Granted Patent B2

US 12,584,101 · App. 18/371,651 · Granted Mar 24, 2026

Inventor: Steven Frese (Oakland, CA)

Assignee: INFINANT HEALTH, INC.

C12N1/205A61K31/702A61K35/745C12R2001/01

Abstract

Claims (70)

1 . A composition comprising a Bifidobacterium longum subsp. infantis comprising a functional H5 gene cluster; wherein the Bifidobacterium longum subsp. infantis is Bifidobacterium longum subsp. infantis deposited under ATCC Accession No. PTA-125180; and

wherein the composition is in the form of a dry powder, or a dry powder suspended in an oil; and/or wherein the composition further comprises a cryoprotectant; and/or

wherein the composition further comprises a stabilizer.

2 . The composition of claim 1 , wherein the H5 cluster comprises Blon_2175, Blon_2176, and Blon_2177;

wherein the functional H5 cluster comprises Blon_2171, Blon_2173, Blon_2174, Blon_2175, Blon_2176, Blon_2177, and galT;

wherein the Bifidobacterium comprises upregulated genes selected from the group consisting of Blon_0042, Blon_R0015, Blon_R0017, Blon_R0021, Blon_R0022, and combinations thereof;

wherein the Bifidobacterium comprises downregulated genes selected from the group consisting of Blon_0518, Blon_0785, Blon_2167, Blon_2168 and combinations thereof;

wherein the Bifidobacterium comprises an upregulated Blon_0042 gene;

wherein the Bifidobacterium comprises a downregulated Blon_2168 gene;

wherein the Bifidobacterium comprises upregulated genes selected from the group consisting of Blon_0879, Blon_0880, Blon_0881, Blon_0882, Blon_2177, Blon_2334, Blon_2335, Blon_2336, Blon_2337, Blon_2338, Blon_2339, Blon_2343, Blon_2344, Blon 2346 , Blon 2347 , and Blon_ 2331 ;

wherein the Bifidobacterium expresses a gene coding for a sialidase or a fucosidase; and/or

wherein the Bifidobacterium expresses a gene coding for a sialic acid or a fucose transporter.

3 . The composition of claim 1 , wherein the Bifidobacterium is activated by an activator, wherein the activator is selected from the group consisting of N-acetyl-glucosamine/galactosamine (NAG), Dimeric N-acetylglucosamine, Fucose, Sialic Acid, Lacto-N-biose (LNB), Galacto-N-biose and Fuc α1,2Galβ;

wherein the Bifidobacterium has been cultured in the presence of at least one mammalian milk oligosaccharide; and/or

wherein the composition further comprises an activator selected from the group consisting of N-acetyl-glucosamine/galactosamine (NAG), Dimeric N-acetylglucosamine, Fucose, Sialic Acid, Lacto-N-biose (LNB), Galacto-N-biose and Fuc α1,2Galβ.

4 . The composition of claim 1 , wherein the Bifidobacterium contains a LNB transport system capable of internalizing one or more oligosaccharide having a Type I or Type II core before the oligosaccharide is hydrolyzed and is capable of hydrolyzing the internalized oligosaccharide, wherein the oligosaccharide is obtained from mammalian milk selected from human, bovine, pig, rabbit, goat, sheep, camel milk, or mixtures thereof.

5 . The composition of claim 1 , wherein the Bifidobacterium has a higher binding affinity to mammalian mucosal cells than Bifidobacteria of the same species cultivated in the absence of complex oligosaccharides.

6 . The composition of claim 1 , wherein the Bifidobacterium is present at a concentration of from 1 Million cfu/g to 500 Billion cfu/g;

wherein the Bifidobacterium is present at a concentration of from 5 Billion cfu/g to 100 Billion cfu/g; or

wherein the Bifidobacterium is present at a concentration of from 10 Billion cfu/g to 50 Billion cfu/g or from 50 million cfu/g to 5 billion cfu/g.

7 . The composition of claim 1 , further comprising an isolated complex oligosaccharide.

8 . The composition of claim 7 , wherein the complex oligosaccharide is a mammalian milk oligosaccharide (MMO);

wherein the complex oligosaccharide is isolated from a mammalian milk source selected from human, bovine, pigs, rabbits, goats, sheep, or camel;

wherein the mammalian milk oligosaccharide (MMO) comprises oligosaccharide molecules found in human milk oligosaccharides (HMO), bovine milk oligosaccharides (BMO), bovine colostrum oligosaccharides (BCO), goat milk oligosaccharides (GMO), or a combination thereof;

wherein the bovine source is from bovine milk, bovine colostrum, bovine colostrum concentrate, or mixtures thereof;

wherein the bovine colostrum oligosaccharide comprises any of Hex(4); Hex(4) HexNAc(2); or Hex(3) HexNAc(1) NeuAc(1) at levels greater than 1%;

wherein the complex oligosaccharide is from whey permeate;

wherein the mammalian milk oligosaccharide (MMO) comprises lacto-N-biose, lacto-N-triose, N-acetyllactosamime, lacto-N-neotriose, lacto-N-tetraose, lacto-N-neotetraose, fucosyllactose, lacto-N-fucopentose, lactodifucotetraose, sialyllactose, disialyllactone-N-tetraose, 2′-fucosyllactose, 3′-sialyllactoseamin, 3′-fucosyllactose, 3′-sialyl-3-fucosyllactose, 3′-sialyllactose, 6′-sialyllactosamine, 6′-sialyllactose, difucosyllactose, lacto-N-fucosylpentose I, lacto-N-fucosylpentose II, lacto-N-fucosylpentose III, lacto-N-fucosylpentose V, sialyllacto-N-tetraose, their derivatives, or combinations thereof;

wherein the mammalian milk oligosaccharide (MMO) comprises lacto-N-biose; and/or

wherein the mammalian milk oligosaccharide (MMO) comprises lacto-N-triose.

9 . The composition of claim 7 , wherein the complex oligosaccharide comprises at least one of (3Hex,4HexNac, 1Fuc), (1Gal, 1GlcNAc,1NeuAc), or (1Glu, 1Gal, 1NeuAc (3′ or 6′));

wherein the complex oligosaccharide is less than 50% fucosylated;

wherein the complex oligosaccharide comprise one of the following ratios of constituents: 1) a ratio of Hex(2) NeuAc(1): Hex(2) HexNAc(1) less than 5.0; 2) a ratio of Hex(2) HexNAc(1): Hex (3) HexNAc(1) of greater than 1.0; 3) a ratio of Hex(2) HexNAc(1):

Hex (3) HexNAc(2) of greater than 2.0; 4) a ratio of Hex(3): Hex (3) HexNAc(1) NeuAc(1) of less than 100; or 5) a ratio of Hex(2) HexNAc(1): Hex (4) NeuAc(2) NeuGc(1) of greater than 10; and/or

wherein the complex oligosaccharide comprises a plurality of oligosaccharides with 3 to 10 residues (DP3-10 oligosaccharides);

wherein at least one of the oligosaccharide has a Type I core; and/or

wherein at least one of the oligosaccharide has a Type II core.

10 . The composition of claim 7 , wherein the complex oligosaccharide is at least 20% of the weight of the composition;

wherein the complex oligosaccharide is at least 50% of the weight of the composition;

wherein the complex oligosaccharide is at least 80% of the weight of the composition;

wherein fucosyllactose and/or sialyllactose comprises 1-5% of the total oligosaccharides;

wherein fucosyllactose and/or sialyllactose comprises 5-20% of the total oligosaccharides;

wherein fucosyllactose and/or sialyllactose comprises 20-50% of the total oligosaccharides;

wherein the mass ratio of the complex oligosaccharide to fucosyllactose and/or sialyllactose is from 20:1 to 1:10;

wherein the composition provides a total dietary intake of oligosaccharide in an amount of 0.001-100 grams per day;

wherein the oligosaccharide is in an amount of 1-20 grams, 3-20 grams, or 5-10 grams; and/or

wherein the oligosaccharide is in an amount of 10, 15, 20, 25, 30, 35, 40, 45, or 50 grams.

11 . The composition of claim 7 , wherein the complex oligosaccharide comprises a plant-derived oligosaccharide;

wherein the plant oligosaccharide is from carrots, peas, broccoli, onions, tomatoes, peppers, rice, wheat, oats, bran, oranges, cocoa, olives, apples, grapes, sugar beets, cabbage, corn, or a mixture thereof;

wherein the plant oligosaccharide is from orange peels, cocoa hulls, olive pomace, tomato skins, grape pomace, corn silage, or a mixture thereof; and/or

wherein the plant-derived oligosaccharides are between 2 and 10 sugar residues (DP2-DP10), between 3 and 10 sugar residues (DP3-DP10), between 5 and 10 sugar resides (DP5-DP10), or up to DP20.

12 . The composition of claim 1 , wherein the composition further comprises galactooligosaccharide (GOS);

wherein the composition further comprises a protein source rich in threonine, N-acetyl-threonine, gamma-glutamylthreonine, or a combination thereof; and/or

wherein the composition further comprises a secondary metabolite.

13 . The composition of claim 1 ,

wherein the dry powder is spray dried or freeze-dried; and/or

wherein the composition is freeze-dried in the presence of a suitable cryoprotectant.

14 . The composition of claim 1 , wherein the composition further comprises a cryoprotectant; wherein the cryoprotectant is glucose, lactose, raffinose, sucrose, trehalose, adonitol, glycerol, mannitol, methanol, polyethylene glycol, propylene glycol, ribitol, alginate, bovine serum albumin, carnitine, citrate, cysteine, dextran, dimethyl sulphoxide, sodium glutamate, glycine betaine, glycogen, hypotaurine, peptone, polyvinyl pyrrolidone, or taurine, mammalian milk oligosaccharides, chitin, chitosan, other polysaccharides, or a combination thereof.

15 . The composition of claim 1 , further comprising a stabilizer;

wherein the stabilizer is a flow agent or a milk protein.

16 . The composition of claim 1 , wherein the composition is a powder with a water activity level of less than 0.35, less than 0.30, less than 0.25, less than 0.2, or less than 0.1;

wherein the composition is an anhydrous composition;

wherein the composition is suspended in an oil; and/or

wherein the composition is suspended in syrup having oligosaccharide at least 57% where water activity is low enough to keep Bifidobacterium dormant.

17 . The composition of claim 16 , wherein the oil is a medium chain triglyceride.

18 . The composition of claim 1 , wherein the composition is in the form of a packet, sachet, orally disintegrating tablet, foodstuff, capsule, lozenge, effervescent tablet, suppository, enema, capsule, dry powder, dry powder suspended in an oil, chewable composition, syrup, or gel;

wherein the capsule or tablet has an enteric coating;

wherein the enteric coating comprises one or more of fatty acids, waxes, shellac, plastics, plant fibers, methyl acrylate-methacrylic acid copolymers, cellulose acetate succinate, hydroxy propyl methyl cellulose phthalate, hydroxy propyl methyl cellulose acetate succinate, polyvinyl acetate phthalate (PVAP), methyl methacrylate-methacrylic acid copolymers, cellulose acetate trimellitate, sodium alginate, and zein;

wherein the composition is a pharmaceutical composition, dietary supplement, nutritional product, food product, probiotic, and/or prebiotic; and/or

wherein the composition is formulated as a unit dose medicament.

Assignments (2)

Continuity (4)

References Cited (33)