OLIGOSACCHARIDES COMPRISING AN AMINOOXY GROUP AND CONJUGATES THEREOF
The invention provides methods for the synthesis of oligosaccharides comprising an aminooxy group. The invention further provides oligosaccharides comprising an aminooxy group, methods for coupling oligosaccharides comprising an aminooxy group to glycoproteins, and oligosaccharide-protein conjugates. Also provided are methods of treating a lysosomal storage disorder in a mammal by administration of an oligosaccharide-protein conjugate.
1 - 55 . (canceled)
56 : A method of treating Fabry disease, comprising administering to a patient in need thereof an α-galactosidase A conjugate, wherein the α-galactosidase A conjugate comprises α-galactosidase A conjugated to an oligosaccharide through an oxime group, wherein the oligosaccharide is:
wherein m and p are independently chosen from integers ranging from 1 to 10.
57 : The method of claim 56 , wherein m is 3.
58 : The method of claim 56 , wherein p is 1.
59 : The method of claim 56 , wherein the oligosaccharide is:
60 : The method of claim 56 , further comprising administering one or more of acetaminophen, azathioprine, cyclophosphamide, cyclosporin A, methotrexate, mycophenolate mofetil, oral steroids, and rapamycin to the patient in need thereof before, after, or during treatment with the α-galactosidase A conjugate.
61 : A method of treating Niemann-Pick disease, comprising administering to a patient in need thereof an acid sphingomyelinase conjugate, wherein the acid sphingomyelinase conjugate comprises acid sphingomyelinase conjugated to an oligosaccharide through an oxime group, wherein the oligosaccharide is:
wherein m and p are independently chosen from integers ranging from 1 to 10.
62 : The method of claim 61 , wherein m is 3.
63 : The method of claim 61 , wherein p is 1.
64 : The method of claim 61 , wherein the oligosaccharide is:
65 : The method of claim 61 , further comprising administering one or more of acetaminophen, azathioprine, cyclophosphamide, cyclosporin A, methotrexate, mycophenolate mofetil, oral steroids, and rapamycin to the patient in need thereof before, after, or during treatment with the acid sphingomyelinase conjugate.
66 : A method of treating mucopolysaccharidosis, comprising administering to patient in need thereof an α- L -iduronidase conjugate, wherein the α- L -iduronidase conjugate comprises α- L -iduronidase conjugated to an oligosaccharide through an oxime group, wherein the oligosaccharide is:
wherein m and p are independently chosen from integers ranging from 1 to 10.
67 : The method of claim 66 , wherein m is 3.
68 : The method of claim 66 , wherein p is 1.
69 : The method of claim 66 , wherein the oligosaccharide is:
70 : The method of claim 66 , further comprising administering one or more of acetaminophen, azathioprine, cyclophosphamide, cyclosporin A, methotrexate, mycophenolate mofetil, oral steroids, and rapamycin to the patient in need thereof before, after, or during treatment with the α-L-iduronidase conjugate.