Oligosaccharide compositions and use thereof in the treatment of infection

Abstract

Oligosaccharides and oligosaccharides linked to backbones such as proteins, methods for making such oligosaccharides and methods for using them to treat and/or prevent various disorders are described.

1 - 9 . (canceled) 
     
     
         10 . A pharmaceutical composition, comprising a purified protein that includes at least two different oligosaccharide groups selected from
 2′-Fucosyllactose;   Lacto-N-fucopentaose I;   Lacto-N-fucopentaose II;   3-Fucosyllactose;   Lacto-N-fucopentaose III;   Lacto-N-difucohexaose I;   Lactodifucotetraose;   LactoN-tetraose;   LactoN-neotetraose;   3′-Sialyllactose;   3′-Sialyllactosamine;   6′-Sialyllactose;   6′-Sialyllactosamine;   Sialyllacto-N-neotetraose c;   Monosialyllacto-N-hexaose;   Disialyllacto-N-hexaose I;   Monosialyllacto-N-neohexaose I;   Monosialyllacto-N-neohexaose II   Disialyllacto-N-neohexaose   Disialyllacto-N-tetraose;   Disialyllacto-N-hexaose II;   Sialyllacto-N-tetraose a;   Disialyllacto-N-hexaose I;   Sialyllacto-N-tetraose b;   3′-Sialyl-3-fucosyllactose;   Disialomonofucosyllacto-N-neohexaose;   Monofucosylmonosialyllacto-N-octaose (sialyl Lea);   Sialyllacto-N-fucohexaose II;   Disialyllacto-N-fucopentaose II; and   Monofucosyldisialyllacto-N-tetraose, or a variant thereof wherein a sugar at the reducing end is GlcNAc.   
     
     
         11 . (canceled) 
     
     
         12 . The composition of  claim 10 , wherein the protein contains multiple copies of each of the at least two different oligosaccharide groups. 
     
     
         13 . The composition of  claim 10 , wherein the protein is a human milk protein. 
     
     
         14 . The composition of  claim 10 , wherein the human milk protein is selected from κ-casein, α-lactalbumin, lactoferrin, bile salt-stimulated lipase, lysozyme, serum albumin, folate-binding protein, haptocorrin, lipoprotein lipase, glycosaminoglycan, mucin, lactoperoxidase, and amylase. 
     
     
         15 . The composition of  claim 10 , wherein the composition is synthetic. 
     
     
         16 . The composition of  claim 10 , wherein the composition is free of mammalian milk. 
     
     
         17 - 29 . (canceled) 
     
     
         30 . A synthetic nutrition composition comprising a purified protein that includes at least two oligosaccharide groups selected from
 2′-Fucosyllactose;   Lacto-N-fucopentaose I;   Lacto-N-fucopentaose II;   3-Fucosyllactose;   Lacto-N-fucopentaose III;   Lacto-N-difucohexaose I;   Lactodifucotetraose;   LactoN-tetraose;   LactoN-neotetraose;   3′-Sialyllactose;   3′-Sialyllactosamine;   6′-Sialyllactose;   6′-Sialyllactosamine;   Sialyllacto-N-neotetraose c;   Monosialyllacto-N-hexaose;   Disialyllacto-N-hexaose I;   Monosialyllacto-N-neohexaose I;   Monosialyllacto-N-neohexaose II   Disialyllacto-N-neohexaose   Disialyllacto-N-tetraose;   Disialyllacto -N-hexaose II;   Sialyllacto-N-tetraose a;   Disialyllacto-N-hexaose I;   Sialyllacto-N-tetraose b;   3′-Sialyl-3-fucosyllactose;   Disialomonofucosyllacto-N-neohexaose;   Monofucosylmonosialyllacto-N-octaose (sialyl Lea);   Sialyllacto-N-fucohexaose II;   Disialyllacto-N-fucopentaose II; and   Monofucosyldisialyllacto-N-tetraose or a variant thereof in which a sugar at the reducing end is GlcNAc wherein the at least two oligosaccharide groups are the same or different.   
     
     
         31 . The composition of  claim 30  wherein the at least two oligosaccharide groups are different. 
     
     
         32 - 37 . (canceled) 
     
     
         38 . A method for reducing the risk of enteric disease in a patient, the method comprising:
 (a) identifying the two most prevalent agents capable of causing enteric disease in the geographic location of the patient; and   (b) administering to the patient a composition containing a molecule that includes a first glycan which interferes with the binding to epithelial cells of the first of the two most prevalent agents and a second glycan which interferes with the binding to epithelial cells of the second of the two most prevalent agents   
       wherein said composition is free of breast milk. 
     
     
         39 . A method for reducing the risk of enteric disease in a patient, the method comprising:
 (a) identifying the two most prevalent agents capable of causing enteric disease in the geographic location of the patient,   (b) administering to the patient a composition comprising
 i) a first molecule containing a first glycan which interferes with the binding to epithelial cells of the first of the two most prevalent agents; and 
 ii) a second molecule containing a glycan which interferes with the binding to epithelial cells of the second of the two most prevalent agents, 
   
       wherein said composition is free of breast milk. 
     
     
         40 . A yeast cell harboring a recombinant vector, comprising a nucleotide sequence encoding GDP-mannose 4, 6 dehydratase and a nucleotide sequence encoding GDP-L-fucose synthetase. 
     
     
         41 . The yeast cell of  claim 40 , wherein the GDP-mannose 4, 6 dehydratase is  H. pylori  GDP-mannose 4, 6 dehydratase. 
     
     
         42 . The yeast cell of  claim 40 , wherein the GDP-L-fucose synthetase is  H. pylori  GDP-L-fucose synthetase. 
     
     
         43 . The yeast cell of  claim 40 , wherein the yeast cell harbors a nucleic acid molecule encoding a GDP-fucose/GMP antiporter fusion protein. 
     
     
         44 . The yeast cell of  claim 43 , wherein the fusion protein comprises a golgi-membrane location sequence. 
     
     
         45 . The yeast cell of  claim 43  wherein the golgi-membrane location sequence is from Vrg4p. 
     
     
         46 . An isolated nucleic acid molecule encoding a fusion protein, said protein comprising a first portion and a second portion, the first portion including the active domain of a GDP-fucose/GMP antiporter and the second portion including a golgi localization sequence. 
     
     
         47 . The isolated nucleic molecule of  claim 46  wherein the golgi localization sequence is a yeast golgi localization sequence. 
     
     
         48 . A yeast harboring the isolated nucleic acid molecule of  claim 46 . 
     
     
         49 . The yeast of  claim 48  further harboring a nucleic acid molecule encoding a fucosyltransferase or a galactosyltransferase. 
     
     
         50 . The yeast of  claim 49 , wherein the fucosyltransferase is selected from
   Homo sapiens  fucosyltransferase 1 (galactoside 2-alpha-L-fucosyltransferase, Bombay phenotype included) (FUT1);     Homo sapiens  fucosyltransferase 2 (secretor status included) (FUT2);     Homo sapiens  fucosyltransferase 3 (galactoside 3(4)-L-fucosyltransferase, Lewis blood group included) (FUT3);     Homo sapiens  fucosyltransferase 4 (alpha (1,3) fucosyltransferase, myeloid-specific) (FUT4);     Homo sapiens  fucosyltransferase 5 (alpha (1,3) fucosyltransferase) (FUT5);     Homo sapiens  fucosyltransferase 6 (alpha (1,3) fucosyltransferase) (FUT6);     Homo sapiens  fucosyltransferase 7 (alpha (1,3) fucosyltransferase) (FUT7);     Homo sapiens  fucosyltransferase 8 (alpha (1,6) fucosyltransferase) (FUT8);     Homo sapiens  fucosyltransferase 9 (alpha (1,3) fucosyltransferase) (FUT9); and     Homo sapiens  protein o-fucosyltransferase (POFUT1).   
     
     
         51 . (canceled) 
     
     
         52 . A pharmaceutical composition, comprising an oligosaccharide or a glycoconjugate, wherein the oligosaccharide or the glycoconjugate includes a molecule containing a fucose group in an α1,4 linkage to an N-acetylglucosamine group, a fucose group in an α 1,3 linkage to an N-acetylglucosamine group, or a fucose group in an α 1,3 linkage to a glucose group; and a pharmaceutically acceptable carrier. 
     
     
         53 . The composition of  claim 52 , wherein the molecule is selected from the group consisting of lacto-N-difucohexaose I (LDFH-I), lactodifucotetraose (LDFT), disialyllacto-N-neohexaose (DSLNnH), lacto-N-fucopentaose II (LNF-II), lactodifucohexaose I (LDFH-I), monosialyllacto-N-neohexaose II (MSLNnH-II), monofucosylmonosialyllacto-N-octaose (MFMSLNO), sialyllacto-N-fucohexaose II (SLNFH-II), disialyllacto-N-fucopentaose II (DSLNFP-II), monofucosyldisialyllacto-N-tetraose (MFDLNT), lacto-N-fucopentaose III (LNF-III), monosialyllacto-N-neohexaose I (MSLNnH-I), disialomonofucosyllacto-N-neohexaose (DSFLNH), 3-fucosyllactose (3-FL), and 3′-sialyl-3-fucosyllactose (3′-S-FL), or a variant thereof in which a sugar at the reducing end is GlcNAc. 
     
     
         54 . The composition of  claim 52 , further comprising a molecule including a fucose group in an α 1,2 linkage to a galactose group. 
     
     
         55 . The composition of  claim 52 , wherein the glycoconjugate is a glycan, a glycolipid, or a glycoprotein. 
     
     
         56 . The composition of  claim 52 , wherein the glycoconjugate further includes a fucose group in an α 1,2 linkage to a galactose group. 
     
     
         57 . A method for treating or reducing the risk of infection, the method comprising administering to a subject in need thereof an effective amount of a composition containing an oligosaccharide or a glycoconjugate, wherein the oligosaccharide or the glycoconjugate includes a fucose group in an α1,4 linkage to an N-acetylglucosamine group, a fucose group in an α 1,3 linkage to an N-acetylglucosamine group, or a fucose group in an α 1,3 linkage to a glucose group. 
     
     
         58 . The method of  claim 57 , wherein the composition further contains an oligosaccharide including a fucose group in an α 1,2 linkage to a galactose group. 
     
     
         59 . The method of  claim 57 , wherein the glycoconjugate further includes an oligosaccharide including a fucose group in an α 1,2 linkage to a galactose group. 
     
     
         60 . The method of  claim 57 , wherein the infection is caused by  V. cholerea  or  C. jejuni.    
     
     
         61 . The method of  claim 57 , wherein the infection is an enteric infection. 
     
     
         62 . The method of  claim 57 , wherein the glycoconjugate is a glycan, a glycolipid, or a glycoprotein.