# US 10,245,316 B2 · Hypo-allergenic cross-linked proteins for use in the prevention of an allergy against milk-proteins and for use in the induction of oral tolerance > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 10,245,316 B2 - Document ID: US10245316B2 - Status: Granted - Kind: B2 - Application number: 14/414,387 - Filed: 2013-07-12 - Published: 2015-07-16 - Granted: 2019-04-02 - Earliest claimed: 2012-07-13 - Assignees: Friesland Brands B.V. - Applicants: Friesland Brands B.V. - Inventors: Elisabeth Catharina Adriana Maria Van Esch; Marjan Gros-Van Hest; Erik Labij; Johannes Martinus Maria Westerbeek - Web page: https://patentgrep.com/patent/US10245316B2 ## CPC - A61K 39/35: Allergens - A23L 33/19: Dairy proteins - A23L 33/40: {Complete food formulations for specific consumer groups or specific purposes, e.g. infant formula} - A61K 38/1709: {from mammals} - A61P 3/02: Nutrients, e.g. vitamins, minerals - A61P 37/02: Immunomodulators - A61P 37/08: Antiallergic agents (antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14) - C07K 14/4732: {Casein (in foodstuffs A23J)} - A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D) - A23L: FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES, NOT OTHERWISE PROVIDED FOR; PREPARATION OR TREATMENT THEREOF (preservation thereof A23B) - A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS - C07K: PEPTIDES (peptides in foodstuffs A23; obtaining protein compositions for foodstuffs, working-up proteins for foodstuffs A23J; preparations for medicinal purposes A61K; peptides containing beta-lactam rings C07D; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, C07D; ergot alkaloids of the cyclic peptide type C07D519/02; macromolecular compounds having statistically distributed amino acid units in their molecules, i.e. when the preparation does not provide for a specific; but for a random sequence of the amino acid units, homopolyamides and block copolyamides derived from amino acids C08G69/00; macromolecular products derived from proteins C08H1/00; preparation of glue or gelatine C09H; single cell proteins, enzymes C12N; genetic engineering processes for obtaining peptides C12N15/00; compositions for measuring or testing processes involving enzymes C12Q; investigation or analysis of biological material G01N33/00) ## Abstract The present invention provides a hypo-allergenic cross-linked protein for use in the prevention of an allergy against milk proteins, or for use in the induction of oral tolerance for milk proteins, said cross-linked protein being selected from cross-linked casein, cross-linked caseinate and combinations thereof. The invention further provides a nutritional composition for use in the prevention of an allergy against milk proteins or for use in the induction of oral tolerance against milk proteins. ## Claims ### Claim 1 A method of reducing the risk of developing an allergy against milk proteins in a human subject predisposed to develop a milk protein allergy by inducing oral tolerance against milk proteins, comprising orally administering to the human subject a composition comprising, by weight of dry matter: (a) 10 to 15% protein, of which at least 20% is a hypo-allergenic cross-linked protein selected from cross-linked casein, cross-linked caseinate and combinations thereof: (b) 50 to 65% carbohydrates; (c) 22 to 30% fat and optionally (d) 1-6% oligosaccharides. ### Claim 2 (depends on 1) The method according to claim 1, wherein the milk protein is casein, caseinate, milk serum protein, lactoferrin, transferrin or a combination thereof. ### Claim 3 (depends on 2) The method according to claim 2, wherein the milk protein is casein, caseinate or both. ### Claim 4 (depends on 1) The method according to claim 1, wherein the cross-linked protein has been cross-linked by enzymatic treatment. ### Claim 5 (depends on 1) The method according to claim 1, wherein the cross-linked protein comprises on average 0.1 to 2 cross-links per casein or caseinate molecule. ### Claim 6 (depends on 5) The method according to claim 5, wherein the cross-linked protein comprises on average 0.5 to 1 cross-links per casein or caseinate molecule. ### Claim 7 (depends on 1) The method according to claim 1, wherein the human subject is up to 36 months of age. ### Claim 8 (depends on 4) The method according to claim 4, wherein the enzymatic treatment is with transglutaminase. ### Claim 9 A method of reducing the risk of developing an allergy against milk proteins in a human subject up to 36 months of age by inducing oral tolerance against milk proteins, comprising orally administering to the human subject a composition comprising, by weight of dry matter: (a) 10 to 15% protein, of which at least 20% is a hypo-allergenic cross-linked protein selected from cross-linked casein, cross-linked caseinate and combinations thereof; (b) 50 to 65% carbohydrates; (c) 22 to 30% fat and optionally (d) 1-6% oligosaccharides. ### Claim 10 (depends on 9) The method according to claim 9, wherein the milk protein is casein, caseinate, milk serum protein, lactoferrin, transferrin or a combination thereof. ### Claim 11 (depends on 10) The method according to claim 10, wherein the milk protein is casein, caseinate or both. ### Claim 12 (depends on 9) The method according to claim 9, wherein the cross-linked protein comprises on average 0.1 to 2 cross-links per casein or caseinate molecule. ### Claim 13 (depends on 12) The method according to claim 12, wherein the cross-linked protein comprises on average 0.5 to 1 cross-links per casein or caseinate molecule. ### Claim 14 (depends on 9) The method according to claim 9, wherein the human subject is predisposed to develop a milk protein allergy. ### Claim 15 A method of reducing the risk of developing an allergy against milk proteins in a human subject in need thereof by inducing oral tolerance against milk proteins, comprising orally administering to the human subject a composition comprising, by weight of dry matter: (a) 10 to 15% protein, of which at least 20% is a hypo-allergenic cross-linked protein selected from cross-linked casein, cross-linked caseinate and combinations thereof; (b) 50 to 65% carbohydrates; (c) 22 to 30% fat and optionally (d) 1-6% oligosaccharides, wherein the cross-linked protein comprises on average 0.1 to 2 cross-links per casein or caseinate molecule. ### Claim 16 (depends on 15) The method according to claim 15, wherein the milk protein is casein, caseinate, milk serum protein, lactoferrin, transferrin or a combination thereof. ### Claim 17 (depends on 16) The method according to claim 16, wherein the milk protein is casein, caseinate or both. ### Claim 18 (depends on 17) The method according to claim 17, wherein the cross-linked protein comprises on average 0.5 to 1 cross-links per casein or caseinate molecule. ### Claim 19 (depends on 15) The method according to claim 15, wherein the human subject is up to 36 months of age. ### Claim 20 (depends on 15) The method according to claim 15, wherein the human subject is predisposed to develop a milk protein allergy.