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 .
Priority
This application is a national stage entry of PCT/KR2022/005189 filed on 04/11/2022. Acknowledgment is made of applicant's claim for foreign priority based on an application filed in Korea on April 13, 2021. Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Election/Restrictions
Applicant’s election without traverse of Group I (claims 1-16) drawn to a method for prevention or treatment of mTORopathy comprising administering a pharmaceutical composition comprising athyriol or a pharmaceutically acceptable salt thereof as an active ingredient; autism spectrum disorder (ASD) as a species of the mTORopathy; and norathyriol as a species of an additional agent in the reply filed on March 20, 2026 is acknowledged.
Claims 17 and 18 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected group, there being no allowable generic or linking claim.
Claims 1-16 are being examined as they read on the elected species.
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.
Claims 1-9 are rejected under 35 U.S.C. 103 as being unpatentable over Berk et al. U.S. Publication No. 2016/0367521 A1 in view of Bjørklund et al. (Molecular Neurobiology (2020) 57:2314-2332); Guo et al. (J. Agric. Food Chem. 2018, 66, 12227−12235); and Noro et al. (Chem. Phar. Bull. 32(11), pages 4455-4459, 1984).
Claims 1-9 of the instant application claim a method for prevention or treatment of mTORopathy comprising administering a pharmaceutical composition comprising athyriol
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(1,6,7-Trihydroxy-3-methoxy-9H-xanthen-9-on) or a pharmaceutically acceptable salt thereof as an active ingredient, wherein the mTORopathy is autism spectrum disorder (ASD), and further comprising administering norathyriol
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(1,3,6,7-tetrahydroxy-9H- xanthen-9-one).
Berk et al. teaches a method of treatment and/or prophylaxis of a disease or disorder of the central nervous system comprising administering to a mammal in need thereof an effective amount of a xanthone-rich plant extract, or a compound derived from a xanthone-rich plant extract (abstract and [0001]). Berk et al. teaches that these disorders are associated with an abnormality in oxidation homeostasis systemically and centrally [0007]. Berk et al. teaches that the origin of this oxidative stress is still unknown, however, the brain exhibits many chemical hallmarks of oxidative attack, in addition to indications of altered antioxidant defense [0007]. Berk et al. teaches that any tissue under sustained radical attack may suffer a depletion of the key free radical/H2O2 scavenger in the brain, glutathione [0007].
Berk et al. teaches Mangosteen (Garcinia mangostana) is an evergreen tall tree which belongs to the Clusiaceae (Guttiferae) family Garcinia mangostana is related to other mangosteens, such as the button mangosteen (G. prainiana) or the charichuelo (G. madruno) [0012]. Berk et al. teaches that the mangosteen fruit pericarp and exocarp contain a number of bioactive compounds, including, but not limited to, polyphenols, such as xanthones and tannins, as well as anthocyanins, procyanins, prodelophinidins and associated stereoisomers, such as epi-catechins [0013]. Over 85 secondary metabolites have been isolated from the pericarp of mangosteen, which includes over 60 xanthones [0013]. Xanthones have been isolated from a number of plant sources, but are particularly common to the Bonnetiaceae and Clusiaceae families and in some species in the family Podostemaceae [0013].
Berk et al. teaches that mangosteen is a popular eating fruit throughout South East Asia and various parts of the plant have also been used in traditional medicine as an anti-inflammatory, an antimicrobial or to treat skin infections, wounds, dysentery [0014]. Berk et al. teaches that they have now surprising found that plant extracts, such as those derived from mangosteen pericarp, and the specific compounds they contain, offer an effective adjunct or replacement therapy for the treatment and/or prophylaxis of diseases or disorders of the central nervous system, including neuro-degenerative or neuro-psychotic disorders [0014]. Berk et al. teaches that the central nervous system disease or disorder is a neurodegenerative disorder, a neuropsychiatric disorder, or a disease or disorder related to neurodegenerative or neuropsychiatric disorders, wherein examples of diseases or disorders relevant to the present invention include autism ([0016] [0053] [0057] and claim 3).
Berk et al. teaches administering an effective amount of plant extract which is a xanthone-rich plant extract, in particular, plant extracts from the genus Clusiaceae, Bonnetiaceae and Podostemaceae are particularly advantageous, more particularly, a plant extract from Clusiaceae Garcinia mangostana (mangosteen), especially an extract from the pericarp of the fruit of Clusiaceae Garcinia mangostana (mangosteen) [0018].
Berk et al. further teaches the plant extract or compound derived from a plant extract to be administered includes a compound selected from the group consisting of xanthones, xanthenes, polyphenols, tannins, flavonoids, triterpenoids, benzophenones, biphenyl compounds, pyrroles, benzofurans, anthocyanins, procyannins, prodelphinidins, epicatechins, and combinations thereof ([0019] [0025]). Suitable compounds include
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(pages 5, 14, 19).
Berk et al. teaches that the plant extract and/or compound isolated from a plant extract provided herein may be administered by any route, including enteral (e.g., oral), parenteral, intravenous, intramuscular, intra-arterial, intramedullary, intrathecal, subcutaneous, intraventricular, transdermal, interdermal, rectal, intravaginal, intraperitoneal, topical (as by powders, ointments, creams, and/or drops), mucosal, nasal, buccal, sublingual; by intratracheal instillation, bronchial instillation, and/or inhalation; and/or as an oral spray, nasal spray, and/or aerosol [0102]. In particular embodiments, the plant extract and/or component compound of the present invention are administered orally [0102].
Claims 1-3 and 5-9 of Berk et al. specifically claim a method of treatment and/or prophylaxis of a disease or disorder of the central nervous system comprising administering to a mammal in need thereof an effective amount of a xanthone-rich plant extract, or a compound derived from a xanthone-rich plant extract, wherein the disease or disorder of the central nervous system is a neurodegenerative disorder, a neuropsychiatric disorder, or a disease or disorder related to neurodegenerative or neuropsychiatric disorders, wherein the disease or disorder may be selected as autism, and the compound may be from Clusiaceae Garcinia mangostana (mangosteen), and the compound may be a xanthone such as a compound having the following structure
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. Although Berk et al. does not teach the substituents for R1 and R2, based on the structures presented in Berk et al., it is clear that R1 and R2 may be chosen from hydrogen, hydroxy, methoxy or prenyl (see structures on pages 2-7).
Berk et al. does not specifically exemplify the treatment of autism. Berk et al. does not specifically exemplify norathyriol. Berk et al. does not teach athyriol.
Although Berk et al. does not specifically exemplify the treatment of autism, as detailed above, Berk et al. specifically teaches a method of treatment and/or prophylaxis of a disease or disorder of the central nervous system (abstract and [0001]), wherein these disorders are associated with an abnormality in oxidation homeostasis systemically and centrally wherein, the brain exhibits many chemical hallmarks of oxidative attack, in addition to indications of altered antioxidant defense [0007]. Berk et al. also teaches that the central nervous system disease or disorder is a neurodegenerative disorder, a neuropsychiatric disorder, or a disease or disorder related to neurodegenerative or neuropsychiatric disorders, wherein examples of diseases or disorders relevant to the present invention include autism ([0016] [0053] [0057] and claim 3). Thus Berk et al. teaches the treatment of central nervous system disorders associated with oxidative stress which may be selected as autism.
In addition, prior to the effective filing date of the claimed invention, oxidative stress was known in the art to be associated with autism spectrum disorder (Bjørklund et al. title). Bjørklund et al. teaches that autism spectrum disorder (ASD) is a complex neurodevelopmental syndrome, which usually occurs before 3 years of age and generally characterized by (1) pervasive deficits in social interaction, (2) impairments in verbal and nonverbal communication, and (3) stereotyped patterns of interests and activities (page 2314). Bjørklund et al. teaches that ASD neurobiology is thought to be associated with oxidative stress, as shown by increased levels of reactive oxygen species and increased lipid peroxidation, as well as an increase in other indicators of oxidative stress (abstract). Bjørklund et al. teaches that there is growing evidence supporting the role of oxidative stress in the pathophysiology of a number of neuropsychiatric diseases and especially in ASD (page 2135). The response to oxidative stress is a key stone in neuroinflammation, in as much the latter is still considered one of the leading cause of ASD (page 2315). Children with ASD diagnosis are considered more vulnerable to oxidative stress because of their imbalance in intracellular and extracellular glutathione levels and decreased glutathione reserve capacity (abstract). Bjørklund et al. teaches that several studies have suggested that the redox imbalance and oxidative stress are integral parts of ASD pathophysiology and as such, early assessment and treatment of antioxidant status may result in a better prognosis as it could decrease the oxidative stress in the brain before it can induce more irreversible brain damage (abstract). For example, increased excretion of oxidative stress biomarkers has been reported in children with ASD (Table 1 page 2316 and page 2322). Bjørklund et al. teaches that the antioxidant enzyme xanthine oxidase has been shown to be an oxidative stress marker in patients with autism spectrum disorder (Table 1 page 2316 and page 2322).
Accordingly, prior to the effective filing date of the claimed invention, it would have been obvious to a person of ordinary skill in the art to treat autism spectrum disorder, according to the teachings of Berk et al. since as detailed above Berk et al. teaches the treatment of central nervous system disorders associated with oxidative stress which may be selected as autism, and Bjørklund et al. specifically teaches that ASD neurobiology is thought to be associated with oxidative stress, as shown by increased levels of reactive oxygen species and increased lipid peroxidation, as well as an increase in other indicators of oxidative stress, wherein children with ASD diagnosis are considered more vulnerable to oxidative stress because of their imbalance in intracellular and extracellular glutathione levels and decreased glutathione reserve capacity (abstract). Thus since Bjørklund et al. specifically teaches that several studies have suggested that the redox imbalance and oxidative stress are integral parts of ASD pathophysiology, an ordinary skilled artisan would have been specifically motivated to select autism as a central nervous system disorder to treat based on the teachings of Berk et al. with a reasonable expectation of success.
Although Berk et al. does not specifically exemplify norathyriol administration, Berk et al. specifically teaches that the compound may be from Clusiaceae Garcinia mangostana (mangosteen), and the compound may be a xanthone such as a compound having the following structure
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. Said compound of Berk et al. is norathyriol when R2 is OH and R1 is H.
Furthermore, Guo et al. teaches that Norathyriol, an aglycone of mangiferin, is a bioactive tetrahydroxyxanthone present in mangosteen and many medicinal plants (abstract). Guo et al. teaches that norathyriol can be found in the fruit hulls and heartwood of Garcinia mangostana (mangosteen) and medicinal plants belonging to the families of Guttiferae and Gentianaceae, such as Hypericum perforatum (St. John’s Wort) and Canscora decussata (page 12227). Guo et al. teaches that over the past few years, a wide range of pharmacological activities of norathyriol have been reported, such as antitumor, anti-inflammatory, and cardiovascular protective effects, including vasorelaxation, antiplatelet, and antihemostatic activities (page 12227). Guo et al. teaches that previous studies showed that norathyriol is the primary metabolite of mangiferin (C-glucoside of 1,3,6,7-tetrahydroxyxanthone), a major constituent of mango fruit (page 12227).
Accordingly, prior to the effective filing date of the claimed invention, it would have been obvious to a person of ordinary skill in the art to select norathyriol as a compound useful in the method of Berk et al. since Berk et al. teaches the use of a plant extract or compound derived from a plant extract such as Garcinia mangostana (mangosteen) including a xanthones compound having the following structure:
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and Guo et al. specifically teaches that norathyriol can be found in the fruit hulls and heartwood of Garcinia mangostana (mangosteen) and has a wide range of pharmacological activities including anti-inflammatory. Thus an ordinary skilled artisan would have been motivated to select norathyriol which is specifically found in mangosteen and has anti-inflammatory properties for administration in the method of Berk et al. which includes treating central nervous system disorders such as autism wherein these disorders are associated with an abnormality in oxidation homeostasis systemically and centrally. Thus norathyriol would have been reasonably expected to treat oxidative stress associated with autism spectrum disorder based on the prior art references cited.
In addition, a person of ordinary skill in the art would have been further motivated to select norathyriol for the treatment of autism based on the teachings of Berk et al. since as detailed above Bjørklund et al. teaches that several studies have suggested that the redox imbalance and oxidative stress are integral parts of ASD pathophysiology such as, increased excretion of oxidative stress biomarkers including the antioxidant enzyme xanthine oxidase which has been shown to be an oxidative stress marker in patients with autism spectrum disorder (Table 1 page 2316 and page 2322).
Noro et al. specifically demonstrates that the xanthone derivatives having the following structure
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, including norathyriol (compound 1 wherein R1 and R3-R5 are hydroxy and R2 and R6 are hydrogen) inhibits xanthine oxidase (Table 1 page 4457). In addition, Noro et al. further demonstrates that other xanthone compounds including compound 3 which is athyriol ( R1, R4 and R5 are hydroxy, R3 is methoxy, and R2 and R6 are hydrogen) is a potent xanthine oxidase inhibitor (Table 1 page 4457).
Accordingly, prior to the effective filing date of the claimed invention, it would have been obvious to a person of ordinary skill in the art to administer the xanthone derivative compounds of Noro et al. including norathyriol and athyriol for the treatment of autism according to the teachings of Berk et al. since Berk et al. teaches the treatment of central nervous system disorders such as autism involving oxidative stress and as detailed above Bjørklund et al. teaches that several studies have suggested that the redox imbalance and oxidative stress are integral parts of ASD pathophysiology such as, increased excretion of oxidative stress biomarkers including the antioxidant enzyme xanthine oxidase which has been shown to be an oxidative stress marker in patients with autism spectrum disorder and Noro et al. specifically demonstrates that both norathyriol and athyriol are potent xanthine oxidase inhibitors. Thus, an ordinary skilled artisan following the teachings of Berk et al. would have been specifically motivated to administer norathyriol in the methods of Berk et al. since norathyriol would have been expected to have anti-inflammatory properties as well as inhibition of the oxidative stress marker xanthine oxidase leading to further anti-inflammatory properties as taught by Horo et al. Furthermore, since Horo et al. teaches that athyriol is also a potent xanthine oxidase inhibitor, an ordinary skilled artisan would have been motivated to combine athyriol with norathyriol with a reasonable expectation to providing an improved anti-inflammatory composition for the treatment of autism spectrum disorder. "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).
Thus the cited references render obvious the combination of athyriol and norathyriol for the treatment of autism spectrum disorder. Claims 4-6, 8 and 9 of the instant application are rendered obvious since the references cited render obvious the administration of the same compound as claimed and thus the same results of administering the compound will necessarily result. Thus administration of a composition comprising athyriol will necessarily selectively inhibit mTORC2 activity twice or more than mTORC1 activity located in the endosome as claimed, and will necessarily enhance memory ability and improve anxiety disorder as claimed. A compound and its properties are inseparable. In re Papesch, 315 F.2d 381, 137 USPQ 43 (CCPA 1963). "Products of identical chemical composition cannot have mutually exclusive properties." A chemical composition and its properties are inseparable. Therefore, if the prior art teaches the identical chemical structure, the properties applicant discloses and/or claims are necessarily present. In re Spada, 911 F.2d 705,709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990).
Thus claims 1-9 of the instant application are rendered obvious in view of the cited prior art teachings.
Claims 10-16 are rejected under 35 U.S.C. 103 as being unpatentable over Berk et al. U.S. Publication No. 2016/0367521 A1 in view of Bjørklund et al. (Molecular Neurobiology (2020) 57:2314-2332); Guo et al. (J. Agric. Food Chem. 2018, 66, 12227−12235); and Noro et al. (Chem. Phar. Bull. 32(11), pages 4455-4459, 1984) as applied to claims 1-9 above and further in view of Watabe et al. JP-2014114250A (Machine English Translation Provided).
Claims 10-16 of the instant application further claim the composition comprising athyriol as an active ingredient and further comprising norathyriol is a food composition.
Berk et al. in view of Bjørklund et al., Guo et al. and Noro et al. is as set forth above.
Berk et al. in view of Bjørklund et al., Guo et al. and Noro et al. is do not teach a food composition.
However, although the cited references do not teach a food composition, each of the cited references teach oral administration. Thus, it would have been within the skill of an artisan practicing the invention to determine an appropriate oral dosage form suitable for administration.
Prior to the effective filing date of the claimed invention, natural substance-derived components were known in the art to be administered as a health food. Watabe et al. teaches a highly safe natural substance-derived component that can also be used as a health food as an active ingredient [0008]. Watabe et al. teaches that norathyriol can be added to food and drink, as well as cosmetics or pharmaceuticals [0031]. Watabe et al. teaches that the food and drink containing the agent are not particularly limited, and for example, sweets such as chewing gum, chocolate, candies, jellies, biscuits and crackers mixed with food and drink materials; frozen desserts such as ice cream and frozen desserts; beverages such as tea, soft drinks, nutritional drinks and beauty drinks; Noodles such as udon, Chinese noodles, spaghettis, instant noodles; Kneaded products such as chopsticks, bamboo rings, and pens; Seasonings such as dressings, mayonnaise and sauces; Margarine, butter Oil, such as salad oil; It can be used for all common foods and drinks such as bread, ham, soup, retort food, frozen food and so on [0032]. Furthermore, it can be formulated into pharmaceutical products of granule or tablet type, health functional foods such as food for specified health, nutritional function foods or health food or supplement [0032].
Accordingly, prior to the effective filing date of the claimed invention, it would have been obvious to a person of ordinary skill in the art as well as within the skill of the ordinary artisan to combine the natural components norathyriol and athyriol rendered obvious over the prior art teachings for the treatment of autism spectrum disorder to food and drink as a suitable form for administering the compounds as taught by Watabe. Thus since a food form is a suitable alternative to a pharmaceutical dosage form such as a pill or tablet, an ordinary skilled artisan would have been motivated to formulate a food composition comprising athyriol and norathyriol for the treatment of autism spectrum disorder with a reasonable expectation of similar success.
Thus claims 10-16 are rendered obvious in view of the cited prior art teachings.
Claims 1-6, 8 and 9 are rejected under 35 U.S.C. 103 as being unpatentable over Vanwong et al. (Frontiers in Pharmacology, January 2017, Volume 7, Article 527, pages 1-8) in view of ZHOU et al. CN- 102499934 A (Provided on IDS Machine English Translation provided).
Claims 1-6, 8 and 9 of the instant application claim a method for prevention or treatment of mTORopathy comprising administering a pharmaceutical composition comprising athyriol
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(1,6,7-Trihydroxy-3-methoxy-9H-xanthen-9-on) or a pharmaceutically acceptable salt thereof as an active ingredient, wherein the mTORopathy is autism spectrum disorder (ASD).
Vanwong et al. teaches that uric acid is the final oxidation product of the purine degradation in humans, and uric acid at normal plasma levels acts as a free-radical scavenger, which contributes to the neuroprotective effect (page 2). Vanwong et al. further teaches that studies, however, have demonstrated that an excessive amount of uric acid or hyperuricemia is correlated with the risk of cardiovascular disease; has been associated with abdominal obesity, type 2 diabetes, dyslipidemia and metabolic syndrome (page 2). Vanwong et al. teaches that an excessive amount of uric acid is considered to be a mediator of proinflammatory endocrine imbalance in adipose tissue, contributing to the development of dyslipidemia and low-grade inflammation (page 2).
Vanwong et al. teaches that patients with autism spectrum disorder (ASD) may have increased levels of uric acid (page 2). Mitochondrial and purinergic dysfunction have been associated with mental illnesses such as bipolar disorder, ASD, and schizophrenia (page 2). Vanwong et al. teaches that atypical antipsychotic agents are widely used psychopharmacological interventions for autism spectrum disorder (ASD), and among the atypical antipsychotic agents, risperidone has demonstrated considerable benefits in reducing several behavioral symptoms associated with ASD (page 2). Vanwong et al. teaches that previous studies reported that treatment with olanzapine was associated with the increase in uric acid concentrations (page 2). Vanwong et al. teaches that the purposes of this study were to determine the prevalence of hyperuricemia in ASD patients treated with risperidone and to determine the association between serum uric acid levels and risperidone dosage, treatment duration, and metabolic parameters (page 2).
Vanwong et al. studied children and adolescent patients with ASD, 127 patients with ASD treated with risperidone and 76 patients with ASD without risperidone treatment (page 2). Vanwong et al. demonstrates that hyperuricemia was found in 34(44.70%) patients from the risperidone-naïve group and 73(57.50%) subjects from the risperidone group (Table1 page 3). Vanwong et al. demonstrates that the levels of uric acid were significantly higher in the risperidone treatment group than in the risperidone-naïve group (5.70 mg/dl vs. 5.35 mg/dl, P = 0.01) (page 4). Vanwong et al. also demonstrates that the levels of uric acid in the risperidone naïve group were higher than in the normal children and adolescent group (page 4). Vanwong et al. further teaches that other studies demonstrate the de novo purine synthesis is increased 3 to 4-fold in the hyperuricosuric autistic patients compared to normal controls (page 4). Therefore, Vanwong et al. teaches that the altered uric acid concentrations in patients with ASD may be the result of the disease itself. The treatment with antipsychotics may be directly or secondarily the result of the adverse treatment-induced hyperuricemia (pages 4-6).
Thus Vanwong et al. teaches that patients with autism spectrum disorder (ASD) have increased uric acid concentrations/hyperuricemia as a result of the ASD itself and as a result of treatment with risperidone.
Vanwong et al. does not teach the administration of athyriol.
Zhou et al. teaches the application of 3-methoxy xanthone compound in preparation of medicament for preventing and treating hyperuricemia (title). Zhou et al. teaches that uric acid is the end product of purine metabolism in the human body, and hyperuricemia is a metabolic disease caused by excessive uric acid production in the body and/or decreased uric acid excretion due to purine metabolism disorders in the human body, mainly manifested by excessive uric acid in the blood (page 2). Zhou et al. teaches that when uric acid concentration in the human plasma reaches greater than 417 μmol/L; it is easy to crystallize and precipitate and deposit in distal limbs with low body temperature and tissues with high acidity, such as frequently exercised muscles, joint cavities, joint bursa membrane and articular cartilage, kidneys and connective tissue, etc., causing gout and urinary tract stones and other diseases (page 2).
Zhou et al. teaches that at present, there are two main types of drugs for the treatment of hyperuricemia: one is drugs that inhibit uric acid production such as allopurinol, and the other is drugs that promote uric acid excretion, such as probenecid and benzbromarone (page 2). However, these drugs have serious toxic side effects, such as allopurinol has serious toxic side effects such as allergic reactions (incidence of 10-15%), hypersensitivity syndrome (can lead to death in 27.5% of patients with maculopapular rash), and bone marrow suppression; Probenecid and benzbromarone have side effects such as gastrointestinal reactions, renal colic and acute gout attacks, so it is of great significance to develop a safe and low-toxicity drug for the treatment of hyperuricemia (page 2).
Zhou et al. teaches the following compounds for the treatment of hyperuricemia:
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wherein R1 is OCH3 and R2 is hydrogen or glucose (pages 2-3). Zhou et al. specifically teaches homomangiferin aglycone wherein R1 is OCH3 and R2 is H having the name 1,6,7-trihydroxy-3-methoxyxanthone (page 3). Zhou et al. teaches that homomangiferin aglycone which is athyriol can reduce serum uric acid concentration similar to the xanthine oxidase inhibitor allopurinol (page 4 and embodiment 1 pages 5-6). Claims 1-6 of Zhou et al. claim the application of homomangiferin aglycone (athyriol) or homomangiferin for the prevention and treatment of hyperuricemia and related diseases, wherein the drug is an oral preparation such as any of the tablets, capsules, oral liquids, powders, drops, or granules (page 10).
Accordingly, prior to the effective filing date of the claimed invention, it would have been obvious to a person of ordinary skill in the art to combine the teachings of Vanwong et al. which demonstrates that patients with autism spectrum disorder (ASD) have increased levels of uric acid and hyperuricemia which is correlated with the risk of cardiovascular disease; has been associated with abdominal obesity, type 2 diabetes, dyslipidemia and metabolic syndrome, with the teachings of Zhou et al. which teaches a method of treating and preventing hyperuricemia comprising the administration of athyriol. Thus, an ordinary skilled artisan would have been motivated to administer athyriol to treat ASD with a reasonable expectation of improving hyperuricemia associated with ASD and ASD treatment.
Thus the cited references render obvious the administration of athyriol for the treatment of autism spectrum disorder. Claims 4-6, 8 and 9 of the instant application are rendered obvious since the references cited render obvious the administration of the same compound as claimed and thus the same results of administering the compound will necessarily result. Thus administration of a composition comprising athyriol will necessarily selectively inhibit mTORC2 activity twice or more than mTORC1 activity located in the endosome as claimed, and will necessarily enhance memory ability and improve anxiety disorder as claimed. A compound and its properties are inseparable. In re Papesch, 315 F.2d 381, 137 USPQ 43 (CCPA 1963). "Products of identical chemical composition cannot have mutually exclusive properties." A chemical composition and its properties are inseparable. Therefore, if the prior art teaches the identical chemical structure, the properties applicant discloses and/or claims are necessarily present. In re Spada, 911 F.2d 705,709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990).
Thus claims 1-6, 8 and 9 of the instant application are rendered obvious in view of the cited prior art teachings.
Claims 7 and 10-16 are rejected under 35 U.S.C. 103 as being unpatentable over Vanwong et al. (Frontiers in Pharmacology, January 2017, Volume 7, Article 527, pages 1-8) in view of ZHOU et al. CN- 102499934 A (Provided on IDS Machine English Translation provided) as applied to claims 1-6, 8 and 9 above and further in view of Watabe et al. JP-2014114250A (Machine English Translation Provided).
Claim 7 of the instant application further claims administering norathyriol
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(1,3,6,7-tetrahydroxy-9H- xanthen-9-one). Claims 10-16 of the instant application further claim the composition comprising athyriol as an active ingredient and further comprising norathyriol is a food composition.
Vanwong et al. in view of Zhou et al. is as set forth above.
Vanwong et al. in view of Zhou et al. do not teach further administering northyriol. Vanwong et al. in view of Zhou et al. do not teach a food composition.
Watabe et al. teaches a Xanthine oxidase inhibitor composition, for the treatment and/or prevention of hyperuricemia which contains the active ingredient compound of norathyriol (abstract).
Watabe et al. teaches a composition that inhibits the activity of xanthine oxidase and suppresses increases in blood uric acid concentration which is useful for the amelioration of gout and hyperuricemia [0001]. Watabe et al. teaches that hyperuricemia is the underlying disease of gout and is defined as having serum uric acid levels above 7.0 mg/dl and hyperuricemia is also regarded as a lifestyle-related disease not only related to gout but also related to obesity, hypertension, hyperlipidemia, diabetes and the like, and as a part of the metabolic syndrome [0003]. Watabe et al. teaches that at present, allopurinol having a mechanism of action of uric acid production inhibition by xanthine oxidase (XO) inhibition, is one of the therapeutic agents for hyperuricemia, however, allopurinol is known to have side effects such as causing liver dysfunction, and there is a need for a xanthine oxidase inhibitor composition having no side effects [0004].
Watabe et al. teaches a highly safe natural substance-derived component that can also be used as a health food as an active ingredient, and further has an extremely excellent xanthine oxidase activity inhibitory activity, a xanthine oxidase inhibitory composition and a hyperuricemia therapeutic/preventive agent [0008]. The examples of Watabe et al. demonstrate that norathyriol is a potent xanthine oxidase inhibitor with activity better than allopurinol ([0030] and Table 2).
Watabe et al. teaches that the norathyriol used in Example 2 are added to food and drink, cosmetics or pharmaceuticals, to which they have a xanthine oxidase inhibitory action for hyperuricemia and can be given for preventive or therapeutic action [0031]. Watabe et al. teaches that the food and drink containing the agent are not particularly limited, and for example, sweets such as chewing gum, chocolate, candies, jellies, biscuits and crackers mixed with food and drink materials; frozen desserts such as ice cream and frozen desserts; beverages such as tea, soft drinks, nutritional drinks and beauty drinks; Noodles such as udon, Chinese noodles, spaghettis, instant noodles; Kneaded products such as chopsticks, bamboo rings, and pens; Seasonings such as dressings, mayonnaise and sauces; Margarine, butter Oil, such as salad oil; It can be used for all common foods and drinks such as bread, ham, soup, retort food, frozen food and so on [0032]. Furthermore, it can be formulated into pharmaceutical products of granule or tablet type, health functional foods such as food for specified health, nutritional function foods or health food or supplement [0032].
Accordingly, prior to the effective filing date of the claimed invention, it would have been obvious to a person of ordinary skill in the art to combine the teachings of Vanwong et al. which demonstrates that patients with autism spectrum disorder (ASD) have increased levels of uric acid and hyperuricemia which is correlated with the risk of cardiovascular disease; has been associated with abdominal obesity, type 2 diabetes, dyslipidemia and metabolic syndrome, with the teachings of Zhou et al. which teaches a method of treating and preventing hyperuricemia comprising the administration of athyriol; and with the teachings of Watabe et al. which teaches norathyriol as a potent xanthine oxidase inhibitor useful for the treatment and prevention of hyperuricemia. Thus, an ordinary skilled artisan would have been motivated to administer athyriol and norathyriol to treat ASD with a reasonable expectation of improving hyperuricemia associated with ASD and ASD treatment. Furthermore, it would have been obvious to a person of ordinary skill in the art to combine norathyriol with athyriol since both compounds are taught to be useful in the treatment and prevention of hyperuricemia. "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).
Moreover, an ordinary skilled artisan would have been motivated to add both compounds to food and drink as a suitable form for administering the compounds as taught by Watabe et al. and as a suitable alternative to other oral pharmaceutical formulations such as pills and tablets taught in the prior art. Thus a food or drink dosage form is an obvious alternative to other pharmaceutical forms such as tablets and other pill forms.
Thus the cited claims of the instant application are rendered obvious in view of the cited prior art teachings.
Conclusion
Claims 1-16 are rejected. Claims 17 and 18 are withdrawn. No claims are allowed.
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/KARA R. MCMILLIAN/Primary Examiner, Art Unit 1623
KRM
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