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Title:
PREVENTION OF TREE NUT AND SEED ALLERGY IN HUMANS
Document Type and Number:
WIPO Patent Application WO/2024/085750
Kind Code:
A1
Abstract:
The present invention relates to a composition for use in the prevention, reduction and/or treatment of tree nut and seed allergy in humans. Furthermore, the invention provides methods for prevention, reduction and/or treatment of tree nut and seed allergy in humans. The composition is administered in a series of 3 to 6 dose increment steps from an initial dose to a maximum dose and can be continued with a weekly dose for a time period of 3 to 12 months.

Inventors:
LANCEE LAURIE (NL)
BOERSMA JOZIEN (NL)
Application Number:
PCT/NL2023/050534
Publication Date:
April 25, 2024
Filing Date:
October 13, 2023
Export Citation:
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Assignee:
VINI MINI B V (NL)
International Classes:
A61K36/185; A23L33/00; A61K36/22; A61K36/48; A61K36/52; A61P37/08
Domestic Patent References:
WO2017014954A12017-01-26
WO2020237181A12020-11-26
WO2012123759A12012-09-20
Foreign References:
US20170360922A12017-12-21
Other References:
BYRNE A M ET AL: "How do we know when peanut and tree nut allergy have resolved, and how do we keep it resolved?", CLINICAL & EXPERIMENTAL ALLERGY, WILEY INTERSCIENCE, UK, vol. 40, no. 9, 20 July 2010 (2010-07-20), pages 1303 - 1311, XP071887186, ISSN: 0954-7894, DOI: 10.1111/J.1365-2222.2010.03554.X
POOJA VARSHNEY ET AL: "A randomized controlled study of peanut oral immunotherapy: Clinical desensitization and modulation of the allergic response", JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, ELSEVIER, AMSTERDAM, NL, vol. 127, no. 3, 27 December 2010 (2010-12-27), pages 654 - 660, XP028196576, ISSN: 0091-6749, [retrieved on 20110110], DOI: 10.1016/J.JACI.2010.12.1111
MIDUN ELISE ET AL: "Recent advances in the management of nut allergy", WORLD ALLERGY ORGANIZATION JOURNAL, vol. 14, no. 1, 1 January 2021 (2021-01-01), London, UK, pages 100491, XP093114155, ISSN: 1939-4551, DOI: 10.1016/j.waojou.2020.100491
Attorney, Agent or Firm:
NEDERLANDSCH OCTROOIBUREAU (NL)
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Claims:
CLAIMS 1. A composition for use in preventing, reducing and/or treating of allergy against a tree nut and/or a seed in a human subject, wherein said composition comprises 0.1 – 100% by weight of a protein of the tree nut and/or the seed, and wherein said composition is administered to a human subject in need thereof at intervals of at least one hour in a series of 3 – 6 dose increment steps from an initial dose to a maximum dose and wherein the dosages comprise 0.01 – 5 gram, preferably 1 – 5 gram, or preferably 0.01 – 4 gram of said composition and wherein each dose is administered in 1 to 3 consecutive portions. 2. Composition for use according to claim 1, wherein the composition comprises 0.5 – 50% by weight protein of the tree nut and/or the seed. 3. Composition for use according to any of the previous claims, wherein the composition comprises 0.5 – 50% by weight of protein of the tree nut and/or the seed and a carrier, such as a flour, preferably tapioca flour. 4. Composition for use according to any of the preceding claims, wherein the dose increment steps range from 0.01 to 2.0 gram. 5. Composition for use according to any of the preceding claims, wherein the human subject is a child, preferably a child 4 – 24 months of age, more preferably 4 – 14 months of age, most preferably 4 – 8 months of age. 6. Composition for use according to any of the previous claims, wherein the tree nut and/or the seed is selected from cashews, hazelnuts, peanuts, walnuts, almonds, and pistachios, preferably cashews, hazelnuts, peanuts, and walnuts. 7. Composition for use according to any of the previous claims, wherein the dose is administered in one or two portions, preferably in one portion.

8. Composition for use according to any of the previous claims, wherein the dose increment steps are carried out in six increment steps. 9. Composition for use according to the previous claim, wherein the first four doses are administered on day 1 and the fifth and sixth doses are administered on day 2. 10.Composition for use according to any one of the previous claims, wherein the dose increment steps range from 0.01 to 2.0 gram, preferably the dose increments are from the initial dose to the final dose: 0.01 gram, 0.03 gram, 0.1 gram, 0.3 gram, 1 gram, and 2 gram. 11.Composition for use according to any one of the previous claims, wherein the composition is mixed with an edible carrier, such as a fruit composition or vegetable composition. 12.Composition for use according to any one of the previous claims, wherein the human subject in need thereof is administered: - at least 0.01 – 4 gram of the composition according to any of the previous claims and - at least 1 – 3 gram of a fruit composition or vegetable composition. 13.Composition for use according to any one of the previous claims, wherein the composition is present in a capsule and/or a sachet. 14.Composition for use according to any one of the previous claims, wherein the doses are provided as unit dose formulations that are separately packaged. 15.Composition for use according to any of the previous claims, wherein children 4 – 24 months of age are at intervals of at least one hour administered six dosages of the composition, wherein the first four doses are administered on day 1 and the fifth and sixth doses are administered on day 2, and wherein the dose increment steps range from 0.01 to 2.0 gram, preferably the dose increments are from the initial dose to the final dose: 0.01 gram, 0.03 gram, 0.1 gram, 0.3 gram, 1 gram, and 2 gram. 16.A composition comprising 0.1 and 100% by weight of protein of 1 – 6 tree nut(s) and/or protein of 1 – 6 seed(s), wherein the tree nut and/or the seed are selected from cashews, hazelnuts, peanuts, walnuts, almonds, and pistachios, preferably from cashews, hazelnuts, peanuts, and walnuts. 17.The composition of claims 1 – 16 for use in preventing, reducing and/or treating of allergy against tree nut(s) and/or a seed(s) in a human subject, wherein said composition is administered to a human subject in need thereof, wherein the dose comprises 1 – 5 gram of said composition and wherein each dose is administered once a week for a period of 3 – 12 months. 18.A kit for use in preventing, reducing and/or treating of allergy against a tree nut and/or a seed in a human subject, said kit comprising a composition that comprises 0.1 – 100% by weight of a protein of the tree nut and/or the seed, wherein the tree nut and/or the seed are selected from cashews, hazelnuts, peanuts, walnuts, almonds, and pistachios, preferably from cashews, hazelnuts, peanuts, and walnuts, and wherein the dosages comprise 0.01 – 4 gram of said composition.

Description:
PREVENTION OF TREE NUT AND SEED ALLERGY IN HUMANS TECHNICAL FIELD OF THE INVENTION The present invention relates to a composition for use in the prevention, reduction and/or treatment of tree nut and seed allergy in humans. Furthermore, the invention provides methods for prevention, reduction and/or treatment of tree nut allergy and/or seed allergy in humans. BACKGROUND OF THE INVENTION Tree nut allergies and seed allergies are a worldwide phenomenon and its prevalence is increasing over the years. A worldwide prevalence for tree nut allergy has been reported of up to 4.9% of the general population. Peanut allergy is one of the most well-known tree nut and seed allergies. But there is a whole range of tree nuts and seeds that can cause allergies including but not limited to almonds, Brazil nuts, cashews, chestnuts, hazelnuts, macadamia nuts, peanuts, pecans, pine nuts, pistachios, sesame seeds, soybeans, and walnuts. Tree nut and seed allergies can have a serious impact on the quality of life of humans, both adults and children. Although symptoms can vary in severity and may be mild to moderate such as gastrointestinal problems including abdominal pain and diarrhoea, and/or other symptoms such as itching and cutaneous rash, or can be more severe i.e. respiratory problems, there is also the risk for an anaphylactic shock which can have fatal consequences. The impact on the quality of life of the patients is mainly affected by this continuous treat, and the daily consideration with food intake. The most common underlying mechanism is an immune response to the tree nut and seed allergens causing an immunoglobulin E (IgE) mediated reaction. The allergen is the food protein of the tree nuts and seeds. The immune response is associated with the release of histamine. As such, current treatment, i.e. antihistamine drugs, is based on lowering the histamine levels. More serious symptoms can be treated with adrenaline. With anaphylactic shock the body is making adrenaline as a natural antidote. To facilitate this response, adrenaline is given as a medication to enhance this natural defend mechanism of the body. Other types of medications that are used to treat food allergies are medicines to suppress the immune system such as corticosteroids or immunotherapy. However, those type of medications are symptomatic and prevention is better than cure. Tree nuts and seeds allergies can be prevented in the majority of cases (about 80%) by early intervention of allergen exposure. The current guidelines in The Netherlands from the Dutch Association of Pediatrics (Nederlandse Vereniging voor Kindergeneeskunde, NVK) recommends an exposure in babies before the age of 8 months, most likely in the age between 4 and 8 months of age, although later exposure can still be helpful too if that time window has been passed. There are different introduction schemes available to get children and adults familiar with tree nuts and seeds, for example schemes for peanuts, cashews, pistachios and walnuts. The common factor in those introduction schemes is that there is an increase in exposure within a certain time window. It is usually recommended to give i) part of the tree nut or seed or ii) to give a whole tree nut or seed or iii) to give multiple tree nuts or seeds depending on the step of the process. Alternatively, people may wish to choose for a paste if that is commercially available, for example peanut butter. However, there are limitations for giving this to humans. First, there is the difficulty with giving whole nuts to humans, especially babies and young children, since it increases the choking risk. Second, it is difficult to determine the exact dose as tree nuts and seeds vary in size within their own sort, and thus can vary in protein content. This is even more of a problem for lower doses where you have to break the tree nut or seed in smaller parts. It is also an issue for dose increment as it is not easy to go from an eighth of a tree nut or seed to a quarter of a tree nut or seed for example. Third, there is the issue of compliance as you do not have an exact dose of protein, which makes it more easy to miss a dose. Furthermore, it may not be convenient to find the right tree nuts or seeds and have to break them in smaller parts for people. Convenience can influence if people start at all with tree nut and seed exposure, and it also affects compliance. For pastes, there is the limitation that there is not a paste available for each tree nut or seed. The same limitations as mentioned above, apart from the choking risk, also do apply for pastes since it is difficult to determine the exact tree nut or seed protein content of each paste, and there are variations in tree nut and seed protein levels between pastes. For babies, there are more concerns that need to be taken into account in regards to their nutritional intake. Babies can be inconsistent in their food intake and easily can miss part of a portion or the whole portion of their nutritional composition. Also, they need to get used to a new nutritional composition which can take various attempts, e.g. 10 to 15 times, before the baby is familiar with the nutritional composition. The adherence to food intake plays even a larger role in the continuation of food intake. The current guidelines in The Netherlands from the Dutch Association of Pediatrics (Nederlandse Vereniging voor Kindergeneeskunde, NVK) recommend to continue tree nut or seed intake till the age of at least 1 year to prevent further allergies. This can result in a period of 8 months of tree nut or seed intake if the baby starts at the age of 4 months. It is difficult to keep administering the tree nut or seed (paste) for a longer period of time, if the baby doesn’t enjoy the taste thereof. There are patent applications published that focussed on one particular tree nut or seed and there are patent applications covering a wide range of allergies. For example, WO 2012/123759 discloses a treatment for only peanut allergy. It relates to oral immunotherapy for the desensitisation of patients who are hypersensitive to peanut allergy and describes a therapeutic composition of peanut protein. US 2017/0360922 on the other hand, is related to a wide category of food allergies including peanuts, tree nuts, milk, egg, soy, wheat, fish and shellfish. However, there is still room for improvement in the prevention of tree nut and seed allergies, especially when it relates to babies and young children. When it comes to allergen exposure in babies and young children, compliance and convenience are the major factors that need to be improved as doses can easily be missed. Hence, there is a need for a convenient way to provide the exact dose of tree nut or seed protein to humans, preferably babies and young children. SUMMARY OF THE INVENTION A first aspect of the present invention relates to a composition for use in preventing, reducing and/or treating of allergy against a tree nut and/or seed in humans. In said composition, the weight of the protein of the tree nut and/or the seed of the composition is between 0.1 – 100%. The composition is administered at intervals of at least one hour in a series of 3 – 6 dose increment steps from an initial dose to a maximum dose. The dosages comprise 0.01 – 5 gram, preferably 1 – 5 gram, or preferably 0.01 – 4 gram of said composition and each dose is administered in 1 to 3 consecutive portions. The present inventors established that a desired dose of protein of tree nut and/or seed can be reached with the current invention. It has surprisingly been found that intervention of allergen exposure to prevent, reduce and/or treat allergy against a tree nut and/or seed in humans can be done in multiple increment steps. It has even more surprisingly been found that administering the composition in a small portions, such as 1 to 3 consecutive portions, is expected to increase compliance and convenience of the intake of the protein of the tree nut and/or seed. A second aspect of the present invention relates to a composition of protein of 1 – 6 tree nut(s) and/or protein of 1 – 6 seed(s). The weight of a protein of the tree nut(s) and/or the seed(s) of the composition is between 0.1 – 100%. The tree nut and/or seeds are preferably selected from cashews, hazelnuts, peanuts, walnuts, almonds, and pistachios, more preferably from cashews, hazelnuts, peanuts, and walnuts, even more preferably form cashews, hazelnuts, and walnuts, such as cashews and/or hazelnuts and/or walnuts. A third aspect of the present invention relates to a kit for use in preventing, reducing and/or treating of allergy against a tree nut and/or seed in humans. The weight of a protein of the tree nut and/or the seed of the composition between 0.1 – 100%. The tree nut and/or seeds are preferably selected from cashews, hazelnuts, peanuts, walnuts, almonds, and pistachios, preferably from cashews, hazelnuts, walnuts, almonds, and pistachios, or from peanuts, more preferably, from cashews, hazelnuts, and walnuts, such as cashews and/or hazelnuts and/or walnuts. The dosages comprise 0.01 – 4 gram of said composition. DEFINITIONS The term “allergy” as used herein has its conventional meaning and refers to the condition of an immune response to tree nut and/or seed allergens. For example, an immunoglobulin (IgE) mediated reaction of which the antibodies may be present in the blood levels of the human subject. The term “carrier” as used herein refers to an adjuvant, diluent, excipient or vehicle with which the protein of the tree nut and/or the seed is administered. For example, it can be a flour such as tapioca flour. It can also be an edible carrier, such as a fruit composition or vegetable composition. The term “composition” as used herein refers to a nutritional composition. Preferably the composition contains a protein of a tree nut and/or seed. The term “dose” as used herein refers to a single amount of intake of the composition. This can be administered once or on a more regular basis such as a weekly basis. The term “human subject” as used herein refers to the general population, not specifically a human subject suffering from a disease but that is not a limitation either. Preferably, the human subject is a child. For example, a child in the range of 4 – 24 months of age, more preferably 4 – 14 months of age, most preferably 4 – 8 months of age. The invention is particularly useful for children who are at risk for tree nut and/or seed allergy such as children who have allergies for other (food) allergens, eczema or other signs of immune deficiencies, but the definition of “human subject” is not limited by any (such) theory. The term “portion” as used herein refers to the amount of the composition being eating at one time containing a portion size in the range of 1 – 10 gr. More specifically, as it is most likely that the portion will be administered orally using a spoon, the portion is expect to be the size that fits to a spoon. For children and babies this is on average about 3 – 5 gr. The term “tree nut” as used herein refers to any edible tree nut belonging to one of the five orders of plants: beech (Fagales), soapwood (Sapindales), silverberry (Proteales), heather (Ericales), and rosewood (Rosales). For example, this includes but is not limited to almonds, Brazil nuts, cashews, chestnuts, hazelnuts, macadamia nuts, pecans, pistachios, and walnuts. Preferably the tree nuts are selected from cashews, hazelnuts, peanuts, walnuts, almonds, and pistachios, and more preferably cashews, hazelnuts, peanuts, and walnuts, and most preferably cashews, hazelnuts, and walnuts. The term “seed” as used herein refers to a general, wider meaning of edible seeds. Which means the seed can also refer to the fruit or seed of a legume. Preferably the seed is selected from peanuts, pine nuts, sesame seeds, and soybeans, and more preferably the seed is a peanut. “And/or” where used herein is to be taken as specific disclosure of each of the two specified features or components with or without the other. For example, “A and/or B” is to be taken as specific disclosure of each of “A”, “B”, “A and B”. "A", "an", and "the" as used herein refer to both singular and plural forms unless the context clearly dictates otherwise. By way of example, "a compartment" refers to one or more than one compartment. "About" as used herein referring to a measurable value such as a parameter, an amount, a temporal duration, and the like, is meant to encompass variations of +/- 10% or less, more preferably +/-5% or less, even more preferably +/-1% or less of and from the specified value, in so far such variations are appropriate to perform in the disclosed invention. However, it is to be understood that the value to which the modifier "about" refers is itself also specifically disclosed. "Comprise", "comprising", "comprises" and "comprised of" as used herein are synonymous with "include", "including", "includes" or "contain", "containing", "contains" and are inclusive or open-ended terms that specify the presence of what follows, e.g. a component, and do not exclude or preclude the presence of additional, non-recited components, features, element, members, steps, known in the art or disclosed therein. Throughout this text, the use of terms in brackets, usually means that the term within brackets specifies a possible option or a possible meaning and should thus not be considered limiting. The embodiments of the invention described herein can operate in combination and cooperation, unless specified otherwise. Unless otherwise defined, all terms used in disclosing the invention, including technical and scientific terms, have the meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. DETAILED DESCRIPTION OF THE INVENTION A first aspect of the present invention relates to a composition for use in preventing, reducing and/or treating of allergy against a tree nut and/or a seed in a human subject, wherein said composition comprises 0.1 – 100% by weight of a protein of the tree nut and/or the seed, and wherein said composition is administered to a human subject in need thereof at intervals of at least one hour in a series of 3 – 6 dose increment steps from an initial dose to a maximum dose and wherein the dosages comprise 0.01 – 5 gram, preferably 1 – 5 gram, or preferably 0.01 – 4 gram of said composition and wherein each dose is administered in 1 to 3 consecutive portions. In an embodiment of the invention, the weight of a protein of the tree nut and/or the seed of the composition is between 0.5 – 50%. Furthermore, the weight of a protein of the tree nut and/or the seed of the composition is between 0.5 – 50% with the addition of presence of a carrier. The carrier may be a flour, preferably tapioca flour. The benefit of selecting a flour as a carrier is that it easily can be used in capsules, sachets or bags. The composition may be formulated as a single unit dose, such as a capsule, sachet or a bag. However, the invention is not limited to such single unit dosages as there may be other formulations that are also easily transported and mixed with nutrition such as a container provided with for example a measuring cup. Other formulations may be solutions or suspensions so that the invention may be present as a nutritional drink. In a preferred embodiment, the dosages comprise 0.01 – 2 gram of above mentioned composition. The composition is intended to be administered to children and/or babies. Here, the preferred age of the child is between 4 – 24 months of age, more preferably 4 – 14 months of age, most preferably 4 – 8 months of age. Although it is preferred to start as early as 4 months of age, it is still helpful to start at a later age after 1 year. As such, the broadest age range is defined from 4 to 24 months of age. There is a range of tree nuts and/or seeds that may be part of the invention including but not limited to almonds, Brazil nuts, cashews, chestnuts, hazelnuts, macadamia nuts, peanuts, pecans, pine nuts, pistachios, sesame seeds, soybeans, and walnuts. Preferably, the tree nut and/or the seed is selected from cashews, hazelnuts, peanuts, walnuts, almonds, and pistachios, more preferably cashews, hazelnuts, peanuts, and walnuts, most preferably, from cashews, hazelnuts, and walnuts, or from peanuts. In a certain embodiment of the invention, the dose is administered in one or two portions, preferably in one portion. In another embodiment, the dose increment steps are carried out in six increment steps. In another embodiment, the first four doses are administered on day 1 and the fifth and sixth doses are administered on day 2. In a further embodiment, the dose increment steps range from 0.01 to 2.0 gram from an initial dose to a final dose. The preferred dose increment steps are 0.01 gram, 0.03 gram, 0.1 gram, 0.3 gram, 1 gram, and 2 gram. In accordance with a preferred embodiment of the present invention, the composition is mixed with an edible carrier. This may be a fruit composition or a vegetable composition. In a preferred embodiment, the composition comprises the protein of the tree nut and/or the seed and an edible carrier. Here, the dosage of the protein of the tree nut and/or the seed is at least 0.01 to 4 gram as mentioned in the embodiments above and the dosage of the carrier is at least 1 to 3 gram of a fruit or vegetable composition. In an embodiment, the doses that are mentioned in the above embodiments are provided as unit dose formulations that are separately packaged. Lastly, in a further embodiment, the composition is administered to children and/or babies. Here, the children and/or babies are between 4 – 24 months of age. In total six doses are administered, wherein the first four doses are administered on day 1 and the fifth and sixth doses are administered on day 2. The dose increment steps range from 0.01 to 2.0 gram from an initial dose to a final dose. The preferred dose increment steps are 0.01 gram, 0.03 gram, 0.1 gram, 0.3 gram, 1 gram, and 2 gram. The present invention demonstrates that the exact dose of protein of tree nut and/or seed can be reached with the current composition. A surprising effect of the present invention is the lower amount or volume of nutrition that is needed to reach a certain protein level in comparison with the more standard way of administering a tree nut and/or seed in a paste, which requires a higher volume to reach the same dose level and is often difficult to achieve in young children. It has surprisingly been found that intervention of allergen exposure to prevent, reduce and/or treat allergy against a tree nut and/or seed in humans can be done in multiple increment steps. It has even more surprisingly been found that giving the composition in a small amount of portions, such as 1 to 3 consecutive portions, is expected to increase compliance and convenience of the allergen intake. Hereby, the preferred dose is 1 portion. For some young children and babies, more than 1 portion might be needed with higher dose levels as the nutrition intake of one portion is restricted to the way of administration to the child or baby. Most likely, this is administered orally with a spoon which results in a portion size in the range of 1–10 gr, on average about 3 – 5 gr. The tree nut and/or seed protein is most likely present in the form of flour. Tapioca flour may be added to the tree nut and/or seed flour as a carrier. Flour is a convenient way to administer the protein of the tree nut and/or seed as it can easily be mixed with other food, such as a fruit or vegetable composition. In addition, it can be stored in capsules, sachets and/or bags which can easily be transported to the customer. As such, the current invention demonstrates user convenience which helps to start at a very early age with tree nut and/or seed intake. Hence, the current invention facilitates early intake of the tree nut and/or seed protein as early as the age of 4 months old. Even more surprisingly, the tree nut and/or seed can be given in combination with a carrier, which can be a fruit or vegetable composition that is generally appreciated by young children. This highly contributes to compliance, especially for young children and babies, since the fruit or vegetable composition can be selected from a composition that has been previously well tolerated by the child or baby. This differs from a paste (such as peanut butter) which may not have a familiar taste for young children and/or babies and can thus have a negative effect on compliance. A second aspect of the present invention relates to a composition comprising 0.1 and 100% by weight of protein of 1 – 6 tree nut(s) and/or protein of 1 – 6 seed(s), wherein the tree nut and/or the seed are selected from cashews, hazelnuts, peanuts, walnuts, almonds, and pistachios, preferably from cashews, hazelnuts, peanuts, and walnuts, more preferably from cashews, hazelnuts, and walnuts, or from peanuts. A further aspect of the present invention related to the composition, as described above for use in preventing, reducing and/or treating of allergy against tree nut(s) and/or a seed(s) in a human subject, wherein said composition is administered to a human subject in need thereof, wherein the dose comprises 1 – 5 gram of said composition and wherein each dose is administered once a week for a period of 3 – 12 months. It has surprisingly been found that a weekly administration in the form of the invention, e.g. as capsules, sachets and/or bags or a box comprising tree nut and/or seed flour, which can be sent by post, contributes to the convenience and compliance of the protein intake by humans, especially young children and babies. More surprisingly, the current invention demonstrates good storage conditions of the tree nut and/or seed flour giving it a shelf-life that is long enough to store and administer the tree nut and/or seed flour for at least a year. A last aspect of the present invention relates to a kit for use in preventing, reducing and/or treating of allergy against a tree nut and/or a seed in a human subject, said kit comprising a composition that comprises 0.1 – 100% by weight of a protein of the tree nut and/or the seed, wherein the tree nut and/or the seed are selected from cashews, hazelnuts, peanuts, walnuts, almonds, and pistachios, preferably from cashews, hazelnuts, peanuts, and walnuts, more preferably from cashews, hazelnuts, and walnuts, or from peanuts, and wherein the dosages comprise 0.01 – 4 gram of said composition. The present invention will be illustrated further by means of the following non- limiting examples. EXAMPLES Example 1: Protein content of the 6 step increment Table 1 shows the 6 step increment of administration of cashew, hazelnut, walnut and/or peanut protein. The protein content is shown, as well as the corresponding amount of flour that is needed to reach that amount of protein. The flour content varies because of the amount of protein may vary between the different tree nuts and/or seeds (protein %). Not only may the protein content vary between the different tree nuts and/or seeds, it also may vary within a tree nut and/or seed. For example, Table 2 shows a different amount of flour for cashew, hazelnut and walnut because of a higher range in protein content in comparison with the results from Table 1. In this example, the carrier may be tapioca flour. The amount of tapioca flour is shown for each step at (Table III). The formulation is present in the form of capsules. The flour content of the tree nut and/or seed protein and the tapioca flour are stored in the same capsule resulting in one capsule for each step. The level of protein content is similar for the different tree nuts and/or seeds. Table 1 Tree nut and/or seed protein content Tree nut and/or seed flour content (gram) (gram) Ste Cashe Hazelnu Walnu Peanu p Formulation Cashew Hazelnut Walnut Peanut w t t t Protein (%) 28.00 27.80 44.00 50.00 Capsule or 1 sachet 0.01 0.01 0.01 0.01 0.04 0.04 0.02 0.02 Capsule or 2 sachet 0.03 0.03 0.03 0.03 0.11 0.11 0.07 0.06 Capsule or 3 sachet 0.10 0.10 0.10 0.10 0.36 0.36 0.23 0.20 Capsule or 4 sachet 0.30 0.30 0.30 0.30 1.07 1.08 0.68 0.60 Capsule or 5 sachet 1.00 1.00 1.00 1.00 3.57 3.60 2.27 2.00 Capsule or 6 sachet 2.00 2.00 2.00 2.00 7.14 7.19 4.55 4.00 Total protein 3.44 3.44 3.44 3.44 Table 2 Tree nut and/or seed protein content Tree nut and/or seed flour content (gram) (gram) Ste Cashe Hazelnu Walnu Peanu p Formulation Cashew Hazelnut Walnut Peanut w t t t Protein (%) 50.00 41.60 45.70 50.00 Capsule or 1 sachet 0.01 0.01 0.01 0.01 0.04 0.04 0.02 0.02 Capsule or 2 sachet 0.03 0.03 0.03 0.03 0.11 0.11 0.07 0.06 Capsule or 3 sachet 0.10 0.10 0.10 0.10 0.36 0.36 0.23 0.20 Capsule or 4 sachet 0.30 0.30 0.30 0.30 1.07 1.08 0.68 0.60 Capsule or 5 sachet 1.00 1.00 1.00 1.00 3.57 3.60 2.27 2.00 Capsule or 6 sachet 2.00 2.00 2.00 2.00 7.14 7.19 4.55 4.00 Total protein 3.44 3.44 3.44 3.44 Table 3 Tapioca flour content (gram) Step Formulation Cashew Hazelnut Walnut Peanut 1 Capsule or sachet 0.28 0.28 0.30 0.28 2 Capsule or sachet 0.23 0.24 0.30 0.24 3 Capsule or sachet 0.00 0.00 0.30 0.10 4 Capsule or sachet 0.00 0.00 0.00 0.00 5 Capsule or sachet 0.00 0.00 0.00 0.00 6 Capsule or sachet 0.00 0.00 0.00 0.00 Total tapioca flour 0.51 0.52 0.90 0.62 Example 2: Protein content of the 3 step increment Table 4 shows the 3 step increment of administration of cashew, hazelnut, walnut and/or peanut protein. The protein content is shown, as well as the corresponding amount of flour that is needed to reach that amount of protein. Table 5 shows a different amount of flour for cashew, hazelnut and walnut because of a higher range in protein content in comparison with the results from Table 4. Table 4 Tree nut and/or seed flour content Tree nut and/or seed protein content (gram) (gram) Ste Formulati Hazeln Pean p on Cashew Hazelnut Walnut Peanut Cashew ut Walnut ut Protein 50.0 (%) 28.00 27.80 44,00 0 1 Sachet 0.30 0.30 0.30 0.30 1.07 1.08 0.68 0.60 2 Sachet 1.00 1.00 1.00 1.00 3.57 3.60 2.27 2.00 3 Sachet 2.00 2.00 2.00 2.00 7.14 7.19 4.55 4.00 Total protein 3.30 3.30 3.30 3.30 Table 5 Tree nut and/or seed flour content Tree nut and/or seed protein content (gram) (gram) Ste Formulati Cashe Hazeln Waln Pean p on Cashew Hazelnut Walnut Peanut w ut ut ut Protein (%) 50.00 41.60 45.70 50.00 1 Sachet 0.30 0.30 0.30 0.30 0.60 0.72 0.66 0.60 2 Sachet 1.00 1.00 1.00 1.00 2.00 2.40 2.19 2.00 3 Sachet 2.00 2.00 2.00 2.00 4.00 4.81 4.38 4.00 Total protein 3.30 3.30 3.30 3.30 Example 3: Protein content of weekly dose (follow-up administration) Table 6 shows the weekly administration of cashew, hazelnut, walnut and/or peanut protein. The protein content is shown, as well as the corresponding amount of flour that is needed to reach that amount of protein. In this example, there is an administration of at least 26 weeks. This is an illustrative example and as such the amount of weeks may vary resulting in a shorter or larger amount of time period. Table 7 shows a different amount of flour for cashew, hazelnut and walnut because of a higher range in protein content in comparison with the results from Table 6. Table 6 Protein content (gram) Flour content (gram) Cash Hazel Waln Pean Cash Hazel Waln Pean Step Formulation ew nut ut ut ew nut ut ut Protein (%) 28,00 27,80 44,00 50,00 Capsule or weekly sachet 2.00 2.00 2.00 2.00 7.14 7.19 4.55 4.00 number of weeks 26 26 26 26 26 26 26 26 Total protein 52.00 52.00 52.00 52.00 Table 7 Protein content (gram) Flour content (gram) Cash Hazel Waln Pean Cash Hazel Waln Pean Step Formulation ew nut ut ut ew nut ut ut Protein (%) 50.00 41.60 45.70 50.00 Capsule or weekly sachet 2.00 2.00 2.00 2.00 4.00 4.81 4.38 4.00 number of weeks 28 27 26 26 28 27 26 26 Total protein 56.00 54.00 52.00 52.00