of mitochondrial dysfunction. One would have been motivated to do so from the teachings of Pranesh on a composition comprising nitazoxanide for treating mitochondrial dysfunction disorders and the teachings of Gupta on Magnolol and Honokiol compositions for treating mitochondrial dysfunction along with the compositions of Fowler on mitochondrial dysfunction. There is a reasonable expectation of treating age-related condition of mitochondrial dysfunction comprising nitazoxanide with the agents taught by Fowler in combination with Magnolol and Honokiol taught by Gupta.
Conclusion
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MIKHAIL O'DONNEL. ROBINSON
Examiner
Art Unit 1627
/MIKHAIL O'DONNEL ROBINSON/Examiner, Art Unit 1627
/SARAH PIHONAK/Primary Examiner, Art Unit 1627