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 .
Status of the Claims
Currently, claims 1-39 are pending in the instant application. Claims 16-39 are withdrawn as being directed to an unelected invention (See Election/Restriction section below).
Election/Restrictions
Restriction to one of the following inventions was required per the Restriction Requirement submitted on 11/03/2025:
Claims 1-15, drawn to a method for improving metabolic performance, classified in A61K 38/27
Claims 16-27, drawn to a composition for oral supplementation, classified in A61K 9/0053
Claims 28-39, drawn to compositions for transdermal supplementation, classified in A61K 9/0014
Applicant has elected Group I with traverse. Applicant contends that the Restriction requirement is improper. Applicant alleges that the restriction is improper because Examiner’s examples of materially different products (i.e., caffeine, green tea extract, choline, forskolin) do not include a “plurality of amino acids” and a “plurality of forms of beta-hydroxybutyrate”. Per Applicant remarks, said examples are not proper because they fall outside the scope of the claimed method. Applicant provides MPEP 806.05(h) in support of the aforementioned argument. Applicant’s remarks are acknowledged, however, additional search has revealed Lowery (US 2020/0129463 A1) which teaches compositions comprising BHB, cannabidiol, and amino acids, and uses thereof for the improving health, including the improvement of glucose metabolism. Lowery indicates that such compositions may be administered in the form of a powder as a food or beverage additive, which provides a materially different composition from the independent claims 16 and 28, but still falls within the bounds of claim 1. For at least the discovery of Lowery, the Restriction is hereby maintained. Additionally, the search burden has not been alleviated, as the scope of the claims are directed to a combination of any form of BHB and any and all combinations of amino acids.
Claim Rejections - 35 USC § 112 – Second Paragraph
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 6-7 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.
Claim 6 is indefinite for reciting the phrase “the salt cation”, because a person of ordinary skill in the art would not reasonably be able to understand the metes and bounds of the claim. Parent claim 5 recites “an ionic salt”, while the instant claim recites “the salt cation”. As the parent claim does not recite a salt cation, the instant claim provides improper antecedence.
Claim 7 is indefinite for reciting the phrase “the salt cation”, because a person of ordinary skill in the art would not reasonably be able to understand the metes and bounds of the claim. Parent claim 5 recites “an ionic salt”, while the instant claim recites “the salt cation”. As the parent claim does not recite a salt cation, the instant claim provides improper antecedence.
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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claim(s) 1 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Lowery (US 2020/0129463 A1).
Claim 1 recites a method of treatment for improving metabolic performance using supplementation, comprising the step of: applying a supplement formulation to a human subject via a selected administration route, the supplement formulation comprising therapeutically-effective amounts of: a plurality of amino acids; a plurality of forms of beta-hydroxybutyrate.
Lowery teaches compositions comprising beta hydroxybutyrate (BHB), cannabidiol, and one or more additional compounds (specification [0005])1, wherein the one or more additional compounds may include amino acids (specification [0006])2. Lowery further indicates methods of use of said compositions, including administration to subjects for weight loss, weight maintenance, elevating blood ketone levels, maintaining blood ketone levels, reducing blood glucose levels, maintaining blood glucose levels (specification [0005])3, among other benefits which may be considered as improvements to metabolic performance. In particular, Lowery provides two examples highly relevant to the instant invention. The first example shows synergistic effect between BHB and amino acids when administered together. Lowery conducts concurrent administration of 5g of R-BHB and 2g of leucine. Co-administration of both R-BHB and leucine showed higher resulting blood ketone level as compared to R-BHB control (Fig. 16):
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Lowery concludes from the measured blood ketone levels that the synergistic effect is more than additive (specification [0123])4.
The second example provided by Lowery are exemplary compositions comprising BHB and amino acids. More specifically, Lowery provides two exemplary compositions comprising BHB, cannabidiol, and leucine (specification [0132]-[0133])5.
Accordingly, the teachings of Lowery anticipate a method for improving metabolic performance by administering a supplement formulation comprising amino acids and BHB.
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.
Claim(s) 2 is/are rejected under 35 U.S.C. 103 as being unpatentable over Lowery (previously referenced) in view of Fan (International Journal of Toxicology Volume 41, Issue 4, August 2022, Pages 329-346).
Claim 2 further limits the method of claim 1 wherein the plurality of amino acids comprises L-beta-aminoisobutyric acid (L-BAIBA).
As indicated in the 102 rejection of claim 1, Lowery anticipates a method of improving metabolic performance by administering a formulation comprising amino acids and BHB. Lowery does not explicitly teach the inclusion of L-BAIBA. However, it would be obvious to modify the teachings of Lowery to include L-BAIBA because Fan teaches that L-BAIBA is an amino acid which improves metabolic performance, thereby providing the reasonable expectation that the inclusion of L-BAIBA would yield synergistic activity with the composition of Lowery.
Fan provides a general overview on the established effects of in-vivo L-BAIBA supplementation, and further conducts an in-vivo toxicity study of L-BAIBA in rats. Fan indicates that BAIBA (a combination of enantiomers L-BAIBA and D-BAIBA), has been shown to reduce body fat percentage via an increase in fatty acid oxidation and a decrease in hepatic lipogenesis (page 329, Abstract)6. Fan further teaches that BAIBA induces hepatic fatty acid beta-oxidation, browning of white adipose tissue, and contributes to exercise-induced protection from metabolic diseases by enhancing the expression of peroxisome proliferator-activated receptor-gamma co-activator-1α, and is further capable of inhibiting insulin resistance and mitigating inflammation (page 329)7. Furthermore, Fan’s safety testing revealed that L-BAIBA administration provided no toxic or adverse effects up to 900 mg/kg/day (page 345)8.
Given that Lowery teaches the administration of combinations of amino acids and BHB for improving metabolic performance, and that Fan teaches that L-BAIBA is an amino acid effective for likewise providing various improvements to metabolic performance, it would have been prima facie obvious for a person of ordinary skill in the art to combine the teachings of the aforementioned to arrive at a combination of BHB and L-BAIBA. There would have been a reasonable expectation that the administration of a combination of both BHB and L-BAIBA would provide various synergistic improvements to metabolic performance.
Claim(s) 3-4 is/are rejected under 35 U.S.C. 103 as being unpatentable over Lowery in view of Santaniello (US 6051608 A).
Claim 3 further limits the method of claim 1 wherein the plurality of amino acids comprises carnitine.
As indicated in the 102 rejection of claim 1, Lowery anticipates a method of improving metabolic performance by administering a formulation comprising amino acids and BHB. Lowery does not explicitly teach the use of carnitine in their methods and compositions. However it would be obvious for a person of ordinary skill in the art to include carnitine because Santaniello teaches the use of carnitine supplements for metabolic improvements, thereby providing a reasonable expectation of success in creating a combination with synergistic effect.
Santaniello teaches supplement compositions comprising carnitine for administration to human subjects. In particular, the compositions of Santaniello are contain L-carnitine or alkanoyl-L-carnitine. Santaniello indicates that both forms of carnitine have various therapeutic uses, and provide health benefits. Of particular relevance to the instant invention and the teachings of Lowery is the indication that L-carnitine facilitates the oxidation of fatty acids, thereby providing greater amounts of energy available to skeletal muscle, and resulting in enhanced physical performance (specification col. 2, lines 1-6)9. A further relevant effect of the use of carnitine is the reduction of serum fat levels and normalization of the ratio between the various cholesterol fractions in order to prevent diseases related to lipid metabolism disorders (specification col. 2, lines 7-11)10.
Given that the teachings of Lowery are drawn to inducing various metabolic improvements by administration of a combination of amino acids and BHB, and that the teachings of Santaniello are likewise aligned, but drawn to the administration of carnitine (i.e., a type of amino acid), it would have been prima facie obvious at the time of invention for a person of ordinary skill in the art to combine the aforementioned teachings and apply the inclusion of carnitine to the composition and methods of Lowery. The reason being that there would be a reasonable expectation of success in improving metabolic performance using such a combination.
Claim 4 further limits the method of claim 3 wherein the carnitine is provided in the form of L-carnitine fumarate.
As indicated in the claim 3 rejection, Santaniello teaches the administration of carnitine. Santaniello, in particular, indicates the use of non-hygroscopic salts of carnitine (specification col. 1, lines 6-12)11, including L-carnitine fumarate (specification )
Claim(s) 5-8 is/are rejected under 35 U.S.C. 103 as being unpatentable over Lowery.
Claim 5 further limits the method of claim 1 wherein the plurality of forms of BHB comprises an ionic salt.
As indicated in the 102 rejection of claim 1, the teachings of Lowery anticipate a method of improving metabolic performance by administration of a composition comprising BHB and amino acids. In particular, Lowery provides two exemplary compositions comprising BHB, cannabidiol, and leucine (specification [0132]-[0133]). While Lowery does not explicitly teach a composition comprising amino acids, BHB, and an ionic salt, such a composition would be obvious because Lowery teaches the use of BHB salts as obvious substitutes for BHB. Such substitutable salts include sodium, magnesium, and/or potassium variants (specification [0079])12. Accordingly, it would have been obvious to substitute BHB for a BHB ionic salt, as there would be a reasonable expectation that such ionic salts would be successful in providing the aforementioned metabolic improvements.
Claim 6 further limits the method of claim 5 wherein the salt cation comprises at least one of sodium, potassium, calcium, or magnesium.
Lowery teaches the reasonable substitution of sodium, magnesium, and potassium BHB salts in composition.
Claim 7 further limits the method of claim 5 wherein the cation comprises a transition metal ion.
Lowery teaches additional substitutable BHB salts including zinc BHB salt (specification [0040])13, wherein zinc would be considered a transition metal cation.
Claim 8 further limits the method of claim 1 wherein the plurality of forms of BHB comprises an ester.
Lowery teaches that esters of BHB are substitutable alternates to BHB (specification [0079]).
Claim(s) 9-10 is/are rejected under 35 U.S.C. 103 as being unpatentable over Lowery in view of Clarke (Regul Toxicol Pharmacol. 2012 August ; 63(3)).
Claim 9 further limits the method of claim 8 wherein the ester comprises an organyl group.
As indicated in the 102 rejection of claim 1, the teachings of Lowery anticipate a method of improving metabolic performance by administration of a composition comprising BHB and amino acids. Lowery further teaches the use of BHB esters. However, Lowery does not explicitly teach the use of a BHB ester comprising an organyl group. However, it would be obvious to utilize such a BHB ester because Clarke teaches one such BHB ester comprising an organyl group, and there would be reasonable expectation of success in utilizing said ester to confer improvements to metabolic performance.
Clarke teaches the administration of the compound (R)-3-hydroxybutyl (R)-3-hydroxybutyrate, the structure of which is provided below for reference:
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As can be seen from the structure above, the esterified portion of the compound terminates in an organyl group (CH3). More specifically, the teachings of Clarke are directed towards the safety and tolerability testing of the above compound in human subjects, however, Clarke also provides an overview of the effects and mechanism of action of the compound. Clarke teaches that the administration of (R)-3-hydroxybutyl (R)-3-hydroxybutyrate elevates blood ketone levels. The elevated blood ketone levels are a result of the compound hydrolyzing to D-BHB and R-1,3 butanediol throughout the body, wherein the R-1,3 butanediol is further metabolized to D-BHB in the liver (page 2)14. Clarke further indicates that ketones may be used as an energy source by the body, wherein said ketones provide a higher metabolic efficiency than glucose, resulting in enhanced energy production, improved physical performance, and improved cognitive function (page 2)15. Such effects would be considered as improvements to metabolic performance. Furthermore, Clarke found that the compound was well tolerated up to the tested 2142 mg/kg/day (page 10)16.
Given that Lowery teaches administration of compositions comprising amino acids and BHB esters for the improvement of metabolic performance, and Clarke teaches that the BHB ester (R)-3-hydroxybutyl (R)-3-hydroxybutyrate is also capable of providing improvement of metabolic performance, it would have been prima facie obvious for a person of ordinary skill in the art to apply the (R)-3-hydroxybutyl (R)-3-hydroxybutyrate of Clarke to the composition of Lowery because there would have been a reasonable expectation that the resulting composition would be effective for improving metabolic performance in a subject.
Claim 10 further limits the method of claim 9 wherein the organyl group comprises at least one of alkyl alkenyl, acyl, or aryl.
The (R)-3-hydroxybutyl (R)-3-hydroxybutyrate of Clarke contains an alkyl group.
Claim(s) 11-13 is/are rejected under 35 U.S.C. 103 as being unpatentable over Lowery.
Claim 11 further limits the method of claim 1 wherein the therapeutically effective amount of the plurality of amino acids is between 0.1 and 1 g.
Lowery indicates an amount of amino acid in composition in a range between 0.5-10g (Claim 8)17. As the range set forth in the instant claim overlaps with the range taught by Lowery, a case of obviousness exists per MPEP 2144.05(I):
In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990) (The prior art taught carbon monoxide concentrations of "about 1-5%" while the claim was limited to "more than 5%." The court held that "about 1-5%" allowed for concentrations slightly above 5% thus the ranges overlapped.); In re Geisler, 116 F.3d 1465, 1469-71, 43 USPQ2d 1362, 1365-66 (Fed. Cir. 1997) (Claim reciting thickness of a protective layer as falling within a range of "50 to 100 Angstroms" considered prima facie obvious in view of prior art reference teaching that "for suitable protection, the thickness of the protective layer should be not less than about 10 nm [i.e., 100 Angstroms]." The court stated that "by stating that ‘suitable protection’ is provided if the protective layer is ‘about’ 100 Angstroms thick, [the prior art reference] directly teaches the use of a thickness within [applicant’s] claimed range."). See also In re Bergen, 120 F.2d 329, 332, 49 USPQ 749, 751-52 (CCPA 1941) (The court found that the overlapping endpoint of the prior art and claimed range was sufficient to support an obviousness rejection, particularly when there was no showing of criticality of the claimed range).
Claim 12 further limits the method of claim 1 wherein the plurality of forms of BHB is present in a concentration between 10-40%.
As indicated in the 102 rejection of claim 1, the teachings of Lowery anticipate a method of improving metabolic performance by administration of a composition comprising BHB and amino acids. Lowery further provides an exemplary formulation comprising BHB, cannabidiol, and leucine. While Lowery does not explicitly teach a BHB concentration between 10-40%, a case of obviousness exists per MPEP 2144.05(II) Routine Optimization:
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) (Claimed process which was performed at a temperature between 40°C and 80°C and an acid concentration between 25% and 70% was held to be prima facie obvious over a reference process which differed from the claims only in that the reference process was performed at a temperature of 100°C and an acid concentration of 10%.); see also Peterson, 315 F.3d at 1330, 65 USPQ2d at 1382 ("The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages."); In re Hoeschele, 406 F.2d 1403, 160 USPQ 809 (CCPA 1969) (Claimed elastomeric polyurethanes which fell within the broad scope of the references were held to be unpatentable thereover because, among other reasons, there was no evidence of the criticality of the claimed ranges of molecular weight or molar proportions.).
As the teachings of Lowery meet the limitations of parent claim 1, the only differentiating factor between the teachings of Lowery and the instant claim is the BHB concentration. A person of ordinary skill in the art would have been motivated to find the optimal BHB concentration by processes of routine optimization.
Claim 13 further limits the method of claim 1 wherein the selected administration route comprises oral administration.
Lowery teaches various forms of oral administration for their composition, including forms such as tablets, capsules, and as a food additive (specification [0135])18.
Claim(s) 14-15 is/are rejected under 35 U.S.C. 103 as being unpatentable over Lowery in view of Millet (US 20250049805 A1)
Claim 14 further limits the method of claim 1 wherein the selected administration route comprises transdermal administration.
As indicated in the 102 rejection of claim 1, the teachings of Lowery anticipate a method of improving metabolic performance by administration of a composition comprising BHB and amino acids. Lowery does not explicitly teach the transdermal administration of their compositions. However, it would have been obvious to administer such a composition via transdermal route because Millet teaches compositions comprising BHB and amino acids capable of administration by various routes, including transdermal, and provides a reasonable expectation of success in formulating such a transdermal formulation.
Millet teaches stimulant compositions and methods of use of said compositions for providing enhanced cognitive flexibility, improved sustained attention, improved working memory, and neuroprotection in a mammal. More specifically, these effects are partially attributed to the metabolism of ketone bodies such as BHB, over typical glucose metabolism. The composition of Millet comprises a non-caffeine stimulant or nootropic, a ketone body such as BHB, and an optional pharmaceutically acceptable carrier (specification [0014])19. Millet further indicates that the composition may contain BHB anions and amino acid cations (claim 8)20. Furthermore, Millet provides various acceptable topical forms of dosage administration, including lotions, creams, salves, balms, transdermal patches, gels, shampoo, conditioner, deodorant, lip balm, lipstick, and makeup (specification [0176])21.
Given that the teachings of Millet appear to align with the teachings of Lowery at least in regards to a composition including BHB and amino acids, and the resulting metabolic benefits of the administration of such compositions, a person of ordinary skill in the art would have found it prima facie obvious at the time of invention to combine the teachings of the aforementioned and administer the composition of Lowery via transdermal route. The teachings of Millet provide a reasonable expectation that a composition comprising BHB and amino acids could be successfully formulated and administered via transdermal route.
Claim 15 further limits the method of claim 14 wherein the supplement formulation comprises an aqueous gel.
As indicated in the rejection of claim 14, the teachings of Millet indicate various topical forms of administration, including gels.
Conclusion
Claims 1-15 are rejected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ERIC TRAN whose telephone number is (571)272-7854. The examiner can normally be reached Mon-Fri 8:00-5:00.
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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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/ERIC TRAN/Examiner, Art Unit 1629
/JEFFREY S LUNDGREN/Supervisory Patent Examiner, Art Unit 1629
1 “In various implementations, a pharmaceutically effective amount of: butyrate, beta-hydroxybutyrate, and/or related compounds; cannabidiol and/or related compounds; and/or one or more other compounds may be administered to an individual. For example, a first compound may include pharmaceutically effective amounts of beta-hydroxybutyrate, cannabidiol, and/or one or more other compounds, which may be administered to improve and/or maintain a health of an individual.”
2 “The first composition may include other compounds may include short chain fatty acids, short chain triglycerides, medium chain fatty acids, medium chain triglycerides, long chain fatty acids, long chain triglycerides, berberine, berberine metabolites, dihydroberberine, tetrahydroberberine, amino acids such as leu cine, and/or combinations thereof.”
3 “The administered first compound may cause weight loss, weight maintenance, elevate blood ketone levels, maintain blood ketone levels, reduce blood glucose levels, maintain blood glucose levels, improve focus, improve energy, improve cognitive function, improve traumatic brain injury, improve and/or facilitate maintenance of blood glucose levels, improve and/or facilitate maintenance of diabetes, improve and/or facilitate maintenance of neurological disorders, improve and/or facilitate maintenance of cancer, inflammatory conditions, suppress appetite, reduce and/or slow down the effects of aging, have anti-glycation properties, improve and/or facilitate maintenance of epilepsy, improve and/or facilitate maintenance of neurodegenerative disease(s), improve and/or facilitate maintenance of depression, decrease immune function, facilitate reduction of substance abuse, reduce relapse and/or withdrawal associated with substance abuse, improve performance, improve strength, improve muscle mass, improve fat loss, improve body composition, and/or be used as a medicament etc.”
4 “A composition for administration may include R-beta-hydroxybutyrate and an amino acid, such as Leucine. The R-beta-hydroxybutyrate and leucine maybe complexed and/or mixed together for administration. The R-beta-hydroxybutyrate and leucine may be administered separately but approximately concurrently. FIG. 16 illustrates the blood ketone levels after administration of R-beta-hydroxybutyrate (5 g) and leucine (2 g). As illustrated, the administration of R-beta-hydroxybutyrate and leucine causes greater elevation of blood ketone levels than the administration of R-beta-hydroxybutyrate (5 g). The administration of R-beta- hydroxybutyrate and leucine causes greater elevation of blood ketone levels than merely the additive effect of similar quantities of R-beta-hydroxybutyrate and leucine administered separately.”
5 “A composition for administration is prepared by mixing approximately 10 g of beta-hydroxybutyrate, approximately 100 mg of cannabidiol, and leucine. The composition is orally administered as a food, drink, or capsule. A composition for administration is prepared by mixing approximately 5 g of beta-hydroxybutyrate salt, 10 g of a polymer of beta-hydroxybutyrate, and approximately 5 mg of cannabidiol. The composition is orally administered as a food, drink, or capsule.”
6 “BAIBA has been shown to reduce body fat percentage via an increase in fatty acid oxidation and a decrease in hepatic lipogenesis.”
7 “BAIBA was reported to induce hepatic fatty acid beta-oxidation, browning of white adipose tissue, and contribute to exercise-induced protection from metabolic diseases, by enhancing the expression of peroxisome proliferator-activated receptor-gamma co-activator-1α (PGC-1α). The characterization of brown adipose tissue in the study was conducted through quantification of the uncoupling protein-1 (UCP1)and PGC-1α expressions. Furthermore, BAIBA mitigates insulin resistance (caused by incomplete fatty acid oxidation),inhibits inflammation, and promotes fatty acid oxidation in skeletal muscle tissue by activating the AMP-activated protein kinase (AMPK)-peroxisome proliferator-activated receptor(PPAR)-delta. 10 Increased fatty acid oxidation in skeletal muscle tissue is associated with many beneficial effects such as reduced body fat percentage, reduced body weight, and increased skeletal muscle metabolic rate.”
8 “The results demonstrated that repeated oral administration of L-BAIBA at doses up to 900 mg/kg body weight/day are safe and would not result in toxic effects or treatment-related changes.”
9 “The former use L-carnitine or nutritional/dietary supplements containing L-carnitine because it facilitates the oxidation of fatty acids and makes a larger amount of energy available to skeletal muscle, thus allowing enhanced performance and giving rise to less accumulation of lactic acid in the athletes' muscles.”
10 “People in good health use these nutritional supplements as health foods, i.e. for the purposes of favouring a reduction in serum fat levels and normalisation of the ratio between the various cholesterol fractions in order to prevent diseases related to lipid metabolism disorders.”
11 “The present invention relates to stable, non-hygroscopic, pharmacologically acceptable salts of L-carnitine and lower alkanoyl-L-carnitines which favourably lend themselves to the preparation of solid, orally administrable compositions, which are useful not only as pharmaceuticals but also for the "health food" and "nutraceutical" market.”
12 “The R-beta-hydroxybutyrate in the composition may include any appropriate and/or appropriate number of forms, such as salts, derivatives (e.g., esters), polymers, and/or complexes with other compounds. For example, the composition may include R-beta-hydroxybutyrate salt (e.g., sodium R-beta-hydroxybutyrate, magnesium R-beta-hydroxybutyrate, and/or potassium R-beta-hydroxybutyrate) and/or another form of R-beta-hydroxybutyrate (e.g., ester, polymer, complex, etc.).”
13 “In some implementations, the beta-hydroxy butyrate may include beta-hydroxybutyrate salts including (calcium, sodium, magnesium, potassium, zinc, selenium, chromium, other appropriate minerals, and/or combinations thereof).”
14 “Recently, (R)-3-hydroxybutyl (R)-3-hydroxybutyrate (referred to as ketone monoester hereafter) was synthesized as a method to elevate blood ketone levels without the need to adhere to the strict ketogenic diet. Following ingestion, the ketone monoester was expected to undergo complete hydrolysis into its component parts (i.e., D-β-hydroxybutyrate and R-1,3 butanediol) by carboxylesterases and esterases located throughout the gastrointestinal tract, blood, liver and other tissues (Anders, 1989; Heymann, 1980). R-1,3-butanediol would then be further metabolized to the ketones, D-β-hydroxybutyrate and acetoacetate, in the liver by alcohol and aldehyde dehydrogenase (Desrochers et al., 1995; Tate et al., 1971).”
15 “There is evidence to suggest that ketones have a higher metabolic efficiency compared to glucose, providing more energy per unit of oxygen consumed (Cahill and Veech, 2003; Veech, 2004). Early studies suggest β-hydroxybutyrate and acetoacetate increased the motility of sperm, while decreasing oxygen consumption, in contrast to carbohydrates, lipids and other intermediary metabolites (Veech et al., 2001)… The high metabolic efficiency of ketones has important implications for the brain, as ketones can be utilized to meet high energy demands, especially during times of limited glucose availability (Owen, 2005; Owen et al., 1967). It has been proposed that artificially inducing a mild state of ketosis will provide additional acetyl-CoA substrates for the citric acid cycle. This is expected to enhance energy production and thereby improve physical performance and cognitive function, particularly during states of fatigue.”
16 “The ketone monoester was completely hydrolyzed to its components (D-β-hydroxybutyrate and R-1,3-butanediol), resulting in increased plasma levels of the ketones, D-β-hydroxybutyrate and acetoacetate. Ingestion of the ketone monoester over a period of 5 days was generally well tolerated. Some gastrointestinal disturbances were observed in individuals who consumed the highest dose (2142 mg/kg bw/ day taken in three divided doses of 714 mg/kg bw/day daily), though these were considered to be related to the large volumes (>1 l) of a milk-based drink consumed in a short period, rather than effects caused by the ketone monoester.”
17 “8. The composition of claim 1 further comprising approximately 0.5 g to approximately 10 g of amino acid.”
18 “In some implementations, the described composition may be administered via a tablet and/or capsule. The described composition may be provided in a powdered form that allows the described composition to be sprinkled on food, mixed with a liquid to provide a beverage, and/or directly administered.”
19 “Disclosed are compositions that include a combination of: (1) a non-caffeine stimulant or nootropic (e.g., paraxanthine); (2) beta-hydroxybutyrate (“BHB”); and (3) optionally a dietetically or pharmaceutically acceptable carrier.”
20 “The synergistic composition of claim 1, wherein the composition comprises a mixed salt comprising a plurality of cations selected from the group consisting of lithium ions, sodium ions, potassium ions, magnesium ions, calcium ions, and amino acid cations in combination with BHB anions.”
21 “Topicals include lotions, creams, salves, balms, transdermal patches, gels, shampoo, conditioner, deodorant, lip balm, lipstick, and makeup.”
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