US 2016.007 3659A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2016/0073659 A1 ZEMEL et al. (43) Pub. Date: Mar. 17, 2016

(54) COMPOSITIONS, METHODS, AND KITS FOR (52) U.S. Cl. TREATMENT OF PETS CPC ...... A23K 1/1603 (2013.01); A23K 1/1634 (2013.01); A23K I/009 (2013.01); A23K I/003 (71) Applicant: NUSIRT SCIENCES, INC., Nashville, (2013.01); A23K I/004 (2013.01); A23K TN (US) 1/1853 (2013.01); A23Y 2300/00 (2013.01); A23Y 2320/00 (2013.01); A23Y 2240/00 (72) Inventors: Michael ZEMEL. Knoxville, TN (US); (2013.01); A23Y 2280/00 (2013.01); A23Y t BRUCKBAUER, Knoxville, TN 2220/00 (2013.01); A23Y 2260/00 (2013.01)

(21) Appl. No.: 14/770,148 (57) ABSTRACT (22) PCT Filed: Feb. 25, 2014 The present invention provides for systems, compositions, methods and kits for regulating energy metabolism in pets. (86). PCT No.: PCT/US14f18418 The systems, compositions, and kits can comprise, and meth ods can make use of pet foods, pet treats, pet Supplements, (2)S371 Date: (c)(1), Aug. 25, 2015 and pet drinks. In one aspect, the 1nVent1On provides for pet food, treat, Supplement, and drink compositions that com Related U.S. Application Data prise a combination of (a) leucine, and (b) Vitamin B6, or any (60) Provisional application No. 61/800,094, filed on Mar. precursors or metabolites of (a) or (b). These combinations 15, 2013. may be effective for reducing weight O adipose Volume in the s pet. In another aspect, the invention provides for methods of Publication Classification regulating energy metabolism by the administration of one or more compositions comprising leucine, a leucine metabolite, (51) Int. Cl. and/or vitamin B6. The invention also provides for kits com A23K L/I6 (2006.01) prising compositions of leucine, a leucine metabolite, and/or A23K L/18 (2006.01) Vitamin B6 packaged in an oral dose form with usage instruc A23K L/00 (2006.01) tions. Patent Application Publication Mar. 17, 2016 Sheet 1 of 3 US 2016/0073659 A1

"p=0.0013 vs placebo; no significant difference between Leucine-B6 Supplemented Diet & RD Diet

w 2 O 92 ? d & c d H c Figure 1

Weight Change RD Diet vs Placebo, p40.05; RD Diet vs Leu-B6 Sup. Diet, no sign difference; Leu-B6 Sup. Diet vs. Placebo, p=0.06)

O O d

Figure 2 Patent Application Publication Mar. 17, 2016 Sheet 2 of 3 US 2016/0073659 A1

BCS Change

RD Diet vs Placebo: p30.007: RD Diet vs Leu-B6 Sup. Diet, no sign difference; Leu-B6 Sup. Diet vs. Placebo, p=0.0235 | Figure 3 Patent Application Publication Mar. 17, 2016 Sheet 3 of 3 US 2016/0073659 A1

Application pp User/Client Devices Servers

Internet

Figure 4 US 2016/0073659 A1 Mar. 17, 2016

COMPOSITIONS, METHODS, AND KITS FOR 0008. The present invention addresses the need for TREATMENT OF PETS improved compositions and Supplements for regulating energy metabolism in pets. The regulation of energy metabo CROSS-REFERENCE TO RELATED lism can allow for decreases in weight or adipose tissue, APPLICATIONS increases in fat oxidation or insulin sensitivity, and/or the 0001. This application claims benefit from U.S. Patent decrease of inflammation or oxidative stress in pets. These Application No. 61/800,094 (Attorney Docket No. 42736 effects can be by way of an increase in or regulation of a pets 706. 101), filed Mar. 15, 2013, the full disclosure of which is energy metabolism, including cellular metabolism and mito incorporated herein by reference. chondrial biogenesis. 0009. The subject compositions can be administered to a BACKGROUND OF THE INVENTION pet orally or through other routes Such as intravenous admin istration. Compositions for oral administration can include 0002 Studies have shown that a significant portion of pet food, pet treats, and pet Supplements. Alternatively, the companion animal (e.g., dog and cat) populations are over Subject compositions can be in a form that can be mixed with weight or obese. Obesity in domesticated dogs and cats has or Supplemented into a pet food by a pet owner. been linked to the development of numerous diseases includ 0010. In some embodiments, a pet food composition com ing renal failure, diabetes, and arthritis. Overweight dogs prises about 0.05 to 5 wt % of leucine and/or about 0.005 to 1 have an increased risk of developing transitional cell carci wt % of one or more leucine metabolites; and about 0.001 to noma of the bladder. Further, it is well established that obesity 0.05 wt % of vitamin B6. In some embodiments, a pet food, is a predisposing factor to idiopathic hepatic lipidosis in cats. treat or Supplement composition comprises: at least about 50 0003 Generally, obesity is considered present when body mg of leucine and/or at least about 5 mg of one or more weight of the companion pet is 15% or more greater than leucine metabolites; and at least about 1 mg of vitamin B6. optimum, which is the point at which health problems begin 0011. In some embodiments, the pet food composition increasing with increasing weight. Generally speaking, the comprises: about 0.05 to 5 wt % of leucine and/or about 0.005 incidence of obesity in domestic animals increases with age. to 1 wt % of one or more leucine metabolites; about 0.001 to Similar to humans, as a dog ages, body fat increases, and lean 0.05 wt % of vitamin B6; and an additional component body mass decreases. However, obesity commonly goes selected from the group consisting of omega-3 fatty acid, unnoticed by the animal’s owner and, thus, poses a life eicosapentanoic acid, choline, manganese, methionine, cys threatening problem to domesticated animals. teine, L-carnitine, lysine, alpha lipoic acid, dimethylamino 0004 Main meal pet foods are usually sold as complete ethanol, pyruvic acid, actyl L-carnitine, L-carnitine, conju and balanced foods that fulfill nutritional requirements for the gated linoleic acid, diacylglyceride, chondroitin, pet. Average required daily caloric intakes for animals are glucosamine, ginger (or extract thereof), chicory pulp, and based on their body weight. Average required daily nutrient myrtle. intakes are generally based on caloric intake. The serving 0012. In some embodiments, the pet food, treat or supple sizes of food generally vary according to an animals weight ment composition comprises: at least about 50 mg of leucine or may be targeted for specific breeds, specific sizes of ani and/or at least about 5 mg of one or more leucine metabolites: mals or ages of the animals. Complete and balanced serving at least about 1 mg of vitamin B6, and an additional compo sizes of pet foods mean that when fed to an animals caloric nent selected from the group consisting of omega-3 fatty acid, requirements for the animals weight, the animal receives all eicosapentanoic acid, choline, manganese, methionine, cys of its required daily nutritional and caloric requirements. teine, L-carnitine, lysine, alpha lipoic acid, dimethylamino 0005. Current weight loss diets for companion animals ethanol, pyruvic acid, actyl L-carnitine, L-carnitine, conju (e.g., dogs) rely on severe calorie restrictions and caloric gated linoleic acid, diacylglyceride, chondroitin, dilution for effectiveness. However, the metabolism of many glucosamine, ginger (or extract thereof), chicory pump, and animals cannot tolerate calorie restriction diets, and they can myrtle. end up causing more harm than good. For example, caloric 0013. In some embodiments, said omega-3 fatty acid com restriction can trigger metabolic changes in liver fat storage. prises at least about 0.05%, at least about 3.5%, or between As the animal stores more fat in its liver, it reduces the capac about 0.05 to 3.5% of the weight of the pet food composition. ity for normal healthy cells to grow which can lead to hepa Eicosapentanoic acid can comprise at least about 0.4 wt % of titis. the pet food composition. Vitamin E can comprise at least 0006 Additionally, many companion animal weight loss about 100 ppm of the pet food composition. Vitamin C can products require a prescription by a veterinarian. This can be comprise at least about 50 ppm of the pet food composition. disadvantageous because it makes pet weight management a L-carnitine can comprise at least about 50 ppm of the pet food costly and time-consuming effort for the owner. Accordingly, composition. Alpha-lipoic acid can comprise at least about 25 there remains a great need for effective compositions, meth ppm of the pet food composition. Choline can comprise at ods, and kits for the safe regulation of energy metabolism least about 1000 ppm of the pet food composition. Manga and/or associated metabolic disorders in pets. nese can comprise at least about 50 ppm, or from about 50 ppm to about 150 ppm, or from about 100 ppm to about 150 SUMMARY OF THE INVENTION ppm, or from about 100 ppm to about 110 ppm of the pet food 0007. The present invention generally relates to the field of composition. Methionine can comprise at least about at least regulation of energy metabolism in pets. In some embodi about 0.4 to 1.5% methionine by weight of the pet food ments, the present invention provides for compositions, composition. Lysine can comprise at least about 0.4%, methods, and kits for regulating energy metabolism using between about 0.4 to 2%, between about 0.9 to 2%, or leucine and/or leucine metabolites in combination with vita between about 0.9 to 1.2% by weight of the pet food compo min B6. sition. In some embodiments, said amount of ginger or extract US 2016/0073659 A1 Mar. 17, 2016

thereof is about 0.005 to 12% by weight of the pet food on a dry matter basis, about 20 to 35% by weight of a protein, composition. Chicory pulp can comprise from 0.5 to 20% dry about 4 to 10% by weight of a fat, about 2 to 25% by weight weight of the pet food composition. Chondroitin can com of a fiber, about 25 to 70% by weight of a carbohydrate, and prise at least about 0.5 wt % of the pet food composition. In about 0.1 to 2% by weight of a functional ingredient, wherein Some embodiments, said glucosamine comprises at least said functional ingredient is selected from the group consist about 0.3 wt % of the pet food composition. In some embodi ing of L-carnitine and conjugated linoleic acid, wherein the ments, said myrtle comprises at least about 1% or between protein content of the second stage pet food composition is about 1 to 10% by weight of the pet food composition. about 10 to 45% less than the protein content of the first stage 0014. In some embodiments, said omega-3 fatty acid is pet food composition. present in an amount of at least about 250 mg. In some 0018. In some embodiments, a pet food composition com embodiments, said eicosapentanoic acid is present in an prises: a live probiotic microorganism; about 0.05 to 5 wt % amount of at least about 300 mg. In some embodiments, said of leucine and/or about 0.005 to 1 wt % of one or more leucine Vitamin E is present in an amount of at least about 200 mg. In metabolites; and about 0.001 to 0.05 wt % of Vitamin B6. In Some embodiments, said vitamin C is present in an amount of Some embodiments, the pet food composition comprises: a at least about 250 mg. In some embodiments, said L-carnitine live probiotic microorganism; at least about 50 mg of leucine is present in an amount of at least about 250 mg. In some and/or at least about 5 mg of one or more leucine metabolites embodiments, said alpha-lipoic acid is present in an amount by weight of the pet food composition; and at least about 1 mg of at least about 180 mg. In some embodiments, said choline of vitamin B6 by weight of the pet food composition. In some is present in an amount of at least about 1000 mg. In some embodiments, the probiotic microorganism is selected from embodiments, said manganese is present in an amount of at the group consisting of Bifidobacterium, Bacteroides, least about 50 mg. or from about 50 mg to about 150 mg. or Clostridium, Fusobacterium, MelissocOccus, Propionibacte from about 100 mg to about 150 mg. or from about 100 mg to rium, Streptococcus, Enterococcus, Lactococcus, Staphyllo about 110 mg. In some embodiments, said methionine is coccus, Peptostrepococcus, Bacillus, Pediococcus, Micro present in an amount of at least about 7.5 mg. In some coccus, Leuconostoc, Weissella, Aerococcus, Oenococcus, or embodiments, said lysine is present in an amount of at least Lactobaccillus. In some embodiments, said composition about 400 mg. In some embodiments, said amount of ginger comprises a starch Source. In some embodiments, said starch or extract thereof is present at an amount of at least about 500 Source has a degree of gelatinization less than about 7.5 mg. In some embodiments, said chondroitin is present in an Joules/g of starch. amount of at least about 500 mg. In some embodiments, said 0019. In some embodiments, pet food compositions com glucosamine is present in an amount of at least about 300 mg. prise: about 0.05 to 5 wt % of leucine and/or about 0.005 to 1 In some embodiments, said myrtle is present in an amount of wt % of one or more leucine metabolites; about 0.001 to 0.05 at least about 750 mg. wt % of Vitamin B6; and a pre-selected balance of metabo 0015. In some embodiments, the pet food composition lizable cations to metabolizable anions, wherein the DCAB is comprises: about 0.05 to 5 wt.% of leucine and/or about between about 50 to 300. In some embodiments, a method for 0.005 to 1 wt % of one or more leucine metabolites on a dry treating a puppy Susceptible to or Suffering from diarrhea matter basis; about 0.001 to 0.05 wt.% of vitamin B6 on a dry and/or loose stool comprises: feeding the puppy a food com matter basis; about 26 to 35 wt.% of crude protein on a dry position comprising (i) about 0.05 to 5 wt % of leucine and/or matter basis; about 7.5 to 8.5 wt.% of crude fat on a dry matter about 0.005 to 1 wt % of one or more leucine metabolites and basis; about 20 to 30 wt.% of total dietary fiber on a dry (ii) about 0.001 to 0.05 wt % of Vitamin B6; and adjusting the matter basis; and about 10 to 20 wt.% of crude fiber on a dry balance of metabolizable cations to metabolizable anions matter basis. consumed by the puppy by an amount Sufficient to improve 0016. In some embodiments, the pet food composition stool quality by increasing the balance of metabolizable cat comprises: N pieces wherein N pieces provide the complete ions to metabolizable anions consumed by the puppy to pro and balanced daily nutritional requirements of an animal, and duce firmer stool. N equals 1 to less than 15 pieces, wherein each piece has a 0020. In another aspect, a pet food composition for reduc caloric content between 50 to 2500 kcal, and wherein N ing odor of stool of a companion animal comprises: Stool pieces comprise at least about 100 mg of leucine and/or 10 mg odor-reducing effective amount of ginger oran extract thereof of one or more leucine metabolites and at least about 1 mg of about 0.05 to 5 wt % of leucine and/or about 0.005 to 1 wt % vitamin B6. of one or more leucine metabolites; and about 0.001 to 0.05 0017. In some embodiments, a diet for promoting compre wt % of Vitamin B6. In some embodiments, said amount of hensive weight management in companion animals com ginger or extract thereof is present at an amount of at least prises: a first stage pet food composition for promoting about 500 mg. In some embodiments, said amount of ginger weight loss and a second stage pet food composition for or extract thereof is about 0.005 to 12% by weight. In some maintaining the weight loss, (a) said first stage pet food com embodiments, a method for reducing odor of stool of a com position comprising, on a dry matter basis, about 35 to 70% panion animal, the method comprising causing the animal to by weight of a protein, about 4 to 10% by weight of a fat, ingest a pet food composition comprises: a stool odor-reduc about 2 to 25% by weight of a fiber, about 10 to 35% by ing effective amount of ginger or an extract thereof, about weight of a carbohydrate, about 0.05 to 5% by weight of 0.05 to 5 wt % of leucine and/or about 0.005 to 1 wt % of one leucine and/or about 0.005 to 1% by weight of one or more or more leucine metabolites; and about 0.001 to 0.05 wt % of leucine metabolites, about 0.001 to 0.05% by weight of vita Vitamin B6. In some embodiments of the method, said min B6, and about 0.1 to 2% by weight of a functional ingre amount of ginger or extract thereof is about 0.005 to 12% by dient, wherein said functional ingredient is selected from the weight In some embodiments of the method, said amount of group consisting of L-carnitine and conjugated linoleic acid; ginger or extract thereof is present at an amount of at least and (b) said second stage pet food composition comprising, about 500 mg. US 2016/0073659 A1 Mar. 17, 2016

0021. In some embodiments, a pet food composition com feel; about 0.05 to 5 wt % of leucine and/or about 0.005 to 1 prises: chicory pulp in an amount which: i) maintains good wt % of one or more leucine metabolites; and about 0.001 to feces quality or improves the feces quality of a pet and/or ii) 0.05 wt % of vitamin B6. In some embodiments, the pet food maintains good gastrointestinal tract health and/or improves composition comprises a textured layer bonded to a base the gastrointestinal tract health of a pet; about 0.05 to 5 wt % layer, wherein the textured layer comprises textured compo of leucine and/or about 0.005 to 1 wt % of one or more leucine nents bonded to the base layer; about 0.05 to 5 wt % of leucine metabolites; and about 0.001 to 0.05 wt % of Vitamin B6. In and/or about 0.005 to 1 wt % of one or more leucine metabo Some embodiments, said chicory pulp comprises from 0.5 to lites; and about 0.001 to 0.05 wt % of vitamin B6. 20% dry weight of the pet food product. In some embodi 0027. In some embodiments, a pet food composition com ments, said chicory pulp comprises from 2 to 10% dry weight prises: less than about 19% on a dry weight basis of carbo of the pet food product. In some embodiments, said chicory hydrate; about 0.05 to 5 wt % of leucine and/or about 0.005 to pulp is present at an amount of at least about 350 mg. 1 wt % of one or more leucine metabolites; and about 0.001 to 0022. In some embodiments, a pet food composition com 0.05 wt % of vitamin B6. In some embodiments, said pet food prises an inner layer comprising kibble; an outer layer; about composition is dimensionally stable. 0.05 to 5% of leucine and/or about 0.005 to 1% of one or more 0028. In some embodiments, a method for feeding a pet leucine metabolites by weight of the pet food composition; comprises: providing, over an extended and preselected and about 0.001 to 0.05% of vitamin B6 by weight of the pet period of time, different food compositions to said animal in food composition. In some embodiments, the inner layer which each composition provides an enriched source of fat, comprises about 0.05 to 5% of leucine and/or about 0.005 to protein or carbohydrate. Such that said animal can select and 1% of one or more leucine metabolites by weight of the pet consume different and preferred quantities of each said food food composition; and about 0.001 to 0.05% of vitamin B6 by compositions in order to achieve an preferred consumption of weight of the pet food composition. In some embodiments, fat, protein and carbohydrate for said animal; wherein at least the outer layer comprises about 0.05 to 5% of leucine and/or one of said food compositions comprises about 0.05 to 5 wt % about 0.005 to 1% of one or more leucine metabolites by of leucine and/or about 0.005 to 1 wt % of one or more leucine weight of the pet food composition; and about 0.001 to 0.05% metabolites; and about 0.001 to 0.05 wt % of vitamin B6; of vitamin B6 by weight of the pet food composition. allowing said animal to consume the different and preferred 0023. In some embodiments, a pet food or supplement quantities of fat, protein and carbohydrate from each of said composition comprises an inner layer comprising kibble; an compositions over the extended preselected period of time; outer layer; and at least about 50 mg of leucine and/or at least and determining, from the consumed amount of fat, protein about 5 mg of one or more leucine metabolites by weight of and carbohydrate from each of said compositions, a custom the pet food composition; and at least about 1 mg of vitamin ized dietary regime that provides the preferred macronutrient B6 by weight of the pet food composition. In some embodi content of a diet for said individual animal. ments, said inner layer comprises at least about 50 mg of 0029. In some embodiments, a computer-readable leucine and/or at least about 5 mg of one or more leucine medium comprises code that, upon execution by one or more metabolites by weight of the pet food composition; and at processors, implements a method of producing a customized least about 1 mg of vitamin B6 by weight of the pet food dry pet food composition formulated from a dry pet food composition. In some embodiments, said outer layer com kibble recipe and selected functional ingredients, the formu prises at least about 50 mg of leucine and/or at least about 5 lation being selected on the basis of an individual pets mg of one or more leucine metabolites by weight of the pet attributes and physical conditions, the method comprising: food composition; and at least about 1 mg of vitamin B6 by receiving information on the individual pets attributes and weight of the pet food composition. physical conditions; selecting a predetermined Volume of dry 0024. In some embodiments, a pet food composition com kibble pieces from a plurality different formulations of pre prises: about 0.05 to 5 wt % of leucine and/or about 0.005 to made dry kibble pieces; selecting one or more functional 1 wt % of one or more leucine metabolites; about 0.001 to ingredients from a plurality functional ingredients; coating 0.05 wt % of vitamin B6; and a palatability enhancer selected the predetermined volume of dry kibble pieces with the one or from the group consisting of butyric acid, 3-methylbutyric more functional ingredients; and packaging and labeling the acid, tetrasodium pyrophosphate, 2-piperidione, 2.3 pen predetermined volume of coated dry kibble pieces; wherein tanedione, 2-ethyl-3,5-dimethylpyrazine, furfural, sulfurol, the selection of the predetermined volume of dry kibble and indole. In some embodiments, a pet food or Supplement pieces and one or more functional ingredients is based on the composition comprises at least about 50 mg of leucine and/or individual pets attributes and physical conditions to provide at least about 5 mg of one or more leucine metabolites by the customized dry pet food product, and wherein the coating weight of the pet food composition; at least about 1 mg of and/or the kibble pieces comprise leucine and/or a leucine vitamin B6 by weight of the pet food composition; and a metabolite and vitamin B6. In some embodiments, the leu palatability enhancer selected from the group consisting of cine, if present, is in an amount that is about 0.05 to 5 wt %: butyric acid, 3-methylbutyric acid, tetrasodium pyrophos the leucine metabolites, if present, are in an amount that is phate, 2-piperidione, 2.3 pentanedione, 2-ethyl-3,5-dimeth about 0.005 to 1 wt %; and the vitamin B6, if present, is in an ylpyrazine, furfural, Sulfurol, and indole. amount that is about 0.001 to 0.05 wt %. 0025. In some embodiments, a pet food composition com 0030. In some embodiments, a method of producing a prises an outer layerjoined to an inner layer, wherein the outer customized dry pet food product formulated from a dry pet layer is harder than the inner layer; about 0.05 to 5 wt % of food kibble recipe and selected functional ingredients, the leucine and/or about 0.005 to 1 wt % of one or more leucine formulation being selected on the basis of an individual pets metabolites; and about 0.001 to 0.05 wt % of vitamin B6. attributes and physical conditions, the method comprises: 0026. In some embodiments, a pet food composition com providing a plurality of different formulations of pre-made prises: a structurant for providing a textured appearance and dry kibble pieces; selecting a predetermined volume of dry US 2016/0073659 A1 Mar. 17, 2016

kibble pieces from the plurality of different formulations of or protects the composition from bacterial growth, wherein pre-made dry kibble pieces; providing a plurality of func the film comprises a starch/synthetic polymer selected from tional ingredients; coating the Volume of dry kibble pieces the group consisting of starch/polyethylene, and starch/low with one or more of the plurality of functional ingredients: density polyethylene, wherein the thickness of said coating is and packaging and labeling the predetermined Volume of 1-2000 microns; and wherein the pet food composition com coated dry kibble pieces; wherein the selection of the prede prises about 0.05 to 5 wt % of leucine and/or about 0.005 to 1 termined volume of dry kibble pieces and the one or more wt % of one or more leucine metabolites and about 0.001 to functional ingredients is based on the individual pets 0.05 wt % of Vitamin B6. attributes and physical conditions to provide the customized 0035. In some embodiments, a method for making kibble dry pet food product, and wherein the coating and/or the at one location and finishing the pet food at another location kibble pieces comprise leucine and/or a leucine metabolite comprises: forming a dry, stable intermediate of the pet food and vitamin B6. In some embodiments, the leucine, if present, composition at a first location; finishing the dry, stable inter is in an amount that is about 0.05 to 5 wt %; the leucine mediate pet food composition to form a finished pet food metabolites, if present, are in an amount that is about 0.005 to composition at a second location remote from the first loca 1 wt %; and the vitamin B6, if present, is in an amount that is tion, wherein said finished pet food composition contains about 0.001 to 0.05 wt %. about 0.05 to 5 wt % of leucine and/or about 0.005 to 1 wt % 0031. In some embodiments, a diet for companion animals of one or more leucine metabolites and about 0.001 to 0.05 wt comprises: a first stage pet food composition and a second % of Vitamin B6. stage pet food composition for maintaining the weight loss, 0036. In some embodiments, a hypoallergenic pet food wherein each of said first stage pet food composition and said composition comprises: proteinaceous component that has second stage pet food composition comprise, on a dry matter been hydrolyzed whereby said component is rendered basis, about 0.05 to 5 wt % of leucine and/or about 0.005 to 1 hypoallergenic to a pet, wherein said proteinaceous compo wt % of one or more leucine metabolites, and about 0.001 to nent is made up of polypeptides and free amino acids having 0.05 wt % of vitamin B6, and wherein said second stage pet an average molecular weight of less than about 3,000 Daltons; food comprises at least about 5% higher fat content compared about 0.05 to 5 wt % of leucine and/or about 0.005 to 1 wt % to said first stage pet food. of one or more leucine metabolites; and about 0.001 to 0.05 0032. In some embodiments, a vegetarian pet food com wt % of Vitamin B6. position comprises: a vegetarian kibble which incorporates a non-meat based flavor-enhancing additive; about 0.05 to 5 wt 0037. In some embodiments, a method of increasing pro % of leucine and/or about 0.005 to 1 wt % of one or more duction of irisin in a pet comprises administering to the pet a leucine metabolites; and about 0.001 to 0.05 wt % of vitamin pet food, pet treat, pet Snack or pet drink composition that B6. In some embodiments, a vegetarian pet food or Supple comprises: about 0.05 to 5 wt % of leucine and/or about 0.005 ment composition comprises: a vegetarian kibble which to 1 wt % of one or more metabolites thereof, and about 0.001 incorporates a non-meat based flavor-enhancing additive; at to 0.05 wt % of vitamin B6, wherein the production of irisin least about 50 mg of leucine and/or at least about 5 mg of one in the pet is increased. In some embodiments, a method of or more leucine metabolites by weight of the pet food com increasing production of irisin in a pet comprises administer position; and at least about 1 mg of vitamin B6 by weight of ing to the pet a pet food, pet treat, pet Snack or pet drink the pet food composition. composition that comprises: (a) about 50 mg of leucine and/ 0033. In some embodiments, a multi-component pet food or 5 mg of one or more metabolites thereof; and (b) at least composition comprises two or more compartmentalized food about 1 mg of vitamin B6, wherein the production of irisin in compositions, wherein the at least two compartmentalized the pet is increased. compositions differ in their content in at least two of fat, 0038. In some embodiments, a method of increasing insu protein or carbohydrate, and further wherein one of the two or lin sensitivity in a pet comprises administering to the peta pet more compartmentalized compositions comprises about 0.05 food, pet treat, pet Snack or pet drink composition that com to 5 wt % of leucine and/or about 0.005 to 1 wt % of one or prises: (a) about 0.05 to 5 wt % of leucine and/or about 0.005 more leucine metabolites, and about 0.001 to 0.05 wt % of to 1 wt % of one or more metabolites thereof; and (b) about vitamin B6. 0.001 to 0.05 wt % of vitamin B6, wherein the insulin sensi 0034. In some embodiments, a pet food composition for tivity in the pet is increased. In some embodiments, a method increasing the shelf life of a physically discrete dry pet food of increasing insulin sensitivity in a pet comprises adminis comprises: a coat covering the physically discrete pet food tering to the pet a pet food, pet treat, pet Snack or pet drink composition comprising a polymer film, wherein the film or composition that comprises: (a) about 50 mg of leucine and/ an agent in the film protects the composition from oxidation or 5 mg of one or more metabolites thereof; and (b) at least decomposition and/or protects the composition from bacte about 1 mg of vitamin B6, wherein the level of insulin sensi rial growth, wherein the film comprises a starch/synthetic tivity in the pet is increased. polymer selected from the group consisting of starch/poly 0039. In some embodiments, a method of reducing ethylene, and starch/low-density polyethylene, and wherein inflammation in a pet comprises administering to the peta pet the thickness of said coat is 1-2000 microns about 0.05 to 5 wt food, pet treat, pet Snack or pet drink composition that com % of leucine and/or about 0.005 to 1 wt % of one or more prises: (a) about 0.05 to 5 wt % of leucine and/or about 0.005 leucine metabolites; and about 0.001 to 0.05 wt % of Vitamin to 1 wt % of one or more metabolites thereof; and (b) about B6. In some embodiments, a method for increasing the shelf 0.001 to 0.05 wt % of vitamin B6, wherein the inflammation life of a physically discrete dry pet food composition com in the pet is reduced. In some embodiments, a method reduc prises: coating the physically discrete pet food composition ing inflammation in a pet comprises administering to the pet with a polymer film, wherein the film or an agent in the film a pet food, pet treat, pet Snack or pet drink composition that protects the composition from oxidation decomposition and/ comprises: (a) about 50 mg of leucine and/or 5 mg of one or US 2016/0073659 A1 Mar. 17, 2016

more metabolites thereof; and (b) at least about 1 mg of 0044. In some embodiments of the composition of the vitamin B6, wherein the inflammation in the pet is reduced. invention, the leucine metabolite is selected from the group 0040. In some embodiments, a method of reducing and/or consisting of keto-isocaproic acid (KIC), alpha-hydroxy-iso preventing diabetes in a pet comprises administering to the caproic acid, and hydroxymethylbutyrate (HMB). pet a pet food, pet treat, pet Snack or pet drink composition 0045. In some embodiments, the composition is substan that comprises: (a) about 0.05 to 5 wt % of leucine and/or tially free of alanine in free form or salt form. In some about 0.005 to 1 wt % of one or more metabolites thereof, and embodiments, the composition is substantially free of (b) about 0.001 to 0.05 wt % of vitamin B6, wherein diabetes glutamic acid in free form or salt form. In some embodiments, is prevented or the effects of diabetes is reduced. In some the composition is substantially free of glycine in free form or embodiments, a method of reducing and/or preventing diabe salt form. In some embodiments, the composition is Substan tes in a pet comprises administering to the pet a pet food, pet tially free of proline in free form or salt form. In some treat, pet Snack or pet drink composition that comprises: (a) embodiments, the composition is Substantially free of alanine about 50 mg of leucine and/or 5 mg of one or more metabo in free form or salt form. In some embodiments, the compo lites thereof; and (b) at least about 1 mg of vitamin B6, sition is Substantially free of non-leucine amino acids in free wherein diabetes is prevented or the effects of diabetes is of salt form. reduced. 0046. In some embodiments, the composition comprises less than 1% of alanine in free form or salt form. In some 0041. In some embodiments, a pet food composition com embodiments, the composition comprises less than 1% of prises: about 0.05 to 5 wt % of leucine and/or about 0.005 to glutamic acid in free form or salt form. In some embodiments, 1 wt % of one or more leucine metabolites; about 0.001 to the composition comprises less than 1% of glycine in free 0.05 wt % of vitamin B6; and about 1.5 g/kg metformin, about form or salt form. In some embodiments, the composition 0.75 g/kg metformin, or about 0.25 g/kg metformin. In some comprises less than 1% of proline in free form or salt form. In embodiments, a pet food, treat or Supplement composition Some embodiments, the composition comprises less than 1% comprises: at least about 50 mg of leucine and/or at least of non-leucine amino acids in free form or salt form. about 5 mg of one or more leucine metabolites; at least about 0047. In some embodiments, the amount of leucine is 1 mg of vitamin B6; and at least about 125 mg metformin between about 50-400, 50-300, 50-250, or 50-200 mg. In 0042. In some embodiments, a method of administering a Some embodiments, the amount of leucine metabolites is pet food, treat, Supplement, or drink to a pet comprises admin between about 5-50, 5-25, or 5-10 mg. In some embodiments, istering a composition of any of the preceding claims to the the amount of vitamin B6 is between about 1-10, 1-5, or 1-2 pet. In some embodiments, a method of facilitating weight ng. loss in a pet in need thereof comprises administering a com position wherein the pet experiences weight loss. In some INCORPORATION BY REFERENCE embodiments, the pet loses about 10% of its weight relative to 0048 All publications, patents, and patent applications the weight of the pet prior to administration of the composi mentioned in this specification are herein incorporated by tion. In some embodiments, a method of facilitating fat loss in reference to the same extent as if each individual publication, a pet in need thereof comprises administering a composition patent, or patent application was specifically and individually to the pet, wherein the pet experiences fat loss. In some indicated to be incorporated by reference. embodiments, the pet loses about 10% fat relative to the amount of fat prior to administration of the composition. In BRIEF DESCRIPTION OF THE DRAWINGS Some embodiments, a method of reducing body condition score of a pet in need thereof comprises administering a 0049. The novel features of the invention are set forth with composition, wherein the pet experiences a reduction in body particularity in the appended claims. A better understanding condition score. In some embodiments, the pet's body con of the features and advantages of the present invention will be dition score is reduced by about 2 relative to the pet's body obtained by reference to the following detailed description condition score prior to administration of the composition. that sets forth illustrative embodiments, in which the prin ciples of the invention are utilized, and the accompanying 0043. In some embodiments, a method of administering a drawings of which: pet food, treat, Supplement, or drink to a pet comprises admin 0050 FIG. 1 shows the effect of a leucine--B6 supple istering a composition of any of the preceding claims to the mented diet on percentage body fat in dogs. pet. In some embodiments, a method of facilitating weight loss in a pet in need thereof comprises administering a com 0051 FIG. 2 shows the effect of leucine+B6 supple position wherein the pet experiences weight loss. In some mented diet on weight loss in dogs. embodiments, the pet loses about 10% of its weight relative to 0052 FIG. 3 illustrates the effect of leucine--B6 supple the weight of the pet prior to administration of the composi mented diet on body composition score in dogs. tion. In some embodiments, a method of facilitating fat loss in 0053 FIG. 4 shows a non-limiting example of a computer a pet in need thereof comprises administering a composition system useful in the methods of the invention. to the pet, wherein the pet experiences fat loss. In some DETAILED DESCRIPTION OF THE INVENTION embodiments, the pet loses about 10% fat relative to the amount of fat prior to administration of the composition. In 0054 While preferred embodiments of the present inven Some embodiments, a method of reducing body condition tion have been shown and described herein, it will be obvious score of a pet in need thereof comprises administering a to those skilled in the art that such embodiments are provided composition, wherein the pet experiences a reduction in body by way of example only. Numerous variations, changes, and condition score. In some embodiments, the pet's body con substitutions will now occur to those skilled in the art without dition score is reduced by about 2 relative to the pet's body departing from the invention. It should be understood that condition score prior to administration of the composition. various alternatives to the embodiments of the invention US 2016/0073659 A1 Mar. 17, 2016

described herein may be employed in practicing the inven and ferrets; domesticated farm animals such as cows, buffalo, tion. It is intended that the following claims define the scope bison, horses, donkey, Swine, sheep, and goats; or exotic of the invention and that methods and structures within the animals typically found in Zoos, Such as bear, lions, tigers, Scope of these claims and their equivalents be covered panthers, elephants, hippopotamus, rhinoceros, giraffes, thereby. antelopes, sloth, gazelles, Zebras, wildebeests, prairie dogs, 0055. The terms “administer”, “administered, “adminis koala bears, kangaroo, pandas, giant pandas, hyena, Seals, Sea ters' and “administering are defined as the providing a com lions, and elephant seals. position to a subject via intravenous, intraarterial, oral, 0062. The term “substantially free,” as used herein, refers parenteral, buccal, topical, transdermal, rectal, intramuscular, to compositions that have less than about 10%, less than about Subcutaneous, intraosseous, transmucosal, or intraperitoneal 5%, less than about 1%, less than about 0.5%, less than 0.1% routes of administration. In certain embodiments of the sub or even less of a specified component. For example a compo ject application, oral routes of administering a composition sition that is Substantially free of non-branched chain amino may be preferred. acids may have less than about 1% of non-branched chain 0056. As used herein, the terms “animal' or “pet mean a amino acids. domestic animal including, but not limited to domestic dogs, cats, horses, cows, ferrets, rabbits, pigs, rats, mice, gerbils, Compositions hamsters, horses, and the like. Domestic dogs and cats are 0063. The present invention provides for systems, compo particular examples of pets. sitions, methods, and kits for promoting and for maintaining 0057. As used herein, the terms “animal feed”, “animal weight loss in companion animals. The systems, composi feed compositions”, “animal feed kibble”, “pet food, or “pet tions, methods, and kits can avoid utilizing severe calorie food composition' all mean a composition intended for restriction or caloric dilution, and the problems associated ingestion by a pet. Pet foods may include, without limitation, with such diets. The present invention also provides for a nutritionally balanced compositions suitable for daily feed, weight management system for domestic animals that allows Such as kibbles, as well as Supplements and/or treats, which for the selection of a desired animal body composition using may or, may not be nutritionally balanced. a nutritionally complete pet food product. 0058. The term “effective amount” or “therapeutically 0064. The pet food of the present invention can be formu effective amount” refers to that amount of an inhibitor lated to provide the daily nutritional and caloric requirements described herein that is sufficient to effect the intended appli of an animal without a prescription. Feeding the prescription cation including but not limited to disease treatment, as free comprehensive weight management system of the sub defined below. The therapeutically effective amount may vary ject invention to companion animals can help a domestic depending upon the intended application (in vitro or in vivo), animal achieve a desired body composition by modulating or the Subject and disease condition being treated, e.g., the metabolism, decreasing body fat, and/or building lean body weight and age of the Subject, the severity of the disease a SS. condition, the manner of administration and the like, which 0065. The subject compositions include pet foods (includ can readily be determined by one of ordinary skill in the art. ing pet treats), pet Supplements, and pet drinks. The Subject The term also applies to a dose that will induce a particular compositions can be formulated to include active ingredients response in target cells, e.g., reduction of proliferation or that promote weight loss in pets, including leucine, a leucine down regulation of activity of a target protein. The specific metabolite, and vitamin B6. The subject pet food composi dose will vary depending on the particular compounds cho tions can provide a domestic animal with its daily nutritional sen, the dosing regimen to be followed, whether it is admin requirements, or can be a treat or Snack that is occasionally istered in combination with other compounds, timing of fed to a pet, and may not be designed to provide the pet with administration, the tissue to which it is administered, and the its daily nutritional requirements. physical delivery system in which it is carried. 0066. The compositions can be comprise: an effective 0059. The term “energy metabolism,” as used herein, amount of (a) leucine and/or one or more metabolites thereof, refers to the transformation of energy that accompanies bio and (b) vitamin B6, wherein the combination when adminis chemical reactions in the body, including cellular metabolism tered to a Subject in need thereof enhances energy metabo and mitochondrial biogenesis. Energy metabolism can be lism, including cellular metabolism, and mitochondrial bio quantified using the various measurements described herein, genesis. The composition, when administered to a subject in for example, weight-loss, fat-loss, insulin sensitivity, fatty need thereof, can enhance energy metabolism, including cel acid oxidation, glucose utilization, triglyceride content, Sirt 1 lular metabolism and mitochondrial biogenesis, as measured expression level, AMPK expression level, oxidative stress, by a decrease in weight gain of a subject, a decrease in adipose and mitochondrial biomass. Volume of a Subject, an increase in fat oxidation of a Subject, 0060 A “sub-therapeutic amount of an agent or therapy an increase in insulin sensitivity of a Subject, a decrease in is an amount less than the effective amount for that agent or oxidative stress markers of a Subject, and/or a decrease in therapy, but when combined with an effective or sub-thera inflammatory markers of a Subject. In some embodiments, the peutic amount of another agent or therapy can produce a composition is substantially free of free or individual non result desired by the physician, due to, for example, Synergy branched chain amino acids or non-leucine amino acids. in the resulting efficacious effects, or reduced side effects. 0067. The enhanced energy metabolism can be quantified 0061 “Subject” refers to animals, including domesticated by an increase in weight loss of a subject by at least 5, 10, 30, animals and agricultural animals. The methods described or 40%, a decrease in weight of about 1, 2, or 3 kg, a decrease herein can be useful in Veterinary applications. In some in body condition score of at least about 1, 2 or 3, an increase embodiments, the Subject is a mammal, including apes, chim in fat loss of a subject by at least about 1, 5, 10, 20,30, or 50%, panzees, orangutans, monkeys; domesticated animals (pets) or an increase in insulin sensitivity by at least about 1, 5, 10. Such as dogs, cats, guinea pigs, hamsters, mice, rats, rabbits, or 15% when the composition is administered to the subject. US 2016/0073659 A1 Mar. 17, 2016

The enhanced energy metabolism can be measured relative to 0073. In some embodiments, any of the compositions the dosing of the subject with a placebo, or relative to the described herein can include salts, derivatives, metabolites, Subject prior to administration of the Subject composition. catabolites, anabolites, precursors, and analogs of any of the 0068. In some embodiments, the body condition score is branched chain amino acids, such as a leucine salt. For on a scale of 1 to 9, where scores of 1-3 are represent a body example, the metabolites can include hydroxymethylbutyrate condition that is toothin, 4-5 is ideal, and 6-8 is too heavy. The (HMB), C-hydroxyisocaproic acid, and keto-isocaproic acid 1 to 9 scale can be based on that developed by Purina, where (KIC), keto isovalerate, and keto anteliSocaproate. Non-lim 1=Ribs, lumbar vertebrae, pelvic bones and all bony promi iting exemplary anabolites of branched chainamino acids can nences evident from a distance. No discernible body fat. include glutamate, glutamine, threonine, C.-ketobytyrate, Obvious loss of muscle mass; 2=Ribs, lumbar vertebrae and O-aceto-O-hydroxybutyrate, C.B-dihydroxy-3-methylvaler pelvic bones easily visible. No palpable fat. Some evidence of ate, C.-keto-3-methylvalerate, C.B-dihydroxyisovalerate, and other bony prominence. Minimal loss of muscle mass; C.-keto isovalerate. The metabolites can include hydroxym 3–Ribs easily palpated and may be visible with no palpable ethylbutyrate (HMB), keto-isocaproic acid (KIC), and keto fat. Tops of lumbar vertebrae visible. Pelvic bones becoming isocaproate. The HMB can be in a variety of forms, including prominent. Obvious waist and abdominal tuck; 4–Ribs easily calcium 3-hydroxy-3-methylbutyrate hydrate. For clarity, the palpable, with minimal fat covering. Waist easily noted, branched chain amino acids, leucine, and metabolites thereof, viewed from above. Abdominal tuck evident; 5–Ribs pal and other related compositions can be in free or individual pable without excess fat covering. Waist observed behind ribs form. when viewed from above. Abdomen tucked up when viewed 0074. In some embodiments, the compositions may be from side: 6–Ribs palpable with slight excess fat covering. Substantially free of one or more, or all non-leucine amino Waist is discernible viewed from above but is not prominent. acids. For example, the compositions can be free of alanine, Abdominal tuck apparent, 7=Ribs palpable with difficulty; arginine, asparagine, aspartic acid, cysteine, glutamic acid, heavy fat cover. Noticeable fat deposits over lumbar area and glutamine, glycine, histidine, isoleucine, lysine, methionine, base of tail. Waist absent or barely visible. Abdominal tuck phenylalanine, proline, serine, threonine, tryptophan, may be present; 8–Ribs not palpable under very heavy fat tyrosine, and/or valine. cover, or palpable only with significant pressure. Heavy fat 0075. In some embodiments, the compositions may be deposits over lumbar area and base of tail. Waist absent. No substantially free of one or more, or all of non-branched chain abdominal tuck. Obvious abdominal distention may be amino acids. For example, the compositions can be substan present: 9-Massive fat deposits over thorax, spine and base of tially free of individual amino acids such as alanine, arginine, tail. Waist and abdominal tuck absent. Fat deposits on neck asparagine, aspartic acid, cysteine, glutamic acid, glutamine, and limbs. Obvious abdominal distention. glycine, histidine, lysine, methionine, phenylalanine, proline, 0069. Alternatively, the body condition score can be on a serine, threonine, tryptophan, and/or tyrosine. The composi scale of 1 to 5, where 1=emaciated, 2=thin, 3-moderate, tions can be substantially free of free amino acids such as 4-stout, and 5-obese. alanine, arginine, asparagine, aspartic acid, cysteine, 0070. In other embodiments, the subject compositions can glutamic acid, glutamine, glycine, histidine, isoleucine, have an effect that is about 50, 75,90, 100, 110, or 125% of lysine, methionine, phenylalanine, proline, serine, threonine, the effect of a prescription weight loss diet, where the effect is tryptophan, tyrosine, and/or valine. The Subject compositions an increase in weight loss, a decrease in weight, a decrease in can be substantially free of the individual amino acids ala body condition score, an increase in fat loss, oran increase in nine, glycine, glutamic acid, and proline. The Subject com insulin sensitivity. positions can be substantially free of one or more of the individual amino acids alanine, glycine, glutamic acid, and Leucine and Leucine Metabolites proline. The subject compositions can be substantially free of alanine. The Subject compositions can be substantially free of 0071. The invention provides for compositions that glycine. The Subject compositions can be substantially free of include leucine and/or leucine metabolites. The leucine and/ Valine. The Subject compositions can comprise less than 10, 5, or leucine metabolites can be used in free form. The term 1, or 0.1% of the individual amino acids alanine, glycine, “free,” as used herein in reference to a component, indicates glutamic acid, and proline. For clarity, the non-branched that the component is not incorporated into a larger molecular amino acids described herein are intact amino acids existing complex. For example a composition can include free leucine in free form or salt form thereof. For example, the subject that is not incorporated in a protein or free hydroxymethyl compositions can be substantially free of free amino acids, butyrate. The leucine can be L-leucine. Such as alanine, glycine, glutamic acid, and proline. The mass 0072. Without being limited to theory, ingestion of or molar amount of a non-branched chain amino acid, any branched chain amino acids, such as leucine, can stimulate amino acid, or any non-leucine amino acid can be less than tissue protein synthesis via both mTOR-dependent and -in about 0.01, 0.1, 0.5, 1, 2, 5, or 10% of the total composition, dependent pathways, as well as to exert an antiproteolytic of the total amino acids in the composition, or of the total free effect. These effects predominate in muscle, but also can amino acids in the composition. manifest in other tissues, including adipose tissue. Given the 0076 A subject composition, which may be a pet food, energetic cost of protein synthesis and turnover, leucine may treat, Snack, Supplement, or drink, can comprise at least increase fatty acid oxidation and net energy utilization and about, about, or more than about 0.005, 0.01, 0.05, 0.075, 0.1, attenuate adiposity. Indeed, leucine has been reported to exert 0.25, 0.5, 1, 2.5, or 5 wt % of leucine, as a percent of the total a thermogenic effect and to augment weight and adipose composition, or any component of the total composition. A tissue loss during energy restriction. Also, leucine and leu Subject composition, which may be a pet food, treat, Snack, cine-rich diets to favorably modulate inflammatory cytokine supplement, or drink, can comprise between about 0.005-5, patterns in adipocytes and mice. 0.005-1, 0.01-5, 0.05-5, 0.05-2, 0.05-1, 0.05-0.5, 0.1-5, or US 2016/0073659 A1 Mar. 17, 2016

0.5-2 wt % of leucine, as a percent of the total composition, or Vitamin B6 any component of the total composition. I0082. Without being limited to any particular theory or 0077. A subject composition, which may be a pet food, mode of action, elevations in the active B6 metabolite (pyri treat, Snack, Supplement, or drink, can comprise at least doxal phosphate) can reduce the tone and activity of the about, about, or more than about 0.0005, 0.001, 0.005, 0.01, adipocyte calcium channel. Because intracellular free Ca" is 0.05, 0.075, 0.1, 0.25, 0.5, 1, 2.5, or 5 wt % of one or more a primary regulator of adipocyte fatty acid synthase expres leucine metabolites, as a percent of the total composition, or sion and activity, this results in a Suppression of both the any component of the total composition. A subject composi expression and activity offatty acid synthase, which is one of tion, which may be a pet food, treat, Snack, Supplement, or the rate limiting steps in neutral lipid synthesis in adipocytes. drink, can comprise between about 0.0005-5, 0.001-5, 0.001 0083. As used herein, vitamin B6 includes its different 1, 0.005-1, 0.005-0.5,0.005-0.05 wt % of one or more leucine forms, including pyridoxine, pyridoxine 5'-phosphate, pyri metabolites, as a percent of the total composition, or any doxal, pyridoxal phosphate, pyridoxal 5'-phosphate, pyridox component of the total composition. amine, pyridoxamine 5'-phosphate. In other embodiments, 0078. A subject composition, which may be a pet food, Vitamin B6 can also include 4-pyridoxic acid, which is a treat, Snack, Supplement, or drink, can comprise about, more catabolite of the above forms of vitamin B6 that is excreted. than about, or less than about 10, 20, 30, 50, 70, 100, 150, 200, The compositions described herein can include any one or 250, 400, 500, 600, 700, 800, 900, 1000, 1100, 1250, or more more of these forms of vitamin B6. mg of leucine. The leucine may be free leucine. In some I0084. The active form of vitamin B6 in the body is pyri embodiments, a unit dose can comprise at least about 50 mg doxal 5-phosphate, which is a coenzyme for all transamina of free leucine. The composition may comprise between tion and some decarboxylation and deamination reactions. about 10-1250, 10-100, 30-100, 40-150, 200-1250, or 500 Furthermore, pyridoxal 5-phosphate is required as a coen 1250 mg of leucine. A subject composition, which may be a Zyme for all transamination reactions which occur in the body pet food, treat, Snack, Supplement, or drink, can comprise (Peterson D L, Martinez-Carrion M. The mechanism of tran about, more than about, or less than about 0.1, 1, 2, 3, 4, 5, 7, samination. Function of the histidyl residue at the active site 10, 20, 30, 50, 100, 200, 250, 400, 500, 600, 700, 800, 900, of supernatant aspartate transaminase. J Biol Chem. 1970 1000 or more mg of a leucine metabolite, such as HMB or Feb. 25: 245(4):806-13). KIC. The leucine metabolite may be a freeleucine metabolite. I0085. In some embodiments, any of the compositions The composition may comprise between about 0.1-10, 1-10, described herein can include salts, derivatives, metabolites, 3-20, 5-200, 10-900, 50-750, or 400-650 mg of the leucine catabolites, anabolites, precursors, and analogs of any of the metabolite, such as HMB or KIC. In some embodiments, a forms of vitamin B6. The forms can be in free form, indi unit dose can comprise at least about 100 mg of free HMB. vidual form, or salt form. Exemplary catabolites of vitamin 0079. In some embodiments, a daily dose of leucine can be B6 include 2-methyl-3-hydroxy-5-formylpyridine-4-car about, less than about, or more than about 0.005 g/day (e.g. boxylate and 3-hydroxy-2-methylpyridine-4,5,-dicarboxy 0.005, 0.01, 0.05, 0.1, 0.5,0.75, 1, 1.25, 1.5, 1.75, 2, 2.5, 3, or late. Exemplary analogs of vitamin B6 are described in U.S. more g/day). A daily dose of HMB or alpha-hydroxy-isoca Pat. Nos. 7,230,009, and 6,369,042. Exemplary precursors of proic acid can be about, less than about, or more than about vitamin B6 are described in U.S. Pat. No. 7,495, 101. 0.0001 g/day (e.g. 0.0001, 0.0005, 0.001, 0.005, 0.01, 0.05, I0086 A subject composition, which may be a pet food, 0.1, 0.2,0.4,0.5,0.75, 1, 1.5, 2, 2.5.3, or more g/day). A daily treat, Snack, Supplement, or drink, can comprise at least dose of KIC can be about, less than about, or more than about about, about, or more than about 0.0001, 0.0005, 0.001, 0.005 g/day (e.g. 0.005, 0.01, 0.05, 0.1, 0.2,0.4,0.5,0.75, 1, 0.005, 0.01, 0.05, 0.075, 0.1, 0.25, 0.5, 1, 2.5, or 5 wt % of 1.25, 1.5, 1.75, 2, 2.5, 3, or more g/day). Vitamin B6, as a percent of the total composition, or any 0080. In some embodiments, the dosing of leucine, any component of the total composition. A subject composition, metabolites of leucine, can be designed to achieve a specified which may be a pet food, treat, Snack, Supplement, or drink, physiological concentration or circulating level of leucine can comprise between about 0.001-0.05, 0.001-0.01, or and/or metabolites of leucine. The physiological concentra 0.005-0.01 wt % of vitamin B6, as a percent of the total tion can be a circulating level as measured in the blood stream composition, or any component of the total composition. of a Subject. The Subject can be a human oran animal. Such as I0087. A subject composition, which may be a pet food, a pet. The amount of leucine in a unit dose can be such that the treat, Snack, Supplement, or drink, can comprise about, more circulating level of leucine in a Subject, Such as a pet, is about than about, or less than about 0.1, 0.2,0.5,0.7, 1,2,3,4, 5, 10, or greater than about 0.25 mM, 0.5 mM, 0.75 mM, or 1 mM. 20, 30, 50, 70, 100, 150, 200, 250, 400, 500, 600, 700, 800, 0081. The amount of leucine in a unit dose, such as a pet 900, 1000, 1100, 1250, or more mg of vitamin B6. The food meal, a pet Snack, or a pet Supplement can be such that vitamin B6 may be free vitamin B6. In some embodiments, a the circulating level of leucine in the pet is about or greater unit dose can comprise at least about 1 mg of free vitamin B6. than about 0.25 mM, 0.5 mM, 0.75 mM, or 1 mM. A dosing The composition may comprise between about 0.1-125, 0.1- of about 1,125 mg leucine can achieve a circulating level of 10, 1-50, 1-25, 3-10, 4-15, 20-125, or 50-125 mg of vitamin leucine in a subject weighing about 150 lb that is about 0.5 B6. mM. A dosing of about 300 mg leucine can achieve a circu 0088. The amount of vitamin B6 in a unit dose can be such lating level of leucine in a subject weighing about 150 lb that that the circulating level of vitamin B6 in a subject is about or is about 0.25 mM. Correspondingly, A dosing of about 225 greater than about 10, 25, 50, 100, 150, or 200 nM. The mg leucine can achieve a circulating level of leucine in a amount of leucine and vitamin B6 in a unit dose can be such subject weighing about 30 lb that is about 0.5 mM. A dosing that the circulating level of leucine in a subject is about 100 of about 60 mg leucine can achieve a circulating level of nM. leucine in a subject weighing about 30 lb that is about 0.25 I0089 Adosing of about 15 mg of vitamin B6 can achieve mM. a circulating level of vitamin B6 in as Subject weighing about US 2016/0073659 A1 Mar. 17, 2016

150 lb that is about 100 nM. A dosing of about 7.5 mg of acid or carboxylate anion of pyruvic acid known as pyruvate. vitamin B6 can achieve a circulating level of vitamin B6 in a In various embodiments, the pyruvic acid or a salt thereof can subject weighing about 150 lb that is about 50 nM. Corre be administered in a composition comprising a wet or dry spondingly, a dosing of about 3 mg of vitamin B6 can achieve food composition, which may be in the form of a moist food, a circulating level of vitamin B6 in as Subject weighing about dry food, Supplement or treat. The pyruvic acid or a salt 30 lb that is about 100 nM. A dosing of about 1.5 mg of thereof may be incorporated therein or on the surface of any vitamin B6 can achieve a circulating level of vitamin B6 in a food composition, Such as, by spraying or precipitation subject weighing about 30 lb that is about 50 nM. thereon or may be added to the diet by way of Snack, Supple 0090. In one aspect, the invention provides for a compo ment, treat or in the liquid portion of the diet Such as water or sition comprising (a) leucine and/or metabolites thereof, and another fluid. The pyruvic acidora salt thereofmay be admin (b) Vitamin B6, wherein mass ratio of component (a) to (b) in istered as a powder, Solid or as a liquid including a gel. An said composition is greater than about 50, 65, 70, 75, 85,90, important aspect is that the animal be provided an effective 100, 200 In some embodiments, the mass ratio of component amount of the pyruvic acid or a salt thereof to provide a (a) to component (b) in said composition is greater than about positive effect. 65. In some embodiments, the mass ratio of leucine to vitamin 0097. A combination of lipoic acid or salt thereof and B6 is about, greater than about, or less than about 45, 50, 55. pyruvic acid or salt thereof for consumption by a companion 60, 65,70, 75, 80, 85,90, 100, 110, 120, 130, 140, 150, 175, animal can provide treatment for obesity. Adding a combina 200, 250, 500, 750, 1000, or more. tion of lipoic acid or salt thereof and pyruvic acid or salt thereof to a composition for consumption can also decrease Additional Active Ingredients body fat and increases lean muscle mass. 0091. The invention provides for the combination of (a) 0.098 Carnitine is found in the body and is enzymatically leucine and/or one or more leucine metabolites and (b) Vita combined with fatty acids to facilitate their transportation min B6 with one or more additional active ingredients. The through mitochondrial membranes, thus aiding in fatty acid additional active ingredients can be directed to weight loss, metabolism (Yalkowsky, S. H., 1970). Oral administration of kidney disease maintenance or prevention, senior or old-age L-carnitine for obesity in mammals has been described in pets, dental diseases and conditions, and stool. U.S. Pat. No. 3,810,994. 0092. The invention also encompasses compositions for 0099. A diacylglyceride is a lipid structurally character preventing, ameliorating one or more symptoms of, or treat ized by a glycerol (a three carbon alcohol) backbone, two ing certain disorders by administering a therapeutically or fatty acid chains and a phosphate group. By definition, a prophylactically effective amount of a composition to a com 1.2-diacylglyceride comprises fatty acid chains located at carbons 1 and 2 and, further, are characterized by a long panion animal in need thereof. hydrocarbon molecule Such as unsaturated, saturated and 0093. In some embodiments, a pet food composition com conjugated hydrocarbons. 1,2-diacylglyceride is a precursor prises about 0.05 to 5 wt % of leucine and/or about 0.005 to 1 to phosphatidylcholine, phosphatidylethanolamine and phos wt % of one or more leucine metabolites; about 0.001 to 0.05 phatidylinositol, which are indispensable components of bio wt % of vitamin B6; and an additional component selected logical membranes. In addition, 1.2-diacylglycerides are pre from the group consisting of omega-3 fatty acid, eicosapen cursors to triglyceride biosynthesis and, therefore, is central tanoic acid, choline, manganese, methionine, cysteine, L-car to energy stores of organisms. However, 1.3-diacylglycerides nitine, lysine, alpha lipoic acid, dimethylaminoethanol, pyru are not metabolized to triglyceride and, thus, are not depos Vic acid, actyl L-carnitine, L-carnitine, conjugated linoleic ited as fat but rather, burned as energy. 1,3-diacylglyceride acid, diacylglyceride, chondroitin, glucosamine, ginger (or differs structurally from 1,2-diacylglycerides by having an extract thereof), chicory pulp, and myrtle. Optionally, the acyl group at C-3 of the glycerol backbone rather than at C-2. amount of leucine, leucine metabolite, and/or Vitamin B6 can Clinical investigations of obesity have included dietary con be any other amount described herein. Sumption of diacylglycerol and indicated that diacylglycerol 0094. In other embodiments, a pet food, treat or supple lowers serum triglyceride and cholesterol levels (Takasaka et ment composition comprises at least about 50 mg of leucine al., 2000) and decreases body weight and regional fat depo and/or at least about 5 mg of one or more leucine metabolites: about 1 mg of vitamin B6, and an additional component sition (Nagao et al., 2000). Rich natural sources of 1,3-dia selected from the group consisting of omega-3 fatty acid, cylglycerides are vegetable oils, such as Econa oil. eicosapentanoic acid, choline, manganese, methionine, cys 0100 Functional ingredients that modulate metabolism teine, L-carnitine, lysine, alpha lipoic acid, dimethylamino and build lean body mass can include L-carnitine, conjugated ethanol, pyruvic acid, actyl L-carnitine, L-carnitine, conju linoleic acid and a diacylglyceride, and can include conju gated linoleic acid, diacylglyceride, chondroitin, gated linoleic acid and diacylglyceride, and can include a glucosamine, ginger (or extract thereof), chicory pump, and diacylglyceride. myrtle. 0101. A subject composition, which may be a pet food, treat, Snack, Supplement, or drink, can comprise pyruvate or Weight Loss pyruvic acid content of at least about 0.01, 0.05, 0.1, 0.5, 1, 2, 3,4,5,6,7,8,9, 10, 14, 18, 20, 24% by weight on a dry matter 0095. In some embodiments, the subject compositions can basis. In some instances, the composition comprises a pyru be include an additional weight loss component that can vate or pyruvic acid content of about 0.1 to 10% by weight on facilitate weight loss. The additional weight loss component a dry matter basis of Subject composition. can be pyruvic acid (pyruvate), L-carnitine, conjugated 0102) A subject composition, which may be a pet food, linoleic acid, diacylglyceride, and econa oil. treat, Snack, Supplement, or drink, can comprise at least about 0096. As used herein, the term "pyruvic acid or a salt 5, 10, 20, 30, 40, 50, 60, 70, 80, 90, 100 ppm L-carnitine. A thereof includes, but is not limited to, for example, pyruvic Subject composition can comprise at least about 0.01%. US 2016/0073659 A1 Mar. 17, 2016

0.05%, 0.1%, 0.5%, 1%, 1.5%, 2%, 2.5%, 3% L-carnitine. In generally referred to as idiopathic glomerulonephritis. The Some instances, a Subject composition comprises about 0.1 to latter conditions are generally referred to as secondary glom 1% L-carnitine of the Subject composition. As used herein, erulonephritis. Whatever the underlying cause, immune com units of ppm can be equivalent to mg/kg. plexes form and result in a series of events leading to glom 0103) A subject composition, which may be a pet food, erular injury and loss of renal function, proteinuria and treat, Snack, Supplement, or drink, can comprise at least about ultimately, in some cases, renal failure. 0.01%, 0.05%, 0.1%, 0.5%, 1%, 1.5%, 2%, 2.5%, 3% linoleic 0113 Diet plays an important role in kidney disease cau acid. In some instances, a Subject composition comprises sation and progression because it is fundamentally involved about 0.1 to 1% L-carnitine of the subject composition. in metabolism. Biological pathways are at Some level regu 0104. A subject composition, which may be a pet food, lated by nutritional factors. Thus, dietary components present treat, Snack, Supplement, or drink, can comprise at least about in foods as nutrients may regulate gene expression at the 0.01%, 0.05%, 0.1%, 0.5%, 1%, 1.5%, 2%, 2.5%, 3% dia transcriptional and translational level, as well as in certain cylglyceride. In some instances, a subject composition com post-translational modifications. They may similarly be prises about 0.1 to 1% diacylglyceride of the subject compo involved in degradation and enzymatic activities. Nutrient sition. levels may influence the equilibrium of metabolic pathways. 0105. A subject composition, which may be a pet food, Metabolic pathways are frequently complex and may involve treat, Snack, Supplement, or drink, can comprise at least about many redundancies and interrelationships among different 0.01%, 0.05%, 0.1%, 0.5%, 1%, 1.5%, 2%, 2.5%, 3% econa metabolic pathways. Altering the concentration of a single oil. In some instances, a Subject composition comprises about enzyme, growth factor, cytokine or metabolite may impact a 0.1 to 1% econa oil of the subject composition. number of metabolic pathways involved in disease-related 0106 A subject composition, which may be a pet food, physiology. Hormones and other cell signaling molecules are treat, Snack, Supplement, or drink, can comprise pyruvate or well-understood to be regulated by diet and can be implicated pyruvic acid content of at least about 10, 50, 100, 200, 300, in the development and progression of disease. 400, 500, 600, 700, 800, 900 mg of the subject composition. 0114. As used herein, the term "pyruvic acid or a salt In some instances, the composition comprises a pyruvate or thereof includes, but is not limited to, for example, pyruvic pyruvic acid content of about 300-700 mg of subject compo acid or carboxylate anion of pyruvic acid known as pyruvate. sition In various embodiments, the pyruvic acid or a salt thereof can 0107 A subject composition, which may be a pet food, be administered in a composition comprising a wet or dry treat, Snack, Supplement, or drink, can comprise at least about food composition, which may be in the form of a moist food, 5, 10, 20, 30, 40, 50, 60, 70, 80, 90, 100 mg L-carnitine. In dry food, Supplement or treat. The pyruvic acid or a salt some instances, L-carnitine comprises about 20 to about 100 thereof may be incorporated therein or on the surface of any mg of the Subject composition. food composition, Such as, by spraying or precipitation 0108. A subject composition, which may be a pet food, thereon or may be added to the diet by way of Snack, Supple treat, Snack, Supplement, or drink, can comprise an linoleic ment, treat or in the liquid portion of the diet Such as water or acid content of at least about 25, 50, 75, 100, 125, 150, 175, another fluid. The pyruvic acidora salt thereofmay be admin 200, 250, 300, 350, 400 mg of the subject composition. In istered as a powder, Solid or as a liquid including a gel. An Some instances the composition comprises an linoleic acid important aspect is that the animal be provided an effective content of at least about 150 to about 300 mg of the subject amount of the pyruvic acid or a salt thereof to provide a composition. positive effect. Typically, the source of pyruvic acid or a salt 0109. A subject composition, which may be a pet food, thereof is present in the composition in an amount of up to an treat, Snack, Supplement, or drink, can comprise diacylglyc amount, which remains non-toxic to the animal. eride content of at least about 25, 50, 75, 100, 125, 150, 175, 200, 250, 300, 350, 400 mg of the subject composition. In 0.115. A subject composition, which may be a pet food, Some instances the composition comprises diacylglyceride treat, Snack, Supplement, or drink, can comprise pyruvate or content of at least about 150 to about 300 mg of the subject pyruvic acid content of at least about 0.01, 0.05, 0.1, 0.5, 1, 2, composition. 3,4,5,6,7,8,9, 10, 14, 18, 20, 24% by weight on a dry matter 0110. A subject composition, which may be a pet food, basis. In some instances, the composition comprises a pyru treat, Snack, Supplement, or drink, can comprise econa oil vate or pyruvic acid content of about 0.1 to 10% by weight on content of at least about 25, 50, 75, 100, 125, 150, 175, 200, a dry matter basis of Subject composition. 250, 300, 350, 400 mg of the subject composition. In some 0116. A subject composition, which may be a pet food, instances the composition comprises econa oil content of at treat, Snack, Supplement, or drink, can comprise pyruvate or least about 150 to about 300 mg of the subject composition. pyruvic acid content of at least about 100, 200,300, 400, 500, 600, 700, 800, 900 mg of the subject composition. In some Kidney Disease instances, the composition comprises a pyruvate or pyruvic acid content of about 300-700 mg of subject composition. 0111. In other embodiments, the subject compositions can include active ingredients directed to kidney disease, for example pyruvate. Senior Pets 0112 Glomerulonephritis or glomerular nephritis (“GN) 0117. In some embodiments, the subject compositions can is a renal disease which is characterized by inflammation of include active ingredients that address issues associated with the glomeruli or capillary loops of the kidney. It is a patho senior or old-age pets or animals. Active ingredients directed logic process associated with a number of diverse underlying to senior or old-age pets can include chondroitin, glu diseases. The condition occurs in acute, Sub-acute and cosamine, omega-3-polyunsaturated fatty acids, choline, chronic forms and also secondary to an infection. The former manganese, methionine, cysteine, L-carnitine, lysine, eicosa conditions, where a concurrent illness cannot be found, are pentanoic acid, vitamin E. Vitamin C, and alpha-lipoic acid. US 2016/0073659 A1 Mar. 17, 2016

0118 Essential fatty acids, consisting of omega-3 and 0.125. A subject composition, which may be a pet food, omega-6 polyunsaturated fatty acids, are critical nutrients for treat, Snack, Supplement, or drink, can comprise an amount of the health of an animal. These nutrients, however, either can Vitamin C or Vitamin E that is at least about or about 10, 20, not be made by animals or cannot be made in Sufficient 30, 50, 75, 100,125, 150, 200,300,500, 1000 or 5000 ppm of amounts to elicit benefits and therefore must be consumed in the pet food composition. A subject composition, which may an animal's diet. See, e.g., Hornstra, G. et al., “Essential fatty be a pet food, treat, Snack, Supplement, or drink, can comprise acids in pregnancy and early human development’. Eur. J. an amount of Vitamin C or Vitamin E that is at least about or Obs. & Gyn. and Reprod. Biology, 61:57-62 (1995). It has about 50, 100, 200, 250300, 600, 1000, 1500, 2000, 3000, or previously been postulated that Docosahexaenoic Acid 5000 mg. (“DHA), an omega-3 polyunsaturated fatty acid, is effective I0126. A subject composition, which may be a pet food, in increasing the maze-learning ability and brain functions in treat, Snack, Supplement, or drink, can comprise an L-car aged mice. See, Lim, S.-Y., “Intakes of dietary docosa nitine content of at least about 5, 10, 20, 30, 40, 50, 60, 70, 80, hexaenoic acid ethyl ester and egg phosphatidylcholine 90, 100 ppm of the subject composition. In some instances the improve maze-learning ability in young and old mice'. J. composition comprises an L-carnitine content of at least Nutr., 130:1629-1632 (2000). about 50 ppm of the subject composition. 0119 The compositions for use in the methods of the I0127. A subject composition, which may be a pet food, present invention generally have an omega-3 polyunsaturated treat, Snack, Supplement, or drink, can comprise an L-car fatty acid content of at least about 25, 50, 75, 100, 125, 150, nitine content of at least about 25, 50, 75, 100, 125, 150, 175, 175, 200, 225, 250, 300, 400, 500 mg. The omega-3 polyun 200, 250, 300, 350, 400 mg of the subject composition. In saturated fatty acid can be DHA. In other embodiments, the Some instances the composition comprises an L-carnitine omega-3 polyunsaturated fatty acid is EPA. In still other content of at least about 250 mg of the subject composition. embodiments, the omega-3 polyunsaturated fatty acid com I0128. A subject composition, which may be a pet food, prises a mixture of DHA and EPA treat, Snack, Supplement, or drink, can comprise an amount of 0120 A subject composition, which may be a pet food, eicosapentanoic acid that is at least about or about 0.1, 0.2, treat, Snack, Supplement, or drink, can comprise an omega-3 0.4, 0.8, or 1 wt % of the pet food composition. A subject polyunsaturated fatty acid content of at least about 0.005%, composition, which may be a pet food, treat, Snack, Supple 0.01%, 0.05%, 0.1%, 0.5%, 1%, 2%, 3%, 3.5%, 4%, 5%, 6%, ment, or drink, can comprise an amount of eicosapentanoic 7% by weight on a dry matter basis. The omega-3 polyun acid that is at least about or about 50, 100, 200, 300, or 600 saturated fatty acid can be DHA. In other embodiments, the ng. omega-3 polyunsaturated fatty acid is EPA. In still other I0129. A subject composition, which may be a pet food, embodiments, the omega-3 polyunsaturated fatty acid com treat, Snack, Supplement, or drink, can comprise a choline prises a mixture of DHA and EPA. content of at least about 100, 200, 300, 500, 600, 700, 800, 0121 The omega-3 fatty acids may be obtained from a 900, 1000, 1200, 1400, 1600, 1800, 2000 ppm. In some variety of sources. One convenient source is fish oils from, for instances the composition comprises a choline content of at example, menhaden, mackerel, herring, anchovy, and least about 1000 ppm of subject composition. salmon. DHA and EPA are typical fatty acids present in such 0.130. A subject composition, which may be a pet food, fish oils, and, together often make up a significant portion of treat, Snack, Supplement, or drink, can comprise a choline the oil, such as from about 25% to about 38% of the oil. content of at least about 100, 200, 300, 500, 600, 700, 800, 0122. In some embodiments, the composition containing 900, 1000, 1200, 1400, 1600, 1800, 2000 mg of the subject omega-3 polyunsaturated fatty acid is a food. Although both composition. In some instances the composition comprises a liquid and solid foods are provided, solid foods are typically choline content of at least about 1000 mg of subject compo preferred. Foods include both dry foods and wet foods. sition. 0123 Rogers discusses the theory of the potential use of I0131 The subject compositions can also include chon antioxidants to slow the deterioration of cognitive function, droitin and glucosamine. The bioavailability of glucosamine particularly in the elderly. See Rogers, P., “A healthy body, a and GAGs, such as chondroitin sulfate, is believed to bolster healthy mind: long-term impact of diet on mood and cogni the restoration of connective tissue in a variety of ways. For tive function’. Proceedings of the Nutrition Society, 60:135 example, glucosamine stimulates the incorporation of other 143 (2001). precursors, such as GAGs, PGs, and collagen, into the con 0124. The term “antioxidant’ means a substance that is nective tissue matrix and serves as a precursor to GAG syn capable of reacting with free radicals and neutralizing them. thesis. Chondroitin sulfate serves to inhibit degradative Illustrative examples of Such substances include beta-caro enzymes and stimulates GAG and PG synthesis in connective tene, selenium, coenzyme Q10 (ubiquinone), luetin, tocot tissue cells, particularly chondrocytes. The vertebrate body rienols, soy isoflavones, S-adenosylmethionine, glutathione, synthesizes GAGs, such as in chondrocytes (cartilage), fibro taurine, N-acetylcysteine, Vitamin E, vitamin C, lipoic acid blasts (skin, ligaments), and osteoblasts (bone). and L-carnitine. Examples of foods containing useful levels 0.132. Without being limited to theory, the connective tis of one or more antioxidants include but are not limited to Sue of vertebrates includes bone and cartilage as well as tissue ginkgo biloba, green tea, broccoli, citrus pulp, grape pomace, that underlies the skin, envelops muscle, and occupies space tomato pomace, carrot spinach, and a wide variety of fruit between internal organs. The primary building blocks of con meals and vegetable meals. Without being bound by theory, nective tissue are proteoglycans (PG), which are linked to health benefits may be the result of physiological effects from collagen fibers to form connective tissue. Proteoglycan Sub the addition of omega-3 polyunsaturated fatty acids to a units are comprised of glycoaminoglycans (also known as senior or Super senior animals diet. Similarly, the antioxi GAGS or mucopolysaccharides) attached in large numbers to dants, choline, and other nutrients may play a role in enhanc a core protein, with these proteoglycan Subunits being ing a senior or Super senior animal’s quality of life. attached to a very long hyaluronic acid molecule via protein US 2016/0073659 A1 Mar. 17, 2016

links to form aggregating proteoglycan. GAGS are long-chain at about 150 mg. or from about 100 mg to about 150 mg. or polymers with monomer units comprising an aminosugar and from about 100 mg to about 110 mg of the subject composi an organic acid or Sugar. One type of GAG is chondroitin tion. Sulfate, which is composed of glucuronic acid and N-acetyl 0140. A subject composition, which may be a pet food, galactosamine Sulfate. Glucosamine is a key precursor to both treat, Snack, Supplement, or drink, can comprise a methionine GAGS and hyaluronic acid molecules, which are the primary content of at least about 0.04%, 0.08%, 0.1%, 0.5%, 1%, components of PGs, as discussed above. In fact, the bioavail 1.5%, 2%, 2.5%. 3% of the subject composition. In some ability of glucosamine is the rate-limiting step in the synthesis instances the composition comprises a methionine content of of GAGS and PGs. at least about 0.4% to 1.5% of the subject composition. 0133) A subject composition, which may be a pet food, 0.141. A subject composition, which may be a pet food, treat, Snack, Supplement, or drink, can comprise a chondroitin treat, Snack, Supplement, or drink, can comprise a methionine content of at least about 50, 100, 150, 200,250, 300,350, 400, content of at least about 0.75, 1, 1.25, 1.5, 1.75, 2, 2.25, 2.5, 450, 500, 550, 600, 650, 700, 750, 800, 850, 900, 950, 1000 3, 3.5 mg of the Subject composition. In some instances the mg of the Subject composition. In some instances the com composition comprises a methionine content of at least about position comprises a chondroitin content of at least about 500 7.5 mg of the Subject composition. mg of the Subject composition. 0142. A subject composition, which may be a pet food, treat, Snack, Supplement, or drink, can comprise a lysine 0134. A subject composition, which may be a pet food, content of at least about 0.04%, 0.08%, 0.1%, 0.5%, 1%, treat, Snack, Supplement, or drink, can comprise a glu 1.5%, 2%, 2.5%. 3%, 4% ppm of the subject composition. In cosamine content of at least about 30, 50, 100, 150, 200, 250, Some instances the composition comprises alysine content of 300, 350, 400, 450, 500, 550, 600 mg of the subject compo at least about 0.4%, between about 0.4 to 2%, between about sition. In some instances the composition comprises a glu 0.9 to 2%, or between about 0.9 to 1.2% of the subject com cosamine content of at least about 300 mg of the subject position. composition. 0.143 A subject composition, which may be a pet food, 0135 A subject composition, which may be a pet food, treat, Snack, Supplement, or drink, can comprise a lysine treat, Snack, Supplement, or drink, can comprise a chondroitin content of at least about 40, 100, 150, 200,250,300,350, 400, content of at least about 0.05%, 0.1%, 0.2%, 0.3%, 0.5%, 450, 500, 550, 600, 650, 700,750,800, 850 mg of the subject 0.6%, 0.7%, 0.8%, 1%, 1.5% of the subject composition. In composition. In some instances the composition comprises a some instances the composition comprises alysine content of lysine content of at least about 400 mg of the subject compo at least about 0.5% of the subject composition. sition 0136. A subject composition, which may be a pet food, treat, Snack, Supplement, or drink, can comprise a glu Dental cosamine content of at least about 0.03%, 0.05%, 0.1%, 0144. In other embodiments, the subject compositions can 0.2%, 0.3%, 0.5%, 0.6%, 0.7%, 0.8%, 1%, 1.5% of the sub include active ingredients that address dental issues, for ject composition. In some instances the composition com example myrtle. prises a lysine content of at least about 0.3% of the subject 0145 The inhibition of certain plaque biofilm forming composition. bacteria by myrtle results in the control or reduction of dental 0.137 The compositions for use in the methods of this plaque in an animal by the reduction of the bacterial content invention further comprise at least one nutrient selected from of the dental plaque. The food product is consumed and the group consisting of manganese, methionine, cysteine, during use the oral cavity of the animal is exposed to the mixtures of methionine and cysteine, L-carnitine, lysine, and myrtle of the food product, and the composition can have arginine. Specific preferred amounts for each component in a direct contact with the surface of a tooth of the animal. The composition will depend on a variety of factors including, for surface of a tooth can be directly contacted with the myrtle of example, the species of animal consuming the composition; the food product, as well as being contacted by the pet food the particular components included in the composition; the composition to physically remove a proportion of the plaque. age, weight, general health, sex, and diet of the animal; the The food product has the benefit of improving or maintaining animals consumption rate, and the like. Thus, the component the oral health of the animal by removing plaque through the amounts may vary widely, and may even deviate from the mechanical (gentle abrasive) action of the product against the proportions given herein. surface of the teeth of the animal, as well as by the action of the myrtle. 0138 A subject composition, which may be a pet food, 0146 A subject composition, which may be a pet food, treat, Snack, Supplement, or drink, can comprise a manganese treat, Snack, Supplement, or drink, can comprise a myrtle content of at least about 5, 10, 20, 40, 50, 60, 80, 100, 120, content of at least about 0.1%, 0.5%, 1%, 2%, 3%, 4%, 5%, 140, 150, 160, 180, 200, 250, 300 ppm. In some instances the 6%, 7%, 8%, 9%, 10%, 12%, 14%, 16%, 18%, 20% of the composition comprises a manganese content of at least about Subject composition. In some instances the composition com 50 ppm, at least about 50 ppm to at about 150 ppm, or from prises myrtle content of about 1 to about 10% of the subject about 100 ppm to about 150 ppm, or from about 100 ppm to composition. about 110 ppm of the subject composition. 0147 A subject composition, which may be a pet food, 0.139. A subject composition, which may be a pet food, treat, Snack, Supplement, or drink, can comprise a myrtle treat, Snack, Supplement, or drink, can comprise a manganese content of at least about 75 100, 150, 200, 250,300,350, 400, content of at least about 5, 10, 20, 40, 50, 60, 80, 100, 120, 450,500,550, 600, 650,700, 750,800,900, 1000, 1500, 2000 140, 150, 160, 180, 200, 250, 300 mg of the subject compo mg of the Subject composition. In some instances the com sition. In some instances the composition comprises a man position comprises myrtle content of about 750 mg of the ganese content of at least about 50 mg, at least about 50 mg to Subject composition. US 2016/0073659 A1 Mar. 17, 2016

Stool 0155 The most common extraction process is of chicory root and is similar to the extraction of sucrose from Sugar beet 0148. In some embodiments, the subject compositions can (diffusion in water). The extraction removes inulin to leave a include active ingredients that improve stool. Such as by chicory pulp. improving the odor or consistency of the stool. Odor-improv 0156 A subject composition, which may be a pet food, ing active ingredients include ginger. Consistency improving treat, Snack, Supplement, or drink, can comprise a chicory active ingredients can include chicory. Additionally, the com content of at least about 0.5%, 1%, 2%, 3%, 4%, 5%, 10%, positions can be formulated to have a selected balance of 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50% of the subject cations and anions such that the stool of the animal is composition. In some instances the composition comprises improved. chicory content of about 5 to about 20% of the subject com 0149 Pet health can be monitored in a number of ways. position. In some instances the composition comprises Two of these are feces quality and gastrointestinal (GI) tract chicory content of about 2 to about 10% of the subject com health. Good quality feces in pet animals is of two-fold impor position. tance. Firstly, it is a good indicator of a healthy pet. Good 0157. A subject composition, which may be a pet food, feces quality can reflect healthy colonic structure and func treat, Snack, Supplement, or drink, can comprise a chicory tion. content of at least about 35, 50, 100, 150, 200, 250, 300,350, 0150 Stool quality and stool frequency are generally 400, 450, 500, 550, 600, 650, 700 mg of the subject compo determined by five factors: food ingredient digestibility, fiber sition. In some instances the composition comprises chicory level, health status, activity level, and water intake. When content of at least about 350 ppm of the subject composition. these factors are balanced, stools are generally formed, firm, 0158 Excreta odor in companion animals is an unpleasant dark, and exhibit a relatively reduced odor. Stools exhibiting reality of living with pets. For owners of animals that live these properties are considered to be good quality stools. If indoors, especially cats and dogs that use litter boxes or are the factors are not balanced, stools are generally soft, loose, confined to kennels or other Small spaces, this problem is watery, light-colored, and exhibit a relatively increased odor. particularly unpleasant. Cat litter containing deodorizers has Stools exhibiting these properties, particularly loose, watery been developed, however this is an imperfect solution to the stools, are considered to be poor quality stools. problem. Excreta odor in animals is partially a result of indi 0151 Poor stool quality and irregular stool frequency can gestion and microbial fermentation caused by inappropriate be caused by various factors, e.g., abnormal intestinal motil bacterial activity, inflammation and poor digestion or motill ity, increases in intestinal permeability, the presence of non ity. absorbable osmotically active substances in the intestine, or 0159 Ginger and extracts thereof can be effective in agents that cause diarrhea. Similarly, some animal foods, reducing odor of excreta from an animal when included in the particularly those known in the art as chunk and gravy animal animal's diet. Without being held to a particular theory, it is foods, can cause poor stool quality. Often, an animal consum believed that the beneficial effects of ginger can result at least ing such foods has a fecal discharge that is irregular and in part from antimicrobial, anti-inflammatory and gastric undesirable. Such discharge is generally characterized by stimulation properties of ginger. Specifically, it is believed frequent loose, watery stools. In some instances, the dis that ginger reduces the level of odor producing compounds charge may be classified as diarrhea. including heterocycles, phenols, thiols, Sulfides and indoles present in excreta, and in this way reduces excreta odor 0152 One method for maintaining normal gastrointestinal including fecal, urinary and flatulence odor. function and ameliorating chronic diarrhea in animals can 0160 The invention provides for a pet food composition include the addition, in pet food products, of a fiber source, for reducing odor of stool of a companion animal comprising: Such as chicory, which contains a significantly higher propor stool odor-reducing effective amount of ginger or an extract tion of insoluble fibers to soluble fibers, which are either thereof about 0.05 to 5 wt % of leucine and/or about 0.005 to non-fermentable or only moderately fermentable. 1 wt % of one or more leucine metabolites; and about 0.001 to 0153. In some embodiments, a pet food composition can 0.05 wt % of Vitamin B6. The invention also provides for a comprise chicory pulp in an amount which: i) maintains good method for reducing odor of stool of a companion animal, the feces quality or improves the feces quality of a pet and/or ii) method comprising causing the animal to ingest a pet food maintains good gastrointestinal tract health and/or improves composition comprising: a stool odor-reducing effective the gastrointestinal tract health of a pet; about 0.05 to 5 wt % amount of ginger or an extract thereof; about 0.05 to 5 wt % of leucine and/or about 0.005 to 1 wt % of one or more leucine of leucine and/or about 0.005 to 1 wt % of one or more leucine metabolites; and about 0.001 to 0.05 wt % of Vitamin B6. metabolites; and about 0.001 to 0.05 wt % of Vitamin B6. Optionally, the amount of leucine, leucine metabolite, and/or Optionally, the amounts of leucine, leucine metabolite, and/ Vitamin B6 can be any other amount described herein. or Vitamin B6 can be any other amount described herein. 0154 Chicory is a blue flowered plant (Cichorium inty 0.161 For purposes of this application, “ginger includes bus), named ENDIVE in the US, which is cultivated for its plant parts, particularly rhizomes (sometimes referred to as salad leaves and its root (roasted and ground for use with, or “roots'), of Zingiber officinale and other Zingiber species. instead of coffee). Its primary components are i) inulinandii) This includes ginger in any form such as powder, dehydrated, soluble and fermentable fibers. Inulin is a soluble polysac fresh, cooked or raw. An "extract of ginger herein is any charide, composed of polymerized fructose molecules, preparation containing Substances extracted from ginger, occurring as stored food material in many plants, such as including fluid extracts, tinctures, essential oils, distillates members of the Compositae species and in dahlia tubers. and oleoresins However, it is not the endogenous inulin of chicory, but rather 0162. A subject composition, which may be a pet food, the fiber, which imparts the advantageous effect in maintain treat, Snack, Supplement, or drink, can comprise a ginger ing and/or improving fecal quality in pet animals. content of at least about 0.0005%, 0.001%, 0.005%, 0.01%, US 2016/0073659 A1 Mar. 17, 2016

0.05%, 0.1%, 0.5%, 1%, 2%, 4%, 6%, 8%, 10%, 12%, 14%, than two-thirds of the feces in a defecation are soft. The feces 16%, 18%, 20%, 22%, 24% of the subject composition. In retain enough form to pile but have lost their firm cylindrical Some instances the composition comprises ginger content of appearance. Grade 4: Firm-soft feces are an intermediate about 0.005 to about 12% of the subject composition. between the grades of firm and soft. Approximately equal 0163 A subject composition, which may be a pet food, amounts of feces in a defecation are firm and soft. Grade 5: treat, Snack, Supplement, or drink, can comprise a ginger Greater than two-thirds of the feces in a defecation are firm. content of at least about 50, 100, 150, 200,250, 300,350, 400, They have a cylindrical shape with little flattening. See also, 450, 500, 550, 600, 650, 700, 750, 800, 850, 900, 950, 1000 Sunvold et al., J. Anim Sci 1995 73:1099-1109; U.S. Pat. No. mg of the Subject composition. In some instances the com 6,280.779; U.S. Pat. No. 5,616,569. Stool quality may also be position comprises ginger content of about 500 mg of the assessed quantitatively using methods to determine the Subject composition. amount of moisture in the feces in g/kg (see, e.g., Yamka et al., (0164 U.S. patent application Ser. No. 11/566,512 (the 2006, Am J Vet Res, 67(1):88-94). 512 application) filed Dec. 4, 2006 (the contents of which are (0169. The balance of metabolizable cations to metaboliz herein incorporated by reference) discloses adjusting the bal able anions can be determined by any means known to skilled ance of metabolizable cations to metabolizable anions con artisans. For example, one method for measuring the balance Sumed by the animal to affect stool quality. It has generally of metabolizable cations to metabolizable anions is to calcu been found that increasing the balance of metabolizable cat late the animal's dietary cation-anion balance (DCAB), ions to metabolizable anions will result in firmer stool quality which is determined by calculating the cumulative amount of and reduced stool output. Conversely, decreasing the balance cations regularly consumed by the animal and Subtracting the of metabolizable cations to metabolizable anions will result cumulative amount of anions consumed by the animal. Cat in looser stool and increased stool output. ions may include, e.g., Sodium, potassium, calcium, and mag (0165 While the 512 application describes methods for nesium cations, or any other ion having a positive charge, altering Stool quality and/or frequency for adult dogs, the including amino acids. Anions may include, e.g., chloride, dietary requirements of adult dogs and puppies are quite Sulfur, and phosphorus anions, or any other ion having a different. For example, puppies generally experience rapid negative charge, including amino acids. For example, the growth and development; thus they generally require signifi DCAB is determined by calculating the cumulative amounts cantly more nutrition than adult dogs and of a different nutri of sodium, potassium, calcium, and magnesium cations regu tional composition. For example, puppies require higher cal larly consumed by the animal and Subtracting the cumulative cium levels due to their rapid bonegrowth. Similarly, the stool amount of chloride, Sulfur, and phosphorus anions regularly of adult dogs and puppies are typically of different quality and consumed by the animal. a dog can produce Substantially firmer stool than a puppy, 0170 In some embodiments, a pet food compositions can partly in response to their different diets and nutritional comprise about 0.05 to 5 wt % of leucine and/or about 0.005 requirements. Thus, the cation and anion balance disclosed in to 1 wt % of one or more leucine metabolites; about 0.001 to the prior art, while suitable for adult dogs, may be unsuitable 0.05 wt % of Vitamin B6; and a pre-selected balance of for improving the stool quality of a puppy. The stool quality of metabolizable cations to metabolizable anions, wherein the a puppy may be improved by modifying the dietary cation and DCAB is between about 50 to 300. Optionally, the amount of anion balance of a food composition consumed by the animal leucine, leucine metabolite, and/or Vitamin B6 can be any such that the dietary cation and anion balance is from about 50 other amount described herein. to about 300 mEq. 0171 The invention also provides for a method for treat 0166 As used herein, “altering stool quality”, “modifying ing a puppy Susceptible to or Suffering from diarrhea and/or stool quality” or “improving stool quality” refers to modify loose stool comprising: feeding the puppy a food composition ing the stool of an animal to produce a desired firmness in the comprising (i) about 0.05 to 5 wt % of leucine and/or about stool and/or a desired stool frequency. Generally, stools that 0.005 to 1 wt % of one or more leucine metabolites and (ii) are loose and watery are not desired, nor are stools that are so about 0.001 to 0.05 wt % of Vitamin B6; and adjusting the firm that constipation is observed. Thus, stool quality is balance of metabolizable cations to metabolizable anions improved in an animal experiencing diarrhea (e.g., frequent consumed by the puppy by an amount Sufficient to improve loose, watery stools) by causing the stool to be more firm and stool quality by increasing the balance of metabolizable cat causing the animal to produce fewer stools; conversely, an ions to metabolizable anions consumed by the puppy to pro animal experiencing constipation will benefit by a change in duce firmer stool. Optionally, the amount of leucine, leucine stool quality such that the stool is less firm. As described metabolite, and/or Vitamin B6 can be any other amount herein, such changes may be achieved by altering the ani described herein. mals dietary cation-anion balance (DCAB). An increase in 0.172. The DCAB can be determined in accordance with DCAB can cause stool to be firmer; a decrease in DCAB can the following equation: DCAB (mEq)=(Na+K+Ca+Mg)- cause stool to be less firm. (C1+S+P). For purposes of calculating the DCAB, sodium, 0167 Stool quality may be scored according to methods potassium and chloride ions have a valance of 1, Sulfur, cal familiar to one of skill in the art. For example, fecal quality is cium and magnesium ions have a valance of 2, and phospho commonly assessed by those of skill in the art by visual rus ions have a valance of 1.8. scoring, e.g., ranking stool visually on a scale from grade 1-5 as follows: Grade 1: Greater than two-thirds of the feces in a Probiotics and Prebiotics defecation are liquid. The feces have lost all form, appearing 0173. In other embodiments, the subject compositions can as a puddle or squirt. include one or more probiotics or prebiotics. In addition to the 0168 Grade 2: Soft-liquid feces are an intermediate optional use of anti-diarrhea agents and anti-constipation between soft and liquid feces. Approximately equal amounts agents in the systems, compositions, methods, and kits of the of feces in a defecation are soft and liquid. Grade 3: Greater present invention, in some embodiments, the balance of US 2016/0073659 A1 Mar. 17, 2016

metabolizable cations to metabolizable anions consumed by for the healthy maintenance of intestinal microflora, or from the animal can be adjusted in conjunction with the adminis about 5 billion to about 10 billion live bacteria per day. Gen tration of one or more compositions comprising a gastrointes erally, prebiotics are administered in amounts sufficient to tinal tract-improving agent. "Gastrointestinal tract-improv positively stimulate the healthy microflora in the gut and ing agents' are generally probiotics and prebiotics. cause these 'good bacteria to reproduce. Typical amounts 0.174. The pet food composition can comprise a live pro are from about one to about 10 grams per serving or from biotic microorganism; about 0.05 to 5 wt % of leucine and/or about 5 percent to about 40 percent of the recommended daily about 0.005 to 1 wt % of one or more leucine metabolites; and dietary fiber for an animal. about 0.001 to 0.05 wt % of Vitamin B6. Optionally, the 0179. In certain embodiments, the probiotic microorgan amount of leucine, leucine metabolite, and/or Vitamin B6 can ism is Saccharomyces cereviseae, Bacillus coagulans, Bacil be any other amount described herein. lus licheniformis, Bacillus subtilis, Bifidobacterium bifidum, 0.175. In other embodiments, the pet food composition Bifidobacterium infantis, Bifidobacterium longum, Entero comprises a live probiotic microorganism; at least about 50 coccus faecium, Enterococcusfaecalis, Lactobacillus bul mg of leucine and/or at least about 5 mg of one or more garicus, Lactobacillus acidophilus, Lactobacillus alimenta leucine metabolites by weight of the pet food composition; rius, Lactobacillus casei Subsp. casei, Lactobacillus casei and at least about 1 mg of vitamin B6 by weight of the pet food Shirota, Lactobacillus curvatus, Lactobacillus delbruckii composition. Optionally, the amount of leucine, leucine Subsp. lactis. Lactobacillus farcininus, Lactobacillus gas metabolite, and/or Vitamin B6 can be any other amount seri, Lactobacillus helveticus, Lactobacillus johnsonii, Lac described herein. tobacillus reuteri, Lactobacillus rhamnosus (Lactobacillus 0176 Probiotics are live microorganisms that have a ben GG), Lactobacillus sake, Lactobacillus sporogenes, Lacto eficial effect in the prevention and treatment of specific medi coccus lactis, Micrococcus varians, Pediococcus acidilactici, cal conditions when ingested. Probiotics are believed to exert Pediococcus pentosaceus, Pediococcus acidilactici, Pedio biological effects through a phenomenon known as coloniza coccus halophilus, Streptococcus faecalis, Streptococcus tion resistance. The probiotics facilitate a process whereby thermophilus, Streptococcus faecium, Staphylococcus carno the indigenous anaerobic flora limits the concentration of sus, Leuconostoc mesenteroides ssp cremoris, Pediococcus potentially harmful (mostly aerobic) bacteria in the digestive acidolactici, Pediococcus cerevisiae, Bifidobacterium bifi tract. Other modes of action, such as Supplying enzymes or dus, Bifidobacterium longum, Brevibacterium linens, Propi influencing enzyme activity in the gastrointestinal tract, may Onibacterium shermanii, Propionibacterium arabinosum, also account for some of the other functions that have been Penicillium roquefortii, Penicillium camembertii, or Staphy attributed to probiotics. Probiotics may enhance an animals lococcus xylosus. systemic cellular immune responses and may be useful as a 0180 A subject composition, which may be a pet food, dietary Supplement to boost natural immunity in otherwise treat, Snack, Supplement, or drink, can comprise a probiotic healthy animals. Probiotics include many types of bacteria content of at least about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 14, 16, but generally are chosen from four genera of bacteria: Lac 18, 20 billion colonies. A subject composition can comprise a tobacillus acidophilus, Bifidobacteria, Lactococcus, and probiotic content of at least about 1,2,3,4,5,6,7,8,9, 10, 12, Pediococcus. 14, 16, 18, 20 billion colony forming units (CFU). A subject 0177 Prebiotics are nondigestible food ingredients that composition can comprise a probiotic content of at least about beneficially affect host health by selectively stimulating the 2 billion CFU/kg, 4 billion CFU/kg, 6 billion CFU/kg, 8 growth and/or activity of bacteria in the colon, and are known billion CFU/kg, 10 billion CFU/kg, 15 billion CFU/kg, 20 by those of skill in the art. For example, fructooligosaccharide billion CFU/kg, 25 billion CFU/kg, 30 billion CFU/kg, 35 (FOS) is found naturally in many foods such as wheat, onions, billion CFU/kg, 40 billion CFU/kg. In some instances the bananas, honey, garlic, and leeks. FOS can also be isolated composition comprises a probiotic content of 20 billion CFU/ from chicory root or synthesized enzymatically from Sucrose. kg of the Subject composition. In some instances, the compo FOS fermentation in the colon results in a large number of sition comprises a probiotic content of 10 billion colonies. physiologic effects including increasing the numbers of bifi dobacteria in the colon, increasing calcium absorption, Pet Treat Formulations increasing fecal weight, shortening of gastrointestinal transit 0181. In certain embodiments, the pet food composition time, and possibly lowering blood lipid levels. The increase in can be a treat. Treats include compositions that are given to an bifidobacteria has been assumed to benefit health by produc animal to entice the animal to eat during a non-meal time, for ing compounds to inhibit potential pathogens, by reducing example, dog bones for canines Treats may be nutritional blood ammonia levels, and by producing vitamins and diges wherein the composition includes one or more nutrients and tive enzymes. Probiotic bacteria such as Lactobacilli or Bifi may have a food-like composition. Non-nutritional treats dobacteria are believed to positively affect the immune encompass any other treats that are non-toxic. The composi response by improving the intestinal microbial balance lead tion or components are coated onto the treat, incorporated ing to enhanced antibody production and phagocytic activity into the treat, or both. Treats of the invention can be prepared of white blood cells. by an extrusion or baking process similar to those used for dry 0.178 The amount of probiotics and prebiotics to be food. Other processes also may be used to either coat the administered to the animal is determined by the skilled artisan composition on the exterior of existing treat forms or inject based upon the type and nature of the probiotic and prebiotic the composition into an existing treat form. and the type and nature of the animal, e.g., the age, weight, 0182. In certain embodiments, the edible composition can general health, sex, extent of microbial depletion, presence of be a toy. Toys include chewable toys such as artificial bones. harmful bacteria, and diet of the animal. Generally, probiotics The at least one pyruvate can form a coating on the Surface of are administered to the animal in amounts of from about one the toy or on the Surface of a component of the toy, be incor to about twenty billion colony forming units (CFUs) per day porated partially or fully throughout the toy, or both. In one US 2016/0073659 A1 Mar. 17, 2016

embodiment, the one or more pyruvate is orally accessible by 12, 16, 20, or 24 hours. The release of the one or more the intended user. The chewable toys can include about 0.05 components can be at a constant or changing rate. to 5 wt % of leucine and/or about 0.005 to 1 wt % of one or 0188 Using the controlled release dosage forms provided more leucine metabolites; and about 0.001 to 0.05 wt % of herein, the one or more cofactors can be released in its dosage vitamin B6. The chewable toy can include a composition format a slower rate than observed for an immediate release comprising: at least about 50 mg of leucine and/or at least formulation of the same quantity of components. In some about 5 mg of one or more leucine metabolites; and at least embodiments, the rate of change in the biological sample about 1 mg of vitamin B6. measured as the change in concentration over a defined time 0183 There are a wide range of suitable toys currently period from administration to maximum concentration for an marketed, for example, U.S. Pat. No. 5,339,771, U.S. Pat. No. controlled release formulation is less than about 80%, 70%, 5,419,283, and references disclosed therein. This invention 60%, 50%, 40%, 30%, 20%, or 10% of the rate of the imme provides both partially consumable toys, for example, toys diate release formulation. Furthermore, in some embodi including plastic components, and fully consumable toys, for ments, the rate of change in concentration over time is less example, rawhides and various artificial bones. than about 80%, 70%, 60%, 50%, 40%, 30%, 20%, or 10% of the rate for the immediate release formulation. Pet Supplement Formulations 0189 Examples of suitable fillers for use in the composi 0184 The invention provides for pet supplements that can tions and dosage forms disclosed herein include, but are not be in the form of pills, tablets, chews, liquids, powders, or the limited to, talc, calcium carbonate (e.g., granules or powder), like that are Suitable for ingestion by a pet. Supplements microcrystalline cellulose, powdered cellulose, dextrates, include, for example, a feed used with another feed to kaolin, mannitol, silicic acid, Sorbitol, starch, pre-gelatinized improve the nutritive balance or performance of the total. starch, and mixtures thereof. Supplements include compositions that are fed undiluted as a 0190. When aqueous suspensions and/or elixirs are supplement to other feeds, offered free choice with other parts desired for oral administration, the active ingredient therein of an animals ration that are separately available, or diluted may be combined with various Sweetening or flavoring and mixed with an animal's regular feed to produce a com agents, coloring matter or dyes and, if so desired, emulsifying plete feed. AAFCO, for example, provides a discussion relat and/or Suspending agents, together with Such diluents as ing to supplements in the Official Publication of The Asso water, ethanol, propylene glycol, glycerin and various com ciation of American Feed Control Officials, Inc. (2009). binations thereof. Supplements may be in various forms including, for example, powders, liquids, syrups, pills, encapsulated compositions, Pet Drinks and the like. In other embodiments, a pet Supplement can be 0191 The present invention also provides for drink com in the form of a powder or liquid that can be mixed in with a positions for pet animals that provides a healthy, nutritional pet’s daily meals. The powder or liquid can be packaged in drink, in which the components can be easily adjusted to individual bottles or packets such that one packet or bottle specific needs and which is palatable to the animals. The corresponds to a half or all of a recommended dosage of drinks can comprise the Subject compositions, such as leu leucine, a leucine metabolite, and/or vitamin B6. cine, a leucine metabolite, and/or Vitamin B6. 0185. The tablets can be uncoated or coated by known 0.192 The drink composition according to the invention techniques to delay disintegration and absorption in the gas has three major components, an olfactory component (i.e., trointestinal tract and thereby provide a Sustained action over Smell), a palatability component (i.e., taste), and a health a longer period. For example, a time delay material Such as component (i.e., pure and/or fortified water). Flavors, both glyceryl monostearate or glyceryl distearate can be natural and synthetic, may be used to promote the olfactory employed. Formulations for oral use can also be presented as component of the invention. Beef, fish, chicken, turkey, liver hard gelatin capsules wherein the active ingredient is mixed and cat nip are flavors that may be used as olfactory and/or with an inert Solid diluent, for example, calcium carbonate, palatability enhancers. Other flavors, both natural and syn calcium phosphate or kaolin, or as Soft gelatin capsules thetic, may used to promote the palatability of the invention. wherein the active ingredient is mixed with water or an oil Dextrose (D-glucose), fructose and mixed long chain medium, for example, peanut oil, liquid paraffin or olive oil. polysaccharides are the carbohydrate palatability enhancers. 0186. In one embodiment, the composition may include a Sodium pyrophosphate, Sodium acid pyrophosphate, Sodium solubilizer to ensure good solubilization and/or dissolution of tripolyphosphate, tetrasodium pyrophosphate, sodium poly the compound of the present invention and to minimize pre phosphate, sodium tripolyphosphate, phosphoric acid, citric cipitation of the compound of the present invention. This can acid, and potassium citrate are noncarbohydrate palatability be especially important for compositions for non-oral use, enhancers that may be in the drinks. e.g., compositions for injection. A solubilizer may also be 0193 Vitamins are major health components of the liquid added to increase the solubility of the hydrophilic drug and/or drinks Vitamins in the liquid drinks may include both water other components, such as Surfactants, or to maintain the soluble and water dispersible vitamins. The antioxidant vita composition as a stable or homogeneous solution or disper mins C, E, A and alpha-tocopherol, as well as vitamin B12, Sion. Vitamin D, folic acid, D-biotin, cyanocobalamin, niacinamide 0187. The compositions described herein can also be for (B3), thiamin, riboflavin, pyridoxin (B6), menadione (K3), mulated as extended-release, Sustained-release or time-re beta-carotene, calciumpantothenate, choline, and inositol lease Such that one or more components are released over may provide added nutrients to the liquid pet drinks. The time. Delayed release can be achieved by formulating the one concentration of the vitamins may be adjusted to deliver or more components in a matrix of a variety of materials or by between 2% to 200% of the recommended daily require microencapsulation. The compositions can be formulated to ments. The dog drink may be formulated with the necessary release one or more components over a time period of 4, 6, 8, daily vitamin requirements for a 14 kg dog in 500 milliliters. US 2016/0073659 A1 Mar. 17, 2016

The cat drink may be formulated with the necessary daily for processing. These ingredients are mixed in a vessel Suit vitamin requirements for a 3 kg cat in 125 milliliters. able for heating while blending the components. Heating of 0194 The drink of the invention may include mineral and the mixture is effected using any Suitable manner, for electrolyte Supplements. Zinc, iron, calcium, manganese, example, direct Steam injection or using a vessel fitted with a copper, iodine, sodium, and potassium may be added to the heat exchanger. Following the addition of the last ingredient, liquid drinks as mineral and electrolyte Supplements. Addi the mixture is heated to a temperature of about 50°F. to about tionally, the invention may include amino acid Supplements. 212° F. Temperatures outside this range are acceptable but Alanine, arginine, aspartic acid, asparagine, cysteine, may be commercially impractical without use of other pro glutamic acid, glycine, glutamine, histidine, isoleucine, leu cessing aids. When heated to the appropriate temperature, the cine, lysine, methionine, phenylalanine, proline, serine, tau material will typically be in the form of a thick liquid. The rine, threonine, tryptophan, tyrosine, and valine are amino thick liquid is filled into cans. A lid is applied, and the con acids that may be added to the invention. tainer is hermetically sealed. The sealed can is then placed 0.195 The drink of the invention may include potassium into conventional equipment designed to sterilize the con Sorbate and Sodium benzoate as preservatives, and may also tents. Sterilization is usually accomplished by heating to tem use low levels of carbon dioxide for improving shelf life and peratures of greater than about 230°F. for an appropriate time in limiting biological growth. depending on the temperature used, the composition, and similar factors. The compositions of the present invention can Pet Food Formulations be added to the food compositions before, during, or after 0196. The invention provides for pet foods that can be in preparation. dry, moist or wet form using one or more food preparation 0200 Food compositions may be prepared in a dry form processes. Foods of any consistency or moisture content are using conventional processes known to skilled artisans. Typi contemplated, e.g., the compositions of the present invention cally, dry ingredients such as animal protein, plant protein, may be, for example, a dry, moist or semi-moist animal food grains, and the like are ground and mixed together. Moist or composition. "Semi-moist” refers to a food composition con liquid ingredients, including fats, oils, animal protein, water taining from about 25 to about 35% moisture. “Moist' food and the like are then added to and mixed with the dry mix. The refers to a food composition that has a moisture content of mixture is then processed into kibbles or similar dry pieces. about 60 to 90% or greater. “Dry” food refers to a food Kibble is often formed using an extrusion process in which composition with about 3 to about 11% moisture content and the mixture of dry and wet ingredients is subjected to is often manufactured in the form of small bits or kibbles. mechanical work at a high pressure and temperature and Also contemplated herein are compositions that may com forced through small openings and cut off into kibble by a prise components of various consistency as well as compo rotating knife. The wet kibble is then dried and optionally nents that may include more than one consistency, for coated with one or more topical coatings such as flavors, fats, example, soft, chewy meat-like particles as well as kibble oils, powders, and the like. Kibble also can be made from the having an outer cereal component and an inner cream com dough using a baking process, rather than extrusion, wherein ponent as described in, e.g., U.S. Pat. No. 6,517,877. The the dough is placed into a mold before dry-heat processing. kibble may then be dried and optionally coated with one or The food compositions can be in the form of a treat using an more topical coatings known by those skilled in the art, for extrusion or baking process similar to those described above example, flavors, fats, oils, powders, and the like. for dry food or a toy such as those disclosed in U.S. Pat. Nos. 0.197 Kibble-type animal feeds, such as dog and cat foods, 5,339,771 and 5,419.283. The compositions of the present can be dried, ready-to-eat pet food products. The kibbles can invention can be added to the food compositions before, be formed by an extrusion process where the kibble raw during, or after preparation. materials are extruded under heat and pressure to form the 0201 In many applications, starch can be added to the pelletized kibble form or core. Extrusion technology can pro protein component of the core feed to improve stability. Such vide an inexpensive and efficient method for formulating as by holding the components in the kibble form. In certain animal feed kibbles, such as those having a starch matrix. applications, it may be desirable to provide a kibble that is During the extrusion process, the kibble raw materials, which Substantially free of starch, using, for example, techniques can comprise the starch matrix, typically results in the starch described in US Patent Application No. 2011/0027416, incor matrix becoming gelatinized under the extrusion conditions, porated herein by reference in its entirety. Thus, one embodi forming a gelatinized starch matrix. ment of the present disclosure provides a protein-based core 0198 A process of manufacture of the pet food product matrix, wherein the protein-based core is substantially free of can generally include mixing components to form a core a gelatinized Starch matrix. Specific embodiments may com material mixture, extruding the core material mixture to form prise a protein-based core that has less than 5%, 2%, 1%, or a core pellet, drying the core pellet, and optionally applying a even 0.5% by weight of gelatinized starch. Still other embodi dusting component to the dried core pellet to form a food ments, the protein-based core matrix may be essentially free pellet, and packaging the food pellets. In one embodiment, of gelatinized starch. As used herein, the term “essentially the food pellet can be the final desired food product. In one free” when used in reference to concentration of a specific embodiment, the food pellet can undergo dusting steps to component in a composition means less than a measurable form the food product as desired. amount using methods of concentration measurements com 0199 Ground animal proteinaceous tissues can be mixed mon in the art. with the other ingredients such as fish oils, cereal grains, 0202 As contemplated herein, the compositions of the balancing ingredients, special purpose additives, such as the present invention are can be nutritionally complete and bal leucine, a leucine metabolite, vitamin B6, other vitamin and anced pet food compositions (also referred to herein simply mineral mixtures, inorganic salts, cellulose and beet pulp. as “nutritionally complete pet food compositions'). Nutrients bulking agents, and the like, and water in amounts sufficient and ingredients as well as others suitable for animal feed US 2016/0073659 A1 Mar. 17, 2016

compositions, and recommended amounts thereof, may be Essential amino acids are amino acids that cannot be synthe found, for example, in the Official Publication of the Associ sized de novo, or in Sufficient quantities by an organism and ate of American Feed Control Officials (AAFCO), Inc., thus must be supplied in the diet. Essential amino acids vary Nutrient Requirements of Dogs and Cats, 2006. For example, from species to species, depending upon the organism’s nutritionally complete foods may contain protein, fat, carbo metabolism. For example, it is generally understood that the hydrate, dietary fiber, amino acids, minerals, vitamins, and essential amino acids for dogs and cats (and humans) are otheringredients in amounts known by those of skill in the art. phenylalanine, leucine, methionine, lysine, isoleucine, 0203 Protein may be supplied by any of a variety of Valine, threonine, tryptophan, histidine and arginine. In addi Sources known by those skilled in the art, including plant tion, taurine, while technically not an amino acid but a deriva Sources, animal sources, or both. Animal sources include, for tive of cysteine, is an essential nutrient for cats. example, meat, meat by-products, seafood, dairy, eggs, etc. 0209. The compositions of the present invention may also Meats include, for example, the flesh of poultry, fish, and contain one or more minerals and/or trace elements, e.g., mammals (e.g., cattle, pigs, sheep,goats, and the like). Meat calcium, phosphorus, sodium, potassium, magnesium, man by-products include, for example, lungs, kidneys, brain, liv ganese, copper, Zinc, choline, or iron salts, in amounts ers, and stomachs and intestines (freed of all or essentially all required to avoid deficiency and maintain health. These their contents). The protein can be intact, almost completely amounts are known by those of skill in the art, for example, as hydrolyzed, or partially hydrolyzed. provided in the Official Publication of the Associate of 0204 Fat can be supplied by any of a variety of sources American Feed Control Officials, Inc. (“AAFCO), Nutrient known by those skilled in the art, including meat, meat by Requirements of Dogs and Cats, 2006. products, fish oil, and plants. Plant fat sources include wheat, 0210. The compositions of the present invention may also flaxseed, rye, barley, rice, Sorghum, corn, oats, millet, wheat include vitamins in amounts required to avoid deficiency and germ, corn germ, soybeans, peanuts, and cottonseed, as well maintain health. These amounts, and methods of measure as oils derived from these and other plant fat sources. A fat ment are known by those skilled in the art. For example, the component can be used in Some embodiments. The fat com Official Publication of the Associate of American Feed Con ponent can comprise poultry fat, chicken fat, turkey fat, pork trol Officials, Inc. (AAFCO), Nutrient Requirements of fat, lard, tallow, beef fat, vegetable oils, corn oil, soy oil, Dogs and Cats, 2006 provides recommended amounts of such cottonseed oil, palm oil, palm kernel oil, linseed oil, canola ingredients for dogs and cats. As contemplated herein, useful oil, rapeseed oil, fish oil, menhaden oil, anchovy oil, and/or Vitamins may include, but are not limited to, Vitamin A, Vita olestra. min B1, vitamin B2, vitamin B6, vitamin B12, vitamin C, 0205 Carbohydrate may be supplied by any of a variety of vitamin D, vitamin E. vitamin H (biotin), vitamin K, folic Sources known by those skilled in the art, including oat fiber, acid, inositol, niacin, and pantothenic acid. cellulose, peanut hulls, beet pulp, parboiled rice, corn starch, 0211. The compositions of the present invention may corn gluten meal, and any combination of those sources. additionally comprise additives, stabilizers, fillers, thicken Grains Supplying carbohydrate include, but are not limited to, ers, flavorants, palatability enhancers and colorants in wheat, corn, barley, and rice. Carbohydrate content of foods amounts and combinations familiar to one of skill in the art. may be determined by any number of methods known by 0212. In one embodiment, the compositions of the present those of skill in the art. Generally, carbohydrate percentage invention are provided as a food, e.g., a nutritionally complete may be calculated as nitrogen free extract (“NFE), which pet food composition. In another embodiment, the composi may be calculated as follows: NFE=100%-moisture 96-pro tions of the present invention may be in the form of a treat, tein 96-fat %-ash 96-crude fiber 96. Snack, Supplement, or partially or fully edible toy. Such items 0206 Fatty acids for inclusion in the compositions of the for consumption by a pet are known to those skilled in the art, present invention can include omega 3 fatty acids such as and can include, for example, compositions that are given to docosahexanenoic acid (DHA), eicosapentaenoic acid an animal to eat during non-meal time, e.g., a dog biscuits, (EPA), alpha-linolenic acid (ALA), octadecatetraenoic acid edible chew toys, etc. (stearidonic acid) or mixtures thereof. 0213. The binder component in any pet food composition 0207 Dietary fiber can refer to components of a plant described herein can comprise any of the following or com which are resistant to digestion by an animal's digestive binations of the following materials: monosaccharides Such enzymes. Dietary fiber includes soluble and insoluble fibers. as glucose, fructose, mannose, arabinose; di- and trisaccha Soluble fiber are resistant to digestion and absorption in the rides Such as Sucrose, lactose, maltose, trehalose, lactulose; Small intestine and undergo complete or partial fermentation corn and rice syrup Solids; dextrins such a corn, wheat, rice in the large intestine, e.g., beet pulp, guar gum, chicory root, and tapioca dextrins; maltodextrins; starches such as rice, psyllium, pectin, blueberry, cranberry, squash, apples, oats, wheat, corn, potato, tapioca starches, or these starches modi beans, citrus, barley, or peas. Insoluble fiber may be supplied fied by chemical modification; oligosaccharides such as fruc by any of a variety of Sources, including cellulose, whole tooligoscCharides, alginates, chitosans: gums such as carrag wheat products, wheat oat, corn bran, flax seed, grapes, cel een, and gum arabic; polyols such as glycerol, Sorbitol, ery, green beans, cauliflower, potato skins, fruit skins, Veg mannitol. Xylitol, erythritol; esters of polyols such as Sucrose etable skins, peanut hulls, and soy fiber. Crude fiber includes esters, polyglycol esters, glycerol esters, polyglycerol esters, indigestible components contained in cell walls and cell con Sorbitan esters; Sorbitol; molasses; honey; gelatins; peptides; tents of plants such as grains, e.g., hulls of grains such as rice, proteins and modified proteins such as whey liquid, whey corn, and beans. powder, whey concentrate, whey isolate, whey protein iso 0208 Amino acids, including essential amino acids, may late, high lactose whey by-product, such as DAIRYLACR 80 be added to the compositions of the present invention as free from International Ingredient Corporation, meat broth solids amino acids, or Supplied by any number of Sources, e.g., Such as chicken broth, chicken broth solids, soy protein, and crude protein, to the compositions of the present invention. egg white. These aforementioned binder components can be US 2016/0073659 A1 Mar. 17, 2016

used in combination with water, especially when added. The ingredients of the Subject composition are in the outer portion binder material can be dissolved or dispersed in water, form or coating of the composition. ing a liquid mixture or solution, which can then be applied 0218. In some embodiments, a pet food composition can over the surface of the core. The liquid mixture can facilitate comprise an inner layer comprising kibble; an outer layer; both even dispersion of the binder component over the core about 0.05 to 5% of leucine and/or about 0.005 to 1% of one surface and the interaction between the core surface and the or more leucine metabolites by weight of the pet food com protein component being applied to the Surface of the core. In position; and about 0.001 to 0.05% of vitamin B6 by weight one embodiment, the liquid mixture can be an about 20% of the pet food composition. Optionally, the amount of leu liquid mixture of binder component, which can be added to cine, leucine metabolite, and/or Vitamin B6 can be any other the kibble at 5% to 10% by weight of the kibble, which, on a amount described herein. dry matter basis, becomes about 1% to 2% by weight of the 0219. In other embodiments, a pet food or supplement kibble. composition comprises an inner layer comprising kibble; an 0214. In embodiments when a binder component is used, outer layer; and at least about 50 mg of leucine and/or at least keeping the binder component on the Surface of the core can about 5 mg of one or more leucine metabolites by weight of be done, thus preventing, or at least attempting to minimize, the pet food composition; and at least about 1 mg of Vitamin absorption of the binder towards and into the core. In one B6 by weight of the pet food composition. Optionally, the embodiment, additives can be added to increase the Viscosity amount of leucine, leucine metabolite, and/or Vitamin B6 can of the binder solution. Those additives can be corn starch, be any other amount described herein. potato starch, flour, and combinations and mixtures thereof. 0220. The inner portion may be in the form of a paste. By These additives can assist in keeping the binder component paste it is meanta Viscous composition that retains its position on the surface of the kibble to prevent or minimize absorption within the outer portion but is soft and can coat (at least from the surface towards and into the core. In another transiently) the teeth of the animal when consumed. The paste embodiment, varying the temperature of the binder solution may be of a similar consistency to, for example, toothpaste. to thicken the solution can be done. For example, when using The outer portion is in the form of a tube. egg white as a binder component, denaturization of the pro 0221 Layering of a protein component, or any of the other teins of the egg whites can create a gel-like solution. This components as described herein, as a coating on a core, as formation of a gel-like solution can occur around 80°C., so in described herein, can also alter the aroma profile of a coated one embodiment raising the temperature of the binder Solu kibble and result in a coated kibble having different aroma tion to 80° C. can be performed. Additionally, the temperature profiles than typical pet food. Certain embodiments of coated of the core can be increased to also assist in minimizing the kibbles as disclosed herein may contain specific compounds absorption of the binder towards the core. In another embodi and components that can give the pet food desirable aromas. ment, additives and temperature variation as just described These compounds and components can cause changes in the can also be done in combination. aroma profile, or aroma attribute changes, which can result in 0215 Thus, in one embodiment, the binder component improved animal preference, or animal acceptance or prefer can act as a glue, or adhesive material, for the protein com ence, using embodiments of a coated kibble as disclosed ponent to adhere to the core. In one embodiment, the protein herein. Without being bound by theory, it is thought that these component can be a solid ingredient at less than 12% mois aroma attribute changes contribute to the improved prefer ture, or water, content, and the binder component can be a ence of a coated kibble wherein the coating comprises a liquid. In one embodiment, the binder component can be protein component, a non-limiting example Such as chicken applied to or layered onto the core to act as the glue for the by-product meal, layered onto a kibble core. Previous con protein component, which can then be applied to or layered Sumer research has suggested that human-like aromas on pet onto the core with binder component. In another embodi food could be perceived as improvements in products. ment, the protein component as a solids ingredient can be 0222. Thus, one non-limiting example of an embodiment mixed with the binder component, and then the mixture can of the present invention relates to a coated kibble, and a be applied to or layered onto the core. method of delivering a coated kibble, having an aroma pro 0216. In one embodiment, lipids and lipid derivatives can file, an analyte concentration, and an aroma correlation, also be used as binder components. Lipids can be used in wherein the aroma correlation relates the aroma profile com combination with water and/or other binder components. prising an analyte concentration to the increase in animal Lipids can include plant fats such as Soybean oil, corn oil, preference. Additionally, another embodiment relates to a rapeseed oil, olive oil, safflower oil, palm oil, coconut oil, coated kibble having an aroma profile, an analyte concentra palm kernel oil, and partially and fully hydrogenated deriva tion, and thus an aroma correlation. With these embodiments, tives thereof animal fats and partially and fully hydrogenated animal preference (PREF) response data, or animal accep derivatives thereof, and waxes. tance or preference, can be correlated with the aroma profile Coatings and analyte concentration, as disclosed herein. Thus, in one embodiment, aroma analyte profiles and concentrations can 0217. In some embodiments, the subject compositions can correlate to positive, or increased, animal preference response have a modular structure. For example, the Subject composi data. Additionally, in one embodiment, the coated kibble tion can have an inner and an outer portion. The inner portion comprises an animal preference enhancing amount of an ana can be initially formed, and the outer portion can be coated on lyte. The animal preference enhancing amount of the analyte or dusted on to the inner portion. The coating and/or modular can be within the coating, within the core, and combinations structure of the Subject composition can allow for increased and mixtures of these. In another embodiment, a method of variety in food selection while maintaining an efficient and enhancing the animal preference of a pet food comprises cost-effective manufacturing process. The Subject composi delivering an animal preference enhancing amount of an ana tions can be manufactured such that the one or more active lyte in a pet food is disclosed. As used herein, animal prefer US 2016/0073659 A1 Mar. 17, 2016 20 ence enhancing amount means an amount that increases the 0227. Another embodiment of the present invention animal preference response, whether ratio percent converted relates to a method of enhancing the animal preference of a intake or ratio first bite, or both of these. Ratio first bite can be pet food comprising delivering an animal preference enhanc an alternative measurement of the animal preference response ing amount of an analyte in a pet food. The method can to a particular food composition. include providing a pet food, as disclosed herein, wherein the 0223 The aroma profile, including analyte concentration, pet food comprises enriched amount, oran animal preference can be determined in accordance with the method as dis enhancing amount, of the analytes 2-Piperidione, 2.3 pen closed hereinafter, using Solid Phase MicroExtraction Gas tanedione, 2-ethyl-3,5-dimethypyrazine, Furfural, Sulfurol, Chromatography/Mass Spectrometry (SPME-GC-MS) to Indole, and mixtures and combinations of these. The method analyze pet food samples for compounds associated with the can also comprise adding to pet food animal preference aroma. The area under the curve was measured as the SPME enhancing amounts of the analytes 2-Piperidione, 2.3 pen analysis number or count. tanedione, 2-ethyl-3,5-dimethypyrazine, Furfural, Sulfurol, 0224 One embodiment of the present invention relates to Indole, and mixtures and combinations of these. a coated kibble and a method of delivery thereof wherein the coated kibble has a particular aroma profile. A non-limiting Shelf Life example of a coated kibble comprises a core comprising a 0228. In other embodiments, the subject compositions can carbohydrate source, a protein source, a fat source, and other be manufactured with a coating on the Surface of the compo ingredients, all as disclosed herein, and a coating comprising sition that increases the shelf life of the subject composition. a protein component, a binder component, a palatant compo The coating can form a gas (Such as oxygen), water or mois nent, a fat component, and other components. In this embodi ture barrier that allows the subject composition to withstanda ment, an aroma profile of the coated kibble can be generated greater range of environmental conditions, such as wet, and analyzed showing specific analyte concentrations the moist, humid, dry, cold, or hot environments, and oxidation. aroma. Concentrations can be determined for each of the 0229. A pet food composition for increasing the shelf life analytes. The concentration of the analytes can then be cor of a physically discrete dry pet food can comprise a coat related with PREF response data that was gathered for each of covering the physically discrete pet food composition com the embodiments to show anaroma correlation with the PREF prising a polymer film, wherein the film oran agent in the film response data. Thus, in one embodiment, an increase in par protects the composition from oxidation decomposition and/ ticular analytes present in the aroma can drive up, or increase or protects the composition from bacterial growth, wherein the PREF response data, meaning a greater PREF response, the film comprises a starch/synthetic polymer selected from resulting in higher animal preference or acceptance. the group consisting of starch/polyethylene, and starch/low 0225. In one embodiment, the analytes 2-Piperidione, 2.3 density polyethylene, and wherein the thickness of said coat pentanedione, 2-ethyl-3,5-dimethypyrazine, Furfural, Sulfu is 1-2000 microns; about 0.05 to 5 wt % of leucine and/or rol, Indole, and mixtures and combinations of these, can be about 0.005 to 1 wt % of one or more leucine metabolites; and elevated or representative of families with elevated levels about 0.001 to 0.05 wt % of Vitamin B6. Optionally, the when compared to off the shelf pet food. Thus, in one embodi amount of leucine, leucine metabolite, and/or Vitamin B6 can ment, a coated kibble comprising particular concentrations of be any other amount described herein. the analytes 2-Piperidione, 2.3 pentanedione, 2-ethyl-3,5- 0230. A method for increasing the shelflife of a physically dimethypyrazine, Furfural, Sulfurol, Indole, and mixtures discrete dry pet food composition can comprise coating the and combinations of these, increases PREF response. Thus, physically discrete pet food composition with a polymer film, an animal preference enhancing amount of the analytes 2-Pi wherein the film or an agent in the film protects the compo peridione, 2.3 pentanedione, 2-ethyl-3,5-dimethypyrazine, sition from oxidation decomposition and/or protects the com Furfural, Sulfurol, Indole, and mixtures and combinations of position from bacterial growth, wherein the film comprises a these, can be present in one embodiment of the coated kibble. starch/synthetic polymer selected from the group consisting This animal preference enhancing amount of the analytes can of starch/polyethylene, and Starch/low-density polyethylene, increase the PREF response. In one embodiment, the Ratio and wherein the thickness of said coating is 1-2000 microns, Percent Converted Intake (PCI) can increase with an animal wherein the pet food composition comprises about 0.05 to 5 preference enhancing amount of the analytes 2-Piperidione, wt % of leucine and/or about 0.005 to 1 wt % of one or more 2.3 pentanedione, 2-ethyl-3,5-dimethypyrazine. Furfural, leucine metabolites and about 0.001 to 0.05 wt % of Vitamin Sulfurol, Indole, and mixtures and combinations of these. In B6. Optionally, the amount of leucine, leucine metabolite, another embodiment, the ratio first bite can increase with an and/or Vitamin B6 can be any other amount described herein. animal preference enhancing amount of the analytes 2-Pip 0231. The external portion of the discrete pet food com eridione, 2.3 pentanedione, 2-ethyl-3,5-dimethypyrazine, position Such as a kibble, Solid, treat or Supplements or even Furfural, Sulfurol, Indole, and mixtures and combinations of a “chunk” in a canned food “chunk and gravy” diet can be these. used a carrier for the benefit agent. However the benefit agent 0226. Thus, one embodiment of the present invention is not applied directly to the surface of the discrete portion of relates to a coated kibble comprising an enriched amount, or the pet food composition. Rather, the benefit agent is deliv an animal preference enhancing amount, of the analytes 2-Pi ered to the solid surface in the matrix of a film which is peridione, 2.3 pentanedione, 2-ethyl-3,5-dimethypyrazine, physically stable and capable of being expressed on the Sur Furfural, Sulfurol, Indole, and mixtures and combinations of face of the physically discrete portion of the pet food compo these. Another embodiment includes a method of delivering a sition. The benefit agent can increase the shelflife of the food coated kibble comprising an animal preference enhancing product. amount of the analytes 2-Piperidione, 2.3 pentanedione, 0232. The chemical used in coating can be physically 2-ethyl-3,5-dimethypyrazine. Furfural, Sulfurol, Indole, and stable during the process of its application and also stable mixtures and combinations of these. during its lifetime on the pet food composition surface while US 2016/0073659 A1 Mar. 17, 2016 being Subjected to any further processing steps. It can remain processing facility. During shipping and storage, the dry, essentially chemically inert with the surface, itself or its envi stable intermediate pet food composition resists deteriora ronment but can be somewhat reactive as long as its function tion. At the remote processing facility, the flakes are re-pro in the system is not significant jeopardized. Its compatibility cessed to produce a finished pet food composition, and then with the oral cavity and digestive tract of the pet can also be packaged for local distribution. present. Examples of these polymers include Zein, casein, starch(es), cellulose(s), gum(s), gelatin, starch/synthetic Palatability polymer(s), e.g. starch/low density polyethylene, and the like. The polymer can have the attribute of rapid dissociation in the 0238. In some embodiments, the subject compositions can oral cavity, particularly in the presence of saliva. The thick include one or more palatability enhancers to improve the ness of the coating is not as important. It can vary from about taste of the Subject composition as perceived by the Subject, 1 to about 2000 microns, or from about 2 to about 1000 Such as a dog, cat, or any other domestic animal. microns, as long as the function of the film is maintained. 0239 Pet food manufacturers have a long-standing desire 0233. In other embodiments of the invention, pet food and to provide foods which combine high nutritional value, and treat compositions that include leucine, a leucine metabolite, resistance to decomposition and bacterial contamination, and/or Vitamin B6 can be prepared in methods that increase with low production costs. In addition, and with particular the shelf-life of the pet food or treat by manufacturing the pet regard to cat foods, pet food manufacturers desire a high food across multiple locations. degree of palatability which can be attained at low cost. 0234 Petfood compositions are subject to deterioration in 0240 A palatant component can be used in some embodi transit, although deterioration is not usually a problem as long ments. The palatant can comprise chicken flavor. Such as as the finished product is not shipped over long distances. liquid digest derived from chicken livers, which can be However, many manufacturers in the United States recognize approximately 70% water and chicken liver digests. A pala a growing demand for premium and Super-premium pet food tant component as used herein means anything that is added to products in developing international markets. Typically, the animal feed for the primary purpose of improving food within such markets, manufacturers have not installed the full acceptance, or preference, by the animal. A palatant compo capacity (meat slurry) plant systems which are required to nent, which can also be considered a flavor, a flavoring agent, process the pet food compositions. Thus, to meet the demand, ora flavoring component, can include a liver or viscera digest, manufacturers face the choice of exporting finished product which can be combined with an acid. Such as a pyrophos over long distances from existing full capacity plants, or phate. Non-limiting examples of pyrophosphates include, but investing in full capacity plants in the newly opened markets. are not limited to, disodium pyrophosphate, tetrasodium 0235 A method for making kibble at one location and pyrophosphate, trisodium polyphosphates, tripolyphos finishing the pet food at another location can comprise form phates, and Zinc pyrophosphate. The palatant component can ing a dry, stable intermediate of the pet food composition at a contain additional palatant aids, non-limiting examples of first location; finishing the dry, stable intermediate pet food which can include methionine and choline. Other palatant composition to form a finished pet food composition at a aids can include aromatic agents or other entities that drive second location remote from the first location, wherein said interest by the animal in the food and can include cyclohex finished pet food composition contains about 0.05 to 5 wt % anecarboxylic acid, peptides, monoglycerides, short-chain of leucine and/or about 0.005 to 1 wt % of one or more leucine fatty acids, acetic acid, propionic acid, butyric acid, 3-meth metabolites and about 0.001 to 0.05 wt % of Vitamin B6. ylbutyrate, Zeolite, poultry hydrolysate, tarragon essential oil, Optionally, the amount of leucine, leucine metabolite, and/or oregano essential oil, 2-methylfuran, 2-methylpyrrole, 2-me Vitamin B6 can be any other amount described herein. thyl-thiophene, dimethyl disulfide, dimethylsulfide, sulfurol, 0236. In an exemplary embodiment of the invention, a algae meal, catnip, 2-Piperidione, 2.3 pentanedione, 2-ethyl process for making a stable intermediate pet food composi 3,5-dimethypyrazine, Furfural, Sulfurol, and Indole. In addi tion includes the steps of combining a plurality of ingredients tion, various meat based flavorants or aroma agents can be specified by a basal pet food formula to form a basal mixture, used, non-limiting examples include meat, beef, chicken, tur and processing the basal mixture to produce a dry, stable key, fish, cheese, or other animal based flavor agents. intermediate pet food composition containing meat. In one 0241 The pet food can have a concentration of butyric embodiment, the step of processing the basal mixture acid of 5 to 1000 ppm, 6 to 200 ppm, and/or a concentration includes extruding the basal mixture, cutting the extruded of 3-methylbutyric acid of 4 to 500 ppm, or 5 to 200 ppm, basal mixture into flakes, and drying the flakes to a moisture and/or salt thereof. Alternatively, a pet food can be provided content of less than about 10% by weight. The intermediate that contains liver but not rumen and that has a concentration pet food composition, in the form of dried flakes, is then ofbutyric acid of 7 ppm to 10,000 ppm and/or a concentration packaged in storage containers and stored until needed to of 3-methylbutyric acid of 4 ppm to 10,000 ppm, and/or salt produce a finished pet food composition. In one embodiment, thereof. The pet food can have a concentration of butyric acid the process further includes the steps of transporting the pet of 10 to 1,000 ppm, 12 to 500 ppm, and/or a concentration of food composition to a processing facility, and re-processing 3-methylbutyric acid of 4 to 500 ppm, 5 to 200 ppm, and/or the dry flakes to produce the finished product. salt thereof. 0237. In one embodiment, the plant further has packaging 0242 Preferred acids are selected from among acetic acid, capability and the process further includes the steps of pack propionic acid, isobutyric acid, 2-methylbutyric acid, pen aging the dry, stable intermediate pet food composition in tanoic acid, hexanoic acid, 2-methylpentanoic acid, 4-meth containers Suitable for storage, and transporting the pet food ylpentanoic acid, 2-methyl-2-pentanoic acid and mixtures of composition for finishing to a processing facility remote from these acids. These acids can be added in an additional amount the plant. In this embodiment, the dry, stable intermediate pet exceeding the amount that is naturally contained in the pet food composition is packaged and shipped to the remote food. US 2016/0073659 A1 Mar. 17, 2016 22

0243 The palatability enhancer can include tetrasodium 0249 Pet foods are generally manufactured and available pyrophosphate and is formulated as a dry mixture in pow in dry, moist and semi-moist formulations. Wet pet foods may dered, granulated or encapsulated form. Tetrasodium pyro be prepared from proteinaceous materials such as meat, phosphate is available in dry, powdered form from, for including meat by-products or fish. Wet pet foods can further example, Solutia of St. Louis, Mo., and is combined with be formed from a combination of farinaceous materials. Such other dry ingredients including known palatability enhancing as wheat or other grains, or proteinaceous materials. While ingredients and preservatives. The tetrasodium pyrophos flavorings and aroma modifiers are used to improve palatabil phate can be used in about 5% to about 1.0% by weight of the ity, wet pet foods often Suffer from lack of appeal to consum total composition. CS. 0250. The wet pet food product and methods of the present Texture invention can comprise, consist of, or consist essentially of the essential elements and limitations of the invention 0244. In some embodiments of the invention, the pet foods described herein, as well as any additional or optional ingre and treats can have one or more textures, or specifically dients, components, or limitations described herein or other selected textures. For example, a pet food composition com wise useful in wet pet food product intended for animal con prising leucine and/or leucine metabolites and vitamin B6 can Sumption. have a dual texture. Additionally, a wet pet food composition comprising leucine and/or leucine metabolites and vitamin 0251. The pet food product of the present invention can be B6 can be manufactured such that the wet pet food mimics a in the form of a wet pet food product. The wet pet food texture that would be appealing to a pet. The wet pet food products of the present invention can be a semi-moist pet food texture can beachieved by utilizing a structurant and/or bond products (i.e. those having a total moisture content of from ing layers or compositions to each other. 16% to 50%, by weight of the product), and/or a moist pet food products (i.e. those having a total moisture content of 0245. In some embodiments, a pet food composition can greater than 50%, by weight of the product). Unless otherwise comprise an outer layer joined to an inner layer, wherein the described herein, semi-moist pet food product, and moist pet outer layer is harder than the inner layer; about 0.05 to 5 wt % food products are not limited by their composition or method of leucine and/or about 0.005 to 1 wt % of one or more leucine of preparation. metabolites; and about 0.001 to 0.05 wt % of vitamin B6. Optionally, the amount of leucine, leucine metabolite, and/or 0252. The wet pet food product can comprise an edible Vitamin B6 can be any other amount described herein. component that can comprise a textured material that can 0246. In some instances, the pet food product can be a comprise a structurant. The textured material has a Moisture shelf-stable dual texture multicomponent pet or animal food Content in the range of from about 16% to about 92%. The product containing a softer lipid based portion contained textured material can have a Moisture Content of at least within a shell or harder matrix material portion having sig about 20%, at least about 25%, at least about 30%, at least nificantly improved palatability, as compared to mono-tex about 35%, at least about 40%, at least about 50%, still at least tured pet or animal food products. about 60%, at least about 70%. 0247 One aspect of the invention provides a dual texture 0253) In some embodiments, a pet food composition can edible product having a lipid-containing softer portion and a comprise a structurant for providing a textured appearance cereal based harder portion. The softer component can be a and feel; about 0.05 to 5 wt % of leucine and/or about 0.005 mixture of lipids and solids which forms a soft cream textured to 1 wt % of one or more leucine metabolites; and about 0.001 matrix. Since this soft matrix has minimal water content and to 0.05 wt % of vitamin B6. Optionally, the amount of leucine, very low water activity levels, it does not require harsh ster leucine metabolite, and/or Vitamin B6 can be any other ilization techniques for preservation, additional ingredients amount described herein. for moisture control, or antimicrobial/antimycotic agents for 0254. In other embodiments, a pet food composition can stabilization. The product of the present invention can be comprise a textured layer bonded to a base layer, wherein the stable, while still maintaining Superior feeding performance, textured layer comprises textured components bonded to the even after one year. The cereal based component can be base layer; about 0.05 to 5 wt % of leucine and/or about 0.005 harder than the lipid-containing component. According to to 1 wt % of one or more leucine metabolites; and about 0.001 one embodiment, the cereal based component can form a to 0.05 wt % of vitamin B6. Optionally, the amount of leucine, shell that surrounds the soft component which is in the form leucine metabolite, and/or Vitamin B6 can be any other of an inner portion. amount described herein. 0248 One of the processes for forming the two textured 0255. The textured material can have a coating associated pet food product is an injection molding process, in which the with the textured material. Additionally, the textured material two different textures are created by the injection of the two can have a first layer bonded to the textured material. In an components into the same mold. The mold can be in the shape embodiment of the present invention the textured material of a chicken drumstick or any other desired shape. The ingre can have a coating associated with the textured material and a dients for each of the components are fed into different first layer bonded to the textured material. The textured mate extruders where the ingredients are mixed to form moldable rial can be a cube, irregular, elongated, cylindrical, geometric masses. Each component is injected into the mold in which shapes, axially elongated, and combinations thereof. The tex the mixture for the inner component is injected into the center tured material can be processed by a variety of well-known portion of the mold and the outer component Surrounds a means including steam tunnel, extrusion, freeze-texturiza portion of the inner component. The mold can be either heated tion, baking, gelling, retort, microwave heating, and combi and/or cooled to set the texture of product for possible down nations thereof. stream processing, which includes, but is not limited to retort 0256 The wet pet food product can comprise an edible ing, baking or irradiating. component comprising a textured material that may comprise US 2016/0073659 A1 Mar. 17, 2016

a structurant. The textured material can have a first coating crustaceans, fish, and combinations thereof including, for associated with the textured material. The first coating can example, muscle meat, meat by-product, meat meal, or fish comprise a binder. meal. 0257 Nonlimiting examples of binders include egg-based 0264. The plant protein may be derived from any of a materials (including egg whites, dried egg whites), undena variety of plant sources. Nonlimiting examples of plant pro tured proteins, food grade polymeric adhesives, gels, polyols, tein include lupin protein, wheat protein, soy protein, and starches (including modified Starches), gums, and mixtures combinations thereof. A portion, or all of the plant protein thereof. Nonlimiting examples of disaccharides which may when present, can be a texturized protein, for example a be utilized herein include Sucrose, maltose, lactitol, maltitol, textured wheat protein. maltulose, and lactose. 0265. The farinaceous matter is commonly known in the 0258. The wet pet food product comprises a base food. pet food industry. Nonlimiting examples of farinaceous mat The base food can have a coating associated with the base ter include grains such as, rice, corn, milo, Sorghum, barley, food. The base food can comprise a structurant that is selected and wheat, and the like, pasta (for example, ground pasta), from the group consisting of animal protein, plant protein, breading, Soy, and combinations thereof. 0266 Vegetables are commonly known in the pet food farinaceous matter, vegetables, fruit, and combinations industry. Nonlimiting examples of vegetables include peas, thereof. carrots, corn, potatoes, beans, cabbage, tomatoes, celery, 0259. Additionally, the base food can have a first layer broccoli, cauliflower, and leeks. Fruits are commonly known bonded to the base food. In an embodiment of the present in the pet food industry. Nonlimiting examples include toma invention the base food can have a coating associated with the toes, apples, avocado, pears, peaches, cherries, apricots, base food and a first layer bonded to the textured material. The plums, grapes, oranges, grapefruit, lemons, limes, cranber base food can be processed by a variety of well-known means ries, raspberries, blueberries, watermelon, cantaloupe, mush including steam tunnel, extrusion, freeze-texturization, bak mellon, honeydew melon, Strawberries, banana, and combi ing, gelling, retort, microwave heating, and combinations nations thereof. thereof. The structurant can be an extruded protein. The base food can be a cube, irregular, elongated, cylindrical, spheri Low Carbohydrate Formulations cal, geometric shapes, axially elongated, and combinations thereof. 0267 In other embodiments of the invention, pet foods 0260 The wet pet food product can comprise a first layer. and treats of the composition that include leucine, a leucine The first layer can comprise a plurality of particles. The metabolite, and/or vitamin B6 can be formulated to have a plurality of particles can be adhered together to form a first low amount of carbohydrates. These low carbohydrate pet layer. Methods of adhering the plurality of particles include, food and treat compositions can facilitate weight loss in a pet. but are not limited to, compressing molding, shaking, extrud 0268 A pet food composition can comprise less than ing, heating, and combinations thereof. Wherein the particles about 19% on a dry weight basis of carbohydrate; about 0.05 can be physically and/or chemically adhere. The particles can to 5 wt % of leucine and/or about 0.005 to 1 wt % of one or be at least about 5 to about 600 microns in size, as measured more leucine metabolites; and about 0.001 to 0.05 wt % of in at least one axis. vitamin B6. Optionally, the amount of leucine, leucine metabolite, and/or Vitamin B6 can be any other amount 0261 The first layer can be bonded with the base food. For described herein. example in an embodiment having the first layer bonded with 0269. Relatively low carbohydrate, relatively high protein the base food a stable wet food product is formed. The meth and fat content pet food can be successfully extruded into a ods of bonding the first layer with the base food of the present discrete particle, which is dimensionally stable. It has the invention, include, but are not limited to, compressing, mold physical attributes of typical commercial pet foods which ing, shaking, extruding, heating, and combinations thereof. include much higher levels of carbohydrate. The resulting wet pet food product can have varying shapes, 0270. By “dimensionally stable' it is meant that the result sizes and appearance. A coating can be used when a first layer ing extruded product when Sufficiently dried has physical is bonded with a base food. integrity i.e., not readily losing its shape or shedding signifi 0262 The first layer and/or plurality of particles is cant amounts offines, particularly when the food is in discrete selected from the group consisting of animal protein, plant particles such as kibbles, bits and the like in a bag filled with protein, farinaceous matter, vegetables, fruit and combina the materials. Additionally, such a food often does not readily tions thereof. The first layer can be processed by a variety of retain its fat content in a cohesive manner, particularly when well-known means including steam tunnel, extrusion, freeze the fat is deposited on the exterior of the discrete particle. texturization, baking, gelling, retort, and combinations Non-adherence can be visually observed. These problems are thereof. Examples of the first layer include steam tunnel meat, further accentuated by using a high quantity of protein. Pro extruded meat, partially cooked meat, baked meat, gelled tein isolates, which are generally used when there is a high meat, retort processed meat and combinations thereof. The protein content, particularly the vegetable isolates, make it first layer can be shredded from about 2 millimeters to about even more difficult to successfully extrude a dry pet food 30 millimeters in size, as measured in at least one axis, from having discrete particles which are dimensionally stable. about 3 millimeters to about 20 millimeters in size, from 0271 Utilizing a standard single screw extruder with a about 6 millimeters to about 15 millimeters in size, as mea preconditioner, under standard operating conditions dimen Sured in at least one axis. sionally stable discrete particles of the pet food described 0263. The animal protein may be derived from any of a herein were not obtainable. After much work, it was found variety of animal sources including, for example, muscle that increasing the shear in the extruder created an extruded meat or meat by-product. Nonlimiting examples of animal pet food which was processed into discrete particles which protein include beef, pork, poultry, lamb, kangaroo, shellfish, were dimensionally stable even with the relatively low levels US 2016/0073659 A1 Mar. 17, 2016 24 of carbohydrate described herein. The increased shear pro herein, Vitamin B6 as described herein, Protein 26 wt.% to 35 duces a pet food discrete particle, which is generally of a wt.% of crude protein on a dry matter basis or 28 wt.% to 33 higher density than the discrete particle produced under nor wt.%, or 30 wt.% to 31 wt.%; or 26 wt.%, 26.5 wt.%, 27 wt. mal shear processing conditions. Increased shear during the %, 27.5 wt.%, 28 wt.%, 28.5 wt.%, 29 wt.%, 29.5 wt.%, 30 processing can be produced by various means such as for wt.%, 30.5 wt.%, 31 wt.%, 31.5 wt.%, 32 wt.%, 32.5 wt.%, example using cut flight screws, lobe locks, steam locks, and 33 wt.%, 33.5 wt.%, 34 wt.%, 34.5 wt.%, 35 wt.%, Crude straight ribbed liners. Fat 7.5 wt.% to 8.5 wt.% of crude fat on a dry matter basis, 0272. The pet foods included are those useful primarily for or 7.6 wt.%, 7.7 wt.%, 7.8wt.%, 7.9 wt.%, 8.0 wt.%, 8.1 wt. dogs and cats. These foods are high in protein and fat and %, 8.2 wt.%, 8.3 wt.%, 8.4 wt.% Total 20 wt.% to 30 wt.% contain a relatively small amount of carbohydrate as com of total dietary fiber on a dry matter basis Dietary Fiber or 22 pared to protein and fat. The resulting pet foods are dry as wt.% to 28 wt.%, or 24 wt.% to 26%; or 20 wt.%, 20.5 wt. opposed to a wet chunk and/or gravy. The carbohydrate con %, 21 wt.%, 21.5 wt.%, 22 wt.%, 22.5 wt.%, 23 wt.%, 23.5 tent based on nitrogen free extract, “NFE, is a minimum of wt.%, 24 wt.%, 24.5 wt.%, 25 wt.%, 25.5 wt.%, 26 wt.%, Zero, 5 or 7 with a maximum of about 22, 15 or 10 wt %. All 26.5 wt.%, 27 wt.%. 27.5 wt.%, 28 wt.%. 28.5 wt.%, 29 wt. numbers are on a dry matter basis. %, 29.5 wt.% Crude Fiber 10 wt.% to 20 wt.% of crude fiber 0273 Very little, if any, carbohydrate can be initially on a dry matter basis, or 12 wt.% to 18 wt.%, or 14 wt.% to present in the food. The carbohydrate can enter the food as 16%; or 10 wt.%, 10.5 wt.%, 11 wt.%, 11.5 wt.%, 12 wt.%, part of another source such as protein but also can be present 12.5 wt.%, 13 wt.%, 13.5 wt.%, 14 wt.%, 14.5 wt.%, 15 wt. through specifically added carbohydrate sources such as %, 15.5 wt.%, 16 wt.%, 16.5 wt.%, 17 wt.%, 17.5 wt.%, 18 starches and grains. Examples of Such carbohydrate sources wt.%, 18.5 wt.%, 19 wt.%, 19.5 wt.%. include a starch Such as corn starch or wheat starch or mix 0279. Feline Food Compositions: Proportion of the com tures thereof and a grain which can be greater than 50% starch position (% of dry weight of Component composition or parts Such as corn, Sorghum, barley, wheat, rice and the like as well per million) Leucine and/or a leucine metabolite as described as mixtures thereof. A specific carbohydrate source Such as a herein, Vitamin B6 as described herein, Protein 30 wt.% to 37 starch, however, is not necessary. wt.% of crude protein on a dry matter basis or 31 wt.% to 36 0274 The protein can come from any source but because wt.%, or 33% to 35%; or 30 wt.%, 30.5 wt.%, 31 wt.%, 31.5 of the relatively low carbohydrate level, a protein source with wt.%, 32 wt.%, 32.5 wt.%, 33 wt.%, 33.5 wt.%, 34 wt.%, low carbohydrates is particularly preferred. Examples of such 34.5 wt.%, 35 wt.%, 35.5 wt.%, 36 wt.%, 36.5 wt.%, 36 wt. protein sources are animal sources such as pork protein iso % Crude Fat 7.5 wt.% to 9 wt.% of crude fat on a dry matter late and veal protein isolate and the like as well as vegetable basis or 7.6 wt.%, 7.7 wt.%, 7.8 wt.%, 7.9 wt.%, 8.0 wt.%, Sources such as soy protein isolate, corn gluten meal and the 8.1 wt.%, 8.2 wt.%, 8.3 wt.%, 8.4 wt.%, 8.5 wt.%, 8.6 wt. like. %, 8.7 wt.%, 8.8 wt.%, 8.9 wt.%, 9.0 Total 30 wt.% to 35 wt. % of total dietary fiber on a dry matter basis Dietary Fiber or Specified Composition Diet 31 wt.% to 34 wt.%, or 32 wt.% to 33%; or 30 wt.%, 30.5 0275. In other embodiments of the invention, pet foods wt.%, 31 wt.%, 31.5 wt.%, 32 wt.%, 32.5 wt.%, 33 wt.%, and treats of the composition that include leucine, a leucine 33.5 wt.%, 34 wt.%, 34.5 wt.%, 35 wt.% Crude Fiber 20 wt. metabolite, and/or vitamin B6 can be formulated to have % to 25 wt.% of crude fiber on a dry matter basis, or 21 wt.% specified levels of protein, fat, and/or fiber. These formula to 24 wt.%, or 22 wt.% to 23%; or 20 wt.%, 20.5 wt.%, 21 tions with specified levels of components can facilitate wt.%, 21.5 wt.%, 22 wt.%, 22.5 wt.%, 23 wt.%, 23.5 wt.%, weight loss in a pet. 24 wt.%, 24.5 wt.%, 25 wt.%. 0276. In some embodiments, a pet food composition com prises about 0.05 to 5 wt.% of leucine and/or about 0.005 to Controlled Quantity of Food 1 wt % of one or more leucine metabolites on a dry matter 0280. In some embodiments, the pet food compositions basis; about 0.001 to 0.05 wt.% of vitamin B6 on a dry matter that include leucine, a leucine metabolite and/or vitamin B6 basis; about 26 to 35 wt.% of crude protein on a dry matter can be formulated to provide a complete and balanced daily basis; about 7.5 to 8.5 wt.% of crude fat on a dry matter basis: nutritional food source for a pet in a specified number of about 20 to 30 wt.% of total dietary fiber on a dry matter pieces. The specified number of pieces can help a pet owner or basis; and about 10 to 20 wt.% of crude fiber on a dry matter caretaker in quantifying and administering the properamount basis. Optionally, the amount of leucine, leucine metabolite, of food to a pet. and/or Vitamin B6 can be any other amount described herein. 0281. In some embodiments, a pet food composition com 0277. In another embodiment, the invention encompasses prises N pieces wherein N pieces provide the complete and a feline pet food composition comprising: 0.05 to 5 wt.% of balanced daily nutritional requirements of an animal, and N leucine and/or about 0.005 to 1 wt % of one or more leucine equals 1 to less than 15 pieces, wherein each piece has a metabolites on a dry matter basis; about 0.001 to 0.05 wt.% caloric content between 50 to 2500 kcal, and wherein N of vitamin B6 on a dry matter basis; 30 wt.% to 37 wt.% of pieces comprise at least about 100 mg of leucine and/or 10 mg crude protein on a dry matter basis, 7.5 wt.% to 9 wt.% of of one or more leucine metabolites and at least about 1 mg of crude fat on a dry matter basis, 30 wt.% to 35 wt.% of total vitamin B6. Optionally, the amount of leucine, leucine dietary fiber on a dry matter basis, and 20 wt.% to 25 wt.% metabolite, and/or Vitamin B6 can be any other amount of crude fiber on a dry matter basis. Optionally, the amount of described herein. leucine, leucine metabolite, and/or Vitamin B6 can be any 0282. The present invention can be directed to a feeding other amount described herein. system for dogs comprising the steps of providing a pet food 0278 Canine Food Compositions: Proportion of the com product in a plurality of sizes wherein each size of the product position (% of dry weight of Component composition or parts has a different caloric content; feeding a dog N pieces of the per million) Leucine and/or a leucine metabolite as described pet food product selected from the plurality of sizes; wherein US 2016/0073659 A1 Mar. 17, 2016

Nequals 1 to 15 in which N pieces provide the complete and 0288. In some instances, the invention generally relates to balanced daily nutritional requirements of the dog. In the a pet food for use in a comprehensive weight management feeding system, N is dependent upon factors selected from a system for companion animals. More particularly, the weight group consisting of an animals weight, size, breed, life stage, management system can include two stages: a weight loss activity level, body condition, health condition and total daily stage (stage I) and a weight maintenance stage (stage II). energy requirements. Stage I can involve a pet food comprising a high protein, low 0283. The pet food of the present invention can be formu calorie daily diet that includes a functional ingredient, which lated to provide the daily nutritional and caloric requirements further modulates metabolism and builds lean body mass in of an animal. Average required daily caloric intakes for dogs companion animals. Stage II can involve a pet food compris are based on their body weight. Average required daily nutri ing a low calorie daily diet that maintains the leaner weight of ent intakes are generally based on caloric intake. The serving the animal and improves health for the life of the animal. sizes of food generally vary according to a dogs weight or 0289. The process of feeding a companion animal the may be targeted for specific breeds, specific sizes of animals stage I pet food product of the present invention can promote or ages of the animals. comprehensive weight management in the companion ani 0284. Nutritional requirements are met with three basic mal, by promoting weight loss, by increasing the animals products: main meal pet food, Snacks and treats. Main meal lean body mass, by enhancing the satiety and decreasing pet foods are usually sold as complete and balanced foods. Voluntary food intake of the animal, by decreasing blood urea Complete and balanced foods mean that when fed to an ani nitrogen levels in the animal and reducing the risk of ketosis mals caloric requirements for the animals weight, the ani in the animal. The process of feeding the companion animal mal receives all of its required daily nutritional and caloric the stage II pet food product of the present invention can requirements. Snack foods and treats on the other hand, may promote comprehensive weight management in the compan not meet these requirements for a number of reasons, such as ion by maintaining the weight loss, the increase in lean body missing one or more of the required nutrients, not providing mass, the enhanced Satiety, the decreased Voluntary food the correct level of all of these nutrients and/or not providing intake, the decreased blood urea nitrogen levels, the reduced enough calories to meet the animals caloric requirements risk of ketosis and/or the reduced risk of renal damage of the using the recommended serving size. animal. 0285 Each of the pieces can be formulated to have a Vegetarian specific caloric content which 1) will meet the animal's nutri tional requirements within the product’s recommended serv 0290. In some embodiments, the subject pet food, treat, ing size, 2) is designed with a serving size that will provide a and Supplement compositions including leucine, a leucine satisfying and satiating meal for the animal and 3) is designed metabolite, and/or vitamin B6, can be formulated such that with a serving size that the animal can consume in a reason they are vegetarian. able amount of time within a day. 0291 Movement towards more convenient delivery for mats for commercial pet foods has seen a great increase in the Two-Stage Diet popularity of dry, packeted pet foods in the form of cereal based kibbles. Typically these foods can be based on cereals 0286 The invention can also provide for a diet system for Such as rice, maize and wheat and are produced by a variety of a pet that includes a pet food composition that comprises well-known extrusion techniques. leucine, a leucine metabolite, and/or Vitamin B6. 0292 A drawback for such products is that dogs and cats 0287. The diet system for promoting comprehensive typically do not find cereal-based products to be as palatable weight management in companion animals can comprise a as meat-based products. To counter this, a wide range of first stage pet food composition for promoting weight loss technologies has been developed to imbue these cereal-based and a second stage pet food composition for maintaining the products with suitably acceptable meat flavors. weight loss, (a) said first stage pet food composition compris 0293. However, it may not always be appropriate to use ing, on a dry matter basis, about 35 to 70% by weight of a Such meat-based flavorings for packeted pet foods. For protein, about 4 to 10% by weight of a fat, about 2 to 25% by example, where such meat-based material are in short Supply, weight of a fiber, about 10 to 35% by weight of a carbohy or where the marketplace demonstrates a clear demand for drate, about 0.05 to 5% by weight of leucine and/or about genuinely meat-free or vegetarian pet diets. Such demands 0.005 to 1% by weight of one or more leucine metabolites, may stem from perceived health benefits for the animal, or about 0.001 to 0.05% by weight of vitamin B6, and about 0.1 from cultural or religious traditions. Therefore, workers in the to 2% by weight of a functional ingredient, wherein said field have sought to provide such vegetarian diets, which functional ingredient is selected from the group consisting of nevertheless are sufficiently palatable that the animal will L-carnitine and conjugated linoleic acid; and (b) said second readily consume them. stage pet food composition comprising, on a dry matter basis, 0294. In some embodiments, a vegetarian pet food com about 20 to 35% by weight of a protein, about 4 to 10% by position comprises a vegetarian kibble which incorporates a weight of a fat, about 2 to 25% by weight of a fiber, about 25 non-meat based flavor-enhancing additive; about 0.05 to 5 wt to 70% by weight of a carbohydrate, and about 0.1 to 2% by % of leucine and/or about 0.005 to 1 wt % of one or more weight of a functional ingredient, wherein said functional leucine metabolites; and about 0.001 to 0.05 wt % of vitamin ingredient is selected from the group consisting of L-carnitine B6. Optionally, the amount of leucine, leucine metabolite, and conjugated linoleic acid, wherein the protein content of and/or Vitamin B6 can be any other amount described herein. the second stage pet food composition is about 10 to 45% less 0295. In other embodiments, a vegetarian pet food or than the protein content of the first stage pet food composi Supplement composition comprises a vegetarian kibble tion. Optionally, the amount of leucine, leucine metabolite, which incorporates a non-meat based flavor-enhancing addi and/or Vitamin B6 can be any other amount described herein. tive; at least about 50 mg of leucine and/or at least about 5 mg US 2016/0073659 A1 Mar. 17, 2016 26 of one or more leucine metabolites by weight of the pet food more, a hydrolysate comprised by a hypoallergenic pet food composition; and at least about 1 mg of vitamin B6 by weight described in various configurations herein can be a hydroly of the pet food composition. Optionally, the amount of leu sate prepared by a method comprising freezing the hydroly cine, leucine metabolite, and/or Vitamin B6 can be any other sate, vacuum drying the hydrolysate, spray drying the amount described herein. hydrolysate, drum drying the hydrolysate or freeze drying the 0296. The disclosure of the invention provides for a pal hydrolysate. In some configurations, the hydrolysate can be atable, nutritionally complete vegetarian food for pet mam prepared by a method which comprises freezing the hydroly mals, including a nutritionally complete, preferably low Sate. moisture, vegetarian kibble which incorporates a non-meat based flavor-enhancing additive. The additive includes a syn Customized Diets ergistic amount of hydrolyzed vegetable protein and Xylose. The combination of these two ingredients provides an espe 0302) In some embodiments, the subject pet food, treat, cially flavorsome character to the pet food. Typically, the and Supplement compositions can be tailored to a subject pet mass ratio of hydrolyzed vegetable protein to Xylose, at which by a pet owner or caretaker. The pet caretaker can specify this synergistic effect is observed, is between 15:1 and 40: 1 characteristics of the pet, Such as weight, height, age, and on a dry mass basis. The hydrolyzed vegetable protein is breed which are then used to create a customized diet, includ available from commercial suppliers. It is typically available ing a pet food, treat, or Supplement, that incorporates leucine, as a liquid dispersion, having a solids content of about 15%. a leucine metabolite, and/or vitamin B6. Alternatively, it is available as a powder with an approximate 0303. In some embodiments, the subject pet food, treat, moisture content of 10%. It will be apparent to those skilled in and Supplement compositions can be tailored to a subject pet the art that if the powdered version is used, commensurate based on the pets indication of its preferences. The pet can adjustments will need to be made to the level of moisture in choose among an array of choices that allow a pet owner to the formulation of e.g. the spray to provide the preferred interpret the pets preferences, which can then in turn be used range of hydrolyzed vegetable protein solids in the additive. to create a customized diet, including a pet food, treat, or Supplement, that incorporates leucine, a leucine metabolite, Hypoallergenic and/or vitamin B6. 0297. In some embodiments, the subject pet food, treat, 0304 One aspect of the present invention provides a and Supplement compositions including leucine, a leucine method for determining the preferred macronutrient content metabolite, and/or vitamin B6, can be formulated Such that of a diet for an individual animal, the method comprising: they are hypoallergenic. providing to said animal food compositions which provide an 0298 Food allergies, or food hypersensitivities, com enriched source offat, protein and/or carbohydrate. Such that monly afflict household pets such as dogs and cats. These said animal can select and consume preferred quantities of allergies can cause the pet to exhibit symptoms Such as exces said food compositions in order to achieve an preferred con sive itching and scratching, diarrhea or other symptoms Sumption offat, protein and carbohydrate; allowing said ani which are aggravating both to owner and pet. A housebroken mal to consume preferred quantities of fat, protein and car dog with diarrhea who is indoors has a major problem. If the bohydrate from said compositions; and determining, from the owner is around, the dog pesters the owner to get outside. If consumed amount offat, protein and carbohydrate from said the owner is not around the owner may later think the dog is compositions, the preferred macronutrient content of a diet exhibiting undesirable behavior and needs to be punished. for said individual animal. Diagnosis is a particular problem for veterinarians, because 0305. In some embodiments, a method for feeding a pet diagnosis of food hypersensitivity is often difficult and con can comprise providing, over an extended and preselected Sumes an inordinate amount of Veterinarians time. period of time, different food compositions to said animal in 0299 Because of the exquisite sensitivity of the immune which each composition provides an enriched source of fat, system to allergens, a pet can be exposed to as few protein protein or carbohydrate. Such that said animal can select and Sources as possible to avoid the risk of inadvertently exposing consume different and preferred quantities of each said food the pet to adventitious allergens. compositions in order to achieve an preferred consumption of 0300. A hypoallergenic pet food composition can com fat, protein and carbohydrate for said animal; wherein at least prise proteinaceous component that has been hydrolyzed one of said food compositions comprises about 0.05 to 5 wt % whereby said component is rendered hypoallergenic to a pet, of leucine and/or about 0.005 to 1 wt % of one or more leucine wherein said proteinaceous component is made up of metabolites; and about 0.001 to 0.05 wt % of vitamin B6; polypeptides and free amino acids having an average molecu allowing said animal to consume the different and preferred lar weight of less than about 300, 500, 1000, 1500, 2000, quantities of fat, protein and carbohydrate from each of said 2500, 3000, 3500, 4000, 4500, 5000, 5500 Daltons; about compositions over the extended preselected period of time; 0.05 to 5 wt % of leucine and/or about 0.005 to 1 wt % of one and determining, from the consumed amount of fat, protein or more leucine metabolites; and about 0.001 to 0.05 wt % of and carbohydrate from each of said compositions, a custom Vitamin B6. Optionally, the amount of leucine, leucine ized dietary regime that provides the preferred macronutrient metabolite, and/or Vitamin B6 can be any other amount content of a diet for said individual animal. Optionally, the described herein. amount of leucine, leucine metabolite, and/or Vitamin B6 can 0301 Thus, a hypoallergenic pet food can comprise a be any other amount described herein. composition comprising a hydrolysate in an acceptable, 0306 In order for the animal to select the preferred macro semi-solid formulation. In some configurations, a hydroly nutrient content from unlimited amounts of said composi sate comprised by a hypoallergenic pet food described herein tions, the fat, protein and carbohydrate must be provided in a can be a frozen hydrolysate, a freshly prepared hydrolysate or format or formats such that the animal can select preferred a hydrolysate that is stored refrigerated before use. Further quantities thereof. Accordingly, the sources offat, protein and US 2016/0073659 A1 Mar. 17, 2016 27 carbohydrate can be provided in two or more different com pieces and one or more functional ingredients is based on the positions, each composition having differing levels of at least individual pets attributes and physical conditions to provide protein and fat. the customized dry pet food product, and wherein the coating 0307 The method can comprise a learning phase. During and/or the kibble pieces comprise leucine and/or a leucine Such a learning phase, the animal can be provided with a metabolite and vitamin B6. single diet composition at any one feeding experience. 0312 One or more steps of methods described herein may Accordingly, the animal has no other choice at that feeding be implemented inhardware. Alternatively, one or more steps experience. Each diet composition comprises a foodstuff may be implemented in Software stored in, for example, one which is enriched in respect of one macronutrient. The length or more memories or other computer readable medium and of the learning phase depends on a number of factors, includ implemented on one or more processors. AS is known, the ing how many feeding experiences the animal has during a processors may be associated with one or more controllers, day/week etc and how much length of time is desired or calculation units, and/or other units of a computer system, or available for the animal to learn. implanted in firmware as desired. If implemented in software, 0308. A helpful tool may be a table or chart which indi the routines may be stored in any computer readable memory cates a preferred diet or foodstuff depending on the quantities such as in RAM, ROM, flash memory, a magnetic disk, a laser of each of the compositions consumed by the animal. Alter disk, or other storage medium, as is also known. Likewise, natively, the quantities of each composition consumed may this Software may be delivered to a computing device via any relate to a figure or number which can be used to obtain an known delivery method including, for example, over a com preferred diet by use, for example, of a vending machine munication channel Such as a telephone line, the internet, a system. Such a system can dispense an preferred diet either as wireless connection, etc., or via a transportable medium, Such a single dietary foodstuff, or as two or more components as a computer readable disk, flash drive, etc. The various steps which are to be available to the animal at the same time. may be implemented as various blocks, operations, tools, 0309. In some embodiments, one or more steps for pro modules and techniques which, in turn, may be implemented viding a food composition for a pet can include selecting or in hardware, firmware, Software, or any combination of hard customizing the pet food based on the pet's characteristics or ware, firmware, and/or software. When implemented inhard preferences. The invention provides for a method of produc ware, some or all of the blocks, operations, techniques, etc. ing a customized dry pet food product formulated from a dry may be implemented in, for example, a custom integrated pet food kibble recipe and selected functional ingredients, the circuit (IC), an application specific integrated circuit (ASIC), formulation being selected on the basis of an individual pets a field programmable logic array (FPGA), a programmable attributes and physical conditions, the method comprising: logic array (PLA), etc. A computer system may be involved in providing a plurality of different formulations of pre-made one or more of sample collection, sample processing, geno dry kibble pieces; selecting a predetermined volume of dry typing, data analysis, calculation of weighted risks, calcula kibble pieces from the plurality of different formulations of tion of aggregated risk score, comparison of aggregated risk pre-made dry kibble pieces; providing a plurality of func score to a threshold score, determination of a Subjects abso tional ingredients; coating the Volume of dry kibble pieces lute or increased risk, generating a report, and reporting with one or more of the plurality of functional ingredients: results to a receiver. and packaging and labeling the predetermined Volume of 0313 A client-server, as shown in FIG.4, relational archi coated dry kibble pieces; wherein the selection of the prede tecture can be used in embodiments of the invention. A client termined volume of dry kibble pieces and the one or more server architecture is a network architecture in which each functional ingredients is based on the individual pets computer or process on the network is either a client or a attributes and physical conditions to provide the customized server. Server computers are typically powerful computers dry pet food product, and wherein the coating and/or the dedicated to managing disk drives (file servers), printers kibble pieces comprise leucine and/or a leucine metabolite (print servers), or network traffic (network servers). Client and vitamin B6. computers include PCs (personal computers) or workstations 0310. In some embodiments, one or more steps for pro on which users run applications, as well as example output viding a food composition for a pet can include selecting or devices as disclosed herein. Client computers rely on server customizing the pet food based on the pet's characteristics or computers for resources, such as files, devices, and even preferences using the aid of a computer system. processing power. In some embodiments of the invention, the 0311. The invention provides for a computer-readable server computer handles all of the database functionality. The medium comprising code that, upon execution by one or more client computer can have software that handles all the front processors, implements a method of producing a customized end data management and can also receive data input from dry pet food composition formulated from a dry pet food USCS. kibble recipe and selected functional ingredients, the formu 0314. As shown in FIG. 4, a user/client device, such as a lation being selected on the basis of an individual pets computer system, can be connected to an analysis system by attributes and physical conditions, the method comprising: a. a network connection. The computer system may be under receiving information on the individual pets attributes and stood as a logical apparatus that can read instructions from physical conditions; selecting a predetermined Volume of dry media and/or a network port, which can optionally be con kibble pieces from a plurality different formulations of pre nected to server having fixed media. The system can include made dry kibble pieces; selecting one or more functional a CPU, disk drives, optional input devices such as keyboard ingredients from a plurality functional ingredients; coating and/or mouse, and optional monitor. Data communication the predetermined volume of dry kibble pieces with the one or can be achieved through the indicated communication more functional ingredients; and packaging and labeling the medium to a server at a local or a remote location. The predetermined volume of coated dry kibble pieces; wherein communication medium can include any means of transmit the selection of the predetermined volume of dry kibble ting and/or receiving data. For example, the communication US 2016/0073659 A1 Mar. 17, 2016 28 medium can be a network connection, a wireless connection, wireless telephone, a mobile phone, a PDA, a flash memory or an internet connection. Such a connection can provide for drive, a light Source, a sound generator, a fax machine, a communication over the World WideWeb. In some embodi computer, a computer monitor, a printer, an iPod, and a ments, a physical report is generated and delivered to a webpage. The user station may be in communication with a receiver. printer or a display monitor to output the information pro 0315. In some embodiments there is provided a computer cessed by the server. readable medium encoded with computer executable soft 0319. It is envisioned that data relating to the present dis ware that includes instructions for a computer to execute closure can be transmitted over a network or connections for functions associated with the identified one or more alleles reception and/or review by a receiver. The receiver can be but and/or genotypes. Such computer system may include any is not limited to an individual; the subject to whom the report combination of Such codes or computer executable software, pertains; a health care provider, manager, other healthcare depending upon the types of evaluations desired to be com professional, or other caretaker, a genetic counselor, a person pleted. The system can have code for that, upon execution by or entity that performed and/or ordered the genotyping analy one or more processors, implements a method of producing a sis; or a local or remote system for storing Such reports (e.g. customized pet food, such as a dry pet food, composition servers or other systems of a "cloud computing architec formulated from a pet recipe, such as a dry pet food kibble ture). recipe, and selected functional ingredients, the formulation being selected on the basis of an individual pets attributes Sterilization and physical conditions, the method comprising receiving 0320 Additional embodiments of the present invention information on the individual pets attributes and physical include a method of making a pet food, Supplement, or treat conditions; selecting a predetermined Volume of food, Such as including at least one heat treating step for microbe deactiva dry kibble pieces, from a plurality different formulations of tion (kill), Such as salmonella, and compositions and kits that pre-made food, Such as dry kibble pieces; selecting one or include pet foods, treats, or Supplements that are substantially more functional ingredients from a plurality functional ingre or essentially free of microbes. The pet food can be in any dients; coating the predetermined Volume of food, such as dry form of the embodiments described herein. In one embodi kibble pieces, with the one or more functional ingredients: ment, a non-limiting example of which is a coated kibble that and packaging and labeling the predetermined Volume of comprises a core and a coating as hereinabove described, two coated food, such as dry kibble pieces. The food can be heat treating deactivation steps can be performed. The core packaged by a manufacturer or by a retailer of pet foods. The can be formed through extruding, as described hereinabove. packaging can be fully automated. Such that human interven After extruding into a core, the core can be heat treated in a tion is not required by the manufacturer to package the food, manner to Sufficiently deactivate any salmonella present in or is minimized. the core. Subsequently, prior to, or contemporaneously, the 0316 The selection of the predetermined volume of food, coating can be formed and heat treated in a similar manner as Such as dry kibble pieces, and one or more functional ingre that of the core to deactivate any salmonella present. The dients is based on the individual pets attributes and physical coated kibble can then be formed, as described hereinabove, conditions to provide the customized pet food product, which by coating the core with the coating. may be dry. Additionally or alternatively, the customized pet 0321 Salmonella deactivation generally requires the food can be based on the pets preferences, as indicated by the application of heat while the microbes are in a moist environ pet’s choice of food when presented with an array of options, ment. Once completely dry, salmonella can become dormant as described herein. Also, the coating and/or the kibble pieces and resist efforts using dry heat to deactivate them. In a moist comprise leucine and/or a leucine metabolite and vitamin B6. environment, salmonella are more readily deactivated. For 0317. The system can also have code for generating a example, the application of heat at 80° C. for greater than report. The report can include one or more recommendations about two minutes can effectively deactivate salmonella for a customized pet diet that is based on the characteristics or when in a moist environment. Application of temperatures preferences of the pet. higher than 80° C. in moist environments results in corre 0318. After performing a calculation, a processor can pro spondingly shorter times needed to deactivate the salmonella. vide the output, such as from a calculation, back to, for 0322 Superheated steam has been used effectively in example, the input device or storage unit, to another storage many industries to deactivate salmonella. Superheated Steam unit of the same or different computer system, or to an output is defined as Steam at a temperature greater than the boiling device. Output from the processor can be displayed by data point of water for the existing pressure. Most industrial use of display. A data display can be a display screen (for example, Superheated Steam utilizes pure or Substantially pure steam. a monitor or a screen on a digital device), a print-out, a data The non-steam component is usually air. signal (for example, a packet), an alarm (for example, a flash 0323. In one embodiment the salmonella deactivation step ing light or a sound), a graphical user interface (for example, may be performed in a vibrating conveyor, Such as a spiral a webpage), or a combination of any of the above. In an elevator, as disclosed herein. In one embodiment, Steam can embodiment, an output is transmitted over a network (for be injected into the vibrating conveyor for microbe control. example, a wireless network) to an output device. The output Steam can be injected into the coils of the vibrating conveyor device can be used by a user to receive the output from the at any point, and eventhrough multiple points. Such injection data-processing computer system. After an output has been can be through ports as disclosed herein. received by a user, the user can determine a course of action, 0324. In one embodiment, steam can be injected into the or can carry out a course of action, such as a medical treatment pipe on one side of a coil of the conveyor and can be extracted when the user is medical personnel. In some embodiments, an from the pipe at the other side of the coil by an exhaust output device is the same device as the input device. Example manifold attached to the coil. In one embodiment, the chan output devices include, but are not limited to, a telephone, a nel, such as a pipe, can be heated to greater than about 100° US 2016/0073659 A1 Mar. 17, 2016 29

C., or greater than about 110°C., or greater than about 125°C. composition may be a pet food product as described herein to prevent condensation of steam inside the pipe. In one which is sold as a pet food, in particular a pet food for a embodiment, the channel can be heated in sections. In another domestic dog or a domestic cat. It may be convenient to embodiment, the pipe can be heated entirely. In other embodi provide the compositions in a dry format, such as dried ready ments, jackets of Steam or water can be used for heating, to-eat cereal products (often referred to as kibbles). electrical tape can be used for heating, and current can be run through the pipe itself for heating. Multi-Formulation Daily Diet 0325 In an embodiment wherein steam is injected, once 0331. In other embodiments, the subject pet food, treat, inside the pipe, the steam contacts and treats all of the fluid and Supplement compositions that include leucine, a leucine ized kibbles such that they are substantially free of microbes, metabolite, and/or vitamin B6 can be utilized in diet systems Such as Salmonella. that include the feeding of a variety of formulations each day. 0332. In some embodiments, a diet for companion animals Compartmentalized Packaging can comprise a first stage pet food composition and a second 0326 In some embodiments of the invention, the pet stage pet food composition for maintaining the weight loss, foods, treats, or Supplements can be packaged such that two wherein each of said first stage pet food composition and said different formulations are compartmentalized within the second stage pet food composition comprise, on a dry matter package. The compartmentalization of the two different for basis, about 0.05 to 5 wt % of leucine and/or about 0.005 to 1 mulations can allow for a pet owner to provide an array of wt % of one or more leucine metabolites, and about 0.001 to choices for the pet. The two different formulations can differ 0.05 wt % of vitamin B6, and wherein said second stage pet in one or more components, such as fat, protein, or carbohy food comprises at least about 5% higher fat content compared drate. to said first stage pet food. Optionally, the amount of leucine, 0327. A multi-component pet food composition can com leucine metabolite, and/or Vitamin B6 can be any other prise two or more compartmentalized food compositions, amount described herein. wherein the at least two compartmentalized compositions 0333. In accordance with typical feeding patterns for com differ in their content in at least two offat, protein or carbo panion animals, food products can be provided as meals in the hydrate, and further wherein one of the two or more compart morning and in the afternoon or evening. Additional food mentalized compositions comprises about 0.05 to 5 wt % of products may be provided in between, Such as mid-morning, leucine and/or about 0.005 to 1 wt % of one or more leucine during the middle part of the day, mid-afternoon, or in the metabolites, and about 0.001 to 0.05 wt % of vitamin B6. evening. Companion animals can have preferences for Optionally, the amount of leucine, leucine metabolite, and/or macronutrient content for Such particular events. In addition, Vitamin B6 can be any other amount described herein. caregiver/owners of companion animals are able to easily 0328. The present invention provides a canine or feline identify suitable food products by their labeling for adminis multi-component foodstuff comprising two or more compart tration for a particular event. mentalized food compositions of which at least two of the 0334. The companion animals of the present inventionare, compositions differ in their content of at least two selected in particular, the domestic cat (Felis domesticus) or the from the group consisting of fat, protein and carbohydrate. domestic dog (Canis domesticus). Other companion animals 0329. By the term compartmentalized it is meant that the include fish, birds and horses. two or more food compositions are not mixed. They may be 0335 The dietary regime of the present invention can provided on or in different containers, such as a bowl, plate, comprise one pet food product for feeding as the morning packaging. The containers may or may not be sealed. The meal and one pet food product for feeding as the afternoon/ multi-component meal comprising the two or more food evening meal. Additional Snacks for in between meals or compositions may be provided in unlimited quantities to the additions to the main meal (e.g. kibbles) may be included. feline animal. 0336. The invention includes any dietary regime or 0330. The compositions encompass any product that a pet sequence of products fed at prescribedtimes or in a prescribed consumes in its diet. Thus, the compositions may include the order that either accommodate a physiological need or standard food products as well as pet food Snacks (for modify a physiological response and/or are designed for example Snack bars, cereal bars, Snacks, treats, biscuits and administration for a particular event and may include: A Sweet products). The composition may be a cooked product. breakfast food for administration as the first food of the day, It may incorporate meat or animal-derived material (such as containing an energy content and a macronutrient profile beef, chicken, turkey, lamb, fish, blood plasma, marrowbone, appropriate to the level of expected activity in the day, a etc or one or more thereof). Alternatively the composition dinner or supper food for administration as the last food of the may be meat-free (preferably including a meat Substitute Such day, with an energy content and macronutrient profile appro as Soya, maize gluten or a Soya product) in order to provide priate to a inactive or sleeping animal, a fiber-controlled diet protein. The composition may contain additional protein for avoiding toileting during the night, and food for particular Sources such as Soya protein concentrate, milk, protein, glu seasons, for example designed in relation to the nutritional ten, etc. The composition may also contain starch, such as one needs of the skin and coat. or more grains (e.g. wheat, corn, rice, oats, barley, etc) or may 0337. One macronutrient preference which has been be starch-free. The composition may incorporate or be a shown by companion animals is for an increase in the total fat gelatinized starch matrix. The composition may incorporate content of the afternoon/evening meal compared to the morn one or more types of fiber Such as Sugar beet pulp, chicory ing meal. Accordingly, the dietary regime of the invention can pulp, chicory, coconut endosperm fiber, wheat fiberetc. Dairy include one of the pet food products having a higher content products, such as those incorporating a cream or a cheese offat than one other pet food product in a daily regime. The sauce, may be suitable. The composition can also be newly product with the higher fat content can be fed to the compan designed products currently not available. The most suitable ion animal as the afternoon/evening meal. US 2016/0073659 A1 Mar. 17, 2016 30

0338 A feature of the present invention results from a despite an increase in appetite. Some untreated diabetes demonstrated increase in relative intake for the higher fat patients also complain of fatigue, nausea, and Vomiting. Pets product in the afternoon/evening meal compared with prod with diabetes are prone to developing infections of the blad ucts with a lower fat content. The higher fat content can be in der, skin, and vaginal areas. Fluctuations in blood glucose replacement of protein or in replacement of carbohydrate. levels can lead to blurred vision. Extremely elevated glucose 0339. The food of the dietary regime of the present inven levels can lead to lethargy and coma (diabetic coma). Diabe tion can be such that the fat content of the afternoon/evening tes can occur in many animals and breeds, especially dogs and food can be higher than the fat content of the morning food by Cats. at least 5% of the total calorie content of the food. Further 0344. In inflammatory diseases, such as rheumatoid preferences are that the calories contributed by the fat content arthritis, pathologic inflammatory processes can lead to mor of the food for the morning can be between 20% and 70% of bidity and mortality. The cytokine tumor necrosis factor the total calorie content of the food and the fat content of the alpha (TNF-alpha) plays a central role in the inflammatory food for the afternoon/evening can contribute between 25% response and has been targeted as a point of intervention in and 75% of the total calorie content of the food. The food fed inflammatory disease. TNF-alpha is a polypeptide hormone in the afternoon/evening can be higher in fat content than the released by activated macrophages and other cells. At low morning food by at least 5% of the total calorific value of the concentrations, TNF-alpha participates in the protective product, by 10%, or by 15%. inflammatory response by activating leukocytes and promot 0340. The pet food products as part of the dietary regime ing their migration to extravascular sites of inflammation according to the present invention encompass any product (Moser et al., J. Clin Invest, 83:444-55, 1989). At higher that a pet consumes in its diet. Thus, the invention covers the concentrations, TNF-alpha can act as a potent pyrogen and standard food products as well as pet food Snacks (for induce the production of other pro-inflammatory cytokines example Snack bars, cereal bars, Snacks, biscuits and Sweet (Haworth et al., EurJImmunol, 21:2575-79, 1991; Brennan products). The food product may be a cooked product. It may et al., Lancet, 2:244-7, 1989). TNF-alpha also stimulates the incorporate meat or animal-derived material (such as beef, synthesis of acute-phase proteins. In rheumatoid arthritis, a chicken, turkey, lamb, fish, blood plasma, marrowbone, etc or chronic and progressive inflammatory disease affecting about one or more thereof). The product alternative may be meat 1% of the adult U.S. population, TNF-alpha mediates the free (preferably including a meat Substitute such as Soya, cytokine cascade that leads to joint damage and destruction maize gluten or a Soya product) in order to provide a protein (Arend et al., Arthritis Rheum, 38:151-60, 1995). Source. The product may contain additional protein sources (0345 Interleukin-6 (IL-6) is another pro-inflammatory Such as Soya protein concentrate, milk, protein, gluten, etc. cytokine that exhibits pleiotropy and redundancy of action. The product may also contain a starch Source such as one or IL-6 participates in the immune response, inflammation and more grains (e.g. wheat, corn, rice, oats, barley, etc) or may be hematopoiesis. It is a potent inducer of the hepatic acute starch-free. The product may incorporate or be a gelatinized phase response and is a powerful stimulator of the hypotha starch matrix. The product may incorporate one or more types lamic-pituitary-adrenal axis that is under negative control by of fiber Such as Sugar beet pulp, chicory pulp, chicory, coco glucocorticoids. IL-6 promotes the Secretion of growth hor nut endosperm fiber, wheat fiber etc. The content of the prod mone but inhibits release of thyroid stimulating hormone. uct/ingredients contributes towards the macronutrient profile Elevated levels of IL-6 are seen in several inflammatory dis of the food. Thus, food products which according to the eases, and inhibition of the IL-6 cytokine subfamily has been present invention provide a higher fat content will be Suggested as a strategy to improve therapy for rheumatoid designed accordingly. Dairy products, such as those incorpo arthritis (Carroll et al., Inflamm Res, 47: 1-7, 1998). In addi rating a cream or a cheese sauce, may be suitable. The present tion, IL-6 has been implicated in the progression of athero invention is particularly relevant for a pet food product as Sclerosis and the pathogenesis of coronary heart disease described herein which is sold as a pet food, in particular a pet (Yudkinet al., Atherosclerosis, 148:209-14, 1999). food for a dog or a cat. 0346. The cytokine IL-1 beta is another protein involved in the inflammatory response. It stimulates thymocyte prolifera Diabetes tion, fibroblast growth factor activity, and the release of pros 0341 Diabetes mellitus is a disease characterized by taglandin from Synovial cells. hyperglycemia; altered metabolism of lipids, carbohydrates 0347 Irisin is a protein believed to replicate the weight and proteins; an increased risk of complications from vascu loss effects of exercise. Irisin may be beneficial in decreasing lar disease; inflammation; and insulin sensitivity. Diabetes is and/or preventing the incidence of diabetes in pets. an increasing pet health problem, as it is associated with both 0348 Metformin is a compound derived from biguanides increasing age and obesity. that primarily acts by reducing hepatic gluconeogenesis, but 0342. There are two major types of diabetes mellitus: 1) also reduces glucose absorption at the gastro-intestinal tract Type I, also known as insulindependent diabetes (IDDM) and level and increases sensitivity to insulin by increasing the 2) Type II, also, known as insulin independent or non-insulin peripheral utilisation of glucose. This may be due to the fact dependent diabetes (NIDDM). Both types of diabetes melli that metformin improves the binding of insulin to its cellular tus are due to insufficient amounts of circulating insulin and a receptor, which is explained by the increased activity that it decrease in the response of peripheral tissue to insulin. induces in the tyrosine kinase postreceptor and the conse 0343. The early symptoms of untreated diabetes mellitus quent increase in the number and activity of GLUT4 carriers. are related to elevated blood Sugar levels, and loss of glucose Metformin is not metabolised; it is directly excreted in the in the urine. High amounts of glucose in the urine can cause urine. Its half-life is 6.2 hours. increased urine output and lead to dehydration. Dehydration 0349. A subject composition, which may be a pet food, causes increased thirst and water consumption. The inability treat, Snack, Supplement, or drink, can comprise a metformin to utilize glucose energy eventually leads to weight loss content of at least about 0.025 g/kg, 0.05 g/kg, 0.075 g/kg, 0.1 US 2016/0073659 A1 Mar. 17, 2016

g/kg, 0.15 g/kg, 0.25 g/kg, 0.5 g/kg, 0.75 g/kg, 1 g/kg, 1.5 Methods of Use g/kg, 2 g/kg, 2.5 g/kg, 3 g/kg of the diet comprising the 0355 The invention provides for methods of regulating Subject composition. In some instances the composition com energy metabolism in a pet by administering one or more prises a metformin content of about 1.5 g/kg of the diet Subject compositions. These compositions include the com comprising the Subject composition. In some instances the bination compositions described herein, such as combination composition comprises a metformin content of about 0.75/kg compositions comprising leucine, a leucine metabolite, and/ of the diet comprising the Subject composition. In some or vitamin B6. The combination compositions can be formu instances the composition comprises a metformin content of lated as a pet food, pet treat, pet Supplement or a pet drink. about 0.25 g/kg of the diet comprising the Subject composi 0356. The methods compositions can be comprise admin tion. istering to a pet an effective amount of (a) leucine and/or one 0350 A subject composition, which may be a pet food, or more metabolites thereof, and (b) Vitamin B6, wherein the treat, Snack, Supplement, or drink, can comprise a metformin combination when administered to a subject in need thereof content of at least about 12.5, 25, 50, 75, 100, 125, 150, 175, enhances energy metabolism, including cellular metabolism, 200, 225, 250 mg of the diet comprising the subject compo and mitochondrial biogenesis. The composition, when sition. In some instances the composition comprises a met administered to a Subject in need thereof, can enhance energy formin content of about 125 mg of the diet comprising the metabolism, including cellular metabolism and mitochon Subject composition. drial biogenesis, as measured by a decrease in weight gain of a Subject, a decrease in adipose Volume of a Subject, an 0351. The invention provides for a method of increasing increase in fat oxidation of a Subject, an increase in insulin irisin production, comprising administering to the Subject any sensitivity of a Subject, a decrease in oxidative stress markers of the compositions described herein, wherein irisin produc of a Subject, and/or a decrease in inflammatory markers of a tion in the Subject increases over a time period. In some Subject. In some embodiments, the composition is Substan embodiments, the increase in irisin production (or in an indi tially free of free or individual non-branched chain amino cator providing evidence thereof) is an increase of about, or acids or non-leucine amino acids. more than about 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 0357 The enhanced energy metabolism can be quantified 80%, 90%, 100%, 125%, 150%, 175%, 200%, or more. In by an increase in weight loss of a subject by at least 5, 10, 30, Some embodiments, the increase in irisin production (or in an or 40%, a decrease in weight of about 1, 2, or 3 kg, a decrease indicator providing evidence thereof) is an increase of about, in body condition score of at least about 1, 2 or 3, an increase or more than about 1-fold, 3-fold, 5-fold, 6-fold, 8-fold, in fat loss of a subject by at least about 1, 5, 10, 20,30, or 50%, 10-fold, 15-fold, 20-fold, 50-fold, or more. In some embodi or an increase in insulin sensitivity by at least about 1, 5, 10. ments, the increase in irisin production is evidenced by an or 15% when the composition is administered to the subject. increase in FNDC5 expression (e.g. as measured from mRNA The enhanced energy metabolism can be measured relative to and/or protein level). the dosing of the subject with a placebo, or relative to the 0352. The invention provides for a method of treating Subject prior to administration of the Subject composition. diabetes, comprising administering to the Subject any of the 0358. The compositions can be administered to a subject compositions described herein over a time period, wherein orally or by any other methods. Methods of oral administra the insulin sensitivity in the subject is increased over the time tion include administering the composition as a liquid, a period. Insulin sensitivity can be increased by about or greater solid, or a semi-solid that can be taken in the form of a dietary than about 1, 2, 3, 5, 10, 20, 50, 100, or 200%. In some Supplement or a food stuff. embodiments, a branched chain amino acid (or a metabolite 0359 The compositions can be administered periodically. thereof) and/or a sirtuin pathway activator are administered in For example, the compositions can be administered one, two, an amount that reduces the therapeutically effective dose of three, four times a day, or even more frequent. The Subject can metformin for a Subject. In some embodiments, the therapeu be administered or fed the subject compositions every 1, 2, 3, tically effective dose of metformin is reduced by about or 4, 5, 6 or 7 days. In some embodiments, the compositions are more than about 50%, 60%, 70%, 80%, 90%, 95%, 97.5%, administered once, twice, or three times daily. The adminis 99.9%, 99.99%, or more. In some embodiments, administra tration can be concurrent with meal time of a subject. The tion of compositions of the invention reduces body fat (e.g. period of treatment or diet supplementation can be for about visceral fat) by about or more than about 5%, 10%, 15%, 1, 2, 3, 4, 5, 6, 7, 8, or 9 days, 2 weeks, 1-11 months, or 1 year, 20%, 25%, 50%, or more. 2 years, 5 years or even longer. In some embodiments of the invention, the dosages that are administered to a Subject can 0353 Insulin sensitivity can be measured using a variety change or remain constant over the period of treatment. For of techniques, including HOMA. HOMA, which is the example, the daily dosing amounts can increase or decrease homeostasis model assessment of insulin resistance can be over the period of administration. used as a screening index of changes in insulin sensitivity. 0360. The compositions can be administered to a subject HOMA can be calculated via standard formula from fasting such that the subject is administered a selected total daily dose plasma insulin and glucose as follows: HOMA Insulin of the composition. The total daily dose can be determined by (ul J/mL)xglucose (mM)/22.5. the sum of doses administered over a 24hour period. The total 0354. In some embodiments, insulin signaling can also be daily dose of the composition can include at least about 10, measured. Insulin signaling can be measured by measuring 50, 100, 150, 200,250, 500, 750, 1000, 1125, 2000, 2250 mg total and phosphorylated Akt, GSK-3?, IGF-1R, IR, IRS-1, or more of a leucine or metabolite thereof, such as HMB. The p70S6K and PRAS40 in tissue lysates via the Luminex Kits total daily dose of the composition can include at least about “Akt Pathway Total 7-Plex Panel” (Cath LHO0002) and “Akt 1, 3, 7.5, 15, 30, 45,90 mg or more of B6. The total daily dose Pathway Phospho 7-Plex Panel” (Cath LHO0001) from Invit of the composition can have a mass ratio of leucine or metabo rogen Life Science. lite thereof to vitamin B6 that is about, greater than about, or US 2016/0073659 A1 Mar. 17, 2016 32 less than about 10, 20,30,45, 50,55, 60, 65,70, 75,80, 85,90, dosages. The kit can be packaged with other dietary Supple 100, 110, 120, 130, 140, 150, 175, 200, 250, 500, 750, 1000, ments, vitamins, and meal replacement bars, mixes, and bev O. O. erages. 0361. The invention also provides for administering to a 0365. In another embodiment, the present invention pro pet an effective amount of leucine, a leucine metabolite, and/ vides kits suitable for improving stool quality and/or stool or vitamin B6 that is effective in inducing a selected circulat frequency for an animal. Said kits may comprise combina ing level in the pet of leucine, the leucine metabolite and/or tions of cations, anions, foods, other compounds, agents or Vitamin B6. The Subject compositions can induce a circulat medicaments, and instructions for using said kit components ing level that is: about or greater than about 0.25,0.5,0.75, or for improving stool quality and/or stool frequency for an 1 mM of leucine or leucine metabolite and/or about or greater animal in need thereof. For example, it is contemplated that than about 10, 25, 50, 100, 150, or 200 nM vitamin B6. kits of the present invention may comprise metabolizable cations chosen from calcium, Sodium, potassium, magne Kits sium, and mixtures thereof metabolizable anions may be 0362. The invention also provides kits. The kits include chosen from phosphorus, chloride, Sulfur, and mixtures one or more compositions described herein, in Suitable pack thereof. Any and all forms of said metabolizable cations and aging, and may further comprise written material that can anions are contemplated, including pharmaceutically accept include instructions for use, discussion of clinical studies, able salt forms. The components of the kits may further com listing of side effects, and the like. Such kits may also include prise a gastrointestinal tract-improving agent, an anti-diar information, Such as Scientific literature references, package rhea agent and/oran anti-constipation agents and instructions insert materials, clinical trial results, and/or Summaries of for use thereof. these and the like, which indicate or establish the activities 0366 For example, a kit may comprise a nutritionally and/or advantages of the composition, and/or which describe complete food, e.g., a puppy food in addition to a metaboliz dosing, administration, side effects, drug interactions, or able cation, and/or a metabolizable anion with instructions other information useful to the health care provider. Such regarding how to increase the DCAB of the food composition information may be based on the results of various studies, for with the metabolizable cation and/or instructions as to how to example, studies using experimental animals involving in decrease the DCAB of the food composition with metaboliz Vivo models and studies based on human clinical trials. A kit able anions in order to achieve a desired improvement in stool may comprise one or more unit doses described herein. In quality in an animal in need thereof. In some embodiments, some embodiments, a kit comprises about, less than about, or the kit may further comprises one or more anti-diarrhea more than about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, agents, anti-constipation agents, and/or gastrointestinal tract 16, 17, 18, 19, 20, 30, 31, 60,90, 120, 150, 180, 210, 365, or improving agents and instructions for use thereof with the more days of Supply. Instructions for use can comprise food and metabolizable cations and anions. It is understood administration instructions, such as instructions to take 1, 2, that addition of cations will cause the stool to be more firm; 3, 4, 5, 6, 7, 8, 9, 10, or more units 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, the addition of anions will cause the stool to be less firm. or more times per day. For example, a kit may comprise a unit Based on the teachings of the present invention, one of skill in Supplied as a tablet, with each tablet package separately, the art will understand how to modify the DCAB in the animal multiples of tablets packaged separately according to the depending on the condition of the stool of the animal to be number of units per administration (e.g. pairs of tablets), orall treated and the change in stool firmness desired. tablets packaged together (e.g. in a bottle). As a further example, a kit may comprise a unit Supplied as a bottled drink, EXAMPLES the kit comprising 1,2,3,4,5,6,7,8,9, 10, 11, 12, 13, 14, 24. Example 1 28, 36, 48, 72, or more bottles. 0363 The kit may further contain another agent. In some embodiments, the compound of the present invention and the Leucine--B6 Supplemented Diet Effect on agent are provided as separate compositions in separate con Percentage Body Fat, Body Weight, and Body tainers within the kit. In some embodiments, the compound of Condition Scores (BCS) the present invention and the agent are provided as a single 0367. An experiment was performed to determine the effi composition within a container in the kit. Suitable packaging cacy of a leucine--B6 Supplemented diet on weight and fat and additional articles for use (e.g., measuring cup for liquid loss in obese dogs. Specifically, the objective was to deter preparations, foil wrapping to minimize exposure to air, and mine the effect of leucine--B6 supplemented diet on the per the like) are known in the art and may be included in the kit. centage body fat, body weight, and body condition scores of Kits described herein can be provided, marketed and/or pro beagles as compared to a placebo and a prescription diet (RD moted to health providers, including physicians, nurses, phar Diet). The leucine--B6 supplemented diet comprised 1 g leu macists, formulary officials, and the like. Kits may also, in cine--13 mg pyridoxine/day. Some embodiments, be marketed directly to the consumer. 0368. Using experimental models of obesity in dogs, dogs 0364. In some embodiments, a kit can comprise a multi were utilized to demonstrate that the Subject compositions are day Supply of unit dosages. The unit dosages can be any unit effective for losing weight more rapidly, maintaining orgain dosage described herein. The kit can comprise instructions ing lean muscle mass while decreasing adiposity, as com directing the administration of the multi-day Supply of unit pared to placebo. dosages over a period of multiple days. The multi-day Supply 0369 Healthy adult beagles (n=18, 9 males and 9 females) can be a one-month Supply, a 30-day Supply, or a multi-week were evaluated for four weeks to establish individual caloric supply. The multi-day supply can be a 90-day, 180-day, requirements. Obesity was induced in the dogs by feeding 3-month or 6-month Supply. The kit can include packaged them a hypercaloric diet by adding 2 lbs offat with some meat daily unit dosages, such as packages of 1, 2, 3, 4, or 5 unit daily in order to induce obesity defined as a body condition US 2016/0073659 A1 Mar. 17, 2016

score of 8 or 9 out of 9 and having a body fat content of at least leucine--B6 Supplemented diet group VS. placebo provided ap 35-40% using dual energy x-ray absorptiometry (Mawby DI, value of 0.06. The variation in statistical difference between Bartges J. W. d’Avignon A, et al. Comparison of various leucine--B6 Supplemented diet group and placebo as com methods for estimating body fat in dogs. J. An Anim Hosp pared to RD diet group and placebo can be attributed to the Assoc 2004; 40:109-114. Ionut V, Liu H, Mooradian V, et al. specificity of the leucine--B6 diet on fat reduction rather than Novel canine models of obese prediabetes and mild type 2 body weight reduction. These data are summarized in FIG. 2. diabetes. Am J Physiol Endocrinol Metab 2010; 298:E38-48. Herein incorporated by reference). Body Condition Score 0370. After achieving a body fat content of 35-40%, dogs were randomly assigned to 1 of 3 groups so that there were 3 0376. There was a significant treatment effect on 12-week males and 3 females per each group: Group 1 was fed the change in body composition score (p=0.016); the placebo maintenance dietatideal body weight and received a leucine-- group exhibited a decrease in BCS of 0.17 units, which was B6 supplemented diet, Group 2 was fed the maintenance diet increased to 1.83 and 3 units, respectively (p=0.0024). Both at ideal body weight and received the placebo, and Group 3 leucine--B6 supplemented diet and RD diet were significantly dogs were fed a high fiber, low fat weight reduction at ideal different from placebo, but there was no significant difference body weight (the RD Diet). Body weight and body condition between the leucine--B6 supplemented diet and RD groups, scoring was performed weekly and body composition was as shown in FIG. 3. determined by dual energy X-ray absorptiometry every 4 0377 Three dogs did not achieve 30% body fat during weeks for 12 weeks or until ideal body condition, 15-20% obesification. They were nonetheless randomized to treat body fat, or initial ideal body weight was achieved. ments (one in each group) and are included in the preceding 0371. The RD Diet was comprised of Prescription Diet analysis. Exclusion of these three dogs yielded qualitatively R/d similar data, as shown in the Table 2, although the mean 0372 Canned 733 kcal/kg (256.55 kcal/per 350 g can) differences were changed. (Table 1.) TABLE 2 TABLE 1. 12 weeks of Nutrient Dry Matter % treatinent Significance Protein 25.3 Weight Change (kg): Placebo 1.241.02 *p = 0.0154 Fat 8.6 Weight Change (kg): 3.38 + 0.63 Carbohydrate (NFE) 39.2 Leucine + B6 supplemented diet Crude Fiber 21.2 Weight Change: RD diet 3.72 + 1.75 Placebo - Change in body fat (%) 2.64 3.21 *p = 0.0005 Leucine + B6 supplemented diet- 12.08 + 3.67 Change in body fat (%) 0373). RD Diet Ingredients: Water, Pork By-Products, RD diet - Change in body fat (%) 15.98 + 4.72 Soybean Mill Run, Rice, Pork Liver, Powdered Cellulose, Placebo - Change in BCS (units) O40 0.36 *p = 0.0034 Soybean Meal, Chicken Liver Flavor, Soybean Oil, Calcium Leucine + B6 supplemented diet- 2.20 + 0.45 Carbonate, Dicalcium Phosphate, Iron Oxide, Iodized Salt, Change in BCS (units) Vitamin E Supplement, Choline Chloride, Taurine, Ascorbic RD diet - Change in BCS (units) 3.20 + 0.45 Acid (source of vitamin C), L-Carnitine, Zinc Oxide, Ferrous Sulfate. Thiamine Mononitrate, Beta-Carotene, Copper Sul 0378. Non-matching superscripts for each variable fate, Manganous Oxide, Niacin, Calcium Pantothenate, Vita denotes significant difference at the indicated level. The sta min B12 Supplement, Pyridoxine Hydrochloride, Biotin, tistical comparison of weight loss for dogs in the leucine--B6 Riboflavin, Vitamin D3 Supplement, Calcium Iodate. Folic group vs. placebo group yielded a p value greater than the p Acid, Sodium Selenite. value for dogs in the RD diet VS placebo group. Comparing mean values along with standard deviations/error shows that Results for all Dogs the leucine--B6 diet did lead to weight reduction as compared Body Fat to placebo, but at a lower level of Statistical significance. 0379 These data demonstrate that obese dogs receiving 0374 Both the leucine--B6 supplemented diet and the RD the leucine--B6 supplemented diet while eating a normal diet groups lost significantly more fat than placebo (p=0. maintenance diet performed as well as dogs consuming a 0013), and there was no significant difference between the prescription high fiber weight loss diet. Dogs on the leucine-- leucine--B6 Supplemented diet and RD diet groups, as shown B6 supplemented diet were able to lose similar amounts of in FIG. 1. body weight and body fat and exhibit comparable improve ments in body condition score to dogs given the prescription Body Weight weight loss diet without having to change diet. 0375. There was a significant treatment effect on 12-week body weight change (p=0.042). The placebo group exhibited REFERENCES minimal change in body weight (0.93 kg), and this was increased to 2.81 and 3.38 kg in the leucine--B6 supple 0380 1. Bartges9. J. W. Kirk CA, Lauten S. Calculating9. a mented diet and RD diet groups, respectively. There was no patient's nutritional requirements. VetMed 2004: 99:632. significant difference between the leucine--B6 supplemented 0381 2. Laflamme D. Development and validation of a diet and RD diet groups. The RD group had a statistical body condition score system for dogs. Canine Practice difference from placebo that was p-0.05. In comparison, the 1997: 22:10-15. US 2016/0073659 A1 Mar. 17, 2016 34

0382. 3. Mawby D I, Bartges J. W. d’Avignon A, et al. 7. The pet food composition of claim3, wherein said vita Comparison of various methods for estimating body fat in min E comprises at least about 100 ppm of the pet food dogs. JAm Anim Hosp Assoc 2004; 40:109-114. composition. 0383 4. Ionut V, Liu H, Mooradian V, et al. Novel canine 8. The pet food composition of claim3, wherein said vita models of obese prediabetes and mild type 2 diabetes. Am min C comprises at least about 50 ppm of the pet food com J Physiol Endocrinol Metab 2010; 298:E38-48. position. 0384. It should be understood from the foregoing that, 9. The pet food composition of claim3, wherein said L-car while particular implementations have been illustrated and nitine comprises at least about 50 ppm of the pet food com described, various modifications can be made thereto and are position. contemplated herein. It is also not intended that the invention 10. The pet food composition of claim 3, wherein said be limited by the specific examples provided within the speci alpha-lipoic acid comprises at least about 25 ppm of the pet fication. While the invention has been described with refer food composition. ence to the aforementioned specification, the descriptions and 11. The pet food composition of claim 3, wherein said illustrations of the preferable embodiments herein are not choline comprises at least about 1000 ppm of the pet food meant to be construed in a limiting sense. Furthermore, it composition. shall be understood that all aspects of the invention are not 12. The pet food composition of claim 3, wherein said limited to the specific depictions, configurations or relative manganese comprises at least about 50 ppm, or from about 50 proportions set forth herein which depend upon a variety of ppm to about 150 ppm, or from about 100 ppm to about 150 conditions and variables. Various modifications in form and ppm, or from about 100 ppm to about 110 ppm of the pet food detail of the embodiments of the invention will be apparent to composition. a person skilled in the art. It is therefore contemplated that the 13. The pet food composition of claim 3, wherein said invention shall also cover any Such modifications, variations methionine comprises at least about at least about 0.4 to 1.5% and equivalents. methionine by weight of the pet food composition. What is claimed is: 14. The pet food composition of claim 3, wherein said 1. A pet food composition comprising: lysine comprises at least about 0.4%, between about 0.4 to a. about 0.05 to 5 wt % of leucine and/or about 0.005 to 1 2%, between about 0.9 to 2%, or between about 0.9 to 1.2% wt % of one or more leucine metabolites; and by weight of the pet food composition. b. about 0.001 to 0.05 wt % of vitamin B6. 15. The pet food composition of claim 3, wherein said 2. A pet food, treat or Supplement composition comprising: amount of ginger or extract thereof is about 0.005 to 12% by a. at least about 50 mg of leucine and/or at least about 5 mg weight of the pet food composition. of one or more leucine metabolites; and 16. The pet food composition of claim 3, wherein said b. at least about 1 mg of vitamin B6. chicory pulp comprises from 0.5 to 20% dry weight of the pet 3. A pet food composition comprising: food composition. a. about 0.05 to 5 wt % of leucine and/or about 0.005 to 1 17. The pet food composition of claim 3, wherein said wt % of one or more leucine metabolites: chondroitin comprises at least about 0.5 wt % of the pet food b. about 0.001 to 0.05 wt % of vitamin B6; and composition. ... an additional component selected from the group con 18. The pet food composition of claim 3, wherein said sisting of omega-3 fatty acid, eicosapentanoic acid, cho glucosamine comprises at least about 0.3 wt % of the pet food line, manganese, methionine, cysteine, L-carnitine, composition. lysine, alpha lipoic acid, dimethylaminoethanol, pyru 19. The pet food composition of claim 3, wherein said Vic acid, actyl L-carnitine, L-carnitine, conjugated myrtle comprises at least about 1% or between about 1 to 10% linoleic acid, diacylglyceride, chondroitin, glu by weight of the pet food composition. cosamine, ginger (or extract thereof), chicory pulp, and 20. The pet food composition of claim 4, wherein said myrtle. omega-3 fatty acid is present in an amount of at least about 4. A pet food, treat or Supplement composition comprising: 250 mg. a. at least about 50 mg of leucine and/or at least about 5 mg 21. The pet food composition of claim 4, wherein said of one or more leucine metabolites: eicosapentanoic acid is present in an amount of at least about b. at least about 1 mg of vitamin B6; and 300 mg. c. an additional component selected from the group con 22. The pet food composition of claim 4, wherein said sisting of omega-3 fatty acid, eicosapentanoic acid, cho Vitamin E is present in an amount of at least about 200 mg line, manganese, methionine, cysteine, L-carnitine, 23. The pet food composition of claim 4, wherein said lysine, alpha lipoic acid, dimethylaminoethanol, pyru Vitamin C is present in an amount of at least about 250 mg. Vic acid, actyl L-carnitine, L-carnitine, conjugated 24. The pet food composition of claim 4, wherein said linoleic acid, diacylglyceride, chondroitin, glu L-carnitine is present in an amount of at least about 250 mg. cosamine, ginger (or extract thereof), chicory pump, and 25. The pet food composition of claim 4, wherein said myrtle. alpha-lipoic acid is present in an amount of at least about 180 5. The pet food composition of claim 3, wherein said ng. omega-3 fatty acid comprises at least about 0.05%, at least 26. The pet food composition of claim 4, wherein said about 3.5%, or between about 0.05 to 3.5% of the weight of choline is present in an amount of at least about 1000 mg. the pet food composition. 27. The pet food composition of claim 4, wherein said 6. The pet food composition of claim 3, wherein said manganese is present in an amount of at least about 50 mg. or eicosapentanoic acid comprises at least about 0.4 wt % of the from about 50 mg to about 150 mg. or from about 100 mg to pet food composition. about 150 mg. or from about 100 mg to about 110 mg. US 2016/0073659 A1 Mar. 17, 2016

28. The pet food composition of claim 4, wherein said wherein the protein content of the second stage pet food methionine is present in an amount of at least about 7.5 mg. composition is about 10 to 45% less than the protein 29. The pet food composition of claim 4, wherein said content of the first stage pet food composition. lysine is present in an amount of at least about 400 mg. 37. A pet food composition comprising: 30. The pet food composition of claim 4, wherein said a. a live probiotic microorganism; amount of ginger or extract thereof is present at an amount of b. about 0.05 to 5 wt % of leucine and/or about 0.005 to 1 at least about 500 mg. wt % of one or more leucine metabolites; and 31. The pet food composition of claim 4, wherein said c. about 0.001 to 0.05 wt % of Vitamin B6. chondroitin is present in an amount of at least about 500 mg. 38. A pet food composition comprising: 32. The pet food composition of claim 4, wherein said a. a live probiotic microorganism; glucosamine is present in an amount of at least about 300 mg. b. at least about 50 mg of leucine and/or at least about 5 mg 33. The pet food composition of claim 4, wherein said of one or more leucine metabolites by weight of the pet myrtle is present in an amount of at least about 750 mg. food composition; and 34. A pet food composition comprising: c. at least about 1 mg of vitamin B6 by weight of the pet a. about 0.05 to 5 wt.% of leucine and/or about 0.005 to 1 food composition. wt % of one or more leucine metabolites on a dry matter 39. The pet food composition of claim 37 or 38, wherein basis; the probiotic microorganism is selected from the group con b. about 0.001 to 0.05 wt.% of vitamin B6 on a dry matter sisting of Bifidobacterium, Bacteroides, Clostridium, Fuso basis; bacterium, Melissococcus, Propionibacterium, Streptococ c. about 26 to 35 wt.% of crude protein on a dry matter CliS, Enterococcus, LactoCOccus, Staphylococcus, basis; Peptostrepococcus, Bacillus, Pediococcus, Micrococcus, d. about 7.5 to 8.5 wt.% of crude fat on a dry matter basis: Leuconostoc, Weissella, Aerococcus, Oenococcus, or Lacto e. about 20 to 30 wt.% of total dietary fiber on a dry matter baccillus. basis; and 40. The pet food composition of claim 37 or 38, wherein f, about 10 to 20 wt.% of crude fiber on a dry matter basis. said composition comprises a starch Source. 35. A pet food composition comprising: 41. The pet food composition of claim 37 or 38, wherein N pieces wherein N pieces provide the complete and bal said starch source has a degree of gelatinization less than anced daily nutritional requirements of an animal, and N about 7.5 Joules/g of starch. equals 1 to less than 15 pieces, 42. A pet food compositions comprising: wherein each piece has a caloric content between 50 to a. about 0.05 to 5 wt % of leucine and/or about 0.005 to 1 2500 kcal, and wt % of one or more leucine metabolites: wherein N pieces comprise (a) at least about 100 mg of b. about 0.001 to 0.05 wt % of Vitamin B6; and leucine and/or at least about 10 mg of one or more c. a pre-selected balance of metabolizable cations to leucine metabolites and (b) at least about 1 mg of metabolizable anions, wherein the DCAB is between vitamin B6. about 50 to 300. 36. A diet for promoting comprehensive weight manage 43. A method for treating a puppy susceptible to or suffer ment in companion animals comprising: ing from diarrhea and/or loose stool comprising: a first stage pet food composition for promoting weight a. feeding the puppy a food composition comprising (i) loss and a second stage pet food composition for main about 0.05 to 5 wt % of leucine and/or about 0.005 to 1 taining the weight loss, wt % of one or more leucine metabolites and (ii) about (a) said first stage pet food composition comprising, on 0.001 to 0.05 wt % of Vitamin B6; and a dry matter basis, b. adjusting the balance of metabolizable cations to about 35 to 70% by weight of a protein, metabolizable anions consumed by the puppy by an about 4 to 10% by weight of a fat, amount Sufficient to improve stool quality by increasing about 2 to 25% by weight of a fiber, the balance of metabolizable cations to metabolizable about 10 to 35% by weight of a carbohydrate, anions consumed by the puppy to produce firmer stool. about 0.05 to 5% by weight of leucine and/or about 44. A pet food composition for reducing odor of stool of a 0.005 to 1% by weight of one or more leucine companion animal comprising: metabolites, a. Stool odor-reducing effective amount of ginger or an about 0.001 to 0.05% by weight of vitamin B6, and extract thereof about 0.1 to 2% by weight of a functional ingredient, b. about 0.05 to 5 wt % of leucine and/or about 0.005 to 1 wherein said functional ingredient is selected from wt % of one or more leucine metabolites; and the group consisting of L-carnitine and conju c. about 0.001 to 0.05 wt % of Vitamin B6. gated linoleic acid; and 45. The pet food composition of claim 44, wherein said (b) said second stage pet food composition comprising, amount of ginger or extract thereof is present at an amount of on a dry matter basis, at least about 500 mg. about 20 to 35% by weight of a protein, 46. The pet food composition of claim 44, wherein said about 4 to 10% by weight of a fat, amount of ginger or extract thereof is about 0.005 to 12% by about 2 to 25% by weight of a fiber, weight. about 25 to 70% by weight of a carbohydrate, and 47. A method for reducing odor of stool of a companion about 0.1 to 2% by weight of a functional ingredient, animal, the method comprising causing the animal to ingest a wherein said functional ingredient is selected from pet food composition comprising: the group consisting of L-carnitine and conju a. a stool odor-reducing effective amount of ginger or an gated linoleic acid, extract thereof US 2016/0073659 A1 Mar. 17, 2016 36

b. about 0.05 to 5 wt % of leucine and/or about 0.005 to 1 a. at least about 50 mg of leucine and/or at least about 5 mg wt % of one or more leucine metabolites; and of one or more leucine metabolites by weight of the pet c. about 0.001 to 0.05 wt % of Vitamin B6. food composition; and 48. The method of claim 47, wherein said amount of ginger b. at least about 1 mg of vitamin B6 by weight of the pet or extract thereof is about 0.005 to 12% by weight. food composition. 49. The method of claim 47, wherein said amount of ginger 60. A pet food composition comprising: or extract thereof is present at an amount of at least about 500 a. about 0.05 to 5 wt % of leucine and/or about 0.005 to 1 ng. wt % of one or more leucine metabolites: 50. A pet food composition which comprises: b. about 0.001 to 0.05 wt % of vitamin B6; and a. chicory pulp in an amount which: i) maintains good feces c. a palatability enhancer selected from the group consist quality or improves the feces quality of a pet and/or ii) ing of butyric acid, 3-methylbutyric acid, tetrasodium maintains good gastrointestinal tract health and/or pyrophosphate, 2-piperidione, 2.3 pentanedione, improves the gastrointestinal tract health of a pet; 2-ethyl-3,5-dimethylpyrazine, furfural, sulfurol, and b. about 0.05 to 5 wt % of leucine and/or about 0.005 to 1 indole. wt % of one or more leucine metabolites; and 61. A pet food or Supplement composition comprising c. about 0.001 to 0.05 wt % of Vitamin B6. a. at least about 50 mg of leucine and/or at least about 5 mg 51. The pet food composition of claim 50, wherein said of one or more leucine metabolites by weight of the pet chicory pulp comprises from 0.5 to 20% dry weight of the pet food composition; b. at least about 1 mg of vitamin B6 by weight of the pet food product food composition; and 52. The pet food composition of claim 50, wherein said c. a palatability enhancer selected from the group consist chicory pulp comprises from 2 to 10% dry weight of the pet ing of butyric acid, 3-methylbutyric acid, tetrasodium food product. pyrophosphate, 2-piperidione, 2.3 pentanedione, 53. The pet food composition of claim 50, wherein said 2-ethyl-3,5-dimethylpyrazine, furfural, sulfurol, and chicory pulp is present at an amount of at least about 350 mg. indole. 54. A pet food composition comprising 62. A pet food composition comprising: a. an inner layer comprising kibble; a. an outer layer joined to an inner layer, wherein the outer b. an outer layer, layer is harder than the inner layer; c. about 0.05 to 5% of leucine and/or about 0.005 to 1% of about 0.05 to 5 wt % of leucine and/or about 0.005 to 1 one or more leucine metabolites by weight of the pet wt % of one or more leucine metabolites; and food composition; and b. about 0.001 to 0.05 wt % of vitamin B6. d. about 0.001 to 0.05% of vitamin B6 by weight of the pet 63. A pet food composition comprising: food composition. a. a structurant for providing a textured appearance and 55. The pet food composition of claim 54, wherein the feel; inner layer comprises about 0.05 to 5 wt % of leucine and/or about 0.005 to 1 a. about 0.05 to 5% of leucine and/or about 0.005 to 1% of wt % of one or more leucine metabolites; and one or more leucine metabolites by weight of the pet b. about 0.001 to 0.05 wt % of vitamin B6. food composition; and 64. A pet food composition comprising: b. about 0.001 to 0.05% of vitamin B6 by weight of the pet a textured layer bonded to a base layer, wherein the tex food composition. tured layer comprises textured components bonded to 56. The pet food composition of claim 54, wherein the the base layer; outer layer comprises about 0.05 to 5 wt % of leucine and/or about 0.005 to 1 wit a. about 0.05 to 5% of leucine and/or about 0.005 to 1% of % of one or more leucine metabolites; and one or more leucine metabolites by weight of the pet about 0.001 to 0.05 wt % of vitamin B6. food composition; and 65. A pet food composition comprising: b. about 0.001 to 0.05% of vitamin B6 by weight of the pet less than about 19% on a dry weight basis of carbohydrate; food composition. about 0.05 to 5 wt % of leucine and/or about 0.005 to 1 wit 57. A pet food or Supplement composition comprising % of one or more leucine metabolites; and a. an inner layer comprising kibble; about 0.001 to 0.05 wt % of vitamin B6. b. an outer layer, and 66. The pet food composition of claim 65, wherein the pet c. at least about 50 mg of leucine and/or at least about 5 mg food composition is dimensionally stable. of one or more leucine metabolites by weight of the pet 67. A method for feeding a pet comprising: food composition; and a. providing, over an extended and preselected period of d. at least about 1 mg of vitamin B6 by weight of the pet time, different food compositions to said animal in food composition. which each composition provides an enriched source of 58. The pet food or supplement composition of claim 57. fat, protein or carbohydrate, such that said animal can wherein the inner layer comprises Select and consume different and preferred quantities of a. at least about 50 mg of leucine and/or at least about 5 mg each said food compositions in order to achieve an pre of one or more leucine metabolites by weight of the pet ferred consumption of fat, protein and carbohydrate for food composition; and said animal; b. at least about 1 mg of vitamin B6 by weight of the pet wherein at least one of said food compositions com food composition. prises about 0.05 to 5 wt % of leucine and/or about 59. The pet food or supplement composition of claim 57. 0.005 to 1 wt % of one or more leucine metabolites: wherein the outer layer comprises and about 0.001 to 0.05 wt % of vitamin B6; US 2016/0073659 A1 Mar. 17, 2016 37

b. allowing said animal to consume the different and pre a. the leucine, if present, is in an amount that is about 0.05 ferred quantities of fat, protein and carbohydrate from to 5 wt %: each of said compositions over the extended preselected b. the leucine metabolites, if present, are in an amount that period of time; and is about 0.005 to 1 wt %; and c. determining, from the consumed amount of fat, protein c. the vitamin B6, if present, is in an amount that is about and carbohydrate from each of said compositions, a O.OO1 to 0.05 wt % customized dietary regime that provides the preferred 72. A diet for companion animals comprising: macronutrient content of a diet for said individual ani a first stage pet food composition and a second stage pet mal. food composition for maintaining the weight loss, 68. A computer-readable medium comprising code that, wherein each of said first stage pet food composition and upon execution by one or more processors, implements a said second stage pet food composition comprise, on a method of producing a customized dry pet food composition dry matter basis, about 0.05 to 5 wt % of leucine and/or formulated from a dry pet food kibble recipe and selected about 0.005 to 1 wt % of one or more leucine metabo functional ingredients, the formulation being selected on the lites, and about 0.001 to 0.05 wt % of vitamin B6, and basis of an individual pets attributes and physical conditions, wherein said second stage pet food comprises at least the method comprising: about 5% higher fat content compared to said first a. receiving information on the individual pets attributes stage pet food. and physical conditions; 73. A vegetarian pet food composition comprising: b. selecting a predetermined volume of dry kibble pieces a.a vegetarian kibble which incorporates a non-meat based from a plurality different formulations of pre-made dry flavor-enhancing additive; kibble pieces; b. about 0.05 to 5 wt % of leucine and/or about 0.005 to 1 c. Selecting one or more functional ingredients from a plurality functional ingredients; wt % of one or more leucine metabolites; and d. coating the predetermined volume of dry kibble pieces c. about 0.001 to 0.05 wt % of vitamin B6. with the one or more functional ingredients; and 74. A vegetarian pet food or Supplement composition com e. packaging and labeling the predetermined Volume of prising: coated dry kibble pieces: a.a vegetarian kibble which incorporates a non-meat based wherein the selection of the predetermined volume of dry flavor-enhancing additive; kibble pieces and one or more functional ingredients is b. at least about 50 mg of leucine and/or at least about 5 mg based on the individual pets attributes and physical of one or more leucine metabolites by weight of the pet conditions to provide the customized dry pet food prod food composition; and uct, and c. at least about 1 mg of vitamin B6 by weight of the pet wherein the coating and/or the kibble pieces comprise leu food composition. cine and/or a leucine metabolite and vitamin B6. 75. A multi-component pet food composition comprising 69. The method of claim 68, wherein two or more compartmentalized food compositions, wherein a. the leucine, if present, is in an amount that is about 0.05 the at least two compartmentalized compositions differ in to 5 wt %: their content in at least two offat, protein or carbohydrate, and b. the leucine metabolites, if present, are in an amount that further wherein one of the two or more compartmentalized is about 0.005 to 1 wt %; and compositions comprises about 0.05 to 5 wt % of leucine c. the vitamin B6, if present, is in an amount that is about and/or about 0.005 to 1 wt % of one or more leucine metabo O.OO1 to 0.05 wt %. lites, and about 0.001 to 0.05 wt % of vitamin B6. 70. A method of producing a customized dry pet food 76. A pet food composition for increasing the shelf life of product formulated from a dry pet food kibble recipe and a physically discrete dry pet food comprising: selected functional ingredients, the formulation being a. a coat covering the physically discrete pet food compo selected on the basis of an individual pets attributes and sition comprising a polymer film, wherein the film oran physical conditions, the method comprising: agent in the film protects the composition from oxida a. providing a plurality of different formulations of pre tion decomposition and/or protects the composition made dry kibble pieces: from bacterial growth, wherein the film comprises a b. selecting a predetermined volume of dry kibble pieces starch/synthetic polymer selected from the group con from the plurality of different formulations of pre-made sisting of starch/polyethylene, and Starch/low-density dry kibble pieces: polyethylene, and wherein the thickness of said coat is c. providing a plurality of functional ingredients; 1-2000 microns; d. coating the volume of dry kibble pieces with one or more b. about 0.05 to 5 wt % of leucine and/or about 0.005 to 1 of the plurality of functional ingredients; and wt % of one or more leucine metabolites; and e. packaging and labeling the predetermined Volume of c. about 0.001 to 0.05 wt % of Vitamin B6. coated dry kibble pieces: 77. A method for increasing the shelf life of a physically wherein the selection of the predetermined volume of dry discrete dry pet food composition comprising: kibble pieces and the one or more functional ingredients coating the physically discrete pet food composition with a is based on the individual pets attributes and physical polymer film, wherein the film or an agent in the film conditions to provide the customized dry pet food prod protects the composition from oxidation decomposition uct, and wherein the coating and/or the kibble pieces and/or protects the composition from bacterial growth, comprise leucine and/or a leucine metabolite and Vita wherein the film comprises a starch/synthetic polymer min B6. Selected from the group consisting of starch/polyethyl 71. The method of claim 70, wherein ene, and starch/low-density polyethylene, US 2016/0073659 A1 Mar. 17, 2016 38

wherein the thickness of said coating is 1-2000 microns: 89. A method of increasing insulin sensitivity in a pet and comprising wherein the pet food composition comprises about 0.05 to administering to the pet a pet food, pet treat, pet Snack or 5 wt % of leucine and/or about 0.005 to 1 wt % of one or pet drink composition that comprises: (a) about 0.05 to 5 more leucine metabolites and about 0.001 to 0.05 wt % wt % of leucine and/or about 0.005 to 1 wt % of one or of Vitamin B6. more metabolites thereof; and (b) about 0.001 to 0.05 wt 78. A method for making kibble at one location and finish % of vitamin B6, wherein the insulin sensitivity in the ing the pet food at another location comprising: pet is increased. a. forming a dry, stable intermediate of the pet food com 90. A method of increasing insulin sensitivity in a pet position at a first location; comprising b. finishing the dry, stable intermediate pet food composi administering to the pet a pet food, pet treat, pet Snack or tion to form a finished pet food composition at a second pet drink composition that comprises: (a) about 50 mg of location remote from the first location, leucine and/or 5 mg of one or more metabolites thereof; wherein said finished pet food composition contains and (b) at least about 1 mg of vitamin B6, wherein the about 0.05 to 5 wt % of leucine and/or about 0.005 to level of insulin sensitivity in the pet is increased. 1 wt % of one or more leucine metabolites and about 91. A method of reducing inflammation in a pet comprising 0.001 to 0.05 wt % of Vitamin B6. administering to the pet a pet food, pet treat, pet Snack or pet 79. A hypoallergenic pet food composition comprising: drink composition that comprises: (a) about 0.05 to 5 wt % of a. proteinaceous component that has been hydrolyzed leucine and/or about 0.005 to 1 wt % of one or more metabo whereby said component is rendered hypoallergenic to a lites thereof; and (b) about 0.001 to 0.05 wt % of vitamin B6, pet, wherein said proteinaceous component is made up wherein the inflammation in the pet is reduced. of polypeptides and free amino acids having an average 92. A method reducing inflammation in a pet comprising molecular weight of less than about 3,000 Daltons; administering to the pet a pet food, pet treat, pet Snack or pet b. about 0.05 to 5 wt % of leucine and/or about 0.005 to 1 drink composition that comprises: (a) about 50 mg of leucine and/or 5 mg of one or more metabolites thereof; and (b) at wt % of one or more leucine metabolites; and least about 1 mg of vitamin B6, wherein the inflammation in c. about 0.001 to 0.05 wt % of Vitamin B6. the pet is reduced. 80. A method of administering a pet food, treat, Supple 93. A method of reducing and/or preventing diabetes in a ment, or drink to a pet comprising administering a composi pet comprising administering to the pet a pet food, pet treat, tion of any of the preceding claims to the pet. pet Snack or pet drink composition that comprises: (a) about 81. A method of facilitating weight loss in a pet in need 0.05 to 5 wt % of leucine and/or about 0.005 to 1 wt % of one thereof comprising administering a composition of any of the or more metabolites thereof; and (b) about 0.001 to 0.05 wt % preceding claims to the pet, wherein the pet experiences of vitamin B6, wherein diabetes is prevented or the effects of weight loss. diabetes is reduced. 82. The method of claim 81, wherein the pet loses about 94. A method of reducing and/or preventing diabetes in a 10% of its weight relative to the weight of the pet prior to pet comprising administering to the pet a pet food, pet treat, administration of the composition. pet Snack or pet drink composition that comprises: (a) about 83. A method of facilitating fat loss in a pet in need thereof 50 mg of leucine and/or 5 mg of one or more metabolites comprising administering a composition of any of the pre thereof; and (b) at least about 1 mg of vitamin B6, wherein ceding claims to the pet, wherein the pet experiences fat loss. diabetes is prevented or the effects of diabetes is reduced. 84. The method of claim 82, wherein the pet loses about 95. A pet food composition comprising: 10% fat relative to the amount offat prior to administration of a. about 0.05 to 5 wt % of leucine and/or about 0.005 to 1 the composition. wt % of one or more leucine metabolites: 85. A method of reducing body condition score of a pet in b. about 0.001 to 0.05 wt % of vitamin B6; and need thereof comprising administering a composition of any c. about 1.5 g/kg metformin, about 0.75 g/kg metformin, or of the preceding claims to the pet, wherein the pet experiences about 0.25 g/kg metformin. a reduction in body condition score. 96. A pet food, treat or Supplement composition compris 86. The method of claim 85, wherein the pets body con 1ng: dition score is reduced by about 2 relative to the pet's body a. at least about 50 mg of leucine and/or at least about 5 mg condition score prior to administration of the composition. of one or more leucine metabolites: 87. A method of increasing production of irisin in a pet b. at least about 1 mg of vitamin B6; and comprising administering to the pet a pet food, pet treat, pet c. at least about 125 mg metformin Snack or pet drink composition that comprises: 97. The pet food, treat, or supplement composition or a. about 0.05 to 5 wt % of leucine and/or about 0.005 to 1 method of any of the preceding claims, wherein the leucine wt % of one or more metabolites thereof, and metabolite is selected from the group consisting of keto b. about 0.001 to 0.05 wt % of vitamin B6, isocaproic acid (KIC), alpha-hydroxy-isocaproic acid, and wherein the production of irisin in the pet is increased. hydroxymethylbutyrate (HMB). 88. A method of increasing production of irisin in a pet 98. The pet food, treat, or supplement composition or comprising method of any of the preceding claims, wherein the compo administering to the pet a pet food, pet treat, pet Snack or sition is substantially free of alanine in free form or salt form. pet drink composition that comprises: (a) about 50mg of 99. The pet food, treat, or supplement composition or leucine and/or 5 mg of one or more metabolites thereof; method of any of the preceding claims, wherein the compo and (b) at least about 1 mg of vitamin B6, wherein the sition is substantially free of glutamic acid in free form or salt production of irisin in the pet is increased. form. US 2016/0073659 A1 Mar. 17, 2016 39

100. The pet food, treat, or supplement composition or 106. The pet food, treat, or supplement composition or method of any of the preceding claims, wherein the compo method of any of the preceding claims, wherein the compo sition is substantially free of glycine in free form or salt form. sition comprises less than 1% of glycine in free form or salt form. 101. The pet food, treat, or supplement composition or 107. The pet food, treat, or supplement composition or method of any of the preceding claims, wherein the compo method of any of the preceding claims, wherein the compo sition is substantially free of proline in free form or salt form. sition comprises less than 1% of proline in free form or salt 102. The pet food, treat, or supplement composition or form. method of any of the preceding claims, wherein the compo 108. The pet food, treat, or supplement composition or sition is substantially free of alanine in free form or salt form. method of any of the preceding claims, wherein the compo 103. The pet food, treat, or supplement composition or sition comprises less than 1% of non-leucine amino acids in free form or salt form. method of any of the preceding claims, wherein the compo 109. The pet food, treat, or supplement composition or sition is Substantially free of non-leucine amino acids in free method of any of the preceding claims, wherein the amount of of salt form. leucine is between about 50-400, 50-300, 50-250, or 50-200 104. The pet food, treat, or supplement composition or ng. method of any of the preceding claims, wherein the compo 110. The pet food, treat, or supplement composition or sition comprises less than 1% of alanine in free form or salt method of any of the preceding claims, wherein the amount of form. leucine metabolites is between about 5-50, 5-25, or 5-10 mg. 105. The pet food, treat, or supplement composition or 111. The pet food, treat, or Supplement composition or method of any of the preceding claims, wherein the compo method of any of the preceding claims, wherein the amount of sition comprises less than 1% of glutamic acid in free form or vitamin B6 is between about 1-10, 1-5, or 1-2 mg. salt form. k k k k k