[0001 ] This application claims priority from Australian Provisional Patent

Application No. 2017904858 filed on 1 December 2017, the contents of which are to be taken as incorporated herein by this reference.

TECHNICAL FIELD

[0002] The invention relates to milk substitute compositions that closely reflect the composition of human breast milk. Particularly, the invention relates to a milk substitute composition for administration to humans aged 0-36 months.

BACKGROUND OF INVENTION

[0003] The benefits of breastfeeding to the development of infants and young children are well-established. Exclusive breastfeeding is recommend for the first six months of life, with supplemented breastfeeding recommended until at least age two and then for as long as the mother and child wish. It is now widely accepted that breastfeeding offers health benefits to mother and child, including boosting

development of the child’s immune system and decreased risk of diabetes, asthma, obesity and other conditions. There are, however, instances where breastfeeding is not possible and therefore it is necessary to use a milk substitute (also known as milk formula or infant formula) to supplement or, in some cases, replace breastfeeding as a source of infant nutrition.

[0004] The term "milk substitute" as used herein means a manufactured food designed for feeding to infants and children under 36 months of age (although safe for consumption beyond this age) usually prepared for bottle-feeding or cup-feeding from powder (mixed with water) or liquid (with or without additional water).

[0005] Human breast milk contains complex proteins and peptides, lipids including fatty acids and monoglycerides, carbohydrates, vitamins, minerals and other biologically active components. The composition changes over a single feed as well as over the period of lactation. Accordingly, milk substitute formulas can generally be divided into three categories: infant formula (Stage 1 ) which is designed for babies and infants aged 0-6 months, follow-on formula (Stage 2) which is intended for infants aged 6-12 months and toddler milk drinks (Stage 3) which are designed for young children aged 12 months and over. The compositions of these formulas are broadly based on the composition of a human mother’s milk at the various stages of lactation. For example, infant formulas are designed to be roughly based on a human mother's milk at approximately 1 -3 months postpartum. Besides breast milk, infant formula is the only other milk product which is considered nutritionally acceptable for infants under the age of one year. The U.S. Federal Food, Drug, and Cosmetic Act (FFDCA) defines infant formula as "a food which purports to be or is represented for special dietary use solely as a food for infants by reason of its simulation of human milk or its suitability as a complete or partial substitute for human milk".

[0006] Fluman milk contains around 0.8% - 1.0% protein, 4.5% fat, 7.1 %

carbohydrates (mainly lactose), and 0.2% mineral components. The major protein classes are whey and casein, which occur in a whey/casein ratio of about 90:10 in early lactation, approximately 60:40 in mature milk and around 50:50 in late lactation. Alpha-lactalbumin, a whey protein found in the milk of all mammals, is a major protein in human milk but is present at around half the human milk levels in bovine milk. In contrast, beta-lactoglobulin, the major bovine milk whey protein, is absent from human milk altogether.

[0007] The most commonly used milk substitutes contain purified bovine milk whey and casein as a protein source, a blend of vegetable oils as a fat source, lactose as a carbohydrate source, a vitamin-mineral mix, and other ingredients depending on the manufacturer. Some milk substitute formulas use soybean as a protein source or protein hydrolysed into smaller peptides or amino acids for infants who are allergic to other proteins.

[0008] Cow's milk contains, on average, 3.2-3.4% protein, 3.6% fat, 4.6% lactose and around 0.7% minerals. Of the proteins in bovine milk, about 80% are casein proteins and about 20% are whey proteins and the ratio of beta-lactoglobulin to alpha- lactalbumin in bovine whey ranges between 2.5:1 and 4:1 . Although cow's milk is the basis of almost all infant formula, plain cow’s milk is unsuited for infants in part because of its high casein content and low whey content coupled with its overall high total protein load. Despite a total protein concentration three times as high as that of human milk, bovine milk contains less than half as much alpha-lactalbumin as human milk. Human milk does not contain any beta-lactoglobulin. In contrast, beta- lactoglobulin is the most abundant whey protein in bovine milk. The infant intestine is not properly equipped to digest non-human milk, and administration of non-human milk to infants may lead to negative health outcomes such as diarrhoea, adverse immune responses, intestinal bleeding and malnutrition. To reduce the negative effect on the infant's digestive system, cow's milk used for formula must be processed to be made into milk substitute formulas. This includes steps to alter the whey-to- casein protein balance to one closer to human milk, the partial or total replacement of dairy fat with fats of vegetable or marine origin to better reflect the fatty acid profile of human milk, the addition of several other ingredients (often called "fortification"), alteration to the renal solute load and other changes.

[0009] Fats in human breast milk provides about 50% of the energy needed for the development and growth of a newborn infant. About 98% of the fats in human breast milk are in the form of triglycerides which are molecules consisting of mixtures of three fatty acids bonded to the sn-1 , sn-2, and sn-3 positions of a glycerol backbone. Human milk triglycerides are predominantly triglycerides of palmitic and oleic acid (OPO triglycerides, or sn-2 palmitate). Vegetable oils that are commonly used as a source of fat for infant formula have the opposite structure where the palmitic acid is located mainly at sn-1 and sn-3 positions.

[0010] The milk substitutes that are currently available often fall far short of providing the same nutritional profile as that of human breast milk.

[0011 ] It is therefore an aspectof the invention to provide a milk substitute composition which has an improved nutritional profile that is closer to that of human breast milk, or to at least provide a useful alternative to existing compositions.

SUMMARY OF INVENTION

[0012] In a first aspect, the present invention provides a milk substitute

composition comprising bovine milk; additional protein, wherein the additional protein comprises whey and alpha-lactalbumin; additional fats, wherein the additional fats comprise sn-2 palmitate (as OPO triglycerides and/or sn-2 palmitate monoglyceride); prebiotic fibre; and probiotic bacteria; wherein the bovine milk is substantially free from A1 beta-casein protein; and wherein the milk substitute composition is suitable for administration to humans aged 0-36 months. Preferably, the bovine milk contains less than 3% w/w A1 beta-casein protein, preferably less than 2% w/w A1 beta-casein protein, more preferably less than 1 % w/w A1 beta-casein protein, or even more preferably less than 0.5% w/w A1 beta-casein protein.

[0013] The compositions of the present invention advantageously assist with digestion and defecation, increasing fat and calcium absorption and improving gut microflora and so optimising immune system development. The compositions of the present invention also assist with sleep function and reduced crying time in infants and young children.

[0014] In one embodiment, the milk substitute composition of the present invention comprises total protein in an amount of less than around 24 g/1 OOg, preferably less than 20 g/1 OOg, more preferably less than around 15 g/1 OOg

(powdered form).

[0015] In another embodiment, the milk substitute composition of the present invention comprises total protein in an amount of less than around 12 g/1 OOg, preferably around 10 g/1 OOg, more preferably around 7.5 g/1 OOg (powdered form). A lower total protein content is associated with better health outcomes, including reduced likelihood of diabetes and obesity later in life.

[0016] Preferably, the milk substitute composition of the present invention has a whey to casein ratio of approximately 60:40 to approximately 40:60. In one preferred embodiment, the whey to casein ratio will be approximately 60:40. In another preferred embodiment, the whey to casein ratio will be approximately 40:60. A whey to casein ratio that mimics that of human breast milk is advantageous as it leads to better digestion, nutrient absorption and assimilation.

[0017] In a preferred embodiment, the alpha-lactalbumin is present in an amount between 750 and 4000 mg/1 OOg, preferably between 1000 and 3000 mg/1 OOg, more preferably between 2200 and 2400 mg/1 OOg (powdered form). [0018] In another embodiment, the additional protein further comprises lactoferrin. Preferably, the lactoferrin is present in an amount of between 50 and 500 mg/100g, preferably between 65 and 320 mg/100g (powdered form).

[0019] In another embodiment, the milk substitute composition of the present invention further comprises osteopontin.

[0020] In another embodiment, the milk substitute composition of the present invention further comprises milk fat globule membrane (MFGM).

[0021 ] In another embodiment, the milk substitute composition of the present invention is substantially free of beta-lactoglobulin.

[0022] In preferred embodiments of the present invention, the sn-2 palmitate (as OPO triglycerides and/or sn-2 palmitate monoglyceride) is present in an amount of between 0.5 and 7.0 g/1 OOg, preferably between 1 .0 and 4.0g/100g (powdered form). Preferably, the sn-2 palmitate will take the form of OPO triglycerides. Enrichment with sn-2 palmitate is advantageous as it has the same structure as the dominant human milk triglycerides and it is associated with increased fat absorption, reduced calcium soaps formation and stool hardness, increased calcium retention and larger skeletal mineral deposition.

[0023] In various preferred embodiments, the prebiotic fibre is selected from the group comprising galactooligosaccharides (GOS), fructooligosaccharides (FOS), xylooligosaccharide (XOS), isomaltooligosaccharide (IMO), Fluman Milk

Oligosaccharides (HMO) and mixtures thereof. In another preferred embodiment, the prebiotic fibre comprises Human Milk Oligosaccharides (HMO).

[0024] In a preferred embodiment of the present invention, the milk substitute composition of the present invention further comprises docosahexaenoic acid (DHA). Preferably, the docosahexaenoic acid (DHA) is present in an amount of greater than 75 mg/1 OOg, more preferably greater than 95 mg/1 OOg (powdered form). DHA is accumulated specifically in the lipid membranes of the brain and retina, where it is important to visual and neurological function and cognitive development. [0025] In a preferred embodiment of the present invention, the milk substitute composition of the present invention further comprises iodine. Preferably, the iodine is present in an amount of greater than 75 pg/100g, more preferably greater than 95 pg/100g (powdered form). Iodine is an important contributor to cognitive development and normal growth and development.

[0026] In a preferred embodiment of the present invention, the probiotic bacteria of the present invention are selected from the group consisting of Bifidobacterium and Lactobacillus.

[0027] In a preferred embodiment of the present invention, the milk substitute composition comprises total protein in an amount of less than around 24 g/1 OOg, preferably less than 20 g/1 OOg, more preferably around 15 g/1 OOg (powdered form); wherein the alpha-lactalbumin is present in an amount of between 750 and 2500 mg/1 OOg, more preferably around 1000 mg/1 OOg (powdered form); wherein the milk substitute composition is suitable for administration to humans aged 12-36 months.

[0028] In a preferred embodiment of the present invention, the milk substitute composition comprises total protein in an amount of less than around 12 g/1 OOg, more preferably around 10 g/1 OOg, still more preferably around 7.5 g/1 OOg (powdered form); wherein the alpha-lactalbumin is present in an amount of between 1000 and 3000 mg/1 OOg, more preferably between 2200 and 2400 mg/1 OOg (powdered form); wherein the milk substitute composition is suitable for administration to humans aged 0-12 months.

[0029] In a further aspect, the present invention provides a milk substitute composition comprising bovine milk; additional protein, wherein the additional protein comprises whey and alpha-lactalbumin; additional fats, wherein the additional fats comprise sn-2 palmitate (as OPO triglycerides and/or sn-2 palmitate monoglyceride); prebiotic fibre; and probiotic bacteria; wherein the bovine milk is substantially free from A1 beta-casein protein; wherein the milk substitute composition comprises total protein in an amount of less than around 24 g/1 OOg, preferably less than 20 g/1 OOg, more preferably around 15 g/1 OOg (powdered form); wherein the alpha-lactalbumin is present in an amount of between 750 and 2500 mg/1 OOg, preferably around 1000 mg/100g (powdered form); wherein the milk substitute composition is suitable for administration to humans aged 12-36 months.

[0030] In a further aspect, the present invention provides a milk substitute composition comprising bovine milk; additional protein, wherein the additional protein comprises whey and alpha-lactalbumin; additional fats, wherein the additional fats comprise sn-2 palmitate (as OPO triglycerides and/or sn-2 palmitate monoglyceride); prebiotic fibre; and probiotic bacteria; wherein the bovine milk is substantially free from A1 beta-casein protein; wherein the milk substitute composition comprises total protein in an amount of less than around 12 g/1 OOg, preferably around 10 g/1 OOg, more preferably around 7.5 g/1 OOg (powdered form); wherein the alpha-lactalbumin is present in an amount of between 1000 and 3000 mg/1 OOg, more preferably between 2200 and 2400 mg/1 OOg (powdered form); wherein the milk substitute composition is suitable for administration to humans aged 0-12 months.

[0031 ] It is a feature of the present invention that the bovine milk is substantially free from A1 beta-casein protein. Preferably, the bovine milk fat and/or whey protein used in the present invention are sourced from milk that is substantially free from A1 beta-casein protein. This is advantageous as it helps reduce the potentially negative health outcomes associated with A1 beta-casein protein found in bovine milk, including adverse immune response, Type 1 diabetes, neurological disorders, heart disease, and digestive discomfort. This allows for improved immune system

responses and developmental outcomes.

[0032] In another aspect, there is provided a method of improving digestive function in a human aged 0-36 months, comprising administering to the human the milk substitute composition in accordance with the present invention. In another aspect, the milk substitute composition is provided in accordance with the present invention for use in the improvement of digestive function.

[0033] In another aspect, the present invention provides a method of improving sleep function in a human aged 0-36 months, comprising administering to the human the milk substitute composition in accordance with the present invention. In another aspect, the milk substitute composition is provided in accordance with the present invention for use in the improvement of sleep function. [0034] The milk substitute compositions of the present invention advantageously provide a nutritional profile that more closely reflects that of human breast milk. This can assist with digestion, increasing fat and calcium absorption and improving gut microflora, and development. This can also assist in induction and maintenance of sleep. The compositions of the present invention may further provide reduced crying time, as infants and young children are better settled and have improved digestive function. It is further believed that the compositions of the present invention will lead to improved lung development and epithelial development in infants and young children. Improved epithelial development will in turn lead to improvements in immune induction outcomes.

BRIEF DESCRIPTION OF DRAWINGS

[0035] Figure 1 shows the structure of A2 and A1 b-casein differences at position 67 of the beta-casein chains and the release of BCM-7 from A1 but not A2 beta- casein.

[0036] Figure 2 shows calcium soap formation with palmitic acids cleaved from the first and third carbons from common vegetable oil triglycerides, present in standard infant formula.

DETAILED DESCRIPTION

[0037] In one aspect, the milk substitute compositions of the present invention comprise bovine milk; additional protein, wherein the additional protein comprises whey and alpha-lactalbumin; additional fats, wherein the additional fats comprise sn-2 palmitate (as OPO triglycerides and/or sn-2 palmitate monoglyceride); prebiotic fibre; wherein the bovine milk is substantially free from A1 beta-casein protein; and wherein the milk substitute composition is suitable for administration to humans aged 0-36 months.

[0038] The term "milk substitute" as used herein means a manufactured food designed for feeding to infants and children under 36 months of age (although safe for consumption beyond this age). The milk substitute composition is usually prepared for bottle-feeding or cup-feeding from powder (mixed with water or other appropriate diluent) or liquid (with or without additional diluent). The term "powdered form", also referred to as“milk powder”, "powdered milk" or "dried milk", means milk that has been evaporated to dryness and has been formed as a powder or processed to form a powder. Preferably, the milk substitute compositions of the present invention are prepared as milk powder, for subsequent dilution and administration to infants and young children. In an alternate preferred embodiment, the milk substitute

compositions of the present invention are prepared as concentrated liquid, for subsequent dilution and administration to infants and young children. In an alternate preferred embodiment, the milk substitute compositions of the present invention are prepared as liquid that are suitable for administration to infants and young children without the need for additional dilution.

[0039] As used herein, the term“infant” is generally used to refer to a human aged 0-12 months, although the skilled person will understand that the term“infant” can be used to describe humans up to 24 months in age in some contexts. The term“young child” is generally used to refer to a human aged 12-60 months. The term“toddler” is generally used to refer to a human aged 12-36 months.

[0040] Milk substitute formulas for infants and young children are generally divided into three categories: infant formula (Stage 1 ), intended for infants aged 0-6 months; follow-on formula (Stage 2), intended for infants aged 6-12 months; and toddler milk drink (Stage 3); intended for young children aged 12 months and older.

[0041 ] The term“additional protein” refers to proteins and peptides which are added to the bovine milk base, in addition to the proteins and peptides already present in the milk. The term“additional fats” refers to oils, fats, lipids, triglycerides and fatty acids which are added the bovine milk base, in addition to the fats already present in the milk. The term“additional carbohydrates” refers to carbohydrates which are added the bovine milk base, in addition to the carbohydrates already present in the milk.

[0042] It will be appreciated that while milk substitute compositions are generally administered in liquid form, they are often manufactured, supplied, sold and transported in powdered form. [0043] The skilled person will appreciate that nutritional content of milk substitute compositions can be referred to in a number of different ways. These include percentages, as well as g/1 OOg (or mg/100g, or pg/100g, etc.) of the powdered form of the milk substitute composition or alternatively g/1 OOmL (or mg/1 OOmL, or pg/1 OOmL, etc.) of liquid form of the milk substitute composition. Generally, a fixed amount of the powdered form (usually equating to scoop size from the retail container) is mixed with a fixed amount of adequately prepared warm water (or other diluent) to obtain the liquid form. Herein, for consistency and clarity the

concentrations of various nutritional components of the milk substitute composition will generally be referred to in g/1 OOg of the powdered form. The skilled person will appreciate that this is proportional to g/1 OOmL, etc. of liquid form of the milk substitute composition.

[0044] The compositions of the present invention advantageously assist with digestion, increasing fat and calcium absorption and improving gut microflora and thus gut function and development. This aids sleep, digestive and bowel function in infants and young children. The compositions of the present invention

advantageously assist with infant settling, rest and sleep, allowing infants and young children to achieve rest and/or sleep more quickly. The compositions of the present invention may further provide reduced crying time, as infants are better settled and have improved digestive function.

[0045] Protein

[0046] As previously mentioned, bovine milk and human breast milk have significantly different protein content. Human milk contains around 0.8% - 1 .0% protein, whereas cow's milk contains around 3.2-3.4% protein. In bovine milk, the protein is about 80% casein protein and about 20% whey proteins while in humans the whey/casein ratio is about 90:10 in early lactation, approximately 60:40 in mature milk and around 50:50 in late lactation. In bovine milk, the ratio of beta-lactoglobulin to alpha-lactalbumin in bovine whey ranges between 2.5:1 and 4:1 , whereas in human milk, beta-lactoglobulin is absent and alpha-lactalbumin is a major protein.

[0047] In some embodiments, the milk substitute composition of the present invention comprises total protein in an amount of less than around 24 g/1 OOg (powdered form), for example less than around 23 g/1 OOg, less than around 22 g/1 OOg, or less than around 21 g/1 OOg (powdered form). In preferred embodiments, the milk substitute composition of the present invention comprises total protein in an amount of less than around 20 g/1 OOg (powdered form), for example less than around 19 g/1 OOg, less than around 18 g/1 OOg, less than around 17 g/1 OOg, or less than around 16 g/1 OOg (powdered form). Preferably, the milk substitute composition of the present invention comprises total protein in an amount of less than around 15 g/1 OOg (powdered form), for example less than around 14.5 g/1 OOg or less than around 14 g/1 OOg, less than around 13.5 g/1 OOg, less than around 13 g/1 OOg, or less than around 12.5 g/100g(powdered form).

[0048] In other preferred embodiments, the milk substitute composition of the present invention comprises total protein in an amount of less than around 12 g/1 OOg, (powdered form), for example less than around 1 1 .5 g/1 OOg, less than around 1 1 g/1 OOg, or less than around 10.5 g/1 OOg (powdered form). Preferably, the milk substitute composition of the present invention comprises total protein in an amount of less than around 10 g/1 OOg (powdered form), for example less than around 9.5 g/1 OOg, less than around 9 g/1 OOg, less than around 8.5 g/1 OOg, or less than around 8 g/1 OOg (powdered form). More preferably, the milk substitute composition of the present invention comprises total protein in an amount around 7.5 g/1 OOg (powdered form). A lower total protein content is associated with better health outcomes, including reduced likelihood of type 2 diabetes and obesity later in life.

[0049] It will be understood that the proteins present in the composition will be a mixture of whey proteins and casein proteins. In some embodiments, the milk substitute composition of the present invention has a whey to casein ratio of approximately 80:20 to approximately 20:80. In some embodiments, the milk substitute composition of the present invention has a whey to casein ratio of approximately 70:30 to approximately 30:70. Preferably, the milk substitute composition of the present invention has a whey to casein ratio of approximately 60:40 to approximately 40:60. In one preferred embodiment, the whey to casein ratio will be approximately 60:40. In another preferred embodiment, the whey to casein ratio will be approximately 50:50. In another preferred embodiment, the whey to casein ratio will be approximately 40:60. A whey to casein ratio that more closely reflects that of human breast milk is advantageous as it leads to better digestion and absorption and improved utilisation of constituent nutrients.

[0050] Alpha-lactalbumin, a whey protein found in the milk of all mammals, is a major protein in human milk. Alpha-lactalbumin is particularly rich in the essential amino acids tryptophan, lysine and cystine compared to other bovine milk proteins. Tryptophan supplementation of infants shortens the time to onset of sleep.

[0051 ] It will be understood by the skilled person that while alpha-lactalbumin, lactoferrin and beta-lactoglobulin are whey proteins, whey proteins comprise various other proteins in addition to alpha-lactalbumin, lactoferrin and beta-lactoglobulin. Therefore, as used herein, the terms“alpha-lactalbumin”,“lactoferrin” and“beta- lactoglobulin” will refer to isolated, filtered, purified or fortified alpha-lactalbumin protein, lactoferrin and beta-lactoglobulin protein respectively. The term“whey” will refer to a mixture of proteins isolated from whey, generally comprising alpha- lactalbumin, beta-lactoglobulin, lactoferrin, lysozyme, serum albumin,

immunoglobulins, secretory IgA and proteose-peptones.

[0052] In a preferred embodiment, the alpha-lactalbumin is present in an amount between 750 and 4000 mg/100g (powdered form), for example between 750 and 3900 mg/100g, between 750 and 3800 mg/100g, between 750 and 3700 mg/100g, between 750 and 3600 mg/100g, between 750 and 3500 mg/100g, between 750 and 3400 mg/100g, between 750 and 3200 mg/100g, between 750 and 3100 mg/100g, between 750 and 3000 mg/100g, or between 800 and 4000 mg/100g, between 800 and 3900 mg/100g, between 800 and 3800 mg/100g, between 800 and 3700 mg/100g, between 800 and 3600 mg/100g, between 800 and 3500 mg/100g, between 800 and 3400 mg/100g, between 800 and 3200 mg/100g, between 800 and 3100 mg/100g, between 800 and 3000 mg/100g, or between 850 and 4000 mg/100g, between 850 and 3900 mg/100g, between 850 and 3800 mg/100g, between 850 and 3700 mg/100g, between 850 and 3600 mg/100g, between 850 and 3500 mg/100g, between 850 and 3400 mg/100g, between 850 and 3200 mg/100g, between 850 and 3100 mg/100g, between 850 and 3000 mg/100g, or between 900 and 4000 mg/100g, between 900 and 3900 mg/100g, between 900 and 3800 mg/100g, between 900 and 3700 mg/100g, between 900 and 3600 mg/1 OOg, between 900 and 3500 mg/100g, between 900 and 3400 mg/100g, between 900 and 3200 mg/100g, between 900 and 3100 mg/100g, between 900 and 3000 mg/100g, or between 950 and 4000 mg/100g, between 950 and 3900 mg/100g, 950 and 3800 mg/100g, between 950 and 3700 mg/100g, between 950 and 3600 mg/100g, between 950 and 3500 mg/100g, between 950 and 3400 mg/100g, between 950 and 3200 mg/100g, between 950 and 3100 mg/100g, between 950 and 3000 mg/100g, or between 1000 and 4000 mg/100g, between 1000 and 3900 mg/100g, 1000 and 3800 mg/100g, between 1000 and 3700 mg/100g, between 1000 and 3600 mg/100g, between 1000 and 3500 mg/100g, between 1000 and 3400 mg/100g, between 1000 and 3200 mg/100g, or between 1000 and 3100 mg/100g (powdered form).

[0053] Preferably, the alpha-lactalbumin is present in an amount between 1000 and 3000 mg/100g (powdered form), for example between 1000 and 3000 mg/100g, between 1200 and 3000 mg/100g, between 1400 and 3000 mg/100g, between 1600 and 3000 mg/100g, between 1800 and 3000 mg/100g, between 2000 and 3000 mg/100g, between 2200 and 3000 mg/100g, or between 1000 and 2800 mg/100g, between 1200 and 2800 mg/100g, between 1400 and 2800 mg/100g, between 1600 and 2800 mg/100g, between 1800 and 2800 mg/100g, between 2000 and 2800 mg/100g, between 2200 and 2800 mg/100g, or between 1000 and 2600 mg/100g, between 1200 and 2600 mg/100g, between 1400 and 2600 mg/100g, between 1600 and 2600 mg/100g, between 1800 and 2600 mg/100g, between 2000 and 2600 mg/100g, between 2200 and 2600 mg/100g, or between 1000 and 2400 mg/100g, between 1200 and 2400 mg/100g, between 1400 and 2400 mg/100g, between 1600 and 2400 mg/100g, between 1800 and 2400 mg/100g, or between 2000 and 2400 mg/100g (powdered form).

[0054] More preferably, the alpha-lactalbumin is present in an amount between 2200 and 2400 mg/100g (powdered form) for example between 2200 and 2350 mg/100g, between 2200 and 2300mg/100g, between 2200 and 2250 mg/100g, or between 2250 and 2400 mg/100g, between 2250 and 2350 mg/100g, between 2250 and 2300mg/100g, or between 2300 and 2400 mg/100g, between 2300 and 2350 mg/100g, or between 2350 and 2400 mg/100g (powdered form). [0055] In a preferred embodiment, the alpha-lactalbumin is present in an amount of around 2300 mg/100g. In another preferred embodiment, the alpha-lactalbumin is present in an amount of around 2400 mg/100g. In another preferred embodiment, the alpha-lactalbumin is present in an amount of around 1000 mg/100g.

[0056] Beta-lactoglobulin, is the major whey protein of cow and sheep's milk (~3 g/l), and is also present in many other mammalian species; a notable exception being humans. Beta-lactoglobulin has been linked to various allergic reactions. In a preferred embodiment, the composition of the present invention will be substantially free from beta-lactoglobulin. The term“substantially free from beta-lactoglobulin” means that the composition has a beta-lactoglobulin content of less than around 5% w/w, preferably less than around 4% w/w, more preferably less than around 3% w/w, even more preferably less than around 2% w/w, still more preferably less than around 1 % w/w, most preferably less than around 0.5% w/w. This is advantageous as it avoids the potentially negative health outcomes associated with the consumption of beta-lactoglobulin.

[0057] It is a feature of the present invention that the bovine milk is substantially free from A1 beta-casein protein. Preferably, the bovine milk fat and/or whey protein used in the present invention are sourced from milk that is substantially free from A1 beta-casein protein. This advantageously helps reduce the potentially negative health outcomes associated with the consumption of A1 -beta-casein protein.

[0058] There are four different types of casein proteins: alpha-s1 -, alpha-s2-, beta- , and kappa-caseins. A1 and A2 beta-casein types are genetic variants of the beta- casein milk protein that primarily differ by one amino acid at position 67 of their beta- casein chains; a proline occurs at the homologous position of the amino acid chain on the original A2 beta-casein variant, while in A1 beta-casein a histidine occurs at position 67. The A1 beta-casein type is the most common type found in cow's milk in Europe (excluding France), the United States, Australia, and New Zealand. The A1 beta-casein type is not found in human breast milk. In human milk, beta-casein is of the A2 and not A1 type, with a proline at the homologous position on the beta-casein protein chain. The major constituent of the family of human caseins is beta-casein, the highly phosphorylated nature of which contributes to the high bioavailability of calcium from human breast milk. The amino acid present in position 67 of the bovine beta-casein sequence is significant for the release of an exogenous opioid peptide called beta-casomorphin-7 (BCM-7). In the case of the variants containing Proline (i.e. the A2 beta-casein type variant), the enzymatic hydrolysis of the lle ⁶⁶ -Pro ⁶⁷ bond does not occur or occurs at a very low rate. In the case of variants containing a histidine at the homologous position (i.e. A1 beta-casein type) enzymatic hydrolysis of the lle ⁶⁶ -Histidine ⁶⁷ bond does occur, allowing cleavage of the preceding seven amino acids, yielding BCM-7, as shown in Figure 1 . While endogenous opioids such as beta-casomorphins are useful in inducing sleep, bovine beta-casomorphins and the consumption of A1 -beta-casein have been associated with a number of negative health outcomes including elevated immunological reactions and blunted glutathione synthesis, diabetes, neurological disorders, heart disease, and digestive discomfort. Notably, endogenous human A2 beta-casein derived BCM-7 is structurally different to bovine BCM-7 and consequently, has markedly weaker opioid binding affinity compared to bovine BCM-7. Human beta-casomorphins (Tyr-Pro-Phe-Val-Glu-Pro- lle) have been found to be 3 to 30 times less potent than bovine beta-casomorphins (Tyr-Pro-Phe-Pro-Gly-Pro-lle). The compositions of the present invention

advantageously minimise these negative health outcomes associated with bovine BCM-7 and A1 beta casein, whilst still providing improvements in induction and maintenance of sleep, and improvements in digestive function and development.

[0059] The compositions of the present invention comprise bovine milk that is substantially free from A1 beta-casein protein. The term“substantially free from A1 beta-casein protein” means that the bovine milk has an A1 beta-casein content of at least less than 5% w/w, for example less than 4%, less than 3%, less than 2%, less than 1 %, or even less than 0.5% w/w A1 beta-casein protein. Preferably, the bovine milk has an A1 beta-casein content of less than 3% w/w, more preferably less than 1 % w/w, even more preferably less than 2% w/w, most preferably less than 0.5% w/w A1 beta-casein protein. These thresholds can be measured by any technique standard in the art of protein detection such as, for example, mass spectrometry, chromatography and electrophoresis. It will be understood by the skilled person that low levels of A1 beta-casein protein are often beyond detection limits and therefore more accurately measured by measuring the amount of A2 beta-casein protein present.

[0060] In some embodiments, the compositions of the present invention will comprise additional A2 beta-casein protein which has been isolated from mammalian milk. Preferably, the additional A2 beta-casein protein will be added in amounts sufficient to match levels found in human breast milk. This is advantageous as it helps further mimic the protein profile of human milk and minimises the negative health outcomes associated with A1 beta-casein and alpha-caseins.

[0061 ] Milk comprising beta-casein that is substantially free from A1 beta-casein protein (i.e. of the beta-caseins, it contains predominantly or exclusively A2 beta- casein) may be obtained by firstly genotyping cows for the beta-casein gene, identifying those cows that have the ability to produce A2 beta-casein in their milk and no other beta-casein (i.e. cows having the A2A2 allele), and milking those cows. The methodology will be appreciated and understood by those skilled in the fields of animal genotyping, herd formation and the production and supply of bovine milk.

While it is preferred that the beta-casein variant is A2 beta-casein, it should be understood that the A2 beta-casein may be any A2 type beta-casein variant, i.e. any of A2, A3, D, E and F beta-caseins which have proline at the homologous position of the beta-casein amino acid sequence. In some embodiments of the invention the bovine milk is obtained from bovine cows that are known to have the beta-casein A2A2 genotype.

[0062] Lactoferrin is a globular glycoprotein with a molecular mass of about 80 kDa that is widely represented in various secretory fluids, such as the milk of humans and other mammals. Concentrations of lactoferrin in milk vary from around 7 g/L in colostrum to 1 g/L in mature milk. Lactoferrin plays an important role in the binding and transport of iron ions, plays a role in brain metabolism and is implicated in a number of immune response pathways. In one embodiment of the present invention, the additional protein of the milk substitute composition may further comprise lactoferrin. Preferably, the lactoferrin is present in an amount of between 50 and 500 mg/100g (powdered form), for example between 50 and 480 mg/100g, between 50 and 460 mg/100g, between 50 and 440 mg/100g, between 50 and 420 mg/100g, between 50 and 400 mg/100g, between 50 and 380 mg/100g, between 50 and 360 mg/100g, between 50 and 340 mg/100g, between 50 and 320 mg/100g, or between 55 and 500 mg/100g, between 55 and 480 mg/100g, between 55 and 460 mg/100g, between 55 and 440 mg/100g, between 55 and 420 mg/100g, between 55 and 400 mg/100g, between 55 and 380 mg/100g, between 55 and 360 mg/100g, between 55 and 340 mg/100g, between 55 and 320 mg/1 OOg, or between 60 and 500 mg/1 OOg, between 60 and 480 mg/100g, between 60 and 460 mg/1 OOg, between 60 and 440 mg/100g, between 60 and 420 mg/1 OOg, between 60 and 400 mg/1 OOg, between 60 and 380 mg/100g, between 60 and 360 mg/1 OOg, between 60 and 340 mg/1 OOg, between 60 and 320 mg/100g, or between 65 and 500 mg/1 OOg, between 65 and 480 mg/100g, between 65 and 460 mg/1 OOg, between 65 and 440 mg/1 OOg, between 65 and 420 mg/100g, between 65 and 400 mg/1 OOg, between 65 and 380 mg/1 OOg, between 65 and 360 mg/100g, or between 65 and 340 mg/1 OOg (powdered form).

[0063] More preferably, the lactoferrin is present in an amount of between 65 and 320 mg/100g (powdered form), for example between 75 and 320 mg/100g, between 85 and 320 mg/100g, between 95 and 320 mg/100g, between 105 and 320 mg/100g, between 1 15 and 320 mg/100g, between 125 and 320 mg/100g, between 135 and 320 mg/100g, between 145 and 320 mg/100g, between 155 and 320 mg/100g, between 165 and 320 mg/100g, between 175 and 320 mg/100g, between 185 and 320 mg/100g, between 195 and 320 mg/100g, between 205 and 320 mg/100g, between 215 and 320 mg/100g, between 225 and 320 mg/100g, between 235 and 320 mg/100g, between 245 and 320 mg/100g, between 255 and 320 mg/100g, between 265 and 320 mg/100g, between 275 and 320 mg/100g, between 285 and 320 mg/100g, between 295 and 320 mg/100g, between 305 and 320 mg/100g, or between 65 and 310 mg/100g, between 65 and 300 mg/100g, between 65 and 290 mg/100g, between 65 and 280 mg/100g, between 65 and 270 mg/100g, between 65 and 260 mg/100g, between 65 and 250 mg/100g, between 65 and 240 mg/100g, between 65 and 230 mg/100g, between 65 and 220 mg/100g, between 65 and 210 mg/100g, between 65 and 200 mg/100g, between 65 and 190 mg/100g, between 65 and 180 mg/100g, between 65 and 170 mg/100g, between 65 and 160 mg/100g, between 65 and 150 mg/100g, between 65 and 140 mg/100g, between 65 and 150 mg/100g, between 65 and 140 mg/100g, between 65 and 130 mg/100g, between 65 and 120 mg/100g, between 65 and 110 mg/100g, between 65 and 100 mg/100g, between 65 and 90 mg/100g, between 65 and 80 mg/100g, or between 65 and 70 mg/100g (powdered form).

[0064] Osteopontin (OPN) is a multifunctional protein involved in physiological processes such as wound healing, angiogenesis, biomineralisation, tissue

remodelling, and also in immune activation. OPN has been reported to be present in human milk at concentration of ~ 130 mg/L. In one embodiment of the present invention, the additional protein of the milk substitute composition may further comprise osteopontin (OPN). Preferably, the osteopontin is present in amount greater than 100 mg/100, preferably around 145mg/100g (powdered form).

[0065] Milk fat globule membrane (MFGM) is a complex structure composed primarily of lipids and proteins that surrounds milk fat globule secreted from the milk producing cells of humans and other mammals. The MFGM in human milk contains many bioactive components with diverse functions and has been linked to cognitive and health benefits to infants. Some compositional differences are reported to exist between species, but bovine MFGM, the best-studied non-human source, generally contains a lipid and protein composition which is similar to that of human MFGM. The lipid:protein weight of MFGM is around 1 :1. MFGM makes up an estimated 2-6% of the total fat globules. As raw milk has an average total fat content around 4%, it therefore contains around 0.08-0.24% of MFGM. Flowever, infant formulas

traditionally lack MFGM because this fraction is lost during regular dairy processing.

In one embodiment of the present invention, the milk substitute composition of the present invention further comprises bovine milk fat globule membrane (MFGM).

Preferably, the MFGM is present in an amount of between around 2% to around 6% w/w, preferably between around 3% to around 4% w/w of the milk substitute composition. In another preferred embodiment, the MFGM is present in an amount of around around 300 mg proteins/ 100 g powder which substantially accords with those levels found in human breast milk.

[0066] Fats

[0067] Fluman milk triglycerides are predominantly triglycerides of oleic and palmitic acid (OPO triglycerides, or sn-2 palmitate). Triglyceride digestion by endogenous lipases leads to hydrolysis of the oleic acid fatty acids from the

triglyceride sn-1 ,3 positions, to release two fatty acids and one sn-2 palmitate monoglyceride into the intestinal lumen, which undergo improved absorption and reduced excretion. Palmitic acid is associated with improved brain function.

[0068] Vegetable oils that are commonly used as a source for infant formula fat have the opposite structure where the palmitic acid is located mainly at sn-1 and sn-3 positions. Enzymatic processing of vegetable oils enables changing the position of palmitic acid to the sn-2 position.

[0069] Clinical studies in preterm and term infants, as well as preclinical animal model studies, show that enrichment of infant formula with sn-2 palmitate results in increased fat absorption, reduced calcium soaps formation and stool hardness, increased calcium retention and larger skeletal mineral deposition. Figure 2 shows how calcium soaps form during digestion of common vegetable oil-derived sn-1 and sn-3 cleaved palmitic acids. Improved digestion leads to reduced crying time and more settled infants and young children. Improved absorption and availability of palmitic acid leads to improved brain outcomes.

[0070] It will be appreciated that the term“sn-2 palmitate” is used interchangeably in the art to refer to either OPO triglycerides or sn-2 palmitate monoglyceride. It will also be appreciated that the term“ beta-palm itate” is also used to refer to sn-2 palmitate. In preferred embodiments of the present invention, the sn-2 palmitate will take the form of OPO triglycerides or sn-2 palmitate monoglyceride or mixtures thereof. Preferably, the sn-2 palmitate will predominantly take the form of OPO triglycerides.

[0071 ] In a preferred embodiment, the sn-2 palmitate (as OPO triglycerides and/or sn-2 palmitate monoglyceride) is present in an amount of between 0.5 and 7.0 g/1 OOg (powdered form), for example between 0.5 and 6.5 g/1 OOg, between 0.5 and 6.0 g/1 OOg, between 0.5 and 5.5 g/1 OOg, between 0.5 and 5.0 g/1 OOg, between 0.5 and 7.0 g/1 OOg, between 0.5 and 4.5 g/1 OOg, between 0.5 and 4.0 g/1 OOg, or between 1 .0 and 7.0 g/1 OOg, between 1 .0 and 6.5 g/1 OOg, between 1 .0 and 6.0 g/1 OOg, between 1 .0 and 5.5 g/1 OOg, between 1 .0 and 5.0 g/1 OOg, between 1 .0 and 7.0 g/1 OOg, between 1 .0 and 4.5 g/1 OOg (powdered form). [0072] More preferably, the sn-2 palmitate (as OPO triglycerides and/or sn-2 palmitate monoglyceride) is present in an amount of between 1 .0 and 4.0 g/1 OOg (powdered form), for example between 1 .0 and 3.5 g /1 OOg, between 1 .0 and 3.0 g/1 OOg, between 1 .0 and 2.5 g/1 OOg, between 1 .0 and 2.0 g/1 OOg, between 1 .0 and 1 .5 g/1 OOg, or between 1 .5 and 4.0 g/1 OOg, between 1 .5 and 3.5 g / 10Og, between 1 .5 and 3.0 g/1 OOg, between 1 .5 and 2.5 g/1 OOg, between 1 .5 and 2.0 g/1 OOg, or between 2.0 and 4.0 g/1 OOg, between 2.0 and 3.5 g /1 OOg, between 2.0 and 3.0 g/1 OOg, between 2.0 and 2.5 g/1 OOg, or between 2.5 and 4.0 g/1 OOg, between 2.5 and 3.5 g /1 OOg, between 2.5 and 3.0 g/1 OOg, or between 3.0 and 4.0 g/1 OOg, between 3.0 and 3.5 g /1 OOg, or between 3.5 and 4.0 g/1 OOg (powdered form).

[0073] In a preferred embodiment, the sn-2 palmitate (as OPO triglycerides and/or sn-2 palmitate monoglyceride) is present in an amount of around 3.6 g/1 OOg. In another preferred embodiment, the sn-2 palmitate (as OPO triglycerides and/or sn-2 palmitate monoglyceride) is present in an amount of around 1 .1 g/1 OOg.

[0074] The additional fats preferred for use in accordance with the present invention are selected from the group comprising bovine milk fat, canola oil, esterified palm oil or its variations, coconut oil, sunflower oil, sn-2 palmitate (as OPO

triglycerides and/or sn-2 palmitate monoglyceride), olive oil, and mixtures thereof. In a preferred embodiment, the additional fats comprise a mixture of bovine milk fats, canola oil, esterified palm oil, coconut oil, sunflower oil and sn-2 palmitate (as OPO triglycerides and/or sn-2 palmitate monoglyceride). This blend can provide a fatty acid profile that is advantageously similar to that of human breast milk.

[0075] In another preferred embodiment, the additional fats comprise

monounsaturated fatty acids rich in oleic acid, preferably derived from olive oil. This blend can also provide a fatty acid profile that is advantageously similar to that of human breast milk.

[0076] Preferably, the milk substitute composition of the present invention comprises total fat in an amount of between 10 and 30 g/1 OOg (powdered form), for example between 10 and 29 g/1 OOg, 10 and 28 g/1 OOg, 10 and 27 g/1 OOg, 10 and 26 g/1 OOg, 10 and 25 g/1 OOg, or between 1 1 and 30 g/1 OOg, 1 1 and 29 g/1 OOg, 1 1 and 28 g/1 OOg, 1 1 and 27 g/1 OOg, 1 1 and 26 g/1 OOg, 1 1 and 25 g/1 OOg, or between 12 and 30 g/1 OOg, 12 and 29 g/1 OOg, 12 and 28 g/1 OOg, 12 and 27 g/1 OOg, 12 and 26 g/1 OOg, 12 and 25 g/1 OOg, or between 13 and 30 g/1 OOg, 13 and 29 g/1 OOg, 13 and 28 g/1 OOg, 13 and 27 g/1 OOg, 13 and 26 g/1 OOg, 13 and 25 g/1 OOg, or between 14 and 30 g/1 OOg, 14 and 29 g/1 OOg, 14 and 28 g/1 OOg, 14 and 27 g/1 OOg, 14 and 26 g/1 OOg, 14 and 25 g/1 OOg, or between 15 and 30 g/1 OOg, 15 and 29 g/1 OOg, 15 and 28 g/1 OOg, 15 and 27 g/1 OOg, 15 and 26 g/1 OOg (powdered form).

[0077] More preferably, the milk substitute composition of the present invention comprises total fat in an amount of between 15 and 25 g/1 OOg (powdered form), for example between 15 and 24 g/1 OOg, 15 and 23 g/1 OOg, 15 and 22 g/1 OOg, 15 and 21 g/1 OOg, 15 and 20 g/1 OOg, 15 and 19 g/1 OOg, 15 and 18 g/1 OOg, 15 and 17 g/1 OOg,

15 and 16 g/1 OOg, or between 16 and 25 g/1 OOg, 16 and 24 g/1 OOg, 16 and 23 g/1 OOg, 16 and 22 g/1 OOg, 16 and 21 g/1 OOg, 16 and 20 g/1 OOg, 16 and 19 g/1 OOg,

16 and 18 g/1 OOg, 16 and 17 g/1 OOg, or between 17 and 25 g/1 OOg, 17 and 24 g/1 OOg, 17 and 23 g/1 OOg, 17 and 22 g/1 OOg, 17 and 21 g/1 OOg, 17 and 20 g/1 OOg,

17 and 19 g/1 OOg, 17 and 18 g/1 OOg, or between 18 and 25 g/1 OOg, 18 and 24 g/1 OOg, 18 and 23 g/1 OOg, 18 and 22 g/1 OOg, 18 and 21 g/1 OOg, 18 and 20 g/1 OOg,

18 and 19 g/1 OOg, or between 19 and 25 g/1 OOg, 19 and 24 g/1 OOg, 19 and 23 g/1 OOg, 19 and 22 g/1 OOg, 19 and 21 g/1 OOg, 19 and 20 g/1 OOg, or between 20 and 25 g/1 OOg, 20 and 24 g/1 OOg, 20 and 23 g/1 OOg, 20 and 22 g/1 OOg, 20 and 21 g/1 OOg, or between 21 and 25 g/1 OOg, 21 and 24 g/1 OOg, 21 and 23 g/1 OOg, 21 and 22 g/1 OOg, or between 22 and 25 g/1 OOg, 22 and 24 g/1 OOg, 22 and 23 g/1 OOg, or between 23 and 25 g/1 OOg, 23 and 24 g/1 OOg, or between 24 and 25 g/1 OOg

(powdered form).

[0078] In a preferred embodiment of the present invention, the milk substitute composition of the present invention further comprises docosahexaenoic acid (DHA). DHA is a very long chain omega-3 fatty acid that is a primary structural component of the human brain, skin, and retina. Preferably, the DHA is present in an amount of greater than 75 mg/1 OOg (powdered form), for example greater than 76 mg/1 OOg, greater than 77 mg/1 OOg, greater than 78 mg/1 OOg, greater than 79 mg/1 OOg, greater than 80 mg/1 OOg, greater than 81 mg/1 OOg, greater than 82 mg/1 OOg, greater than 83 mg/1 OOg, greater than 84 mg/1 OOg, greater than 85 mg/1 OOg, greater than 86 mg/1 OOg, greater than 87 mg/1 OOg, greater than 88 mg/1 OOg, greater than 89 mg/1 OOg, greater than 90 mg/1 OOg, greater than 91 mg/1 OOg, greater than 92 mg/100g, greater than 93 mg/1 OOg, or even greater than 94 mg/1 OOg (powdered form). More preferably, the DHA is present in an amount of greater than 95 mg/1 OOg (powdered form), for example greater than 96 mg/1 OOg, greater than 97 mg/1 OOg, greater than 98 mg/1 OOg, greater than 99 mg/1 OOg, greater than 100 mg/1 OOg, greater than 101 mg/1 OOg, greater than 102 mg/1 OOg, greater than 103 mg/1 OOg, greater than 104 mg/1 OOg, or even greater than 105 mg 100g (powdered form). 75 mg/1 OOg, more preferably greater than 95 mg/1 OOg (powdered form). Supplementing the levels of DHA in the milk substitute compositions of the invention advantageously supports development of the brain and retina.

[0079] Carbohydrates

[0080] In some embodiments, the milk substitute compositions of the present invention will comprise additional carbohydrates. Preferably, the additional carbohydrates will comprise lactose. Other sources of carbohydrates suitable for use with the present invention comprise sucrose, glucose, dextrins, and natural and modified starches. Carbohydrates are an important source of energy for growing infants, as they account for 35 to 42% of their daily energy intake. Lactose is not only a good source of energy, it also aids in the absorption of the minerals magnesium, calcium, zinc and iron.

[0081 ] Prebiotic Fibre

[0082] The compositions of the present invention contain prebiotic fibre. Prebiotic fibres are typically non-digestible carbohydrate compounds that pass undigested through the upper part of the gastrointestinal tract and stimulate the growth or activity of advantageous bacteria that colonize the large bowel by acting as substrate for them. Common examples of prebiotic fibres include resistant starch, resistant dextrins, inulin, lignin, chitins, pectins, beta-glucans, and oligosaccharides.

[0083] In preferred embodiments of the present invention, the prebiotic fibre is selected from the group comprising galactooligosaccharides (GOS),

fructooligosaccharides (FOS), xylooligosaccharide (XOS), isomaltooligosaccharide (IMO), Human Milk Oligosaccharides (HMO) and mixtures thereof. [0084] In a preferred embodiment, the prebiotic fibre comprises

galactooligosaccharides (GOS). GOS generally comprise a chain of galactose units that arise through consecutive transgalactosylation reactions, with a terminal glucose unit. However, where a terminal galactose unit is indicated, hydrolysis of GOS formed at an earlier stage in the process has occurred. The degree of polymerization of GOS varies, generally ranging from 2 to 8 monomeric units, depending mainly on the type of the enzyme used and the conversion degree of lactose.

[0085] In another preferred embodiment of the present invention, the prebiotic fibre comprises Human Milk Oligosaccharides (HMO). Human milk oligosaccharides (HMOs) are a family of structurally diverse unconjugated glycans that are found in human breast milk. HMOs function as a prebiotic helping to establish commensal bacteria, and also as anti-adhesives that help prevent the attachment of microbial pathogens to mucosal surfaces. HMOs have been implicated in modulating responses of the epithelium and of the immune cells, reducing excessive mucosal leukocyte infiltration and activation, and lowering the risk for necrotizing enterocolitis and possibly also providing the infant with sialic acid as a potentially essential nutrient for brain development and cognition. Their inclusion in milk substitute composition of the present invention would advantageously provide benefits

[0086] Preferably, the milk substitute composition of the present invention comprises total fibre in an amount of between 0.5 and 10 g/1 OOg (powdered form), for example between 0.5 and 9.5 g/1 OOg, between 0.5 and 9.0 g/1 OOg, between 0.5 and

8.5 g/1 OOg, between 0.5 and 8.0 g/1 OOg, between 0.5 and 7.5 g/1 OOg, between 0.5 and 7.0 g/1 OOg, between 0.5 and 6.5 g/1 OOg, or between 1 .0 and 10 g/1 OOg, between 1 .0 and 9.5 g/1 OOg, between 1 .0 and 9.0 g/1 OOg, between 1 .0 and 8.5 g/1 OOg, between 1 .0 and 8.0 g/1 OOg, between 1 .0 and 7.5 g/1 OOg, between 1 .0 and 7.0 g/1 OOg, between 1 .0 and 6.5 g/1 OOg, or between 1 .5 and 10 g/1 OOg, between 1 .5 and

9.5 g/1 OOg, between 1 .5 and 9.0 g/1 OOg, between 1 .5 and 8.5 g/1 OOg, between 1 .5 and 8.0 g/1 OOg, between 1 .5 and 7.5 g/1 OOg, between 1 .5 and 7.0 g/1 OOg, between

1 .5 and 6.5 g/1 OOg, or between 2.0 and 10 g/1 OOg, between 2.0 and 9.5 g/1 OOg, between 2.0 and 9.0 g/1 OOg, between 2.0 and 8.5 g/1 OOg, between 2.0 and 8.0 g/1 OOg, between 2.0 and 7.5 g/1 OOg, between 2.0 and 7.0 g/1 OOg, between 2.0 and

6.5 g/1 OOg, or between 2.5 and 10 g/1 OOg, between 2.5 and 9.5 g/1 OOg, between 2.5 and 9.0 g/1 OOg, between 2.5 and 8.5 g/1 OOg, between 2.5 and 8.0 g/1 OOg, between

2.5 and 7.5 g/1 OOg, between 2.5 and 7.0 g/1 OOg, between 2.5 and 6.5 g/1 OOg, or between 3.0 and 10 g/1 OOg, between 3.0 and 9.5 g/1 OOg, between 3.0 and 9.0 g/1 OOg, between 3.0 and 8.5 g/1 OOg, between 3.0 and 8.0 g/1 OOg, between 3.0 and

7.5 g/1 OOg, between 3.0 and 7.0 g/1 OOg, between 3.0 and 6.5 g/1 OOg, or between 3.5 and 10 g/1 OOg, between 3.5 and 9.5 g/1 OOg, between 3.5 and 9.0 g/1 OOg, between

3.5 and 8.5 g/1 OOg, between 3.5 and 8.0 g/1 OOg, between 3.5 and 7.5 g/1 OOg, between 3.5 and 7.0 g/1 OOg (powdered form).

[0087] More preferably, the milk substitute composition of the present invention comprises total fibre in an amount of between 3.5 and 6.5 g/1 OOg (powdered form), for example between 3.5 and 6.0 g/1 OOg, between 3.5 and 5.5 g/1 OOg, between 3.5 and 5.0 g/1 OOg, between 3.5 and 4.5 g/1 OOg, between 3.5 and 4.0 g/1 OOg, or between 4.0 and 6.5 g/1 OOg, between 4.0 and 6.0 g/1 OOg, between 4.0 and 5.5 g/1 OOg, between 4.0 and 5.0 g/1 OOg, between 4.0 and 4.5 g/1 OOg, or between 4.5 and 6.5 g/1 OOg, between 4.5 and 6.0 g/1 OOg, between 4.5 and 5.5 g/1 OOg, between

4.5 and 5.0 g/1 OOg, or between 5.0 and 6.5 g/1 OOg, between 5.0 and 6.0 g/1 OOg, between 5.0 and 5.5 g/1 OOg, or between 5.5 and 6.5 g/1 OOg, between 5.5 and 6.0 g/1 OOg, or between 6.0 and 6.5 g/1 OOg (powdered form).

[0088] In a preferred embodiment, the milk substitute composition of the present invention comprises total fibre in an amount of around 4.0 g/1 OOg (powdered form).

In another preferred embodiment, the milk substitute composition of the present invention comprises total fibre in an amount of around 6.5 g/1 OOg (powdered form).

[0089] Probiotics

[0090] The milk substitute compositions of the present invention further comprise probiotic bacteria. Preferably, the probiotic bacteria are selected from the group consisting of Bifidobacterium and Lactobacillus. These probiotic bacteria are generally referred to as lactic acid bacteria. Probiotics are defined as microorganisms that provide health benefits when consumed. Boosting the populations of these microorganisms has a number of advantageous health benefits, especially when administered in conjunction with prebiotic fibre. Preferably, the compositions of the present invention comprise combinations of the prebiotic fibre and probiotics that are complementary and positively synergistic. Optimal prebiotic and probiotic

combinations lead to improved digestive and immune function in the developing infant, reflected by a healthy gut microbiota profile which includes increased

Bifidobacterium populations. This in turn facilitates improved sleep function, as infants experience more gentle digestion patterns and defecation processes.

[0091 ] Bifidobacterium is a genus of Gram-positive, non-motile, often branched anaerobic bacteria. They are ubiquitous inhabitants of the gastrointestinal tract, vagina and mouth of mammals, including humans, and one of the major genera of bacteria that make up the colon flora in mammals.

[0092] Lactobacillus is a genus of Gram-positive, facultative anaerobic or microaerophilic, rod-shaped, non-spore-forming bacteria. They are a major part of the lactic acid bacteria group (i.e. they convert sugars to lactic acid). In human infants, they constitute a significant component of the microbiota at a number of body sites.

[0093] In a preferred embodiment, the probiotics are present in an amount of at least 500 million colony-forming units/1 OOg (cfu/100g) (powdered form), for at least 550 million cfu/100g, at least 600 million cfu/100g, at least 650 million cfu/100g, at least 700 million cfu/100g, at least 750 million cfu/100g, at least 800 million cfu/100g, at least 850 million cfu/100g, at least 900 million cfu/100g, or at least 950 million cfu/100g (powdered form). More preferably, the probiotics are present in an amount of at least 1 billion cfu/1 OOg, for example, at least 1 .5 billion cfu/1 OOg, at least 2 billion cfu/100g, at least 2.5 billion cfu/1 OOg, at least 3 billion cfu/1 OOg, at least 3.5 billion cfu/1 OOg, at least 4 billion cfu/1 OOg, at least 4.5 billion cfu/1 OOg, at least 5 billion cfu/1 OOg, at least 5.5 billion cfu/1 OOg, at least 6 billion cfu/1 OOg, at least 6.5 billion cfu/1 OOg, at least 7 billion cfu/1 OOg, at least 7.5 billion cfu/1 OOg, at least 8 billion cfu/1 OOg, at least 8.5 billion cfu/1 OOg, at least 9 billion cfu/1 OOg, at least 9.5 billion cfu/1 OOg, at least 10 billion cfu/1 OOg, at least 1 1 billion cfu/1 OOg, at least 12 billion cfu/1 OOg, at least 13 billion cfu/1 OOg, at least 14 billion cfu/1 OOg, at least 15 billion cfu/1 OOg, at least 16 billion cfu/1 OOg, at least 17 billion cfu/1 OOg, at least 18 billion cfu/1 OOg, at least 19 billion cfu/1 OOg, at least 20 billion cfu/1 OOg, at least 21 billion cfu/1 OOg, at least 22 billion cfu/1 OOg, at least 23 billion cfu/1 OOg, at least 24 billion cfu/100g, or at least 25 billion cfu/1 OOg, or at least 26 billion cfu/1 OOg, or at least 27 billion cfu/100g, or at least 28 billion cfu/1 OOg, or at least 29 billion cfu/1 OOg, or at least 30 billion cfu/100g, or at least 31 billion cfu/1 OOg, or at least 32 billion cfu/1 OOg, or at least 33 billion cfu/100g, or at least 34 billion cfu/1 OOg, or at least 35 billion cfu/100g, or at least 36 billion cfu/1 OOg, or at least 37 billion cfu/1 OOg, or at least 38 billion cfu/100g, or at least 39 billion cfu/1 OOg, or at least 40 billion cfu/1 OOg, or at least 41 billion cfu/100g, or at least 25 billion cfu/1 OOg, or at least 42 billion cfu/1 OOg, or at least 43 billion cfu/1 OOg, or at least 44 billion cfu/1 OOg, or at least 45 billion cfu/100g, or at least 46 billion cfu/1 OOg, or at least 47 billion cfu/1 OOg, or at least 48 billion cfu/1 OOg, or at least 49 billion cfu/1 OOg, or at least 50 billion cfu/1 OOg,

(powdered form).

[0094] Iodine

[0095] In a preferred embodiment of the present invention, the milk substitute composition of the present invention further comprises iodine. Iodine is an essential element for life and is the heaviest element commonly needed by living organisms. It is required for the synthesis of the growth-regulating thyroid hormones thyroxine and triiodothyronine. Iodine deficiency in infants and young children can lead to neurodevelopmental disorders and threaten brain development, with epidemiological studies highlighting that iodine deficiency results in population-level loss of

intelligence in children, so the compositions of the present invention advantageously mitigate these risks.

[0096] Preferably, the iodine is present in an amount of greater than 75 pg/100g (powdered form), for example greater than 76 pg/100g, greater than 77 pg/100g, greater than 78 pg/100g, greater than 79 pg/100g, greater than 80 pg/100g, greater than 81 pg/100g, greater than 82 pg/100g, greater than 83 pg/100g, greater than 84 pg/100g, greater than 85 pg/100g, greater than 86 pg/100g, greater than 87 pg/100g, greater than 88 pg/100g, greater than 89 pg/100g, greater than 90 pg/100g, greater than 91 pg/100g, greater than 92 pg/100g, greater than 93 pg/100g, or even greater than 94 pg/100g (powdered form). More preferably, the iodine is present in an amount of greater than 95 pg/100g (powdered form), for example greater than 96 pg/1 OOg, greater than 97 pg/1 OOg, greater than 98 pg/1 OOg, greater than 99 pg/1 OOg, greater than 100 pg/100g, greater than 101 pg/100g, greater than 102 pg/100g, greater than 103 pg/1 OOg, greater than 104 pg/1 OOg, or even greater than 105 pg/100g (powdered form).

[0097] Nucleotides

[0098] In some embodiments, the compositions of the present invention further comprise nucleotides. Nucleotides are found naturally in human breast milk and are involved in critical metabolic processes, such as energy metabolism and enzymatic reactions. Also, as the building blocks of deoxyribonucleic acid (DNA) and ribonucleic acid (RNA), they are important for normal body functions. Nucleotides that are particularly suitable for use with the present invention comprise adenosine 5’- monophosphate (AMP), guanosine 5’-monophosphate (GMP), cytidine 5’- monophosphate (CMP), uridine 5’-monophospahate (UMP), thymidine 5’- monophosphate (TMP), inosine 5’-monophospahate (IMP), and mixtures thereof.

[0099] Other Ingredients

[0100] It will be appreciated that the compositions of the present invention may comprise further ingredients such as vitamins, minerals, diluents, emulsifiers and stabilisers.

[0101 ] In some embodiments, the compositions of the present invention further comprise vitamins and minerals which may be selected from the group comprising vitamin A, C, D, E, K, thiamin (B1 ), riboflavin (B2), niacin (B3), B6, B12, biotin, folic acid, pantothenic acid, choline, inositol, taurine, L-carnitine, lutein, calcium, magnesium, iron, zinc, manganese, copper, phosphorus, sodium chloride, potassium chloride, selenium, and mixtures thereof. Appropriate mineral salts for use with the present invention may include calcium chloride, calcium carbonate, sodium citrate, potassium hydroxide, potassium bicarbonate, magnesium chloride, ferrous sulphate, potassium citrate, zinc sulphate, calcium hydroxide, cupric sulphate, magnesium sulphate, potassium iodide, sodium selenite, and others.

[0102] As used herein the terms“emulsifiers” and“stabilizers” refer to ingredients added to prevent the separation of the oil from the water (and its soluble components) in the infant formula. Some commonly used emulsifiers include monoglycerides, diglycerides, and gums. As used herein the term“diluent” refers to the liquid component used to provide the bulk of the volume when the composition is presented for consumption. Examples of commonly used diluents include milk and water.

[0103] In a preferred embodiment of the present invention, the milk substitute composition comprises total protein in an amount of less than around 24 g/1 OOg, preferably less than 20 g/1 OOg, more preferably around 15 g/1 OOg (powdered form); wherein the ratio of whey to casein is approximately 40:60; wherein the alpha- lactalbumin is present in an amount of between 750 and 2500 mg/1 OOg, more preferably around 1000 mg/1 OOg (powdered form); wherein the milk substitute composition is suitable for administration to humans aged 12-36 months. Such a composition would be suitable for use as a Stage 3 toddler milk drink.

[0104] In a preferred embodiment of the present invention, the milk substitute composition comprises total protein in an amount of less than around 12 g/1 OOg, more preferably around 10 g/1 OOg, still more preferably around 7.5 g/1 OOg (powdered form); wherein the ratio of whey to casein is approximately 60:40; wherein the alpha- lactalbumin is present in an amount of between 1000 and 3000 mg/1 OOg, more preferably between 2200 and 2400 mg/1 OOg (powdered form); wherein the milk substitute composition is suitable for administration to humans aged 0-12 months. Such a composition would be suitable for use either as a Stage 1 infant formula or as a Stage 2 follow on formula.

[0105] In a further aspect, the present invention provides a milk substitute composition comprising bovine milk; additional protein, wherein the additional protein comprises whey and alpha-lactalbumin; additional fats, wherein the additional fats comprise sn-2 palmitate (as OPO triglycerides and/or sn-2 palmitate monoglyceride); prebiotic fibre; wherein the milk substitute composition is suitable for administration to humans aged 0-36 months.

[0106] In a further aspect, the present invention provides a milk substitute composition comprising bovine milk; additional protein, wherein the additional protein comprises whey and alpha-lactalbumin; additional fats, wherein the additional fats comprise sn-2 palmitate (as OPO triglycerides and/or sn-2 palmitate monoglyceride); prebiotic fibre; wherein the milk substitute composition comprises total protein in an amount of less than around 24 g/1 OOg, preferably less than 20 g/1 OOg, more preferably around 15 g/1 OOg (powdered form); wherein the ratio of whey to casein is approximately 40:60; wherein the alpha-lactalbumin is present in an amount of between 750 and 2500 mg/1 OOg, preferably around 1000 mg/1 OOg (powdered form); wherein the milk substitute composition is suitable for administration to humans aged 12-36 months. Such a composition would be suitable for use as a Stage 3 toddler milk drink.

[0107] In a further aspect, the present invention provides a milk substitute composition comprising bovine milk; additional protein, wherein the additional protein comprises whey and alpha-lactalbumin; additional fats, wherein the additional fats comprise sn-2 palmitate (as OPO triglycerides and/or sn-2 palmitate monoglyceride); prebiotic fibre; wherein the milk substitute composition comprises total protein in an amount of less than around 12 g/1 OOg, preferably around 10 g/1 OOg, more preferably around 7.5 g/1 OOg (powdered form); wherein the ratio of whey to casein is

approximately 60:40; wherein the alpha-lactalbumin is present in an amount of between 1000 and 3000 mg/1 OOg, more preferably between 2200 and 2400 mg/1 OOg (powdered form); wherein the milk substitute composition is suitable for administration to humans aged 0-12 months. Such a composition would be suitable for use either as a Stage 1 infant formula or as a Stage 2 follow on formula.

[0108] In another aspect of the present invention, there is provided a use of the milk substitute compositions of the present invention as a food for a human aged 0-36 months. In a further aspect, the invention provides a use of the milk substitute compositions of the present invention as a food for a human aged 0-6 months, or aged 6-12 months, or aged 12-36 months.

[0109] In another aspect of the present invention, there is provided a method of improving digestive function in a human aged 0-36 months, comprising administering to the human the milk substitute compositions of the present invention. In another aspect, the milk substitute compositions are provided in accordance with the present invention for use in the improvement of digestive function.

[01 10] In another aspect, the present invention provides a method of improving sleep function in a human aged 0-36 months, comprising administering to the human the milk substitute compositions of the present invention. In another aspect, the milk substitute compositions are provided in accordance with the present invention for use in the improvement of rest and sleep function.

[01 11 ] The milk substitute composition of the invention may be prepared using any known manufacturing process. The various ingredients can be added at any suitable stage of the process.

[01 12] It will be appreciated by those skilled in the art that other known methods of manufacture and sterilization can be used for the preparation of the milk substitute compositions. The present milk substitute compositions may be produced as a liquid product ready for consumption. Alternatively, the present milk substitute

compositions may be produced as a concentrated liquid product requiring dilution with a volume of water prior to feeding to an infant or young child. Furthermore, such a milk substitute compositions may be dehydrated, such as in a spray dryer, to create a powdered form that offers advantages of stability and economy of transport, with the said powdered form requiring reconstitution with water prior to feeding to an infant or young child.

[01 13] Powdered milk substitute may be manufactured by any standard method, typically using a dry blending process or a wet mixing/spray drying process. In the dry blending process, the ingredients are in a dehydrated powdered form and are mixed together to achieve a uniform blend of the macro, micro and other nutrients necessary for a complete infant formula product. The blended product is then passed through a sifter to remove oversized particles and extraneous material. The sifted product is then transferred to bags, totes or lined fibreboard drums for storage prior to packaging. In some cases, the powder is transferred directly to the powder packaging line. At the packaging line, the powder is transferred to a filler hopper that feeds powder into the can filling line. Filled cans are flushed with inert gas, seamed, labelled, coded and packed into cartons. The powdered form is preferably prepared for consumption by mixing with a sufficient amount of boiled fresh drinking water, which is allowed to cool until its temperature reaches approx. 40-60 ^Q C. Preferably, a prescribed amount of the powdered form and water are combined in a sterilised bottle or feeding cup. The bottle or cup is then capped and shaken until all formula powder dissolves, ready for consumption.

[01 14] In the wet blending/spray drying process, the ingredients are blended together, homogenised, pasteurised, concentrated and spray dried to produce the powdered product. The ingredients are blended with water in large batches then pumped to a heat exchanger for pasteurisation. The liquid is usually homogenised and any heat sensitive micronutrients (e.g., vitamins, amino acids and fatty acids) are added. The liquid may be concentrated by passing it through an evaporator or it may be pumped directly to a spray dryer. After spray drying, the product may be agglomerated to increase the particle size and to improve its solubility. In an alternative process, the milk can be dried by drum drying where milk is applied as a thin film to the surface of a heated drum. The milk solids can then be scraped off. Freeze drying may also be used. The drying method and the heat treatment of the milk as it is processed alters the properties of the milk powder, such as its solubility in cold water, its flavour and its bulk density. The finished powder is passed through a sifter then transferred to bags, totes or silos for storage, or transferred directly to the powder packaging line.

[01 15] The discussion of documents, acts, materials, devices, articles and the like is included in this specification solely for the purpose of providing a context for the present invention. It is not suggested or represented that any or all of these matters formed part of the prior art base or were common general knowledge in the field relevant to the present invention as it existed before the priority date of each claim of this application.

[01 16] Where the terms "comprise", "comprises", "comprised" or "comprising" are used in this specification (including the claims) they are to be interpreted as specifying the presence of the stated features, integers, steps or components, but not precluding the presence of one or more other features, integers, steps or components, or group thereof. [01 17] Other various aspects of the invention are as follows:

1. A milk substitute composition comprising:

bovine milk;

additional protein, wherein the additional protein comprises whey and alpha-lactalbumin;

additional fats, wherein the additional fats comprise sn-2 palmitate (as OPO triglycerides and/or sn-2 palmitate monoglyceride);

prebiotic fibre;

wherein the bovine milk is substantially free from A1 beta-casein protein; wherein the milk substitute composition is suitable for administration to humans aged 0-36 months.

2. The milk substitute composition according to aspect 1 , comprising total protein in an amount of less than around 20 g/1 OOg, preferably less than around 15 g/1 OOg (powdered form).

3. The milk substitute composition according to aspect 1 or aspect 2, comprising total protein in an amount of less than around 12 g/1 OOg, preferably around 10 g/1 OOg, more preferably around 7.5 g/1 OOg (powdered form).

4. The milk substitute composition according to any one of aspects 1 to 3, wherein the composition has a whey to casein ratio of approximately 60:40 to approximately 40:60.

5. The milk substitute composition according to any one of aspects 1 to 4, wherein the alpha-lactalbumin is present in an amount between 750 and 4000 mg/1 OOg, preferably between 1000 and 3000 mg/1 OOg, more preferably between 2200 and 2400 mg/1 OOg (powdered form).

6. The milk substitute composition according to any one of aspects 1 to 5, wherein the additional protein further comprises lactoferrin.

7. The milk substitute composition according to aspect 6, wherein the lactoferrin is present in an amount of between 50 and 500 mg/1 OOg, preferably between 65 and 320 mg/1 OOg (powdered form). 8. The milk substitute composition according to any one of aspects 1 to 7, wherein the additional fats are selected from the group comprising bovine milk fat, canola oil, esterified palm oil, coconut oil, sunflower oil, sn-2 palmitate (as OPO triglycerides and/or sn-2 palmitate monoglyceride), olive oil, and mixtures thereof.

9. The milk substitute composition according to any one of aspects 1 to 8, wherein the additional fats comprise a mixture of bovine milk fats, canola oil, esterified palm oil, coconut oil, sunflower oil and sn-2 palmitate (as OPO triglycerides and/or sn- 2 palmitate monoglyceride).

10. The milk substitute composition according to any one of aspects 1 to 8, wherein the additional fats comprise monounsaturated fatty acids rich in oleic acid, preferably derived from olive oil.

1 1 . The milk substitute composition according to any one of aspects 1 to 10, comprising total fat in an amount of between 10 and 30 g/1 OOg, preferably 15 and 25 g/1 OOg (powdered form).

12. The milk substitute composition according to any one of aspects 1 to 1 1 , wherein the sn-2 palmitate (as OPO triglycerides and/or sn-2 palmitate monoglyceride) is present in an amount of between 0.5 and 7.0 g/1 OOg, preferably between 1 .0 and 4.0g/100g (powdered form).

13. The milk substitute composition according to any one of aspects 1 to 12, wherein the prebiotic fibre is selected from the group comprising galactooligosaccharides (GOS), fructooligosaccharides (FOS), xylooligosaccharide (XOS), isomaltooligosaccharide (IMO), Human Milk Oligosaccharides (HMO) and mixtures thereof.

14. The milk substitute composition according to any one of aspects 1 to 13, wherein the prebiotic fibre comprises galactooligosaccharides (GOS).

15. The milk substitute composition according to any one of aspects 1 to 13, wherein the prebiotic fibre comprises Human Milk Oligosaccharides (HMO).

16. The milk substitute composition according to any one of aspects 1 to 15, comprising total fibre in an amount of between 0.5 and 10 g/1 OOg, preferably between 3.5 and 6.5 g/1 OOg (powdered form). 17. The milk substitute composition according to any one of aspects 1 to 16, further comprising docosahexaenoic acid (DHA) in an amount of greater than 75 mg/100g, preferably greater than 95 mg/100g (powdered form).

18. The milk substitute composition according to any one of aspects 1 to 17, further comprising iodine, preferably in an amount of greater than 75 pg/100g, more preferably greater than 95 pg/100g (powdered form).

19. The milk substitute composition according to any one of aspects 1 to 18, further comprising probiotic bacteria, preferably selected from the group consisting of Bifidobacterium and Lactobacillus.

20. The milk substitute composition according to any one of aspects 1 to 19, wherein the bovine milk fat and/or whey protein are sourced from milk that is substantially free from A1 beta-casein protein.

21. The milk substitute composition according to any one of aspects 1 to 20, wherein the milk substitute composition comprises total protein in an amount of less than around 20 g/1 OOg, preferably around 15 g/1 OOg (powdered form); wherein the ratio of whey to casein is approximately 40:60;

wherein the bovine milk is substantially free from A1 beta-casein protein;wherein the alpha-lactalbumin is present in an amount of between 750 and 2500 mg/1 OOg, preferably around 1000 mg/1 OOg (powdered form);

wherein the milk substitute composition is suitable for administration to humans aged 12-36 months.

22. The milk substitute composition according to any one of aspects 1 to 20, wherein the milk substitute composition comprises total protein in an amount of less than around 12 g/1 OOg, preferably around 10 g/1 OOg, more preferably around 7.5 g/1 OOg (powdered form); wherein the ratio of whey to casein is approximately 60:40; wherein the alpha-lactalbumin is present in an amount of between 1000 and 3000 mg/1 OOg, more preferably between 2200 and 2400 mg/1 OOg (powdered form);

wherein the milk substitute composition is suitable for administration to humans aged 0-12 months.

23. A milk substitute composition comprising: bovine milk;

additional protein, wherein the additional protein comprises whey and alpha-lactalbumin;

additional fats, wherein the additional fats comprise sn-2 palmitate (as OPO triglycerides and/or sn-2 palmitate monoglyceride);

prebiotic fibre;

wherein the bovine milk is substantially free from A1 beta-casein protein;

wherein the milk substitute composition comprises total protein in an amount of less than around 20 g/1 OOg, preferably around 15 g/1 OOg (powdered form); wherein the ratio of whey to casein is approximately 40:60;

wherein the alpha-lactalbumin is present in an amount of between 750 and 2500 mg/1 OOg, preferably around 1000 mg/1 OOg (powdered form);

wherein the milk substitute composition is suitable for administration to humans aged 12-36 months.

24. A milk substitute composition comprising: bovine milk;

additional protein, wherein the additional protein comprises whey and alpha-lactalbumin;

additional fats, wherein the additional fats comprise sn-2 palmitate (as OPO triglycerides and/or sn-2 palmitate monoglyceride);

prebiotic fibre;

wherein the bovine milk is substantially free from A1 beta-casein protein; wherein the milk substitute composition comprises total protein in an amount of less than around 12 g/1 OOg, preferably around 10 g/1 OOg, more preferably around 7.5 g/1 OOg (powdered form);

wherein the ratio of whey to casein is approximately 60:40;

wherein the alpha-lactalbumin is present in an amount of between 1000 and 3000 mg/1 OOg, more preferably between 2200 and 2400 mg/1 OOg (powdered form); wherein the milk substitute composition is suitable for administration to humans aged 0-12 months.

25. The use of the milk substitute composition according to any one of aspects 1 to 24 as a food for a human aged 0-36 months.

27. A method of improving digestive function in a human aged 0-36 months, comprising administering to the human the milk substitute composition according to any one of aspects 1 to 24.

28. The milk substitute composition according to any one of aspects 1 to 24 for use in the improvement of digestive function.

29. A method of improving sleep function in a human aged 0-36 months, comprising administering to the human the milk substitute composition according to any one of aspects 1 to 24.

30. The milk substitute composition according to any one of aspects 1 to 24 for use in the improvement of sleep function.

[01 18] The invention is further described with reference to the following examples. It will be appreciated that the invention as claimed is not intended to be limited in any way by these examples.

EXAMPLES

[01 19] General Manufacturing Process

[0120] A base milk powder was prepared from bovine milk via a high velocity nutritional powder drying process. Bovine liquid milk was fractionated into its desired nutritional components and then spray dried to arrive at the desired specification of the relevant nutritional base milk powder for each desired composition (e. g. step 1 , step 2, step 3 and potentially step 4 products). Further and variable amounts of other nutritional elements were then added to the base milk powder in line and compliant to the agreed final product specifications of each composition. Further and variable amounts of other nutritional elements were then added to the base milk powder in line and compliant to the agreed final product specifications of each composition. [0121 ] The base milk powder was then packed off into de-oxygenated bulk bags of the desired size (from, for example, 25kg to 1000kg per bag) that are treated with an inert gas flush upon sealing to mitigate oxidation and maintain shelf life. These “bulk” bags containing the base milk powder are only unsealed once transfer to the blending and packing facility is complete, in a manner which minimises any human contact with the bag inner contents. The bag contents were transferred to an inert gas flushed transfer hopper to maintain the low containments handling environment.

[0122] The product was then packed off into pack sizes of the desired size (ranging from, for example, single serve sachets, 400g tins, 800g tins and/or 900g tins). At this“blending and packing” process stage, the desired final product nutritional profile elements in line and compliant to the final desired product specifications were added to the base milk powder so as to deliver a final product mix per pack. These elements comprise, for example, nutritional elements such as DHA, ARA, ALA, prebiotic fibre, probiotics, etc. This base powder with these additional nutritional elements at the“blending and packing stage” was then packed into the finished pack in an environment that is less than a 5% oxygen environment. This achieved the specification limits and limited as low as possible to the desired specifications counts for the required microbiological and other QA parameters.

[0123] Example 1

[0124] A milk substitute composition was manufactured for use as an infant formula (Stage 1 ), intended for administration to infants aged 0-6 months. The powdered form was then prepared for consumption by mixing with boiled fresh drinking water, which had been allowed to cool to approx. 55 ^Q C before mixing in a sterilised bottle.

[0125] The composition had the nutritional content as shown in Table 1 .

TABLE 1

[0126] Example 2

[0127] A milk substitute composition was manufactured for use as a follow-on formula (Stage 2), intended for administration to infants aged 6-12 months. The powdered form was then prepared for consumption by mixing with boiled fresh drinking water, which had been allowed to cool to approx. 55 ^Q C before mixing in a sterilised bottle.

[0128] The composition had the nutritional content as shown in Table 2.

TABLE 2

[0129] Example 3

[0130] A milk substitute composition was manufactured for use as a toddler milk drink (Stage 3), intended for administration to young children aged 12 months and over. The powdered form was then prepared for consumption by mixing with boiled fresh drinking water, which had been allowed to cool to approx. 55 ^Q C before mixing in a sterilised bottle.

[0131 ] The composition had the nutritional content as shown in Table 3.

TABLE 3

[0132] Example 4 [0133] The optimal profile of selected key fatty acids in infant nutrition and the corresponding key fatty acid profile of the compositions from Examples 1 , 2 and 3 was calculated and is shown in Table 4.

TABLE 4

[0134] Table 4 also shows the fatty acid profile of selected key fatty acids in human milk fats ¹ and as can be seen, the profiles of the compositions of Examples 1 , 2 and 3 compare favourably with this profile.

[0135] Example s

[0136] A milk substitute composition was manufactured for use as an infant formula (Stage 1 ), intended for administration to infants aged 0-6 months. The powdered form was then prepared for consumption by mixing with boiled fresh drinking water, which had been allowed to cool to approx. 55 ^Q C before mixing in a sterilised bottle.

[0137] The composition had the nutritional content as shown in Table 5.

TABLE 5

1

Yuhas et al. 2006. Human Milk Fatty Acid Composition from Nine Countries Varies Most in DHA. Lipids. 41 (9): 851 -858.

[0138] Example 6

[0139] A milk substitute composition was manufactured for use as a follow-on formula (Stage 2), intended for administration to infants aged 6-12 months. The powdered form was then prepared for consumption by mixing with boiled fresh drinking water, which had been allowed to cool to approx. 55 ^Q C before mixing in a sterilised bottle.

[0140] The composition had the nutritional content as shown in Table 6.

TABLE 6

[0141 ] Example 7

[0142] A milk substitute composition was manufactured for use as a toddler milk drink (Stage 3), intended for administration to young children aged 12 months and over. The powdered form was then prepared for consumption by mixing with boiled fresh drinking water, which had been allowed to cool to approx. 55 ^Q C before mixing in a sterilised bottle.

[0143] The composition had the nutritional content as shown in Table 7.

TABLE 7

[0144] Example 8

[0145] A milk substitute composition was manufactured for use as an infant formula (Stage 1 ), intended for administration to infants aged 0-6 months. The powdered form was then prepared for consumption by mixing with boiled fresh drinking water, which had been allowed to cool to approx. 45 ^Q C before mixing in a sterilised bottle.

[0146] The composition had the nutritional content as shown in Table 8.

TABLE 8

[0147] Example 9

[0148] A milk substitute composition was manufactured for use as a follow-on formula (Stage 2), intended for administration to infants aged 6-12 months. The powdered form was then prepared for consumption by mixing with boiled fresh drinking water, which had been allowed to cool to approx. 45 ^Q C before mixing in a sterilised bottle.

[0149] The composition had the nutritional content as shown in Table 9.

TABLE 9

[0150] Example 10

[0151 ] A milk substitute composition was manufactured for use as a toddler milk drink (Stage 3), intended for administration to young children aged 12 months and over. The powdered form was then prepared for consumption by mixing with boiled fresh drinking water, which had been allowed to cool to approx. 45 ^Q C before mixing in a sterilised bottle.

[0152] The composition had the nutritional content as shown in Table 10.

TABLE 10

[0153] Example 11

[0154] A milk substitute composition was manufactured for use as a toddler milk drink (Stage 3), intended for administration to young children aged 12 months and over. The powdered form was then prepared for consumption by mixing with boiled fresh drinking water, which had been allowed to cool to approx. 45 ^Q C before mixing in a sterilised bottle.

[0155] The composition had the nutritional content as shown in Table 1 1 .

TABLE 11