Companion animal food composition

Abstract

The present disclosure provides a food composition for use in a method for treating and / or preventing and / or reducing the severity and / or reducing the relapse of otitis externa in a companion animal in need thereof, wherein the said food composition includes, as the sole active agents, glycyrrhizin and curcuminoid.

Description

Attorney Docket No.: 00307-0214-00304Mars Ref.: MARS / P / 393182 / WO / SEC / 1COMPANION ANIMAL FOOD COMPOSITIONCROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application claims priority to European Patent Application No. EP 24214015.0, filed on November 19, 2024, the entirety of which is incorporated herein by reference.FIELD OF THE DISCLOSURE

[0002] The present disclosure relates to the field of animal food compositions, preferentially companion animal food composition, for preventing and / or treating and / or reducing the severity and / or reducing the relapse of otitis externa.BACKGROUND OF THE DISCLOSURE

[0003] Otitis externa, commonly known as an outer ear infection, is one of the most common types of infections seen in dogs, affecting approximately 10% to 20% of this animal species. While less frequently seen in cats, it poses significant management challenges and remains one of the most frustrating diseases to manage. Ear infections can be extremely uncomfortable and painful, leading the affected animals, dogs and cats, to shake their heads or scratch at their ears in an attempt to relieve the discomfort. One of the characteristics of otitis externa is the ears often becoming red and inflamed, frequently developing an unpleasant odor, and may produce a black or yellowish discharge. In chronic cases, the ears may appear crusty or thickened, and the ear canals often become narrowed (stenotic) due to chronic inflammation.

[0004] The clinical evolution of otitis externa can be summarized in three phases: 1 ) acute inflammation and edema, 2) chronic inflammation characterized by glandular changes, fibrosis and scarring, and 3) progressive stenosis and occlusion of the ear canal (Logas 1994; Roth 1988). Otitis externa is considered a multifactorial disorder, with allergy being the most common primary cause, which is often secondarily accompanied by microbial infections.

[0005] For felines, especially cats, the ear mite Otodectes cynotis is the most common primary cause of otitis externa, implicated in 53-69% of clinical cases (Brame & Cain 2021 ). If left untreated, the major risk is to move from otitis externa to a more severe condition, such as otitis media or otitis interna, necessitating complicated treatment approaches, including surgery in some cases.Attorney Docket No.: 00307-0214-00304Mars Ref.: MARS / P / 393182 / WO / SEC / 1

[0006] Although most otitis externa cases can be sufficiently managed with topical therapies, such as topical anti-inflammatory drugs (glucocorticoids) with antifungal and / or antibacterial compounds when secondary infection is present, the relapses of the disease are common if the underlying cause (e.g., allergy) is not addressed.

[0007] In addition, otitis externa is frequently secondarily infected with yeasts and / or bacteria, often complicating the disease.

[0008] It has been recently described the preliminary results of an assay to develop an oral solution for treating otitis externa (Di Cerbo 2016). The specific nutraceutical solution, while not being a diet, was composed by two mixed components: classic kibbles, included in the ideal percentage of 93-94 % by weight, and cold-pressed microcapsules at the 6-7 % by weight of complete food. Microcapsules were composed of 60-80 % of proteins (of fish and vegetable origin), 20-40 % of minerals, used as glidants, and therapeutical substances (Melaleuca alternifolia, 0.00343 %, Tilia platyphyllos scapoli et cordata, 0.0147 %, Allium sativum L, 0.0245 %, Rosa canina L, 0.098 %, and Zinc, 0.00479 %). A significant and encouraging reduction of the main symptoms of otitis externa - as the external ear canal occlusion, erythema, odor and mucus discharge - has been observed. Given the ongoing need for effective, non-drug treatment options for otitis externa, as well as alternative natural products to reduce reliance on conventional medications, there is a critical demand for novel food composition solutions.

[0009] Thus, there remains a need for effective treatment options other than otitis externa medications.

[0010] There also remains a need for alternative natural products for treating or preventing or reducing the relapse of such otitis externa, symptom(s) and / or associated complication(s) thereof by reducing the need of otitis externa medication.

[0011] There remains a need for food compositions designed for reducing the severity and / or reducing the relapse of otitis externa, symptom(s) and / or associated complication(s) thereof in a companion animal in need thereof.

[0012] The present disclosure demonstrates that the use of a food composition can be efficient in the prevention or treatment of otitis externa, symptom(s) and / or associated complication(s) thereof, specifically in the reduction of the relapse of otitis externa.Attorney Docket No.: 00307-0214-00304Mars Ref.: MARS / P / 393182 / WO / SEC / 1SUMMARY

[0013] The present disclosure relates to therapeutic methods and uses of a food composition as disclosed herein for treating and / or preventing and / or reducing the severity and / or reducing the relapse of otitis externa, symptom(s) and / or associated complication(s) thereof in a companion animal in need thereof.

[0014] Specifically, a first aspect of the present disclosure relates to a food composition for use in a method for treating and / or preventing and / or reducing the severity and / or reducing the relapse of otitis externa, including otitis externa symptom(s) and / or otitis externa-associated complication(s) thereof, in a companion animal in need thereof, wherein the said food composition includes, as the sole active agents, glycyrrhizin and curcuminoid.

[0015] Another aspect of the present disclosure relates to a food composition for use in a method for treating and / or preventing and / or reducing the severity and / or reducing the relapse of otitis externa, including otitis externa symptom(s) and / or otitis externa-associated complication(s) thereof, in a companion animal in need thereof, wherein the said food composition includes, as the sole active agents, a source of glycyrrhizin and a source of curcuminoid.

[0016] In some embodiments, the food composition for its use as disclosed herein can be formulated for providing to said companion animal in need thereof a daily amount of glycyrrhizin from about 0.1 mg / kg of the companion animal’s bodyweight (kg Bwt) to about 1 mg / kg Bwt.

[0017] In some embodiments, the food composition for its use as disclosed herein can be formulated for providing to said companion animal in need thereof a daily amount of glycyrrhizin from about 0.2mg / kg Bwt to about 0.6mg / kg Bwt.

[0018] In some embodiments, the food composition for its use as disclosed herein can be formulated for providing to said companion animal in need thereof a daily amount of glycyrrhizin of about 0.4g / kg Bwt.

[0019] In some embodiments, the food composition for its use as disclosed herein can be formulated for providing to said companion animal in need thereof a daily amount of curcuminoid from about 0.5mg / kg Bwt to about 6mg / kg Bwt.

[0020] In some embodiments, the food composition for its use as disclosed herein can be formulated for providing to said companion animal in need thereof a daily amount of curcuminoid from about 1 mg / kg Bwt to about 5mg / kg Bwt.Attorney Docket No.: 00307-0214-00304Mars Ref.: MARS / P / 393182 / WO / SEC / 1

[0021] In some embodiments, the food composition for its use as disclosed herein can be formulated for providing to said companion animal in need thereof a daily amount of curcuminoid of about 4 mg / kg Bwt.

[0022] In some embodiments, the curcuminoid as used herein can be selected from curcumin, demethoxycurcumin, bisdemethoxycurcumin, methoxycurcumin, tetrahydrocurcumin, hexahydrocurcumin, monodemethoxycurcumin, and combinations thereof.

[0023] In some embodiments, the source of glycyrrhizin as used herein can be licorice or an extract thereof containing glycyrrhizin.

[0024] In some embodiments, the source of a curcuminoid as used herein can be turmeric or an extract thereof containing curcuminoid.

[0025] In some embodiments, the food composition for its use as disclosed herein can be provided to the companion animal in need thereof for a period of between about one month to about thirty-six months during or before or after an otitis externa medication.

[0026] In some embodiments, an otitis externa-associated complication can consist of alopecia, excoriation, crusting, erythema, hyperpigmentation or combinations thereof.

[0027] In some embodiments, the relapse of otitis externa in the companion animal can be reduced by about 30% to about 100%.

[0028] In some embodiments, the otitis externa medication can comprise a step of treating the companion animal by administering or applying an anti-otitis externa agent.

[0029] In some embodiments, an anti-otitis externa agent can be antibiotic ear drops, antifungal ear drops, and / or corticosteroid ear drops.

[0030] In some embodiments, the food composition for its use as disclosed herein can be nutritionally complete and balanced.

[0031] In some embodiments, the food composition for its use as disclosed herein can further comprise ERA and / or DHA, linoleic acid, Taurine, Lutein, Vitamin E, or combinations thereof.

[0032] In some embodiments, the food composition for its use as disclosed herein can be formulated for providing to said companion animal in need thereof a daily amount of at least one of:(i) linoleic acid from about 50mg / kg Bwt to about 120mg / kg Bwt; and / orAttorney Docket No.: 00307-0214-00304Mars Ref.: MARS / P / 393182 / WO / SEC / 1(ii) Eicosapentaenoic acid (EPA) and / or Docosahexaenoic acid (DHA) from about 4mg / kg Bwt to about 20mg / kg Bwt; and / or(iii) Taurine from about 15mg / kg Bwt to about 100mg / kg Bwt; and / or(v) Lutein from about 0.015mg / kg Bwt to about 0.1mg / kg Bwt; and / or(v) Vitamin E from about 3mg / kg Bwt to about 20mg / kg Bwt.

[0033] In some embodiments, the food composition for its use as disclosed herein can be formulated for providing to said companion animal in need thereof a daily amount of linoleic acid from about 50mg / kg Bwt to about 110mg / kg Bwt.

[0034] In some embodiments, the said food composition for its use as disclosed herein can be formulated for providing to said companion animal in need thereof a daily amount of linoleic acid of about 90mg / kg Bwt.

[0035] In some embodiments, the food composition for its use as disclosed herein can be formulated for providing to said companion animal in need thereof a daily amount of Eicosapentaenoic acid (EPA) and / or Docosahexaenoic acid (DHA) from about 7mg / kg Bwt to about 15mg / kg Bwt.

[0036] In some embodiments, the food composition for its use as disclosed herein can be formulated for providing to said companion animal in need thereof a daily amount of Eicosapentaenoic acid (EPA) and / or Docosahexaenoic acid (DHA)of about 13mg / kg Bwt.

[0037] In some embodiments, the food composition for its use as disclosed herein can be formulated for providing to said companion animal in need thereof a daily amount of Taurine from about 50mg / kg Bwt to about 90mg / kg Bwt.

[0038] In some embodiments, the food composition for its use as disclosed herein can be formulated for providing to said companion animal in need thereof a daily amount of Taurine of about 75mg / kg Bwt.

[0039] In some embodiments, the food composition for its use as disclosed herein can be formulated for providing to said companion animal in need thereof a daily amount of Lutein from about 0.05mg / kg Bwt to about 0.09mg / kg Bwt.

[0040] In some embodiments, the food composition for its use as disclosed herein can be formulated for providing to said companion animal in need thereof a daily amount of Lutein of about 0.085mg / kg Bwt.

[0041] In some embodiments, the food composition for its use as disclosed herein can be formulated for providing to said companion animal in need thereof a daily amount of Vitamin E from about 7mg / kg Bwt to about 17mg / kg Bwt.Attorney Docket No.: 00307-0214-00304Mars Ref.: MARS / P / 393182 / WO / SEC / 1

[0042] In some embodiments, the food composition for its use as disclosed herein can be formulated for providing to said companion animal in need thereof a daily amount of Vitamin E of about 15.3mg / kg Bwt.

[0043] In some embodiments, the food composition for its use as disclosed herein, wherein the companion animal can be a canine or a feline,

[0044] In some embodiments, the companion animal can be a dog or a cat,

[0045] In some embodiments, the companion animal can be preferably a dog.

[0046] Another aspect of the present disclosure relates to a method of manufacturing a food composition for use in a method for treating and / or preventing and / or reducing the severity and / or reducing the relapse of otitis externa in a companion animal in need thereof, comprising the steps of: a) mixing at least a source of glycyrrhizin and a source of curcuminoid, thereby providing a mixture; and b) heating the mixture, obtaining a food composition, wherein the said food composition is formulated for providing to said companion animal in need thereof a daily amount of glycyrrhizin from about 0.1 mg / kg Bwt to about 1 mg / kg Bwt; and a daily amount of curcuminoid from about 0.5mg / kg Bwt to about 6mg / kg Bwt.DESCRIPTION OF THE FIGURES

[0047] Figure 1 illustrates the severity of otitis externa in dogs fed with the test (black line) or control diet (grey line). The mean observed data (95% confidence interval) are presented for (FIGURE 1A) Otitis Index Score-3 (OTIS-3) and (FIGURE 1B) cytology scores. Data were observed at the baseline (before treatment), Month 3 and End point (6 months).

[0048] Figure 2 illustrates the severity of canine atopic dermatitis(cAD) lesions, pruritus intensity, and medication burden in dogs fed with the test diet (black line) or control diet (grey line). The mean observed data (95% confidence interval) are presented for (FIGURE 2A) the Canine Allergic Dermatitis Extent and Seventy Index, 4th iteration (CADESI-04) score; (FIGURE 2B) the pruritus Visual Analogue Scale (pVAS) score; and (FIGURE 2C) the medication score.Attorney Docket No.: 00307-0214-00304Mars Ref.: MARS / P / 393182 / WO / SEC / 1DETAILED DESCRIPTION

[0049] The present disclosure aims at making available a diet for preventing and / or treating otitis externa, in companion animals, especially in canines and felines, and more especially in canines.

[0050] The present disclosure aims at making available a diet for reducing the severity of otitis externa, in companion animals, especially in canines and felines, and more especially in canines. By reducing the severity of otitis externa, it is reducing the risk of otitis media and / or otitis interna.

[0051] The present disclosure aims at making available a diet for reducing the relapse of otitis externa in companion animals, especially in canines and felines, and more especially in canines.

[0052] The present disclosure provides herein a food composition for use in a method for treating and / or preventing and / or reducing the severity and / or reducing the relapse of otitis externa in a companion animal in need thereof, including, as the sole active agents, at least a source of glycyrrhizin and a source of curcuminoid.

[0053] The present disclosure provides herein a food composition for use in a method for treating and / or preventing and / or reducing the severity and / or reducing the relapse of otitis externa in a companion animal in need thereof, including, as the sole active agents, at least glycyrrhizin and curcuminoid.

[0054] It is already known that an animal food composition including a source of glycyrrhizin (WO2023 / 212233) or a source of glycyrrhizin in combination with a source of curcuminoids (WO2021 / 003280) can be effective in the prevention or the treatment of atopic dermatitis.

[0055] Surprisingly, it has been shown for the first time that such a food composition including at least a source of glycyrrhizin and a source of curcuminoid is capable of acting on otitis externa, including otitis externa symptom(s) and / or associated complication(s) thereof. More surprisingly, as the pathologies are different, it has been shown that a such a food composition including at least a source of glycyrrhizin and at least a source of curcuminoid can be effective in a method for treating and / or preventing and / or reducing the severity and / or reducing the relapse of otitis externa in a companion animal in need thereof, especially a canine or a feline in need thereof, and more especially a canine in need thereof.Attorney Docket No.: 00307-0214-00304Mars Ref.: MARS / P / 393182 / WO / SEC / 1

[0056] As it is shown in the Examples herein, the food composition of the present disclosure, when provided to a companion animal suffering from otitis externa, is well tolerated and significantly improve the management of otitis externa.

[0057] Furthermore, as shown in the present disclosure, the food composition of the present disclosure, when provided to a companion animal suffering from otitis externa, impacts the otitis externa severity score (Otis3), the level of infection inside the ear (cytology score), the number of companion animals relapsing into otitis after successful treatment within 6-months trial period (relapse rate) and the level of medication needed to maintain acceptable quality of life (medication score).Definitions

[0058] The terms used in this specification generally have their ordinary meanings in the art, within the context of this disclosure and in the specific context where each term is used. Certain terms are discussed below, or elsewhere in the specification, to provide additional guidance in describing the compositions and methods of the disclosure and how to make and use them.

[0059] As used in the specification and the appended claims, the singular forms “a” “an” and “the” include plural referents unless the context clearly dictates otherwise. Thus, for example, reference to “a compound” can include one compound or a mixture of two compounds or more. As such, the terms “a” (or “an”), “one or more” and “at least one” can be used interchangeably herein.

[0060] The term “about” or “approximately”, as used herein, means within an acceptable error range for the particular value as determined by one of ordinary skill in the art, which will depend in part on how the value is measured or determined, i.e. , the limitations of the measurement system. For example, “about” can mean within 3 or more than 3 standard deviations, per the practice in the art. Alternatively, “about” can modify a numerical value above and below the stated value by a variance of 10%, or of 5%, or of 1 %.

[0061] As used herein, the terms “comprises,” “comprising,”, “include”, “including” or any other variation thereof, are intended to cover a non-exclusive inclusion, such that a process, method, food composition, or apparatus that comprises a list of elements (products, nutrients, steps, etc.) does not include only those elements but can include other elements not expressly listed or inherent to such process, method, food composition, or apparatus. The term “consisting of’Attorney Docket No.: 00307-0214-00304Mars Ref.: MARS / P / 393182 / WO / SEC / 1 implies the inclusion of the stated element(s), to the exclusion of any additional element(s). The term “consisting essentially of’ implies the inclusion of the stated elements, and possibly other element(s) where the other element(s) do not materially affect the basic and novel characteristic(s) of the disclosure. It is understood that the different embodiments of the disclosure using the term “including” or equivalent cover the embodiments where this term is replaced with “consisting of” or “consisting essentially of”.

[0062] As used herein, the term "active agent" refers to a component of the food composition that is responsible for producing the intended therapeutic or healthimproving effect. This component, or combination of components, exerts a biological activity that directly or indirectly contributes to the treatment and / or prevention and / or reduction of the severity and / or reduction of the relapse of otitis externa in a companion animal in need thereof. In some embodiments, a source of glycyrrhizin and a source of curcuminoid are the sole active agents of the food composition. In some embodiments, glycyrrhizin and curcuminoid are the sole active agents of the food composition. In some embodiments, glycyrrhizin, curcuminoid, ERA and / or DHA, Linoleic acid, Vitamin E, Taurine and / or Lutein are the sole active agents of the food composition.

[0063] In the detailed description herein, references to “embodiment,” “an embodiment,” “one embodiment,” “in various embodiments,” etc., indicate that the embodiment(s) described can include a particular feature, structure, or characteristic, but every embodiment might not necessarily include the particular feature, structure, or characteristic. Moreover, such phrases are not necessarily referring to the same embodiment. Further, when a particular feature, structure, or characteristic is described in connection with an embodiment, it is submitted that it is within the knowledge of one skilled in the art to affect such feature, structure, or characteristic in connection with other embodiments whether or not explicitly described. After reading the description, it will be apparent to one skilled in the relevant art(s) how to implement the disclosure in alternative embodiments.

[0064] As used herein, the term “enantiomers” refers to a pair of stereoisomers that are non-superimposable mirror images of each other. A 1 :1 mixture of a pair of enantiomers is a “racemic” mixture or a racemate. The term is used to designate a racemic mixture where appropriate.Attorney Docket No.: 00307-0214-00304Mars Ref.: MARS / P / 393182 / WO / SEC / 1

[0065] As used herein, the term “diastereoisomer” refers to stereoisomers that have at least two asymmetric atoms, but which are not mirror-images of each other. The absolute stereochemistry is specified according to the Cahn-lngold-Prelog R — S system. When a compound is a pure enantiomer, the stereochemistry at each chiral carbon can be specified by either R or S. Resolved compounds whose absolute configuration is unknown can be designated (+) or (-) depending on the direction (dextro or levorotatory) in which they rotate plane polarized light at the wavelength of the sodium D line. The compounds of the presently disclosed subject matter contain one or more asymmetric centers and can thus give rise to enantiomers, diastereomers, and other stereoisomeric forms that can be defined, in terms of absolute stereochemistry, as (R)- or (S)-. The presently disclosed subject matter is meant to include all such possible isomers, including racemic mixtures, optically pure forms, and intermediate mixtures. Optically active (R)- and (S)-isomers can be prepared using chiral synthons or chiral reagents or resolved using conventional techniques. If the compound contains a double bond, the substituent can be E or Z configuration. If the compound contains a disubstituted cycloalkyl, the cycloalkyl substituent can have a cis- or trans-configuration. All tautomeric forms are also intended to be included.

[0066] As used herein, the term “isomers” refers to different compounds that have the same molecular formula but differ in arrangement and configuration of the atoms. Also, as used herein, the term “stereoisomer” refers to any of the various stereo isomeric configurations which can exist for a given compound of the presently disclosed subject matter and includes geometric isomers. It is understood that a substituent can be attached at a chiral center of a carbon atom. Therefore, the term stereoisomer includes enantiomers, diastereomers, or racemates of the compound. Also, as used herein, the terms “constitutional isomers” refers to different compounds which have the same numbers of, and types of, atoms but the atoms are connected differently, such as, but not limited to tautomers.

[0067] As used herein, the term “weight percent” or “wt %” or “by weight” is meant to refer to the quantity by weight of a constituent / component / ingredient in a food composition as a percentage of the total weight of the food composition. More specifically, as used herein, unless specifically provided otherwise, the term “% by weight,” means the quantity in percentage by weight of the food composition on dry matter basis. Any exception will be clearly specified in the present specification.Attorney Docket No.: 00307-0214-00304Mars Ref.: MARS / P / 393182 / WO / SEC / 1When the “% by weight,” does not refer to the food composition but to another referential, such as a specific component of the food composition, it will be specified.

[0068] As used herein, the term “food composition” or “diet” means a product that is intended and suitable for consumption by a companion animal, in particular a canine or a feline. A food composition contains one or more ingredients in order to incorporate one or more nutrients. Nutrients of a food composition can be typically, without limitation, proteins, fibers, carbohydrates, fats, vitamins and / or minerals, which can be used in combination in the body of an organism to sustain growth, repair and / or vital processes and / or to furnish energy (defined with the metabolizable energy (ME)). (See Merriam- Webster's Collegiate Dictionary, 10th Edition, 1993). A food composition as described herein can be a functional complement or a nutritionally complete and balanced food composition.

[0069] As used herein, the expression nutritionally complete and balanced” for a food compositions means that the food composition comprises all the essential nutrients in appropriate proportions to meet an animal's dietary requirements for maintaining overall health and well-being. A nutritionally complete and balanced food composition can maintain the body weight of the animal without significant change with the Body Condition Score (BCS). A nutritionally complete and balanced animal food composition ensures that the animal receives all the necessary nutrients for optimal health, minimizing the risk of nutritional deficiencies or imbalances that could lead to health issues over time. Specifically, a nutritionally complete and balanced food composition can contain all known required nutrients for the intended recipient of the food composition, in all appropriate amounts and proportions based, for example, on recommendations of recognized and competent authorities in the field of cat nutrition, such as the Association of American Feed Control Officials (AAFCO) or the European Pet Food Industry Federation (FEDIAF), for complete and balanced pet nutrition. Therefore, a nutritionally adequate feed is a feed with which the said animal, e.g., the said dog, can be fed as the sole ration and is capable of sustaining life without additional food (except water). In some embodiments, a nutritionally complete and balanced food composition as described herein can include nutrients and / or ingredients that are formulated to contribute to the nutritional properties of the food composition.

[0070] As used herein, a “food supplement” or “food complement” refers to a concentrated source of nutrients, such as but not limited to vitamins and minerals,Attorney Docket No.: 00307-0214-00304 Mars Ref.: MARS / P / 393182 / WO / SEC / 1 substances for nutritional or physiological purposes, or plants and plant preparations intended to compensate for deficiencies in an animal’s regular diet. In certain embodiments, a food supplement is marketed in the form of capsules, lozenges, tablets, pills, powder packets or liquid forms (ampoules, vials with droppers).

[0071] As used herein, the term “drug” or “anti-otitis externa agent” refers to any substance or composition used specifically to prevent or treat otitis externa, an inflammatory condition of the external auditory canal. An anti-otitis externa agent generally possesses antibacterial, antifungal, anti-inflammatory, and / or analgesic properties, targeting the pathogens responsible for infection or the symptoms associated with the inflammation. Anti-otitis externa agents can be administered as a topical composition, an ointment, or ear drops.

[0072] Illustratively, a food composition as described herein can include, but it is not limited to protein, crude fat, ash, crude fiber, starch, calcium, phosphorus, sodium, chloride, potassium, magnesium, iron, water, copper, manganese, zinc, selenium, vitamin A, vitamin D3, vitamin B1 , vitamin B2, vitamin B6, vitamin B12, vitamin B7, vitamin B9, cholin chloride, arachidonic acid, W3 fatty acid or W6 fatty acid.

[0073] As used herein, the terms “animal” or “companion animal” can be used interchangeably to refer to domestic animals. In particular, a companion animal can refer to a canine or a feline. In some embodiments, a canine can be a dog and a feline can be a cat.

[0074] As used herein, the term “canine” encompasses animals, including companion animals selected from recognized dog breeds (some of which are further subdivided), which may can include afghan hound, airedale, akita, Alaskan malamute, basset hound, beagle, Belgian shepherd, bloodhound, border collie, border terrier, borzoi, boxer, bulldog, bull terrier, cairn terrier, chihuahua, chow, cocker spaniel, collie, corgi, dachshund, dalmatian, doberman, English setter, fox terrier, German shepherd, golden retriever, great dane, greyhound, griffon bruxellois, Irish setter, Irish wolfhound, King Charles spaniel, Labrador retriever, lhasa apso, mastiff, newfoundland, old English sheepdog, papillion, Pekingese, pointer, pomeranian, poodle, pug, rottweiler, St. Bernard, saluki, samoyed, schnauzer, Scottish terrier, Shetland sheepdog, shih tzu, Siberian husky, Skye terrier, springer spaniel, West Highland terrier, whippet, Yorkshire terrier, etc.Attorney Docket No.: 00307-0214-00304Mars Ref.: MARS / P / 393182 / WO / SEC / 1

[0075] As used herein, the terms “treating” or “treatment” in the present disclosure refers to the administration of a food composition according to the disclosure with the purpose to treat, alleviate, relieve, alter, remedy, ameliorate, improve, or affect a disease, the symptoms of said disease, the likelihood of said disease, or to prevent or delay the onset of the symptoms, complications, or otherwise arrest or inhibit further development of said disease in a statistically significant manner. More particularly, “treating” or “treatment” encompasses any approach for obtaining beneficial or desired results in an animal afflicted with a disease. Beneficial or desired clinical results can encompass, but are not limited to, alleviation or amelioration of one or more symptoms or conditions associated with a disease; diminishment or reduction of the severity of a disease or symptoms related to the disease; maintaining the stability (preventing deterioration) of a disease; delaying the progression or slowing down the progression of a disease; minimizing the recurrence of a disease; and remission, whether partial or total and whether detectable or undetectable. In other words, “treatment” as used herein includes any cure, amelioration, or reduction of a disease or related symptom. A “reduction” of a disease, or symptoms of a disease, means decreasing of the severity or frequency of the disease or symptoms of the disease, or elimination of a disease or symptoms of the disease.

[0076] In the context of the present disclosure, a disease is otitis externa. It is intended in the present disclosure that the treatment and / or prevention and / or reduction of the severity and / or reduction the relapse of otitis externa can include the treatment and / or prevention and / or reduction of the severity and / or reduction the relapse of otitis externa symptom(s) and associated complication(s) thereof. In some aspects, a disease in the present disclosure can be otitis externa, or any symptom(s) or complication(s) directly linked, or the consequence, of otitis externa. The otitis externa-associated complications can include, but are not limited to, the presence of alopecia, excoriation, crusting, erythema, and hyperpigmentation. The external ear canal may also exhibit the presence of hyperaemia, ulceration, ceruminous or suppurative discharge, masses, stenosis, glandular changes, or foreign bodies. These are all phenomena the presence or severity of which could be limited by better management of otitis externa. A number of pathologies associated with the presence of otitis externa can include, but are not limited to, hearing loss, middle ear infection, inner ear damage, perichondritis and facial nerve palsy.Attorney Docket No.: 00307-0214-00304Mars Ref.: MARS / P / 393182 / WO / SEC / 1Symptoms which could be reduced or avoided by successful management of otitis externa can be, but are not limited to, external ear canal occlusion, erythema, odor and / or mucus discharge. Other symptoms which could be reduced or avoided by successful management of otitis externa can be head shaking, pain, malodour, erythema, erosion, ulceration, swelling, and / or ceruminous gland inflammation.

[0077] As used herein, the term “preventing”, can also include the reduction of a likelihood of occurrence, or of re-occurrence, of a given condition or disease in an animal.

[0078] As used herein, the term “allergic” refers to a deregulated or unregulated sensitivity, in particular a hypersensitivity, of the immune system to typically harmless substances, such as those which are present in the environment. Common allergy triggers include but are not limited to airborne allergens, such as pollen, animal dander, dust mites and mold; certain foods, such as peanuts, tree nuts, wheat, soy, fish, shellfish, eggs and milk; insect stings, such as but not limited to from a bee or wasp; medications, such as penicillin or penicillin-based antibiotics; latex or other substances which can cause allergic skin reactions; allergic inflammatory skin disease such as atopic dermatitis, flea allergic dermatitis, urticaria, angioedema, inhalant allergy, inhalant allergic dermatitis, food allergic dermatitis, contact dermatitis, miliary dermatitis, eosinophilic granuloma, head and neck pruritus and generalized pruritus. It will thus be understood herein that the term “allergic” can relate both to “auto-antigens” and to exogenous antigens.

[0079] As used herein, the term “OTIS-3 score” or “0-3 Otitis Index Score» refers to a clinical scale designed to estimate the severity of symptoms of otitis externa (OE) in animals, specifically dogs, particularly dogs with atopic dermatitis or other conditions that predispose them to ear problems. It is based on attributing a score of 0 to 3 for each of erythema, edema / swelling, erosions / ulcerations, exudate, and pain in dogs suffering from OE (Nuttal et al. Vet Dermatol. 2014; volume 25: pp 530-537).

[0080] As used herein, the term “Cytology score” for otitis externa in animals, specifically dogs, is used to quantify the presence of bacteria, yeast, and inflammatory or neoplastic cells in the ear canal. The scores help establish the severity of the infection and can be used for monitoring at future veterinary consultations. The score commonly assesses the presence and the abundance of bacteria, yeast and leucocytes / neutrophils.Attorney Docket No.: 00307-0214-00304 Mars Ref.: MARS / P / 393182 / WO / SEC / 1

[0081] As used herein, the term “Relapse” or “relapse rate” for otitis externa is defined as the mean number of occasions that animals’ ears, in particular dog’s ears, change from a well-managed state to a problematic state over a period of time. A relapse can be defined as a worsening in the OTIS-3 score, where the score increases from less than 4 to more than 4 in one or both of an animal’s ear.

[0082] As used herein, the term “CADESI-04” or “Canine Atopic Dermatitis Extent and Severity Index” refers to a scoring system to evaluate the extent and severity of atopic dermatitis (AD) in animals, in particular canines. CADESI-04 assesses the severity of dermatitis by quantifying clinical signs and their extent on the dog's body (e.g., head, neck, trunk, limbs). Each affected area is scored based on the severity of lesions, including signs like erythema (redness), excoriation (scratching), lichenification (thickening of the skin), and / or alopecia (hair loss). The total score is calculated by combining the extent and severity scores, providing a tool to assess the likelihood that an animal has atopic dermatitis.

[0083] As used herein, “Pruritus Visual Analogue Score” or “pVAS” refers to a scoring system used to assess the intensity of itching (pruritus) experienced by animals. This score is generally measured with the Hills’ Pruritus VisualAnalogue Score (Hill et al., 2007). PVAS is scored by the scorer using a zero to ten analog scale, with a score of zero representing no pruritus / chewing and a score of ten equating to incessant and intense pruritus / chewing.

[0084] As used herein, the term “Medication score” refers to a quantitative system designed to measure the frequency and dosage of one or more anti-otitis externa agent administered by an animal to control otitis externa. The scoring system has been described previously (Saridomichelakis et al. Vet Rec 2021 ; 188: e19) with a higher score corresponding to a higher medication burden for the animal.

[0085] As used herein, the term “wet food” or “wet food composition” generally refers to a food composition having a moisture content of about 30wt% or more, generally of more than about 40% by weight, relative to the total weight of the food composition. In certain particular embodiments, the wet food composition has a moisture content lower than about 90% by weight, relative to the total weight of the food composition. In general, it is the final product of a process including a final step of sterilization (instead of a drying step). In some embodiments, the wet food consists of a chunk form, more particularly of chunks in gravy form. In someAttorney Docket No.: 00307-0214-00304Mars Ref.: MARS / P / 393182 / WO / SEC / 1 particular embodiments, the wet food consists of chunks and gravy, chunks in jelly, loaf, mousse, terrine, bites form.

[0086] “Chunks and gravy” products comprise a preformed meat particle prepared by making a meat emulsion and by putting this meat emulsion through a muzzle under pressure and then cooked. A product, such as cooked meat, is diced into chunks, which are eventually mixed with a gravy or sauce. The two components are then filled into a container, usually a can or pouch, which is seamed or sealed and sterilized. As opposed to the ground loaf, chunk and gravy compositions have physically separated, discrete chunks (i.e., pieces of ground meat and grains) as prepared. These discrete particles are present in the gravy-type liquid in the final container. When serving, chunk and gravy products flow out of the can and can be easily mixed with other dry products. While the chunk and gravy products allow better integrity of the individual ingredients, the heterogeneous formulation of the chunk and gravy products are sometimes disfavored by consumers.

[0087] Wet food compositions are generally packaged in can-like containers and are considered “wet” in appearance because of the moisture contained therein. Two types of wet compositions are generally known in the art. The first is known in the art as “ground loaf.” Loaf products are typically prepared by contacting a mixture of components under heat to produce an essentially homogeneous, intracellular honeycomb-type mass or “ground loaf.” The ground loaf mass is then packaged into a cylindrical container, such as a can. Upon packing, ground loaf assumes the shape of the container such that the ground loaf must be cut when serving to a companion animal.

[0088] In certain embodiments, the wet food composition is packaged. In this way, the consumer is able to identify, from the packaging, the ingredients in the food product and confirm that it is suitable for the particular pet in question. The packaging can be metal, plastic, paper or card.

[0089] As used herein, the term “dry food” or “dry food composition” generally refers to a food or composition having a moisture content of less than about 12% by weight, relative to the total weight of the food composition, and commonly even less than about 7% by weight, relative to the total weight of the food composition. In certain particular embodiments, dry food according to the present disclosure has a moisture content of at most about 12% by weight. In certain embodiments, the said dry food has a moisture content of about 7% by weight orAttorney Docket No.: 00307-0214-00304Mars Ref.: MARS / P / 393182 / WO / SEC / 1 less, such as about 5% by weight. In certain particular embodiments, the dry food has a moisture content of more than about 3% by weight, relative to the total weight of the food composition. For instance, the Examples provided herein illustrate a dry food having a moisture content of about 9.5% by weight, relative to the total weight of the food composition. In a certain particular embodiment, the dry food consists of a kibble. In certain embodiments, for example and without limitation, kibbles can include particulates; pellets; pieces of pet food, dehydrated meat, meat analog, vegetables, and combinations thereof; and pet snacks, such as meat or vegetable jerky, rawhide, and biscuits. The dry food composition can be manufactured by mixing together ingredients and kneading in order to make consistent dough that can be cooked. In general, it can be the final product of a process including an extrusion step followed by a drying step.

[0090] The process of creating a dry food is usually done by baking and / or extruding. The dough is typically fed into a machine called an expander and / or extruder, which uses pressurized steam or hot water to cook the ingredients. While inside the extruder, the dough is under extreme pressure and high temperatures. The dough is then pushed through a die (specifically sized and shaped hole) and then cut off using a knife. The puffed dough pieces are made into kibble by passing it through a dryer so that moisture is dropped down to a defined target ensuring stability of the food until consumption. The kibble can then be sprayed with fats, oils, minerals, vitamins, the natural extracts cocktail and optionally sealed into packages. In certain particular embodiments, the dry food composition is packaged. In this way, the consumer is able to identify, from the packaging, the ingredients in the food product and confirm that it is suitable for the particular pet, e.g., dog, in question. The packaging can be metal, plastic, paper or card.

[0091] As used herein, the term “semi-moist food’ or “semi-moist food composition” generally refers to a food composition with an intermediate moisture content of about 12% to about 30% by weight, relative to the total weight of the food composition. Hence, such semi-moist food composition is generally the final product of a process allowing a moisture content value that is intermediate between a dry food and a wet food. In certain embodiments, the said process can comprise a step of adding a humectant agent. In certain embodiments, the said process comprises an extrusion step and a subsequent treatment step with Super-Heated Stream (SHS). In certain embodiments, the semi-moist food according to the presentAttorney Docket No.: 00307-0214-00304 Mars Ref.: MARS / P / 393182 / WO / SEC / 1 disclosure contains more than about 12% by weight and at most about 30% moisture by weight, relative to the total weight of the food composition. In certain embodiments, a semi-moist food composition has about 11% by weight to about 20% moisture by weight, relative to the total weight of the food composition, and / or a water activity of about 0.64 to about 0.75. In certain particular embodiments, a semimoist food composition has about 11 % to about 20% moisture by weight, relative to the total weight of the food composition, and a water activity of about 0.64 to about 0.75.

[0092] As used herein, the term “water activity’’ refers to the ratio of the partial vapor pressure of water in a food composition divided by the standard state partial vapor pressure of water. Several methods, known to the skilled person, can be employed to measure the water activity such as but not limited to a resistive electrolytic, a capacitance or a dew point hygrometer. In certain particular embodiments, it is referred to the method prescribed by the International Standard ISO 21087 relating to determining water activity in animal food and animal feeding stuffs.

[0093] As non-limitative example, semi-moist food can be obtained using Super-Heated Stream (SHS) processes such as processes or methods described in the published patent applications W02009 / 018990, W02009 / 018996,WO2010 / 112097, WO2014 / 122072, WO2016 / 071372 and / or WO2016 / 071367, the disclosures of which are incorporated herein in their entireties.

[0094] In a certain particular embodiment, when the food composition is a semi-moist food, it consists of soft semi-moist kibbles.

[0095] According to certain embodiments, the moisture content of food composition according to the specification can be determined by a Loss on Drying Method, including the steps of:

[0096] Weighing a sample of a food composition, thereby obtained the total weight;

[0097] Heating, such as 135 ± 2 °C for 240 minutes, the sample of step a) in an oven until the moisture is all driven off, thereby obtained a dry sample;

[0098] Weighing the dry sample; thereby obtained the dry weight;

[0099] Calculating the difference between the total weight and the dry weight, thereby obtaining the moisture weight, as:Moisture weight = (total weight) - (dry weight)Attorney Docket No.: 00307-0214-00304Mars Ref.: MARS / P / 393182 / WO / SEC / 1Units

[0100] All weight percentages expressed herein are by weight of the total weight of dry matter of the food composition unless expressed otherwise.

[0101] An amount of a component as expressed as gram per megacalories (Mcal)consists of a weight amount of the said component by unit of Metabolizable Energy (ME) of the total animal food composition.

[0102] As used herein, the ME parameter is intended to represent the energy value of a food composition that is directly metabolized after consumption. Within the scope of the present disclosure, the ME value can be measured by any suitable method known in the art.

[0103] Illustratively, the ME value can be measured using feeding trial. In practice, the gross energy (GE) of the food is determined in the laboratory, and the amounts of food eaten by the animals are recorded. The feces and urine from the animals are collected, and the energy in each is determined and called fecal energy (FE) and urinary energy (UE), respectively. The ME is then calculated as:ME (kcal / kg) = [GE - (FE + UE)] / Kg of food consumed.

[0104] Alternatively, the ME value can be measured by a mathematical method, in particular taking into account the percentage of crude fat (CF), of crude protein (CP), and NFE (carbohydrates) in the composition. In practice each percentage is multiplied by its respective Atwater Factors. The resulting sum is then multiplied by 10. The mathematical method can be represented by the following formula:ME (kcal / kg) = 10 x [(3.5 x CP) + (8.5 x CF) + (3.5 x NFE)].

[0105] Metabolizable Energy is conventionally determinable according to standard methods, and especially according to the NRC, nutrient requirements of dogs and cats, 2006, academy press, Washington DC.

[0106] In a preferred embodiment, the content for major nutrients or ingredients of the food composition according to the specification can be expressed in mg / kg of the companion animal’s bodyweight / day (mg / kg Bwt / day).

[0107] It is well known that the daily amount of food to be fed to an animal, may depend on the animal’s weight. This is particularly true for canines and felines such as dogs and cats.Attorney Docket No.: 00307-0214-00304Mars Ref.: MARS / P / 393182 / WO / SEC / 1

[0108] Illustratively, classification of dogs in regard to their weight encompasses the four groups as follows:- small dogs: less than 10kg;- medium dogs: from 10 kg to 25kg;- large dogs: from 25 kg to 45kg; and- very large dogs: more than 45kg.

[0109] An example of the daily amount of food which is recommended to feed dogs for each of the weight categories discussed above is as follows:- small dogs: from 30g to 200g per day;- medium dogs: from 100g to 400g per day;- large dogs: from 200g to 600g per day; and- very large dogs: from 360g to 900g per day.

[0110] Consequently, the skilled artisan may easily determine the amount, or amount range, of , for instance, glycyrrhizin that shall be included by weight of a food composition, so that a canine, and especially a dog, will be provided with the preferred daily amount of glycyrrhizin disclosed herein, e.g. as expressed as a daily weight amount of glycyrrhizin per kg of the animal’s bodyweight.

[0111] Illustratively, classification of cats in regard to their weight encompasses the four groups as follows:- Small cats: up to 3kg- Medium cats: between 3kg and 4.5kg- Large cats: between 4.5kg and 6 kg- Very large cats: above 6kg

[0112] An example of the daily amount of food which is recommended to feed cats for each of the weight categories discussed above is as follows:- Small cats: 30g-80g per day- Medium cats: 40g-100g per day- Large cats: 50g-120g per day- Very large cats 60g-140g per day

[0113] Consequently, the skilled artisan may easily determine the amount, or amount range, of glycyrrhizin that shall be included by weight of a food composition, so that a feline, and especially a cat, will be provided with the preferred daily amount of glycyrrhizin disclosed herein, e.g. as expressed as a daily amount of glycyrrhizin per kg of the animal’s bodyweight.Attorney Docket No.: 00307-0214-00304 Mars Ref.: MARS / P / 393182 / WO / SEC / 1Glycyrrhizin and curcuminoidsGlycyrrhizin

[0114] The food compositions as described herein include glycyrrhizin. Glycyrrhizin is provided in the food composition by a source of glycyrrhizin.

[0115] As used herein, the term “glycyrrhizin” designates a constituent found in the root of Glycyrrhiza glabra, i.e., licorice or liquorice, plant. Glycyrrhizin, the most prominent compound found in licorice, is a triterpene glycoside. Licorice is a perennial plant naturally occurring or cultivated in Europe and Asia. In some embodiments, licorice can consist of licorice root.

[0116] The structure of glycyrrhizin encompasses a triterpene portion(glycyrrhetinic acid) and two iduronic acid residues. Other names for glycyrrhizin can include Glycyrrhizinic acid, Glycyrrhizic acid, Glycyrrhetinic acid glycoside, and (3- beta,20-beta)-20-Carboxy-11 -oxo-30-norolean-12-en-3-yl-2-O-beta-D- glucopyranuronosyl-alpha-D glucopyranosiduronic acid.

[0117] Glycyrrhizin can be extracted from various natural plants by several extraction techniques known by a skilled person in the art, such as, for example, supercritical CO2 extraction, aqueous two-phase extraction, solvent extraction, third- phase extraction, microwave-assisted extraction or ultrasound-assisted extraction.

[0118] Glycyrrhizin has CAS Registry Number: 1405-86-3 and is characterized by the following structure:

[0119] In certain embodiments, the term glycyrrhizin as used herein can refer to one of its pharmaceutically acceptable salts and / or racemic, enantiomeric, diastereoisomeric or tautomeric forms.Attorney Docket No.: 00307-0214-00304Mars Ref.: MARS / P / 393182 / WO / SEC / 1

[0120] Examples of the pharmaceutically acceptable salts include but are not limited to ammonium salts such as monoammonium glycyrrhizinate, alkali metal salts such as disodium glycyrrhizinate, trisodium glycyrrhizinate and dipotassium glycyrrhizinate.

[0121] Glycyrrhizin can be found in some naturally-occuring extracts and / or plants, or chemically obtained (Shabkhiz et al. Food Chem. 2016, 210: 396-401 ).

[0122] In certain embodiments, glycyrrhizin can be extracted from a glycyrrhizin source such as licorice. A glycyrrhizin source can be a glycyrrhizin- containing extract obtained from a plant material. In certain particular embodiments, a glycyrrhizin-containing extract can be obtained from a plant material containing glycyrrhizin, such as licorice, by an extraction method including at least the steps of:(a) Providing a plant material containing glycyrrhizin;(b) Grinding the plant material of step a), preferably in a solvent, thereby obtained a grinded mixture;(c) Extracting glycyrrhizin from the grinded mixture, thereby obtaining a glycyrrhizin-containing extract;(d) Optionally filtering the glycyrrhizin extract, thereby obtained a filtered glycyrrhizin extract;(e) Optionally concentrating the filtered glycyrrhizin extract;(f) Optionally spray-drying the filtered glycyrrhizin extract, thereby obtained a powder; and(g) Optionally sieving the powder.

[0123] As used herein a plant material containing glycyrrhizin” refers to a glycyrrhizin source. In certain embodiments, a plant material containing glycyrrhizin refers to a Glycyrrhiza root. In certain more particular embodiments, a plant material containing glycyrrhizin refers to a glycyrrhizin-containing licorice extract or a glycyrrhizin-containing licorice.

[0124] A solvent can be acetic acid, n-butanol, isopropanol, n-propanol, ethanol, methanol, formic acid, dimethylformamide, dimethyl sulfoxide, acetonitrile, acetone, dichloromethane, tetra hydrofuran, ethyl acetate, n-hexane, benzene, toluene, diethyl ether, chloroform, 1 ,4-dioxane, water or a combination thereof. In certain particular embodiments, the solvent is water.

[0125] In certain embodiments, a plant material containing glycyrrhizin can be licorice. Specifically, licorice or Glycyrrhiza is selected from the group consisting ofAttorney Docket No.: 00307-0214-00304Mars Ref.: MARS / P / 393182 / WO / SEC / 1 glycyrrhiza acanthocarpa, glycyrrhiza aspera, glycyrrhiza astragalina, glycyrrhiza bucharica, glycyrrhiza echinate, glycyrrhiza eglandulosa, glycyrrhiza eurycarpa, glycyrrhiza foetida, glycyrrhiza foetidissima, glycyrrhiza frearitis, glycyrrhiza glabra, glycyrrhiza gontscharovii, glycyrrhiza iconica, glycyrrhiza inflata, glycyrrhiza korshinskyi, glycyrrhiza lepidota, glycyrrhiza pallidiflora, glycyrrhiza squamulose, glycyrrhiza triphylla, glycyrrhiza uralensis, glycyrrhiza yunnanensis, and combinations thereof.

[0126] In some embodiments, a glycyrrhizin source can be glycyrrhiza glabra. In certain embodiments, licorice can contain from about 1 % to about 30% by weight or from about 2% to about 20% by weight or from about 3% to about 20% by weight of glycyrrhizin based on the dry matter of the licorice.

[0127] In certain embodiments, licorice root can contain from about 1% to about 25% by weight or about 4% to about 12% by weight of glycyrrhizin, based on the dry matter of the licorice root.

[0128] In some embodiments, licorice root can contain from about 6% to about 12% of glycyrrhizin by weight, based on the dry matter of the licorice root. In some embodiments, licorice root can include about 6.0%, or about 6.5%, or about 7.0%, or about 7.5%, or about 8.0%, or about 8.5%, or about 9.0%, or about 9.5%, or about 10.0%, or about 10.5%, or about 11.0%, or about 11.5%, or about 12.0% by weight of glycyrrhizin, based on the dry matter of the licorice root.

[0129] In certain embodiments, licorice could be provided from a commercially available source such as the Licorice root PE 12% Glycyrrhizin preparation supplied by Naturex (Product ref; ED161596).

[0130] In some embodiments, a source of glycyrrhizin can consist of licorice or an extract thereof containing glycyrrhizin. Any other source of glycyrrhizin known by the person skilled in the art, especially any other source of glycyrrhizin apart from licorice, can also be used. In certain embodiments, the glycyrrhizin source can be pure glycyrrhizin.

[0131] In a general manner, the amount of glycyrrhizin in a given plant source or extract, can be expressed in g / Mcal or by weight per total weight of dry matter of the given plant source, extract or composition or in mg / kg animal’s bodyweight (Bwt) / day in a food composition.Attorney Docket No.: 00307-0214-00304Mars Ref.: MARS / P / 393182 / WO / SEC / 1

[0132] In some embodiments, the food composition as described herein is formulated for providing to a companion animal in need thereof a daily amount of glycyrrhizin of at least 0.1 mg / kg of the companion animal’s bodyweight (kg Bwt).

[0133] In some embodiments, the food composition as described herein is formulated for providing to a companion animal in need thereof a daily amount of glycyrrhizin from about 0.1 mg / kg of the companion animal’s bodyweight to about 1 mg / kg of the companion animal’s bodyweight.

[0134] In some embodiments, the food composition as described herein can be formulated for providing to a companion animal in need thereof a daily amount of glycyrrhizin from about 0.2 mg / kg to about 0.8mg / kg Bwt, or from about 0.2 mg / kg Bwt to about 0.6mg / kg Bwt, or from about 0.3 mg / kg Bwt to about 0.8mg / kg Bwt, or from about 0.3 mg / kg Bwt to about 0.6mg / kg Bwt.

[0135] In some embodiments, the food composition as described herein can be formulated for providing to a companion animal in need thereof a daily amount of glycyrrhizin of about 0.1 mg / kg Bwt, 0.15 mg / kg Bwt, 0.2 mg / kg Bwt, 0.25 mg / kg Bwt, 0.3 mg / kg Bwt, 0.35 mg / kg Bwt, 0.4 mg / kg Bwt, 0.45 mg / kg Bwt, 0.5 mg / kg Bwt, 0.55 mg / kg Bwt, 0.6 mg / kg Bwt, 0.65 mg / kg Bwt, 0.7 mg / kg Bwt, 0.75 mg / kg Bwt, 0.8 mg / kg Bwt, 0.85 mg / kg Bwt, 0.9 mg / kg Bwt, 0.95 mg / kg Bwt and 1 mg / kg of the companion animal’s bodyweight.

[0136] Glycyrrhizin is provided in the formulation of the food composition by a glycyrrhizin source.

[0137] Therefore, the present disclosure also relates to a food composition including a source of glycyrrhizin, wherein the source of glycyrrhizin can be licorice containing from about 5% to about 7% of glycyrrhizin.

[0138] In some embodiments, the food composition can include from about 200ppm to about 600ppm by weight or from about 300ppm to about 500ppm by weight of a source of glycyrrhizin, such as licorice.

[0139] In some embodiments, the food composition can include about 200ppm, 210ppm, 220ppm, 230ppm, 240ppm, 250ppm, 260ppm, 270ppm, 280ppm, 290ppm, 300ppm, 310ppm, 320ppm, 330ppm, 340ppm, 350ppm, 360ppm, 370ppm, 380ppm, 390ppm, 400ppm, 410ppm, 420ppm, 430ppm, 440ppm, 450ppm, 460ppm, 470ppm, 480ppm, 490ppm, 500ppm, 510ppm, 520ppm, 530ppm, 540ppm, 550ppm, 560ppm, 570ppm, 580ppm, 590ppm and 600ppm by weight of a source of glycyrrhizin, such as licorice.Attorney Docket No.: 00307-0214-00304 Mars Ref.: MARS / P / 393182 / WO / SEC / 1

[0140] In some embodiments, the food composition can include about 480ppm by weight of a source of glycyrrhizin, such as licorice.

[0141] Such amounts of said source of glycyrrhizin would be easily adapted by the person skilled in the art, depending for example on the concentration of glycyrrhizin in the source such as licorice, to be able to deliver the appropriate daily amount per kg of the companion animal’s bodyweight, of glycyrrhizin to the companion animal in need thereof.Curcuminoids

[0142] The food composition as described herein includes curcuminoids.

[0143] As used herein, the term “curcuminoid(s)” refers to phenols that are present in the Indian spice turmeric. Turmeric is generally derived from the roots of the Curcuma longa plant. Curcuminoids have also been found in roots of other species in the plant family Zingiberaceae of the Curcuma genus. In some embodiments, turmeric can contain from about 60% to about 80% by weight of curcumin, based on the dry matter of turmeric, from about 15% to about 30% by weight of demethoxycurcumin, based on the dry matter of turmeric, and from about 2% to about 6% by weight of bis-demethoxycurcumin, based on the dry matter of turmeric. The curcuminoid in the food composition or the kit of the present disclosure can be of any format, including a powder or lipid extract.

[0144] In certain embodiments, curcuminoids can be found in some naturally- occuring extracts and / or plants, or chemically obtained.

[0145] In some embodiments, the source of curcuminoids consists of a turmeric extract, i.e., Curcuma Longa. Non-limitative examples of turmeric extract are the turmeric extract BCM-95® from Arjuna or the turmeric extract from Naturex. Any other source of curcuminoids known to a person skilled in the art can also be used.

[0146] Other available sources for curcuminoids include but are not limited to liposomal curcumin, curcumin nanoparticles, curcumin phospholipid complex (e.g., M ERIVA sourcing, about 20% total curcuminoids to BCM95 Arjuna with about 90% by weight of total curcuminoids), structural analogues of curcumin (e.g., EF-24) demethoxycurcumin, bisdemethoxycurcumin, tetrahydrocurcumin, and commercial / DM, and any formulation designed to enhance curcumin bioavailability.Attorney Docket No.: 00307-0214-00304 Mars Ref.: MARS / P / 393182 / WO / SEC / 1

[0147] In certain embodiments, curcuminoids can be found in other botanicals in addition to Curcuma longa, such as Curcuma xanthorrhiza and Curcuma zedoania. Curcuminoid in its pure form has poor solubility in water. Curcuminoids can be extracted from curcuminoids-containing plants, e.g., turmeric root, with organic solvent such as ethanol or acetone.

[0148] In some embodiments, curcuminoids according to the present disclosure can include compounds of the general formula (I), pharmaceutically acceptable salts, tautomers and stereoisomers thereof:wherein R1and R2are independently chosen from hydrogen atom, methoxy, methyl, hydroxyl and ethoxy group.

[0149] In certain embodiments, R1and R2are the same. In certain other embodiments, R1and R2are different.

[0150] In certain embodiments, the curcuminoids can be selected from the group including or consisting of curcumin, demethoxycurcumin, bismeth oxy cucurm in, methoxycurcumin, tetrahydrocurcumin hexahydrocurcumin, monodemethoxycurcumin, and combinations thereof.

[0151] In some embodiments, curcuminoid is curcumin.

[0152] In some embodiments, the source of curcuminoids (e.g., curcumin) is turmeric.

[0153] In some embodiments, the food composition as described herein can be formulated for providing to a companion animal in need thereof a daily amount of curcuminoid of at least 0.5mg / kg of the companion animal’s bodyweight (kg Bwt).

[0154] In some embodiments, the food composition as described herein can be formulated for providing to a companion animal in need thereof a daily amount of curcuminoid from about 0.5mg / kg Bwt to about 6mg / kg Bwt.

[0155] In some embodiments, the food composition as described herein can be formulated for providing to a companion animal in need thereof a daily amount of curcuminoid from about 0.7mg / kg Bwt to about 6mg / kg Bwt, or from about 1 mg / kg Bwt to about 5.5mg / kg Bwt, or from about 1 mg / kg Bwt to about 5mg / kg Bwt, or fromAttorney Docket No.: 00307-0214-00304Mars Ref.: MARS / P / 393182 / WO / SEC / 1 about 1 .5 mg / kg Bwt to about 5mg / kg Bwt, or from about 2 mg / kg Bwt to about 4.5mg / kg Bwt.

[0156] In some embodiments, the food composition as described herein can be formulated for providing to a companion animal in need thereof a daily amount of curcuminoid of about 0.5mg / kg Bwt, 0.55mg / kg Bwt, 0.6mg / kg Bwt, 0.65mg / kg Bwt, 0.7mg / kg Bwt, 0.75mg / kg Bwt, 0.8mg / kg Bwt, 0.85mg / kg Bwt, 0.9mg / kg Bwt, 0.95mg / kg Bwt, 0.1 mg / kg Bwt, 0.15mg / kg Bwt, 0.2mg / kg Bwt, 0.25mg / kg Bwt, 0.3mg / kg Bwt, 0.35mg / kg Bwt, 0.4mg / kg Bwt, 0.45mg / kg Bwt, 0.5mg / kg Bwt, 0.55mg / kg Bwt, 0.6mg / kg Bwt, 0.65mg / kg Bwt, 0.7mg / kg Bwt, 0.75mg / kg Bwt, 0.8mg / kg Bwt, 0.85mg / kg Bwt, 0.9mg / kg Bwt, 0.95mg / kg Bwt, 1 mg / kg Bwt, 1.1 mg / kg Bwt, 1.15mg / kg Bwt, 1.2mg / kg Bwt, 1.25; 1.3mg / kg Bwt, 1.35mg / kg Bwt, 1.4mg / kg Bwt, 1.45mg / kg Bwt, 1.5mg / kg Bwt, 1.55mg / kg Bwt, 1.6mg / kg Bwt, 1.65mg / kg Bwt, 1.7mg / kg Bwt, 1.75mg / kg Bwt, 1.8mg / kg Bwt, 1.85mg / kg Bwt, 1.9 mg / kg Bwt, 1.95 mg / kg Bwt or 2mg / kg Bwt, 2.05 mg / kg Bwt, 2.1 mg / kg Bwt, 2.15 mg / kg Bwt, 2.2 mg / kg Bwt, 2.25 mg / kg Bwt, 2.3 mg / kg Bwt, 2.35 mg / kg Bwt, 2.4 mg / kg Bwt, 2.45 mg / kg Bwt,2.5 mg / kg Bwt, 2.55 mg / kg Bwt, 2.6 mg / kg Bwt, 2.65 mg / kg Bwt, 2.7 mg / kg Bwt, 2.75 mg / kg Bwt, 2.8 mg / kg Bwt, 2.85 mg / kg Bwt, 2.9 mg / kg Bwt, 2.95 mg / kg Bwt, 3 mg / kg Bwt, 3.05 mg / kg Bwt, 3.1 mg / kg Bwt, 3.15 mg / kg Bwt, 3.2 mg / kg Bwt, 3.25 mg / kg Bwt, 3.3 mg / kg Bwt, 3.35 mg / kg Bwt, 3.4 mg / kg Bwt, 3.45 mg / kg Bwt, 3.5 mg / kg Bwt, 3.55 mg / kg Bwt, 3.6 mg / kg Bwt, 3.65 mg / kg Bwt, 3.7 mg / kg Bwt, 3.75 mg / kg Bwt, 3.8 mg / kg Bwt, 3.85 mg / kg Bwt, 3.9 mg / kg Bwt, 3.95 mg / kg Bwt, 4 mg / kg Bwt, 4.05 mg / kg Bwt, 4.1 mg / kg Bwt, 4.15 mg / kg Bwt, 4.2 mg / kg Bwt, 4.25 mg / kg Bwt, 4.3 mg / kg Bwt, 4.35 mg / kg Bwt, 4.4 mg / kg Bwt, 4.45 mg / kg Bwt, 4.5 mg / kg Bwt, 4.55 mg / kg Bwt, 4.6 mg / kg Bwt, 4.65 mg / kg Bwt, 4.7 mg / kg Bwt, 4.75 mg / kg Bwt, 4.8 mg / kg Bwt, 4.85 mg / kg Bwt, 4.9 mg / kg Bwt, 4.95 mg / kg Bwt, 5 mg / kg Bwt, 5.05 mg / kg Bwt, 5.1 mg / kg Bwt, 5.15 mg / kg Bwt, 5.2 mg / kg Bwt, 5.25 mg / kg Bwt, 5.3 mg / kg Bwt, 5.35 mg / kg Bwt, 5.4 mg / kg Bwt, 5.45 mg / kg Bwt, 5.5 mg / kg Bwt, 5.55 mg / kg Bwt, 5.6 mg / kg Bwt, 5.65 mg / kg Bwt, 5.7 mg / kg Bwt, 5.75 mg / kg Bwt, 5.8 mg / kg Bwt, 5.85 mg / kg Bwt, 5.9 mg / kg Bwt, 5.95 mg / kg Bwt, or 6 mg / kg Bwt.

[0157] Curcuminoids are provided in the formulation of the food composition by a curcuminoid source.

[0158] Further, the present disclosure relates to a food composition including at least one source of curcuminoids wherein the source of curcuminoids can beAttorney Docket No.: 00307-0214-00304Mars Ref.: MARS / P / 393182 / WO / SEC / 1 turmeric or an extract thereof containing curcuminoids. In some embodiments, the source of curcuminoids can be turmeric extract naturally containing curcuminoids.

[0159] In some embodiments, the food composition can include from about 900ppm to about 1400ppm by weight or from about OOppm to about 1300ppm by weight or from about WOOppm to about WOOppm by weight of a source of curcuminoid, such as a turmeric extract.

[0160] In some embodiments, the food composition can include about 1250ppm by weight of a source of curcuminoids, such as a turmeric extract.

[0161] In some embodiments, the food composition can include about : 900ppm, 910ppm, 920ppm, 930ppm, 940ppm, 950ppm, 960ppm, 970ppm, 980ppm, 990ppm, WOOppm, HOOppm, 1110ppm, 1120ppm, 1130ppm, 1140ppm, 1150ppm, 1160ppm, 1170ppm, 1180ppm, 1190ppm, WOOppm, WWppm, 1220ppm, 1230ppm, 1240ppm, 1250ppm, 1260ppm, 1270ppm, 1280ppm, 1290ppm, WOOppm, WWppm, 1320ppm, 1330ppm, 1340ppm, 1350ppm, 1360ppm, 1370ppm, 1380ppm, 1390 or 1400ppm of a source of curcuminoids, such as turmeric.

[0162] Such amounts of said source of curcuminoid would be easily adapted by the person skilled in the art, depending for example on the concentration of curcuminoid in the source such as turmeric extract, to be able to deliver the appropriate daily amount / kg of bodyweight of curcuminoid to the companion animal in need thereof.Further ingredients

[0163] The food compositions of the present disclosure include glycyrrhizin and curcuminoids, along potentially with a wide variety of components. Non-limiting examples of other components that can be incorporated in the food compositions of the present disclosure, in addition to glycyrrhizin and curcuminoids, are listed below.

[0164] In some embodiments, the food composition can further include linoleic acid.

[0165] In some embodiments, the food composition can further include EPA and / or DHA.

[0166] In some embodiments, the food composition can further include Taurine.

[0167] In some embodiments, the food composition can further include Lutein.Attorney Docket No.: 00307-0214-00304Mars Ref.: MARS / P / 393182 / WO / SEC / 1

[0168] In some embodiments, the food composition can further include Vitamin E.

[0169] In some embodiments, the food composition can further include a combination of at least two ingredients selected from linoleic acid, EPA and / or DHA, Taurine, Lutein and Vitamin E.

[0170] In certain embodiments, the food composition can additionally further include one or more ingredients such as, without limitations, vitamin A, vitamin B3, vitamin C, zinc, vitamin D, one or more fatty acids and / or a combination thereof.Linoleic acid

[0171] In certain embodiments, the food composition described herein can include linoleic acid. As used herein, the term “linoleic acid” refers to a polyunsaturated omega-6 fatty acid, (9Z,12Z)-octadeca-9,12-dienoic acid, which is one of two essential fatty acids for animals.

[0172] For measuring the content of a food composition in linoleic acid, the one skilled in the art can refer to any of well-known techniques. For example, a method based upon the norm NF EN ISO 5508 / 5509 via chromatography in gaseous phase can be used.

[0173] In certain embodiments, the food composition as described herein can include one or more substances, which are sources of linoleic acid.

[0174] Linoleic acid sources, i.e., linoleic acid-containing substances, suitable for the presently disclosed application include but are not limited to vegetable oils, although animal oils or crude fats can also be used. In some embodiments, linoleic sources, i.e., linoleic acid-containing substances, include safflower oil, sunflower oil, soybean oil, sesame oil, canola oil, other plant or animal oils / crude fats, meats or a combination of two or more thereof.

[0175] In certain embodiments, linoleic acid sources, i.e., linoleic acidcontaining substances, that are included in the food composition described herein, can be selected from safflower oil, sunflower oil, soybean oil, sesame oil, canola oil, meats or a combination thereof.

[0176] In some embodiments, the food composition as described herein can be formulated for providing to said companion animal in need thereof a daily amount of linoleic acid from about 25mg / kg of the companion animal’s bodyweight(kg Bwt) to about 120mg / kg of the companion animal’s bodyweight(kg Bwt).Attorney Docket No.: 00307-0214-00304Mars Ref.: MARS / P / 393182 / WO / SEC / 1

[0177] In some embodiments, the food composition as described herein can be formulated for providing to said companion animal in need thereof a daily amount of linoleic acid from about 50mg / kg of the companion animal’s bodyweight(kg Bwt) to about 120mg / kg of the companion animal’s bodyweight(kg Bwt).

[0178] In some embodiments, the food composition as described herein can be formulated for providing to a companion animal in need thereof a daily amount of linoleic acid from about 55mg / kg Bwt to about 110mg / kg Bwt, or from about 60 mg / kg Bwt to about 100mg / kg Bwt, or from about 65mg / kg Bwt to about 95mg / kg Bwt.

[0179] In some embodiments, the food composition as described herein can be formulated for providing to a companion animal in need thereof linoleic acid in a daily amount of about 50mg / kg Bwt, 51 mg / kg Bwt, 52 mg / kg Bwt, 53 mg / kg Bwt, 54 mg / kg Bwt, 55 mg / kg Bwt, 56 mg / kg Bwt, 57 mg / kg Bwt, 58 mg / kg Bwt, 59 mg / kg Bwt, 60 mg / kg Bwt, 61 mg / kg Bwt, 62 mg / kg Bwt, 63 mg / kg Bwt, 64 mg / kg Bwt, 65 mg / kg Bwt, 66 mg / kg Bwt, 67 mg / kg Bwt, 68 mg / kg Bwt, 69 mg / kg Bwt, 70 mg / kg Bwt, 71 mg / kg Bwt, 72 mg / kg Bwt, 73 mg / kg Bwt, 74 mg / kg Bwt, 75 mg / kg Bwt, 76 mg / kg Bwt, 77 mg / kg Bwt, 78 mg / kg Bwt, 79 mg / kg Bwt, 80 mg / kg Bwt, 81 mg / kg Bwt, 82 mg / kg Bwt, 83 mg / kg Bwt, 84 mg / kg Bwt, 85 mg / kg Bwt, 86 mg / kg Bwt, 87 mg / kg Bwt, 88 mg / kg Bwt, 89 mg / kg Bwt, 90 mg / kg Bwt, 91 mg / kg Bwt, 92 mg / kg Bwt, 93 mg / kg Bwt, 94 mg / kg Bwt, 95 mg / kg Bwt, 96 mg / kg Bwt, 97 mg / kg Bwt, 98 mg / kg Bwt, 99 mg / kg Bwt, or 100 mg / kg Bwt.

[0180] In certain embodiments, the food composition described herein can include from about 2.5% to about 6% by weight of linoleic acid.

[0181] In certain embodiments, the food composition described herein can include from about 2.5 to about 6%, or from about 3% to about 5.5%, or from about 3% to about 4.5%, by weight, of linoleic acid.

[0182] In certain embodiments, the food composition described herein can include about 2.5%, 2.6%, 2.7%, 2.8%, 2.9%, 3%, 3.1 %, 3.2%, 3.3%, 3.4%, 3.5%, 3.6%, 3.7%, 3.8%, 3.9%, 4%, 4.1 %, 4.2%, 4.3%, 4.4%, 4.5%, 4.7%, 5%, 5.3%, 5.5%, 5.7%, or 6% by weight of linoleic acid.

[0183] Such amounts source of linoleic acid would be easily adapted by the person skilled in the art to deliver the appropriate daily amount I kg of bodyweight of linoleic acid to the companion animal in need thereof.Attorney Docket No.: 00307-0214-00304Mars Ref.: MARS / P / 393182 / WO / SEC / 1EPA and / or DHA

[0184] In certain embodiments, the food composition described herein can include EPA and / or DHA. As used herein, the term “EPA and / or DHA” designates an omega-3 fatty acid or a mixture of omega-3fatty acids consisting of (i) only eicosapentaenoic acid (EPA), (ii) only docosahexaenoic acid (DHA) or (iii) a combination of eicosapentaenoic acid and docosahexaenoic acid (EPA and DHA).

[0185] Accordingly, an amount of “EPA and / or DHA” refers to EPA, or DHA or a combination of EPA and DHA.

[0186] In certain embodiments, the food composition as described herein, can include a combination of Eicosapentaenoic acid (EPA) and Docosahexaenoic acid (DHA) in a weight ratio of EPA: DHA of from about 0.1 to about 100.

[0187] According to further embodiments, there is no specific requirement regarding the respective amount of EPA and DHA present in the EPA and / or DHA combination. Illustratively, the weight / energy ratio of EPA to DHA can range from 0.0001 to 1000, relative to the total weight of dry matter of the food composition.

[0188] In some embodiments, the food composition described herein can be formulated for providing to said companion animal in need thereof a daily amount of EPA and / or DHA from about 4mg / kg of the companion animal’s bodyweight (kg Bwt) to about 20mg / kg Bwt.

[0189] In some embodiments, the food composition described herein can be formulated for providing to a companion animal in need thereof a daily amount of EPA and / or DHA from about 6mg / kg Bwt to about 17mg / kg Bwt, or from about 7mg / kg Bwt to about 15mg / kg Bwt, or from about 9mg / kg Bwt to about 14mg / kg Bwt.

[0190] In some embodiments, the food composition described herein can be formulated for providing to a companion animal in need thereof a daily amount of EPA and / or DHA of about 4mg / kg Bwt, 4.5mg / kg Bwt, 5mg / kg Bwt, 5.5mg / kg Bwt, 6mg / kg Bwt, 6.5mg / kg Bwt, , 7mg / kg Bwt, 7.5mg / kg Bwt, 8mg / kg Bwt, 8.5mg / kg Bwt, 9mg / kg Bwt, 9.5mg / kg Bwt, 10mg / kg Bwt, 10.5mg / kg Bwt, 11 mg / kg Bwt, 11.5mg / kg Bwt, 12mg / kg Bwt, 12.5mg / kg Bwt, 13mg / kg Bwt, 13.5mg / kg Bwt, 14mg / kg Bwt, 14.5mg / kg Bwt, 15mg / kg Bwt, 15.5mg / kg Bwt, 16mg / kg Bwt, 16.5mg / kg Bwt, 17mg / kg Bwt, 17.5mg / kg Bwt, 18mg / kg Bwt, 18.5mg / kg Bwt, 19mg / kg Bwt, 19.5mg / kg Bwt, or 20mg / kg Bw.

[0191] In certain embodiments, the food composition described herein can include from about 0.1 % to about 1 %, by weight, of EPA and / or DHA.Attorney Docket No.: 00307-0214-00304Mars Ref.: MARS / P / 393182 / WO / SEC / 1

[0192] In certain embodiments, the food composition described herein can include from about 0.5% to about 1%, or from about 0.1% to about 0.7%, or from about 0.5% to about 0.6%, by weight, of ERA and / or DHA.

[0193] In certain embodiments, the food composition described herein can include from about 0.1%, about 0.15%, about 0.2%, about 0.25%, about 0.3%, about 0.35%, about 0.4%, about 0.45%, about 0.5%, about 0.55%, about 0.6%, about 0.65%, about 0.7%, about 0.75%, about 0.8%, about 0.85%, about 0.9%, about 0.95% or about 1% by weight of EPA and / or DHA.

[0194] Such amounts of source of EPA and / or DHA would be easily adapted by the person skilled in the art to deliver the appropriate daily amount I kg of the companion animal’s bodyweight of EPA and / or DHA to the companion animal in need thereof.

[0195] In some embodiments, a source of EPA and / or DHA can be selected from algal oil, fish oil, krill oil, eggs or mixtures thereof.

[0196] In some embodiments, the food composition described herein can include EPA / DHA, wherein at least about 30% by weight or more, about 40% by weight or more, about 50% by weight or more, about 60% by weight or more, about 70% by weight or more, about 80% by weight or more, about 90% by weight or more, about 95% by weight or more, or 100% of EPA and / or DHA is provided from algal oil.

[0197] In some embodiments, the food composition described herein can include EPA / DHA, wherein about 70% by weight or less, about 60% by weight or less, about 50% by weight or less, about 40% by weight or less, about 30% by weight or less, about 20% by weight or less, about 10% by weight or less, about 5% by weight or less, or about 0.5% by weight or less of EPA and / or DHA is provided from fish oil.

[0198] In some embodiments, the food composition described herein can include EPA / DHA, wherein about 95% by weight of EPA and / or DHA is provided form algal oil, and about 5% by weight of EPA and / or DHA is provided from fish oil.

[0199] In some embodiments, the food composition described herein can include EPA / DHA, wherein 100% by weight of EPA and / or DHA is provided form algal oil.

[0200] In this context, the term "provided" means that algal oil and / or fish oil is the, or one of the, source of EPA and / or DHA in the food composition of theAttorney Docket No.: 00307-0214-00304Mars Ref.: MARS / P / 393182 / WO / SEC / 1 disclosure. In other words, it means that these omega-3 fatty acids (EPA and DHA) come from algal oil and / or fish oil, specifying that this oil contributes a certain proportion by weight of EPA and / or DHA in the food composition.Taurine

[0201] In certain embodiments, the food composition described herein can include taurine. Taurine is an organic compound classified as a beta-amino sulfonic acid. Taurine is a non-essential amino acid which is obtained from meat and fish. It stimulates the production of glycosphingolipids in the skin by acting as a precursor molecule. Glycosphingolipids exhibit anti-microbial properties.

[0202] Taurine refers to a compound of the molecular formula C2H7NO3S and of the following chemical structureor one of its pharmaceutically acceptable salts and / or racemic, enantiomeric, diastereoisomeric or tautomeric forms.

[0203] In some embodiments, the food composition described herein can be formulated for providing to said companion animal in need thereof a daily amount of Taurine from about 3mg / kg of the companion animal’s bodyweight (kg Bwt) to about 10Omg / kg Bwt.

[0204] In some embodiments, the food composition described herein can be formulated for providing to said companion animal in need thereof a daily amount of Taurine from about 15mg / kg of the companion animal’s bodyweight (kg Bwt) to about 10Omg / kg Bwt.

[0205] In some embodiments, the food composition described herein can be formulated for providing to a companion animal in need thereof a daily amount of Taurine from about 50mg / kg Bwt to about 90mg / kg Bwt, or from about 60mg / kg Bwt to about 80mg / kg Bwt, or from about 65mg / kg Bwt to about 80mg / kg Bwt.

[0206] In some embodiments, the food composition described herein can be formulated for providing to a companion animal in need thereof a daily amount of Taurine of about 50 mg / kg Bwt, 52 mg / kg Bwt, 55 mg / kg Bwt, 57 mg / kg Bwt, 60 mg / kg Bwt, 62 mg / kg Bwt, 65 mg / kg Bwt, 67 mg / kg Bwt, 70 mg / kg Bwt, 72 mg / kgAttorney Docket No.: 00307-0214-00304Mars Ref.: MARS / P / 393182 / WO / SEC / 1Bwt, 75 mg / kg Bwt, 77 mg / kg Bwt, 80 mg / kg Bwt, 82 mg / kg Bwt, 85 mg / kg Bwt, 87 mg / kg Bwt, or 90 mg / kg Bwt.

[0207] In certain embodiments, the food composition disclosed herein can include from about 0.2% to about 0.7%, by weight, of Taurine.

[0208] In certain embodiments, the food composition described herein can include from about 0.4% to about 0.7%, or from about 0.2% to about 0.5%, or from about 0.4% to about 0.5%, by weight, of Taurine.

[0209] In certain embodiments, the food composition described herein can include about 0.2%, 0.25%, 0.3%, 0.35%, 0.4%, 0.44%, 0.45%, 0.5%, 0.55%, 0.6%, 0.65%, or about 0.7% by weight of Taurine.

[0210] Such amounts of source of Taurine would be easily adapted by the person skilled in the art to deliver the appropriate daily amount I kg of bodyweight of Taurine to the companion animal in need thereof.Lutein

[0211] In certain embodiments, the food composition described herein can include lutein. As used herein, “lutein” refers to a xanthophyll and one of known naturally occurring carotenoids. Lutein is a lipophilic molecule and is generally insoluble in water. Lutein is synthesized only by plants and like other xanthophylls is found in high quantities in green leafy vegetables such as spinach, kale and yellow carrots. Lutein is isomeric with zeaxanthin, differing only in the placement of one double bond. The principal natural stereoisomer of lutein is (3R,3'R,6'R)-beta, epsilon-carotene-3, 3'-diol. Lutein is present in plants as fatty-acid esters, with one or two fatty acids bound to the two hydroxyl-groups.

[0212] Lutein refers to a compound of the following chemical structure:or one of its pharmaceutically acceptable salts and / or racemic, enantiomeric, diastereoisomeric or tautomeric forms.

[0213] In some embodiments, the food composition described herein can be formulated for providing to said companion animal in need thereof a daily amount ofAttorney Docket No.: 00307-0214-00304Mars Ref.: MARS / P / 393182 / WO / SEC / 1 lutein from about 0.0001 mg / kg of the companion animal’s bodyweight (kg Bwt) to about 0. 1 mg / kg Bwt.

[0214] In some embodiments, the food composition described herein can be formulated for providing to said companion animal in need thereof a daily amount of lutein from about 0.015mg / kg of the companion animal’s bodyweight (kg Bwt) to about 0.1 mg / kg Bwt.

[0215] In some embodiments, the food composition described herein can be formulated for providing to a companion animal in need thereof a daily amount of lutein from about 0.05mg / kg Bwt to about 0.095mg / kg Bwt, or from about 0.055mg / kg Bwt to about 0.09mg / kg Bwt, or from about 0.06mg / kg of bodyweight to about 0.085mg / kg of bodyweight.

[0216] In some embodiments, the food composition described herein can be formulated for providing to a companion animal in need thereof a daily amount of lutein of about 0.015 mg / kg Bwt, 0.02 mg / kg Bwt, 0.025 mg / kg Bwt, 0.03 mg / kg Bwt, 0.035 mg / kg Bwt, 0.04 mg / kg Bwt, 0.045 mg / kg Bwt, 0.05 mg / kg Bwt, 0.055 mg / kg Bwt, 0.06 mg / kg Bwt, 0.065 mg / kg Bwt, 0.07 mg / kg Bwt, 0.075 mg / kg Bwt, 0.08 mg / kg Bwt, 0.085 mg / kg Bwt, 0.09 mg / kg Bwt, 0.095 mg / kg Bwt, and 0.1 mg / kg Bwt.

[0217] In certain embodiments, the food composition disclosed herein can include from about 2ppm to about 8ppm, by weight, of lutein.

[0218] In certain embodiments, the food composition described herein can include from about 4ppm to about 8ppm, from about 2ppm to about 6ppm, from about 4ppm to about 6ppm, by weight, of lutein.

[0219] In certain embodiments, the food composition described herein can include of about 2ppm, 2.1 ppm, 2.4ppm, 2.5ppm, 2.6ppm, 2.7ppm, 2.8ppm, 2.9ppm, 3ppm, 3.1 ppm, 3.2ppm, 3.3ppm, 3.4ppm, 3.5ppm, 3.6ppm, 3.7ppm, 3.8ppm, 3.9ppm, 4ppm, 4.1 ppm, 4.2ppm, 4.3ppm, 4.4ppm, 4.5ppm, 4.6ppm, 4.7ppm, 4.8ppm, 4.9ppm, 4.95 ppm, 5ppm, 5.1 ppm, 5.2ppm, 5.3ppm, 5.4ppm, 5.5ppm, 5.6ppm, 5.7ppm, 5.8ppm, 5.9ppm, 6ppm, 6.1 ppm, 6.2ppm, 6.3ppm, 6.4ppm, 6.5ppm, 6.6ppm, 6.7ppm, 6.8ppm, 6.9ppm, 7ppm, 7.1 ppm, 7.2ppm, 7.3ppm, 7.4ppm, 7.5ppm, 7.6ppm, 7.7ppm, 7.8ppm, 7.9ppm, or 8ppm by weight of lutein.

[0220] Such amounts of source of lutein would be easily adapted by the person skilled in the art to deliver the appropriate daily amount I kg of bodyweight of lutein to the companion animal in need thereof.Attorney Docket No.: 00307-0214-00304 Mars Ref.: MARS / P / 393182 / WO / SEC / 1Vitamin E

[0221] In certain embodiments, the food composition described herein can include vitamin E. Vitamin E is a collective term for a group of fat-soluble compounds with antioxidant properties, including those called tocopherols and tocotrienols, which share the same biological activity. The most biologically active biological form of Vitamin E (also the most active antioxidant) in animal tissue is alpha-tocopherol. Vitamin E cannot be synthesized in vivo. Vitamin E protects against the loss of cell membrane integrity, which adversely alters cellular and organelle function.

[0222] Vitamin E refers to a compound of the following structure:or one of its pharmaceutically acceptable salts and / or racemic, enantiomeric, diastereoisomeric or tautomeric forms.

[0223] In some embodiments, Vitamin E can be in any form. In some embodiments, Vitamin E can be liquid, semi-solid or solid. In some embodiments, Vitamin E can be a tocopherol or a tocotrienol. In some embodiments, Vitamin E can be alphatocopherol, (d-x or dl-oc) beta-tocopherol (d-,B or dl-), gamma-tocopherol (dot or dim), delta-tocopherol, alpha-tocotrienol, beta-tocotrienol, gamma-tocotrienol or delta-tocotrienol.

[0224] In some embodiments, Vitamin E is alpha-tocopherol.

[0225] A source of Vitamin E is not limiting. In certain embodiments, a Vitamin E source can include Vitamin E acetate, (e.g., tocopherol acetate), Vitamin E acetate adsorbate or Vitamin E acetate spray dried. In some embodiments, a source of Vitamin E can be synthetic or natural.

[0226] In some embodiments, the food composition described herein can be formulated for providing to a companion animal in need thereof a daily amount of Vitamin E from about 0.1 mg / kg of the companion animal’s bodyweight to about 20mg / kg of the companion animal’s bodyweight (kg Bwt).

[0227] In some embodiments, the food composition described herein can be formulated for providing to a companion animal in need thereof a daily amount ofAttorney Docket No.: 00307-0214-00304Mars Ref.: MARS / P / 393182 / WO / SEC / 1Vitamin E from about 3mg / kg of the companion animal’s bodyweight to about 20mg / kg of the companion animal’s bodyweight (kg Bwt).

[0228] In some embodiments, the food composition described herein can be formulated for providing to a companion animal in need thereof a daily amount of Vitamin E from about 3mg / kg Bwt to about 19mg / kg Bwt, or from about 5mg / kg Bwt to about 18mg / kg Bwt, or from about 10mg / kg Bwt to about 17mg / kg Bwt, or from about 12mg / kg Bwt to about 16mg / kg Bwt.

[0229] In some embodiments, the food composition described herein can be formulated for providing to a companion animal in need thereof a daily amount of Vitamin E of about 3 mg / kg Bwt, 3.5 mg / kg Bwt, 4 mg / kg Bwt, 4.5 mg / kg Bwt, 5 mg / kg Bwt, 5.5 mg / kg Bwt, 6 mg / kg Bwt, 6.5 mg / kg Bwt, 7 mg / kg Bwt, 7.5 mg / kg Bwt, 8 mg / kg Bwt, 8.5 mg / kg Bwt, 9 mg / kg Bwt, 9.5 mg / kg Bwt, 10 mg / kg Bwt, 10.5 mg / kg Bwt, 1 1 mg / kg Bwt, 11.5 mg / kg Bwt, 12 mg / kg Bwt, 12.5 mg / kg Bwt, 13 mg / kg Bwt, 13.5 mg / kg Bwt, 14 mg / kg Bwt, 14.5 mg / kg Bwt, 15 mg / kg Bwt, 15.5 mg / kg Bwt, 16 mg / kg Bwt, 16.5 mg / kg Bwt, 17 mg / kg Bwt, 17.5 mg / kg Bwt, 18 mg / kg Bwt, 18.5 mg / kg Bwt, 19 mg / kg Bwt, 19.5 mg / kg Bwt, or 20 mg / kg Bwt.

[0230] In certain embodiments, the food composition described herein can include from about 500ppm to about 1200ppm by weight, of Vitamin E.

[0231] In certain embodiments, the food composition described herein can include from about 700ppm to about 1200ppm, or from about 500ppm to about 1000ppm, or from about 700ppm to about 1000ppm, by weight, of Vitamin E.

[0232] In certain embodiments, the food composition described herein can include about 500ppm, 510ppm, 520ppm, 530ppm, 540ppm, 550ppm, 560ppm, 570ppm, 580ppm, 590ppm, 600ppm, 610ppm, 620ppm, 630ppm, 640ppm, 650ppm, 660ppm, 670ppm, 680ppm, 690ppm, 700ppm, 710ppm, 720ppm, 730ppm, 740ppm, 750ppm, 760ppm, 770ppm, 780ppm, 790ppm, 800ppm, 810ppm, 820ppm, 830ppm, 840ppm, 850ppm, 860ppm, 870ppm, 880ppm, 890ppm, 900ppm, 910ppm, 920ppm, 930ppm, 940ppm, 950ppm, 960ppm, 970ppm, 980ppm, 990ppm, 1000ppm, 1010ppm, 1020ppm, 1030ppm, 1040ppm, 1050ppm, 1060ppm, 1070ppm, 1080ppm, 1090ppm, 1100ppm, 1100ppm, 1110ppm, 1 120ppm, 1130ppm, 1140ppm, 1150ppm, 1160ppm, 1170ppm, 1180ppm, 1190ppm or 1200ppm by weight of Vitamin E.

[0233] Such amounts of source of Vitamin E would be easily adapted by the person skilled in the art to deliver the appropriate daily amount I kg of bodyweight of Vitamin E to the companion animal in need thereof.Attorney Docket No.: 00307-0214-00304Mars Ref.: MARS / P / 393182 / WO / SEC / 1

[0234] In some embodiments, the animal food composition described herein can be formulated for providing to a companion animal in need thereof a daily amount of at least one of:(i) linoleic acid from about 25mg50mg / kg Bwt to about 50mg120mg / kg Bwt, or from about 30mg50mg / kg Bwt to about 45mg110mg / kg Bwt, or of about 40mg90mg / kg Bwt; and / or(ii) Eicosapentaenoic acid (ERA) and / or Docosahexaenoic acid (DHA) from about 4mg / kg Bwt to about 7mg20mg / kg Bwt, or from about 5mg7mg / kg Bwt to about 6mg15mg / kg Bwt, or of about 5.513mg / kg Bwt; and / or(iii) Taurine from about 3mg15mg / kg Bwt to about 6mg100mg / kg Bwt, or from about 4mg50mg / kg Bwt to about 5mg90mg / kg Bwt, or of about 4.575mg / kg Bwt; and / or(v) Lutein from about 0.001 mg015mg / kg Bwt to about 0.05mg1 mg / kg Bwt, or from about 0.005mg05mg / kg Bwt to about 0.001 mg09mg / kg Bwt, or of about 0.005mg085mg / kg Bwt; and / or(v) Vitamin E from about 0.13mg / kg Bwt to about 2mg20mg / kg Bwt, or from about 0.57mg / kg Bwt to about 1.517mg / kg Bwt, or of about 15.3mg / kg Bwt.

[0235] In some embodiments, the animal food composition for its use according to the present disclosure is formulated for providing to said companion animal in need thereof:(i) a daily amount of glycyrrhizin of at least about 0.1 mg / kg Bwt,(ii) a daily amount of curcuminoid of at least about 0.5mg / kg Bwt; and at least one of:(iii) linoleic acid from about 50mg / kg Bwt to about 120mg / kg Bwt, or from about 50mg / kg Bwt to about 110mg / kg Bwt, or of about 90mg / kg Bwt; and / or(iv) Eicosapentaenoic acid (EPA) and / or Docosahexaenoic acid (DHA) from about 4mg / kg Bwt to about 20mg / kg Bwt, or from about 7mg / kg Bwt to about 15mg / kg Bwt, or of about 13mg / kg Bwt; and / or(v) Taurine from about 15mg / kg Bwt to about 100mg / kg Bwt, or from about 50mg / kg Bwt to about 90mg / kg Bwt, or of about 75mg / kg Bwt; and / or(vi) Lutein from about 0.015mg / kg Bwt to about 0.1 mg / kg Bwt, or from about 0.05mg / kg Bwt to about 0.09mg / kg Bwt, or of about 0.085mg / kg Bwt; and / or(vii) Vitamin E from about 3mg / kg Bwt to about 20mg / kg Bwt, or from about 7mg / kg Bwt to about 17mg / kg Bwt, or of about 15.3mg / kg Bwt.Attorney Docket No.: 00307-0214-00304Mars Ref.: MARS / P / 393182 / WO / SEC / 1

[0236] In some embodiments, the animal food composition for its use according to the present disclosure is formulated for providing to said companion animal in need thereof:(i) a daily amount of glycyrrhizin from about 0.1 mg / kg Bwt to about 1 mg / kg Bwt, or from about 0.2mg / kg Bwt to about 0.6mg / kg Bwt, or of about 0.6mg / kg Bwt, or of about 0.5mg / kg Bwt, or of about 0.4mg / kg Bwt,(ii) a daily amount of curcuminoid from about 0.5mg / kg Bwt to about 6mg / kg Bwt, or from about 1 mg / kg Bwt to about 5mg / kg Bwt, or of about 4mg / kg Bwt, or of about 4.2 mg / kg Bwt; and at least one of:(iii) linoleic acid from about 50mg / kg Bwt to about 120mg / kg Bwt, or from about 50mg / kg Bwt to about 110mg / kg Bwt, or of about 90mg / kg Bwt; and / or(iv) Eicosapentaenoic acid (EPA) and / or Docosahexaenoic acid (DHA) from about 4mg / kg Bwt to about 20mg / kg Bwt, or from about 7mg / kg Bwt to about 15mg / kg Bwt, or of about 13mg / kg Bwt; and / or(v) Taurine from about 15mg / kg Bwt to about 100mg / kg Bwt, or from about 50mg / kg Bwt to about 90mg / kg Bwt, or of about 75mg / kg Bwt; and / or(vi) Lutein from about 0.015mg / kg Bwt to about 0.1 mg / kg Bwt, or from about 0.05mg / kg Bwt to about 0.09mg / kg Bwt, or of about 0.085mg / kg Bwt; and / or(vii) Vitamin E from about 3mg / kg Bwt to about 20mg / kg Bwt, or from about 7mg / kg Bwt to about 17mg / kg Bwt, or of about 15.3mg / kg Bwt.Supplementary Ingredients, Substances or Additives

[0237] In some embodiments, the food composition as described herein can be nutritionally complete and balanced; and can also contain supplementary ingredients, substances or additives, for example, protein, crude fat, crude fibers, NEE, ash, minerals, vitamins or condiments.Protein

[0238] In certain embodiments, a food composition according to the present disclosure can further contain a protein source.

[0239] In certain embodiments, the protein level is high enough so as to ensure maintenance of lean body mass of the animal. In certain embodiments, the food composition of the present disclosure can contain one or more distinct protein sources.Attorney Docket No.: 00307-0214-00304 Mars Ref.: MARS / P / 393182 / WO / SEC / 1

[0240] In certain embodiments, the food composition as described herein can include a plurality of proteins that are contained in a protein source which is used in the manufacture process.

[0241] In certain other embodiments, the food composition as described herein can include a plurality of proteins from a plurality of protein sources.

[0242] In certain embodiments the protein is not hydrolyzed. In certain other embodiments a protein can be present in an at least partially hydrolysed form, or even completely hydrolyzed. In certain embodiments, the animal food composition or the kit according to the present disclosure can incorporate proteins under the form of meat or animal derived material (such as, but not limited to beef, chicken, turkey, lamb, fish, blood plasma, marrow bone etc. or combinations thereof). In certain other embodiments, the animal food composition or the kit as described herein can be meat-free. In certain embodiments, such meat-free compositions / kits include a meat substitute protein source such as soya, maize gluten or any other protein-containing soya product in order to provide a protein source. In certain embodiments, the food composition as disclosed herein can include additional protein sources such as soya protein concentrate, milk proteins, gluten etc.

[0243] In some embodiments, the food composition as described herein can include from about 10% to about 40% by weight of protein, on a dry matter basis.

[0244] In some embodiments, the food composition as described herein can include about 10%, or about 11%, or about 12%, or about 13%, or about 14%, or about 15%, or about 16%, or about 17%, or about 18%, or about 19%, or about 20%, or about 21 %, or about 22%, or about 23%, or about 24%, or about 25%, or about 26%, or about 27%, or about 28%, or about 29%, or about 30%, or about 31 %, or about 32%, or about 33%, or about 34%, or about 35%, or about 36%, or about 37%, or about 38%, or about 39%, or about 40% by weight of protein, on a dry matter basis.Crude fat

[0245] A food composition according to the present disclosure can further contain a nutritionally appropriate amount of crude fat.

[0246] The expression “crude fat” as used in the present specification refers to any food-acceptable crude fat(s) and / or oil (s) irrespective of their consistency at room temperature, i.e. , irrespective whether said “crude fat” is present in essentiallyAttorney Docket No.: 00307-0214-00304 Mars Ref.: MARS / P / 393182 / WO / SEC / 1 fluid form or in essentially solid form. The food composition according to the present disclosure can include crude fat of animal and / or vegetable origin. Crude fat can be supplied by any of a variety of sources known by those skilled in the art. Plant crude fat sources include, without limitation, wheat, sunflower, safflower, rapeseed, olive, borage, flaxseed, peanuts, blackcurrant seed, cottonseed, wheat, germ, corn germ as well as oils derived from these and other plant crude fat sources. Animal sources include, for example and without limitation, chicken crude fat, turkey crude fat, beef crude fat, duck crude fat, pork crude fat, lamb crude fat, etc., fish oil or any meat, meat by-products, seafood, dairy, eggs, etc. Crude fat content of foods can be determined by any number of methods known by those of skill in the art.

[0247] In some embodiments, the food composition as described herein can include from about 7% to about 17% by weight of crude fat, on a dry matter basis.

[0248] In some embodiments, the food composition as described herein can include about 5.0%, or about 5.5%, or about 6.0%, or about 6.5%, or about 7.0%, or about 7.5%, or about 8.0%, or about 8.5%, or about 9.0%, or about 9.5%, or about10.0%, or about 10.5%, or about 11.0%, or about 11.5%, or about 12.0%, or about12.5%, or about 13.0%, or about 13.5%, or about 14.0%, or about 14.5%, or about15.0%, or about 15.5%, or about 16.0%, or about 16.5%, or about 17.0% by weight of crude fat, on a dry matter basis.Fibers

[0249] Fibers are optionally included in the food composition disclosed herein. The expression “fibers” is used herein similarly to “dietary fibers” and shall be interpreted for the purpose of the present disclosure as T otal Fibers, meaning that it includes soluble fibers and insoluble fibers. Soluble fiber, as used herein, refers to a fiber that is resistant to digestion and absorption in the small intestine and undergo complete or partial fermentation in the large intestine. In contrast, insoluble fiber. As used herein refers to non-starch polysaccharides that are resistant to digestion and absorption in the small intestine, and resistant to fermentation in the large intestine.Soluble fibers are considered as having a prebiotic effect by providing short chain fatty acids as a source of energy to colonocytes. Insoluble fibers are considered as useful for transit and ballast effect. As non-limiting examples of fibers include a first group, which includes beet pulp, guar gum, chicory root, psyllium, pectin, blueberry, cranberry, squash, apples, oats, beans, citrus, barley, or peas, and a second group,Attorney Docket No.: 00307-0214-00304Mars Ref.: MARS / P / 393182 / WO / SEC / 1 which includes cellulose, whole wheat products, wheat oat, com bran, flax seed, grapes, celery, green beans, cauliflower, potato skins, fruit skins, vegetable skins, peanut hulls, and soy fiber. Crude fiber refers to the indigestible portion of plant material such as cellulose, hemicellulose, and lignin.

[0250] In some embodiments, the food composition as described herein can include from about 5% to about 15% by weight of crude fibers, on a dry matter basis.

[0251] In some embodiments, the food composition as described herein can include about 5.0%, or about 5.5%, or about 6.0%, or about 6.5%, or about 7.0%, or about 7.5%, or about 8.0%, or about 8.5%, or about 9.0%, or about 9.5%, or about 10.0%, or about 10.5%, or about 11.0%, or about 11.5%, or about 12.0%, or about 12.5%, or about 13.0%, or about 13.5%, or about 14.0%, or about 14.5%, or about 15.0% by weight of crude fiber, on a dry matter basis.Carbohydrates

[0252] In certain embodiments, the food composition described herein can include carbohydrates. As used herein, the term “carbohydrates” designates a mixture of polysaccharides and sugars that are metabolized for energy when hydrolyzed in the body. The carbohydrate content in the food composition and / or the kit can be determined by any number of methods known by those of skilled in the art. Carbohydrates can be supplied under the form of any of a variety of carbohydrate sources known by those skilled in the art, including starch (any kinds, corn, wheat, barley, etc.) beet pulp (which contain a bit of sugars) and psyllium.Starches

[0253] An important source of Nitrogen Free Extract that is optionally included in the food composition disclosed herein can consist of starch. A person skilled in the art will appreciate a wide variety of starches are suitable for use in compositions of the present disclosure.

[0254] The term “starch” as used herein refers to a polysaccharide that is composed of amylose and amylopectin. Starch occurs in many plant tissues as granules, usually between 1 and 100 pm in diameter, depending upon the plant source. Chemically, starches are polysaccharides composed of a-D-glucopyranosyl units linked together with a-D(1-4) and / or a-D(1 -6) linkages and are comprised ofAttorney Docket No.: 00307-0214-00304 Mars Ref.: MARS / P / 393182 / WO / SEC / 1 two molecular types: amylose, the straight chain polyglucan comprised of approximately 1000, a-D(1-4) linked glucoses; and amylopectin, the branched glucan, comprised of approximately 4000 glucose unite with branches occurring as a-D(1-6) linkages.

[0255] As used herein, starch encompasses the various crystalline structures of A-type, B-type and C-type starches, which contain different proportions of amylopectin. A-type starches are found mainly in cereals, while B-type starches are found mainly in tubers and amylose-rich starches. C-type starch consists of a mixture of both A and B forms and is found mainly in legumes.

[0256] In general, digestible starches are broken down (hydrolyzed) by the enzymes a-amylases, glucoamylase and sucrose-iso-maltase in the small intestine to yield free glucose that is then absorbed.

[0257] Starch included in the food composition disclosed herein can consist in any starch suitable for dietary purpose.

[0258] Indeed, the native starch included in the starting materials used for preparing the food composition as described herein is susceptible to undergo changes during the manufacture process. The specified amount of starch included in the food composition of the present disclosure can consist of the amount of starch that is contained in the total amount of the raw materials which are provided for producing the said food composition. However, the amount of starch included in the food composition disclosed herein equates the total amount of starch included in the starting materials used for preparing the said food composition.

[0259] If not already known by advance, the starch content of the starting materials used for preparing the food composition described herein can be determined according to conventional techniques known in the art, and especially according to the known polarimetric method, such as according to NF EN ISO 10520.

[0260] In certain embodiments, wherein the starting materials can include also modified starch or pre-gelatinized starch, the starch content can also be determined according to NF EN ISO 15914.AshAttorney Docket No.: 00307-0214-00304Mars Ref.: MARS / P / 393182 / WO / SEC / 1

[0261] In certain embodiments, the food composition disclosed herein can include ash. Ash can include minerals, such as calcium, phosphorus, sodium, chloride, potassium, magnesium, or combinations thereof. The ash content, if specified as a result of an analytical measure of the food composition described herein, is a measure of the total amount of minerals comprised therein. The mineral content is a measure of the amount of specific inorganic components comprised therein, which includes calcium (Ca), sodium (Na), potassium (K) and chlorine (Cl).

[0262] As it shall be readily understood, every embodiment of the food composition encompassed by the present disclosure can include a variety of ingredients, each comprised in the said food composition at a given weight percentage, as compared to the total weight of dry matter of the food composition.

[0263] In certain embodiments, the food composition as disclosed herein can further include, protein, crude fat, fibers, NFE, carbohydrates, starches,, ash, and optionally one or more further ingredients such as vitamins, minerals, etc., the sum of the weight of each of the ingredients comprised therein amounting to 100% by weight, based on the total weight of dry matter of the said food composition.

[0264] In some embodiments, the food composition as described herein can include from about 2% to about 12% by weight of ash, on a dry matter basis.

[0265] In some embodiments, the food composition as described herein can include about 2.0%, or about 2.5%, or about 3.0%, or about 3.5%, or about 4.0%, or about 4.5%, or about 5.0%, or about 5.5%, or about 6.0%, or about 6.5%, or about 7.0%, or about 7.5%, or about 8.0%, or about 8.5%, or about 9.0%, or about 9.5%, or about 10.0%, or about 10.5%, or about 11.0%, or about 11.5%, or about 12.0% by weight of ash, on a dry matter basis.Methods for the Preparation of a Composition of the present disclosure

[0266] The present disclosure also provides a method for manufacturing the food composition described herein. The process for the manufacture of the food composition as described includes any methods known in the art.

[0267] The food composition described herein can be manufactured by mixing together ingredients and kneading in order to make consistent dough or meat emulsion that can be cooked. This applies also to liquids where ingredients are mixed, homogenized before a cooking step in a packaging. The process of creating an embodiment of a dry food is usually done by baking and / or extruding. The doughAttorney Docket No.: 00307-0214-00304Mars Ref.: MARS / P / 393182 / WO / SEC / 1 is typically fed into a machine called an expander and / or extruder, which uses pressurized steam or water to cook the ingredients. While inside the extruder, the dough is under extreme pressure and high temperatures. The dough is then pushed through a die (specifically sized and shaped hole) and then cut off using a knife. The puffed dough pieces are made into kibble by passing it through a dryer so that moisture is dropped down to a defined target ensuring stability of the food until consumption. The kibble can then be sprayed with fats, oils, minerals, vitamins, the natural extracts cocktail, palatants and optionally sealed into packages.

[0268] The composition can be a dry food, a wet food or a semi-moist food as described in the present disclosure.

[0269] In an embodiment, the present disclosure relates to a method of manufacturing a food composition for use in a method for treating and / or preventing and / or reducing the severity and / or reducing the relapse of otitis externa in a companion animal in need thereof, including the steps of: a) mixing at least 0.1mg / kg Bwt / day of glycyrrhizin and at least about 0.5mg / kg Bwt / day of curcuminoid, thereby providing a mixture; and b) heating the mixture.

[0270] In some embodiment, the method of manufacturing a food composition for use in a method for treating and / or preventing and / or reducing the severity and / or reducing the relapse of otitis externa in a companion animal in need thereof, can include the steps of: a) mixing at least a source of glycyrrhizin and a source of curcuminoid, thereby providing a mixture; and b) heating the mixture; wherein the said food composition is formulated for providing to said companion animal in need thereof a daily amount of glycyrrhizin from about 0.1mg / kg Bwt to about 1mg / kg Bwt; and a daily amount of curcuminoid from about 0.5mg / kg Bwt to about 2mg / kg Bwt.

[0271] In certain embodiments, the present disclosure provides a method of manufacturing food composition for use in a method for treating and / or preventing and / or reducing the severity and / or reducing the relapse of otitis externa in a companion animal in need thereof, including (i) a source of glycyrrhizin, in combination with (ii) a source of one or more curcuminoids; wherein it includes the steps of:Attorney Docket No.: 00307-0214-00304Mars Ref.: MARS / P / 393182 / WO / SEC / 1 a) mixing a source of glycyrrhizin suitable to deliver at least 0.1 mg / kg Bwt / day of glycyrrhizin and a source of one or more curcuminoids suitable to deliver at least 0.5mg / kg Bwt / day of curcuminoid, thereby providing a mixture; and b) heating the mixture.

[0272] In certain embodiments, the food composition manufactured by the methods described herein, is a kibble. In certain embodiments, the food composition manufactured by the methods described herein includes a source of proteins.

[0273] In some embodiments, the source of glycyrrhizin and the source of one or more curcuminoids can be mixed in step a), with ingredients selected from, without limitation, a source of linoleic acid, EPA and / or DHA, taurine, lutein, Vitamin E and a combination thereof.

[0274] In some embodiments, the source of glycyrrhizin and the source of curcuminoids can be mixed with ingredients selected from a source of linoleic acid, EPA and / or DHA, taurine, lutein, Vitamin E, protein, crude fat, fibers and a combination thereof.Therapeutic Applications

[0275] The present disclosure provides uses and methods implementing a food composition as disclosed herein, in particular wherein the said food composition includes, as the sole active agents, glycyrrhizin and curcuminoids, in the prevention and / or the treatment and / or for reducing the severity and / or for reducing the relapse of otitis externa in a companion animal in need thereof.

[0276] In some embodiments, the food composition described herein can be used in a method for preventing otitis externa in a companion animal in need thereof. Notably, the food composition described herein can be used in a method for preventing otitis externa, otitis externa symptom(s) and / or otitis externa-associated complication(s) in a companion animal in need thereof.

[0277] In some embodiments, the food composition described herein can be used in a method for treating otitis externa in a companion animal in need thereof. Notably, the food composition described herein can be used in a method for treating otitis externa, otitis externa symptom(s) and / or otitis externa-associated complication(s) in a companion animal in need thereof.

[0278] In some embodiments, the food composition described herein can be used in a method for reducing the severity of otitis externa in a companion animal inAttorney Docket No.: 00307-0214-00304Mars Ref.: MARS / P / 393182 / WO / SEC / 1 need thereof. Notably, the food composition described herein can be used in a method for reducing the severity of otitis externa, otitis externa symptom(s) and / or otitis externa-associated complication(s) in a companion animal in need thereof.

[0279] In some embodiments, the food composition described herein can be used in a method for reducing the relapse of otitis externa in a companion animal in need thereof. Notably, the food composition described herein can be used in a method for reducing the relapse of otitis externa, otitis externa symptom(s) and / or otitis externa-associated complication(s) in a companion animal in need thereof.

[0280] The present disclosure also provides a method for preventing and / or treating and / or for reducing the severity and / or for reducing the relapse of otitis externa in a companion animal, wherein the method includes at least a step of feeding the companion animal with a food composition as described herein. In particular, the present disclosure provides a method for preventing and / or treating and / or for reducing the severity and / or for reducing the relapse of otitis externa in a companion animal, wherein the method includes at least a step of feeding the companion animal with a food composition including, as the sole active agents, glycyrrhizin and curcuminoids.

[0281] The present disclosure also provides the use of glycyrrhizin and curcuminoid for manufacturing a food composition or a medicament for use in a method for treating and / or preventing and / or reducing the severity and / or reducing the relapse of otitis externa in a companion animal in need thereof.

[0282] As shown in the Examples, a food composition as described herein allows reducing the relapse of otitis externa and symptoms thereof in dogs in remission from otitis externa. Beneficial effects can be obtained in companion animals fed exclusively with the food composition described herein, during, before or after an otitis externa medication.

[0283] In some embodiments, the relapse of otitis externa in the companion animal can be reduced by about 30% to about 100%. In particular, the relapse of otitis externa in the companion animal can be reduced by about 35%, or about 40%, or about 45%, or about 50%, or about 55%, or about 60%, or about 65%, or about 70%, or about 75%, or about 80%, or about 85%, or about 90%, or about 95%, or 100%. The reduction in relapse rate is compared to the relapse rate of otitis externa observed in a companion animal feeding with a control food composition that does not comprise, as the sole active agents, glycyrrhizin and curcuminoids.Attorney Docket No.: 00307-0214-00304Mars Ref.: MARS / P / 393182 / WO / SEC / 1

[0284] In particular, as demonstrated in the Examples, the food composition described herein acts positively on the four various outcomes associated with otitis externa, in particular OTIS-3 score, cytology score, and pVAS, and optionally CADES I-04.

[0285] In some embodiments, the method can reduce the severity or the relapse of erythema in one or both ear, can reduce the severity or the relapse of edema / swelling in one or both ear, can reduce the severity or the relapse of erosions / ulcerations in one or both ear, can reduce the severity or the relapse of exudate in one or both ear, and / or can reduce the severity or the relapse of pain in the companion animal, as determined / assessed by the OTIS-3 score.

[0286] In some embodiments, the relapse of erythema, edema / swelling, erosions / ulcerations, exudate, and / or pain is reduced by about 30% to about 100%. In particular, the relapse of erythema, edema / swelling, erosions / ulcerations, exudate, and / or pain is reduced by about 35%, or about 40%, or about 45%, or about 50%, or about 55%, or about 60%, or about 65%, or about 70%, or about 75%, or about 80%, or about 85%, or about 90%, or about 95%, or 100%. This can be determined / assessed by the OTIS-3 score. In some embodiments, the reduction of the relapse of erythema, edema / swelling, erosions / ulcerations, exudate, and / or pain is significant. The reduction in relapse rate is compared to the relapse rate observed in a companion animal feeding with a control food composition that does not comprise, as the sole active agents, glycyrrhizin and curcuminoids.

[0287] In some embodiments, the method can reduce the severity or the relapse of the presence of bacteria in one or both ear, can reduce the severity or the relapse of the presence of yeast in one or both ear, and / or can reduce the severity or the relapse of the presence of inflammatory or neoplastic cells, in one or both ear canal of the companion animal, as determined / assessed by the cytology score.

[0288] In some embodiments, the relapse of the presence of bacteria, yeast, and / or inflammatory or neoplastic cells in the ear canal is reduced by about 30% to about 100%. In particular, the relapse of the presence of bacteria, yeast, and / or inflammatory or neoplastic cells in one or both ear canal is reduced by about 35%, or about 40%, or about 45%, or about 50%, or about 55%, or about 60%, or about 65%, or about 70%, or about 75%, or about 80%, or about 85%, or about 90%, or about 95%, or 100%. This can be determined / assessed by the cytology score. In some embodiments, the reduction of the relapse of the presence of bacteria, yeast, and / orAttorney Docket No.: 00307-0214-00304 Mars Ref.: MARS / P / 393182 / WO / SEC / 1 inflammatory or neoplastic cells in one or both ear canal is significant. The reduction in relapse rate is compared to the relapse rate observed in a companion animal feeding with a control food composition that does not comprise, as the sole active agents, glycyrrhizin and curcuminoids.

[0289] In some embodiments, the method can reduce the frequency and dosage of an anti-otitis externa agent in a companion animal, as determined / assessed by the medication score.

[0290] In some embodiments, the food composition described herein can be used in a method for reducing the frequency and dosage of an anti-otitis externa agent required to reduce the severity or the relapse of otitis externa in a companion animal previously treated for this condition.

[0291] In some embodiments, the frequency and dosage of an anti-otitis externa agent to control otitis externa in a companion animal is reduced by about 30% to about 100%. In particular, the frequency and dosage of an anti-otitis externa agent to control otitis externa in a companion animal is reduced by about 35%, or about 40%, or about 45%, or about 50%, or about 55%, or about 60%, or about 65%, or about 70%, or about 75%, or about 80%, or about 85%, or about 90%, or about 95%, or 100%. This can be determined / assessed by the medication score. In some embodiments, the reduction of the frequency and dosage of an anti-otitis externa agent to control otitis externa in a companion animal is significant. The reduction in frequency and dosage of an anti-otitis externa agent is compared to the frequency and dosage observed in a companion animal feeding with a control food composition that does not comprise, as the sole active agents, glycyrrhizin and curcuminoids.

[0292] In some embodiments, the method can reduce the severity / intensity or the relapse of itching of the companion animal, as determined / assessed by the pVAS.

[0293] In some embodiments, the severity / intensity or the relapse of itching of the companion animal is reduced by about 30% to about 100%. In particular, the severity / intensity or the relapse of itching of the companion animal is reduced by about 35%, or about 40%, or about 45%, or about 50%, or about 55%, or about 60%, or about 65%, or about 70%, or about 75%, or about 80%, or about 85%, or about 90%, or about 95%, or 100%. This can be determined / assessed by the pVAS score. In some embodiments, the reduction of the severity / intensity or the relapse of itching of the companion animal is significant. The reduction in severity / intensity or theAttorney Docket No.: 00307-0214-00304Mars Ref.: MARS / P / 393182 / WO / SEC / 1 relapse of itching of the companion animal is compared to the severity / intensity or the relapse of itching of the companion animal observed in a companion animal feeding with a control food composition that does not comprise, as the sole active agents, glycyrrhizin and curcuminoids.

[0294] In some embodiments, the food composition described herein can be provided to animals, especially to dogs, on a daily basis.

[0295] In certain embodiments, the food composition disclosed herein can be provided to the animal to be treated as the sole food composition during the period of treatment. According to these embodiments, the food composition is provided to the animal on a daily basis during the time period of treatment.

[0296] It shall be understood that, in the daily practice of feeding animals, especially dogs, the animal owner cannot proceed according to a systemic way of feeding the animal with an animal food composition always on daily basis.

[0297] In certain embodiments, the beneficial effects of preventing and / or treating and / or for reducing the severity and / or for reducing the relapse of otitis externa are fully provided when the animal is fed with the food composition described herein every day for at least 2 months or more, or 3 months or more, or 4 months or more, or 5 months or more, or 6 months or more, or 7 months or more, or 8 months or more, or 9 months or more, or 10 months or more, or 11 months or more, or 12 months or more.

[0298] The period of feeding the companion animal with the food composition as described herein can range from several weeks to several years, depending notably on the severity of the otitis externa or if otitis externa relapse after or during otitis externa medication.

[0299] In some embodiments, the food composition described herein can be provided to the companion animal in need thereof for a period of between about one month to about 36 months during, before or after an otitis externa medication.

[0300] In some embodiments, the food composition described herein can be provided to the companion animal in need thereof for a period about one month, or about two months, or about three months, or about four months, or about five months, or about six months, or about seven months, or about eight months, or about nine months, or about ten months, or about eleven months, or about twelve months, or about thirteen months, or about fourteen months, or about fifteen months, or about sixteen months, or about seventeen months, or about eighteen months, orAttorney Docket No.: 00307-0214-00304Mars Ref.: MARS / P / 393182 / WO / SEC / 1 about nineteen months, or about twenty months, or about twenty-one months, or about twenty-two months, or about twenty-three months, or about twenty-four months, or about twenty-five months, or about twenty-six months, or about twentyseven months, or about twenty-eight months, or about twenty-nine months, or about thirty months, or about thirty-one months, or about thirty-two months, or about thirty- three months, or about thirty-four months, or about thirty-five months, or about thirty- six months during, before or after an otitis externa medication.

[0301] In some embodiments, an otitis externa medication can comprise treating the companion animal by administering or applying an anti-otitis externa agent.

[0302] In some embodiments, an anti-otitis externa agent can be an oral treatment, or a topical treatment.

[0303] In some embodiments, a topical treatment can be in the form of a cream, an ointment, a spray, a gel, a lotion, a shampoo, a patch, ear drops, or a foam.

[0304] In some embodiments, an anti-otitis externa agent can be antibiotic ear drops, antifungal ear drops, and / or corticosteroid ear drops. In some embodiments, an anti-otitis externa agent can be a hydrocortisone aceponate, a miconazole nitrate, a gentamicin sulphate or combinations of those anti-otitis externa agents.

[0305] In some embodiments, a companion animal in need thereof can be a companion animal with otitis externa. In particular, a companion animal in need thereof can be a companion animal with otitis externa, as determ ined / assessed by OTIS-3 score, and optional with pVAS, CADESI-04, and / or cytology score.

[0306] In some embodiments, a companion animal in need thereof can be a companion animal with atopic dermatitis and otitis externa.

[0307] In some embodiments, a companion animal in need thereof can be a companion animal in remission from otitis externa. In some embodiments, a companion animal in need thereof can be a companion animal in remission from otitis externa, as determined / assessed by OTIS-3 less than 4 for each ear.

[0308] In some embodiments, a companion animal in need thereof can be a companion animal recovered from otitis externa.

[0309] The present disclosure further relates to the use of a combination of a source of glycyrrhizin, and of a source of one or more curcuminoids, for the preparation of a composition for the treatment of otitis externa.Attorney Docket No.: 00307-0214-00304Mars Ref.: MARS / P / 393182 / WO / SEC / 1EXAMPLES

[0310] The presently disclosed subject matter will be better understood by reference to the following Examples, which are provided as exemplary of the disclosure, and not by way of limitation. The materials and methods used in the Examples are summarized below.A. Materials and Methods a. Objective

[0311] The objectives of this study were to assess whether a novel animal food composition could reduce the rate of relapse of erythrocerum inous otitis externa in atopic dogs, reduce the severity of inflammation in the ear canal and reduce symptomatic signs of otitis externa generally. b. Materials and MethodsDogs

[0312] Client-owned dogs presenting with an active ceruminous otitis externa, with or without secondary yeast and or bacterial infection, were assessed for study eligibility at baseline by the investigators, all of whom were European College of Veterinary Dermatology-boarded dermatologists working in referral clinics. The initial assessment incorporated a history, a thorough clinical and otoscopic examination, ear canal cytology, and disease scoring as detailed below.

[0313] Inclusion criteria: To be eligible for the study, dogs had to satisfy at least 5 out of 8 of Favrot’s Criteria. Favrot’s Criteria are a set of diagnostic guidelines developed to help veterinarians identify canine atopic dermatitis (CAD).

[0314] Additionally, dogs have to present erythroceruminous otitis externa in one or both ears assessing with an Otitis Index Score (OTIS-3) greater than 4 for each affected ear. The OTIS-3 is the sum of severity scores from 0 (none) to 3 (severe) for erythema, oedema or swelling, erosion or ulceration, exudate, and pain in the vertical and horizontal ear canals (scored separately), resulting in a maximum total score of 30 for each ear.

[0315] Ear canal cytology was required prior to inclusion of dogs and scored according to Nuttal and Bensignor. Briefly, smears of exudate from the junction of the vertical and horizontal ear canals were air dried, then stained with a modified Wright-Giemsa stain with 5-10 dips of 1 second each, rinsed with water and allowedAttorney Docket No.: 00307-0214-00304 Mars Ref.: MARS / P / 393182 / WO / SEC / 1 to dry before microscopic evaluation under 400x magnification. The number of microorganisms and cells in ten random fields were counted from 0 to a maximum of 100, and the mean count was the cytology score.

[0316] Dogs had to have a pruritus score greater than 3 on an owner- assessed pruritus visual analogue scale (pVAS) ranging from 0 to 10.

[0317] The canine Allergic Dermatitis Extent and Severity Index 4th iteration (CADESI-04) was scored, but there was no minimum score required for inclusion.

[0318] The presence of food-induced atopic dermatitis (FIAD) must have been excluded diagnostically with an elimination diet and rechallenge.

[0319] Finally, owners agreed to comply with the feeding requirements and study and procedures for the 6-month duration of the study.

[0320] Exclusion criteria: These included otitis media, ruptured tympanic membrane, FIAD or any other form of food allergy, and intercurrent disease. Dogs with evidence of bacterial rods in the initial cytological assessment, or otitis infection associated with Pseudomonas were excluded; ear canal microbial culture was mandatory when there was any suspicion of a Pseudomonas infection. Allergenspecific immunotherapy initiated less than 6 months before the start of the study, or ongoing and associated with a clinical improvement in the month before the study started was not permitted. Dogs that were not receiving at least 50% of their diet in kibble form, and those that needed any kind of food supplementation were excluded.

[0321] Withdrawal criteria: The presence of bacterial rods in any cytological examination during the study required the dog’s withdrawal. Dogs could be withdrawn by owners for any reason at any time, or at the discretion of the investigator if a disorder other than atopic dermatitis emerged, if the study protocol could not be followed, or if there were safety concerns.

[0322] A total of 34 dogs were enrolled where 16 were randomised to the test diet and 18 to the control diet. All randomized dogs received their assigned diet. Overall, the most represented breeds were Labrador retrievers (n = 10), Beagles (n= 6) and French bulldogs (n = 3), at least one of which was present in both study groups (Table 1 ). There was an equal distribution of sexes in both groups and there were no significant differences between groups in baseline clinical characteristics (Table 1 ). CADESI-04 scores indicated mild cAD in 6 / 16 dogs in the test group and 10 / 18 dogs in the control group; one dog in each group had moderate cAD.Attorney Docket No.: 00307-0214-00304Mars Ref.: MARS / P / 393182 / WO / SEC / 1Table 1. Baseline characteristicsAttorney Docket No.: 00307-0214-00304Mars Ref.: MARS / P / 393182 / WO / SEC / 1tThe age was missing for one dog in each group.fThe score for each dog was the average of the score for the left and right ear.CADESI-04, Canine Allergic Dermatitis Extent and Severity Index, 4th iteration; OTIS-3, Otitis Index Score-3;14pVAS, pruritic visual analogue scale SD, standard deviation.Study diets and their assignment

[0323] The compositions of the test and control diets are presented in Table 2. The base of the two compositions is similar except that the test diet comprises eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) majority sourced from algal oil (95% from Algal oil) rather than majority sourced from fish oil as in the control diet, and comprises glycyrrhizin provided by a licorice extract (containing 5% glycyrrhizin), and curcuminoids provided by a curcuma extract (containing 20% of curcuminoids).Table 2. Nutrition composition of study diets and selected ingredientsAttorney Docket No.: 00307-0214-00304Mars Ref.: MARS / P / 393182 / WO / SEC / 1Attorney Docket No.: 00307-0214-00304Mars Ref.: MARS / P / 393182 / WO / SEC / 1*mg / kg / day with kilogram (kg) of the dog's body weight** Expected Intakes: The nutrients expressed as mg / kg / day referring to the amount an animal would expect to receive per day depending on its bodyweight using the described composition in the table.

[0324] Study diets (test and control) were shipped directly to dog owners and all owners, and their veterinarians were blinded to treatment assignment. Both diets were chicken-based dry kibbles of complete and balanced for dogs with a maintenance energy requirement of 95 kcal / kg. Diets were of similar physical appearance and packaged in identical neutral bags identified only by their code names.Study medications and continuation criteria

[0325] Study starts with topical and oral treatment of otitis externa (pre 10 days): All dogs started a protocol-specified course of treatments at the baseline visit to bring their otitis externa under control and minimize differences in severity between dogs as soon as possible after enrolment. This protocol constituted a 10- day course of a combination topical product of hydrocortisone aceponate (1.11 mg / ml), miconazole nitrate (15.1 mg / ml), and gentamicin sulphate 1505 ILI / mL (EasOtic®, Virbac, Carros, France, 1 ml per external ear canal per day), preceded by ear cleaning. Concurrently, dogs received 10 days of oral prednisolone at a dose of 0.5 mg / kg once daily. During this period, any other immunomodulatory drugs were suspended.

[0326] Diet Assignment and Transition (Day 1 ): The assigned diet was introduced from Day 1 of the study, up to 10 days after the baseline visit, depending on delivery time. Owners were instructed to feed only the study diets provided for the duration of the study. They were advised to transition to the study diet gradually over 6 days by feeding a mixture of their existing diet with the study diet in increasing proportions with a ratio of 3: 1 for 2 days, 1 : 1 for 2 days and 1 :3 for 2 days.

[0327] Day 14 Visit: Dogs were re-examined on Day 14. Dogs with a satisfactory response to the above medications (score OTIS-3 less than 4 for each affected ear) continued to be treated with twice weekly cutaneous hydrocortisone aceponate spray at a dose of 0.584 mg / ml (Cortavance®, Virbac, Carros, France) or twice weekly cutaneous Burow’s solution with 1 % hydrocortisone (Covetrus, Portland, ME, USA) until the Month 1 visit (Day 30) in order to prevent early relapse.Attorney Docket No.: 00307-0214-00304 Mars Ref.: MARS / P / 393182 / WO / SEC / 1

[0328] Dogs with persisting ear canal inflammation (OTIS-3 greater than 4 for either or both ears) were treated with EasOtic® for an additional 10 days, or a different topical treatment depending upon the results of bacterial culture and antibiotic sensitivity tests. If OTIS-3 is then less than 4 and remained so after 10 days’ follow-on treatment with Cortavance®, the dog could continue in the study.

[0329] Month 1 Visit: Dogs with an OTIS-3 less than 4 for each ear continued in the study, receiving their assigned diet (control or test) and twice weekly ear cleanser treatment.

[0330] Relapse Management (After 1 Month visit): After the Month 1 visit, dogs with any relapse of otitis (change from OTIS-3 <4 to OTIS-3 >4 in one or both ears) were treated with a 10-day course of EasOtic® and prednisolone (at a dose of 0.5 mg / kg once daily), similar to the treatment as at the start of the study.

[0331] The following immunomodulatory drugs were permitted during the study if needed to control atopic dermatitis: topical or systemic glucocorticoids, cyclosporine or topical analogues such as tacrolimus, oclacitinib (Apoquel®, Zoetis; Florham Park, NJ, USA), and lokivetmab (Cytopoint®, Zoetis; Parsippany, NJ, USA). Dosage was determined monthly by the investigator, with the goal of reducing the use of these drugs as much as clinically appropriate. Whenever possible adjustments in immunomodulatory therapy were restricted to changes in dosages rather than changes in drug. Any case of pyoderma occurring in the study was treated with a single 3-week treatment course of cefalexin per episode with or without use of antibacterial shampoo.

[0332] Owners were required to maintain effective and ongoing flea control with isoxazolide prophylaxis (e.g., fluralaner [Bravecto®], sarolaner [Simparica®], afoxolaner [Nexgard®]). Shampoo therapy, including antimicrobial shampoo, was permitted, providing the regimen was kept consistent throughout the study.Study visits and outcomes

[0333] After the baseline enrolment visit and subsequent commencement of the assigned study diet on Day 1 , study visits were required on Day 14 and at Month 1 to evaluate the response to the initial protocol-defined treatments, and at Month 3 and Month 6 for study outcome measures and routine clinical management of otitis externa and cAD (if present). Additional intermediary consultations, either in the clinic or by telephone, were at the discretion of investigators. Any adverse eventsAttorney Docket No.: 00307-0214-00304 Mars Ref.: MARS / P / 393182 / WO / SEC / 1 were captured by investigators at study consultations, or other clinical consultations, including owner-reported adverse events. Owners were asked for observations on diet acceptance based on food consumption (not a study measurement).

[0334] The primary outcome was the mean number of relapses per dog during the study (the relapse rate). Relapse was defined as a worsening in the OTIS-3 score from less than 4 to greater than 4 in one or both ears. Other efficacy outcomes were the time to first relapse, the number of relapses during the 6-month study period, and OTIS-3 (mean of both ears), cytology score (mean of both ears), CADESI-04 score, owner-assessed pVAS score and medication score at baseline, Month 3, and Month 6 (study endpoint). Medication scoring accounted for the frequency and dose (prednisolone) of medications taken to control otitis externa and or cAD. The scoring system was as described previously, with a higher score corresponding to a higher medication burden. Owners were instructed to keep a daily diary of treatments from the commencement of the study diet, and the medication score at each timepoint was calculated from treatments administered during the preceding month.

[0335] The global response of individuals was classified as good if two of the three outcomes (CADESI-04 score, pVAS and medication score) improved by more than 50% and the third outcome had not worsened, and excellent if all three outcomes improved by more than 50%.Statistical methods

[0336] The primary null hypothesis was that the test diet would have no significant impact on the frequency of otitis externa relapse flares over a 6-month period. The secondary null hypothesis was that the test diet would have no significant effect on the severity of ear inflammation in dogs over a 6-month period. A power analysis calculated that 22 dogs per diet were needed to give 90% power to detect a significant difference between diets, based on the assumption that 55% of dogs in the control group would have a relapse in otitis externa compared with 20% in the test group, and that statistical significance was taken as a p-value <0.05.

[0337] The experimental unit was the individual dog. The analyses included all dogs that received study diet per protocol for any duration, except those lost to follow up before Month 2. Adverse events are reported in enrolled dogs receiving study diet for any duration.Attorney Docket No.: 00307-0214-00304Mars Ref.: MARS / P / 393182 / WO / SEC / 1

[0338] Descriptive statistics are presented for baseline characteristics and adverse events. Description of Chi-sq / Forest for relapse rate analysis to be provided please. The time to relapse was the month in which the first relapse occurred; if no relapse occurred during the study, Month 7 was imputed as the time of relapse (Mann Whitney test for difference between groups). Differences in response rates were evaluated with Fisher’s exact test. For other outcomes, linear mixed models (LMM) were applied with diet, time-point and their respective interaction as fixed effects and animal as a random term. Data were log or rank transformed as appropriate in order to meet the statistical assumptions for LMM of normally distributed residuals and homoscedasticity. Estimated marginal means (emmeans) and 95% confidence intervals (Cl) are presented. Pairwise contrasts were calculated within time-point between diets and within diet between time-point. Tukey’s honestly significant difference (HSD) was used for correcting for the false rate discovery (FDR). Level of significance was set to 5% after this correction. Effect sizes were calculated for pairwise comparisons between timepoints for each diet and are presented with 95% Cis.B. Results

[0339] In the test group, nine dogs completed the full 6 months of the study, two were excluded after Month 3 due to Pseudomonas infections, two were withdrawn by owners after Month 3 for reasons of convenience, one withdrew after 5 months due to a relapse in otitis externa, and one dog was lost to follow-up after Month 3.

[0340] In the control group, 14 dogs completed the study and four withdrew due to relapse in otitis externa, two after 3 months and one after 2.5 months. The Month 6 visit for four dogs in the test group and two in the control group was delayed and occurred during Month 7; therefore, data at the study endpoint are the last data available in either Month 6 or Month 7.Efficacy outcomes

[0341] The relapse rate was significantly lower in the test group than in the control group: 25.0% (4 relapses) / 16 dogs) vs 61.1 % (11 / 18 dogs, which includes one dog that had two relapses) (p <0.001 ). In the test group, the relapses were reported after 3 months in two dogs and at or after 5 months in two dogs. RelapsesAttorney Docket No.: 00307-0214-00304 Mars Ref.: MARS / P / 393182 / WO / SEC / 1 in the control group were reported after at 2 months in one dog, 2.5 months in one, at 3 months in 4, at 4 months in two and at 5 months in three. The median time of first relapse was 5 months (mean 4.8) in the control group and 7 months (mean 6.3) in the test group; the difference was not significantly different (Mann-Whitney p = .0.01).

[0342] There was a significant effect of time point on OTIS-3 score (p = 0.002) and cytology (p = 0.027), CADESI-04 (p <0.0001), pVAS (p <0.001), and medication (p <0.0001) scores. Diet overall did not have a significant effect on these outcomes, but there was a significant interaction between diet and time point for pVAS (p = 0.025) and medication (p <.0001) scores.

[0343] Mean OTIS-3 score decreased significantly between baseline and Month 3 in both groups (p = 0.003 for the test group and 0.001 for the control group) and the effect sizes were similar (1.25 [0.56, 1 .94] for the control group and 1 .22 [0.50, 21.96] for the test group) (Figure 1a and Table 3). Between Month 3 and the endpoint, OTIS-3 score increased in both groups, but this was statistically significant only in the control group only (p = 0.025; effect size 0.89 [1 .57, 0.22]). At the endpoint, OTIS-3 score was not significantly different from baseline in either diet group. The mean cytology score decreased significantly between baseline and Month 3 in the test group (p = 0.028; effect size 0.93 (0.21 , 1 .65), but after a nonsignificant increase between Month 3 and the endpoint, the final cytology score was not significantly lower than baseline (Figure 1b and Table 3). There were no significant differences in mean cytology score between any timepoints in the control group.Table 3. Pairwise comparisons of outcomes between timepoints in each groupAttorney Docket No.: 00307-0214-00304Mars Ref.: MARS / P / 393182 / WO / SEC / 1P-values are for baseline values minus values at Month 3 or 6.Attorney Docket No.: 00307-0214-00304Mars Ref.: MARS / P / 393182 / WO / SEC / 1CADESI-04, Canine Allergic Dermatitis Extent and Severity Index, 4th iteration; Cl, confidence interval; emmean, estimated marginal mean; OTIS-3, Otitis Index Score-3; pVAS, pruritic visual analogue scale.

[0344] The mean CADESI-04 score decreased significantly from baseline to Month 3 in the test group (p = 0.001 ; effect size 1 .29 [0.56, 2.02]) and after an additional non-significant reduction, it remained significantly lower at the endpoint compared with baseline (p <0.001 ; effect size 1.44 [0.70, 2.18]) (Figure 2a). The mean CADESI-04 score also fell from baseline to Month 3 ( p<0.001) in the control group, but this was followed by a significant rebound (p = 0.026; effect size 0.55 [- 0.12, 1 .22]) and the mean score at the endpoint was not significantly different from baseline. There was a similar evolution of mean pVAS scores; they fell significantly in both groups from baseline to Month 3 (test group, p = 0.002, effect size 1.25 [0.52, 1.98]; control group, p = 0.025), after which the score remained significantly lower than baseline in the test group (p = 0.001 ; effect size 1 .32 [0.59, 2.05]) but increased significantly in the control group (p = 0.034; effect size -0.85, [-1.53, -1.7]) to a value not significantly different from baseline (Figure 2b).

[0345] In the test group, the mean medication score declined significantly between baseline and Month 3 in the test group (p <0.0001 ; effect size 1 .65 [0.91 , 2.40]) and was stable at the endpoint, remaining significantly lower than at baseline (p <0.001 ; 1 .86 [1 .11 , 2.62]). The medication score did not change significantly between any timepoints in the control groups.

[0346] Significantly more dogs in the test group achieved either a good or excellent response (p = 0.02) In the test group, 6 / 16 dogs were excellent responders and an additional two had a good response. In the control group, 1 / 18 dogs had an excellent response, and an additional dog had a good response.C. Conclusions

[0347] The results demonstrated that the test diet significantly reduced the relapse rate compared to the control diet, with 25% of dogs in the test group experiencing relapses versus 61 .1 % in the control group. Additionally, the test diet led to significant improvements in clinical scores, including the Otitis Index Score (OTIS-3), cytology scores, Canine Allergic Dermatitis Extent and Severity Index (CADESI-04), pruritic visual analogue scale (pVAS), and medication scores. TheseAttorney Docket No.: 00307-0214-00304Mars Ref.: MARS / P / 393182 / WO / SEC / 1 findings suggest that the test dietary composition, particularly the inclusion of glycyrrhizin and curcuminoids, can effectively reduce the severity and frequency of otitis externa in atopic dogs, as well as reducing the relapse of otitis externa in dogs with atopic dermatitis.

[0348] Furthermore, the novel food composition as disclosed herein can reduce the dose and frequency of anti-otitis externa agents intakes required to manage the condition of otitis externa in a dog.

[0349] Although the presently disclosed subject matter and its advantages have been described in detail, it should be understood that various changes, substitutions and alterations can be made herein without departing from the spirit and scope of the application as defined by the appended claims. Moreover, the scope of the present application is not intended to be limited to the particular embodiments of the process, machine, manufacture, composition of matter, means, methods and steps described in the specification. As one of ordinary skill in the art will readily appreciate from the disclosure of the presently disclosed subject matter, processes, machines, manufacture, compositions of matter, means, methods, or steps, presently existing or later to be developed that perform substantially the same function or achieve substantially the same result as the corresponding embodiments described herein can be utilized according to the presently disclosed subject matter. Accordingly, the appended claims are intended to include within their scope such processes, machines, manufacture, compositions of matter, means, methods, or steps.

[0350] For any patents, patent applications, publications, product descriptions, and protocols are cited throughout this application, the disclosures of all of which are incorporated herein by reference in their entireties for all purposes.

Claims

Attorney Docket No.: 00307-0214-00304 Mars Ref.: MARS / P / 393182 / WO / SEC / 1CLAIMS1 . A food composition for use in a method for treating and / or preventing and / or reducing the severity and / or reducing the relapse of otitis externa in a companion animal in need thereof, wherein the said food composition includes, as the sole active agents, glycyrrhizin and curcuminoid.

2. The food composition for use according to claim 1 , wherein the said food composition is formulated for providing to said companion animal in need thereof a daily amount of glycyrrhizin from about 0.1 mg / kg of the companion animal’s bodyweight (kg Bwt) to about 1 mg / kg Bwt, or, optionally, from about 0.2mg / kg Bwt to about 0.6mg / kg Bwt, or preferably of about 0.4g / kg Bwt.

3. The food composition for use according to claim 1 or 2, wherein the said food composition is formulated for providing to said companion animal in need thereof a daily amount of curcuminoid from about 0.5mg / kg Bwt to about 6mg / kg Bwt, or, optionally, from about 1 mg / kg Bwt to about 5mg / kg Bwt, or preferably of about 4 mg / kg Bwt.

4. The food composition for use according to any one of claims 1 to 3, wherein the curcuminoid is selected from curcumin, demethoxycurcumin, bisdemethoxycurcumin, methoxycurcumin, tetrahydrocurcumin, hexahydrocurcumin, monodemethoxycurcumin, and combinations thereof.

5. The food composition for use according to any of the preceding claims, wherein the source of glycyrrhizin is licorice or an extract thereof containing glycyrrhizin.

6. The food composition for use according to any of the preceding claims, wherein the source of curcuminoid is turmeric or an extract thereof containing curcuminoid.

7. The food composition for use according to any of the preceding claims, wherein the food composition is provided to the companion animal in need thereofAttorney Docket No.: 00307-0214-00304 Mars Ref.: MARS / P / 393182 / WO / SEC / 1 for a period of between about one month to about thirty-six months during, before or after an otitis externa medication.

8. The food composition for use according to any of the preceding claims, wherein the relapse of otitis externa in the companion animal is reduced by about 30% to about 100%.

9. The food composition for use according to claim 8, wherein the otitis externa medication comprises treating the companion animal by administering or applying an anti-otitis externa agent, in particular an anti-otitis externa agent is antibiotic ear drops, antifungal ear drops, and / or corticosteroid ear drops.

10. The food composition for use according to any one of the preceding claims, wherein the food composition is nutritionally complete and balanced.11 . The food composition for use according to any of the preceding claims, wherein the composition further comprises EPA and / or DHA, linoleic acid, Taurine, Lutein, Vitamin E, or combinations thereof.

12. The animal food composition for use according to claim 11 , wherein the food composition is formulated for providing to said companion animal in need thereof a daily amount of at least one of:(i) linoleic acid from about 50mg / kg Bwt to about 120mg / kg Bwt, or from about 50mg / kg Bwt to about 110mg / kg Bwt, or of about 90mg / kg Bwt; and / or(ii) Eicosapentaenoic acid (EPA) and / or Docosahexaenoic acid (DHA) from about 4mg / kg Bwt to about 20mg / kg Bwt, or from about 7mg / kg Bwt to about 15mg / kg Bwt, or of about 13mg / kg Bwt; and / or(iii) Taurine from about 15mg / kg Bwt to about 100mg / kg Bwt, or from about 50mg / kg Bwt to about 90mg / kg Bwt, or of about 75mg / kg Bwt; and / or(v) Lutein from about 0.015mg / kg Bwt to about 0.1 mg / kg Bwt, or from about 0.05mg / kg Bwt to about 0.09mg / kg Bwt, or of about 0.085mg / kg Bwt; and / or(v) Vitamin E from about 3mg / kg Bwt to about 20mg / kg Bwt, or from about 7mg / kg Bwt to about 17mg / kg Bwt, or of about 15.3mg / kg Bwt.Attorney Docket No.: 00307-0214-00304Mars Ref.: MARS / P / 393182 / WO / SEC / 113. The food composition for use according to any of the preceding claims, wherein the companion animal is a canine or a feline, preferentially a dog or a cat, and more preferentially a dog.

14. The food composition for use according to any of the preceding claims, the food composition being for treating and / or preventing and / or reducing the severity and / or reducing the relapse of otitis externa or symptoms thereof and / or an otitis externa-associated complication, optionally, an otitis externa-associated complication consists of alopecia, excoriation, crusting, erythema, hyperpigmentation or combinations thereof.

15. A method of manufacturing a food composition for use in a method for treating and / or preventing and / or reducing the severity and / or reducing the relapse of otitis externa in a companion animal in need thereof, comprising the steps of: a) mixing at least a source of glycyrrhizin and a source of curcuminoid, thereby providing a mixture; and b) heating the mixture; wherein the said food composition is formulated for providing to said companion animal in need thereof a daily amount of glycyrrhizin from about 0.1mg / kg Bwt to about 1mg / kg Bwt; and a daily amount of curcuminoid from about 0.5mg / kg Bwt to about 6mg / kg Bwt.

16. A method for preventing and / or treating and / or for reducing the severity and / or for reducing the relapse of otitis externa in a companion animal, wherein the method includes at least a step of feeding the companion animal with a food composition including, as the sole active agents, glycyrrhizin and curcuminoid.

17. The method of claim 16, wherein the method being for preventing and / or treating and / or for reducing the severity and / or for reducing the relapse of otitis externa or symptoms thereof.

18. The method of claim 16, wherein the method being for preventing and / or treating and / or for reducing the severity and / or for reducing the relapse of otitis externa and / or an otitis externa-associated complication.Attorney Docket No.: 00307-0214-00304Mars Ref.: MARS / P / 393182 / WO / SEC / 119. The method of claim 18, wherein the otitis externa-associated complication consists of alopecia, excoriation, crusting, erythema, hyperpigmentation or combinations thereof.

20. The method of claim 16, wherein the said food composition is formulated for providing to said companion animal in need thereof a daily amount of glycyrrhizin from about 0.1 mg / kg of the companion animal’s bodyweight (kg Bwt) to about 1 mg / kg Bwt, or from about 0.2mg / kg Bwt to about 0.6mg / kg Bwt, or of about 0.4g / kg Bwt.21 . The method of claim 16, wherein the said food composition is formulated for providing to said companion animal in need thereof a daily amount of curcuminoid from about 0.5mg / kg Bwt to about 6mg / kg Bwt, or from about 1 mg / kg Bwt to about 5mg / kg Bwt, or of about 4 mg / kg Bwt.

22. The method of claim 16, wherein the said food composition is formulated for providing to said companion animal in need thereof a daily amount of curcuminoid from about 0.5mg / kg Bwt to about 6mg / kg Bwt, or from about 1 mg / kg Bwt to about 5mg / kg Bwt, or of about 4 mg / kg Bwt.

23. The method of claim 16, wherein the curcuminoid is selected from curcumin, demethoxycurcumin, bisdemethoxycurcumin, meth oxy curcumin, tetrahydrocurcumin, hexahydrocurcumin, monodemethoxycurcumin, and combinations thereof.

24. The method of claim 16, wherein the source of glycyrrhizin is licorice or an extract thereof containing glycyrrhizin.

25. The method of claim 16, wherein the source of curcuminoid is turmeric or an extract thereof containing curcuminoid.Attorney Docket No.: 00307-0214-00304Mars Ref.: MARS / P / 393182 / WO / SEC / 126. The method of claim 16, wherein the food composition is provided to the companion animal in need thereof for a period of between about one month to about thirty-six months during, before or after an otitis externa medication.

27. The method of claim 16, wherein the relapse of otitis externa in the companion animal is reduced by about 30% to about 100%.

28. The method of claim 16, wherein the otitis externa medication comprises treating the companion animal by administering or applying an anti-otitis externa agent.

29. The method of claim 28, wherein an anti-otitis externa agent is antibiotic ear drops, antifungal ear drops, and / or corticosteroid ear drops.

30. The method of claim 16, wherein the food composition is nutritionally complete and balanced.31 . The method of claim 16, wherein the composition further comprises EPA and / or DHA, linoleic acid, Taurine, Lutein, Vitamin E, or combinations thereof.

32. The method of claim 31 , wherein the food composition is formulated for providing to said companion animal in need thereof a daily amount of at least one of:(i) linoleic acid from about 50mg / kg Bwt to about 120mg / kg Bwt; and / or(ii) Eicosapentaenoic acid (EPA) and / or Docosahexaenoic acid (DHA) from about 4mg / kg Bwt to about 20mg / kg Bwt; and / or(iii) Taurine from about 15mg / kg Bwt to about 100mg / kg Bwt; and / or(v) Lutein from about 0.015mg / kg Bwt to about 0.1 mg / kg Bwt; and / or(v) Vitamin E from about 3mg / kg Bwt to about 20mg / kg Bwt.

33. The method of claim 32, wherein the food composition is formulated for providing to said companion animal in need thereof a daily amount of at least one of:(i) linoleic acid from about 50mg / kg Bwt to about 110mg / kg Bwt; and / or(ii) Eicosapentaenoic acid (EPA) and / or Docosahexaenoic acid (DHA) from about 7mg / kg Bwt to about 15mg / kg Bwt; and / orAttorney Docket No.: 00307-0214-00304Mars Ref.: MARS / P / 393182 / WO / SEC / 1(iii) Taurine from about 50mg / kg Bwt to about 90mg / kg Bwt; and / or(v) Lutein from about 0.05mg / kg Bwt to about 0.09mg / kg Bwt; and / or(v) Vitamin E from about 7mg / kg Bwt to about 17mg / kg Bwt.

34. The method of claim 33, wherein the food composition is formulated for providing to said companion animal in need thereof a daily amount of at least one of:(I) linoleic acid of about 90mg / kg Bwt; and / or(ii) Eicosapentaenoic acid (EPA) and / or Docosahexaenoic acid (DHA) of about 13mg / kg Bwt; and / or(iii) Taurine of about 75mg / kg Bwt; and / or(v) Lutein of about 0.085mg / kg Bwt; and / or(v) Vitamin E of about 15.3mg / kg Bwt.

35. The method of claim 16, wherein the companion animal is a canine or a feline.

36. The method of claim 35, wherein the canine is a dog and the feline is a cat.

37. The method of claim 16, wherein the companion animal is a dog.

38. The method of claim 16, wherein an otitis externa-associated complication consists of alopecia, excoriation, crusting, erythema, hyperpigmentation or combinations thereof.

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