Oligosaccharide-protein conjugates
Provided herein are conjugates comprising a protein and an oligosaccharide of one of Formulae I-VI. Also provided herein are pharmaceutical compositions comprising such conjugates. Further provided herein are methods of treating a lysosomal storage disorder in a mammal by administration of an oligosaccharide-glycoprotein conjugate.
1. An oligosaccharide-protein conjugate, comprising (1) a protein and (2) an oligosaccharide of Formula 2:
wherein k is selected from α, β, and a mixture of α and β.
2. An oligosaccharide-protein conjugate, comprising (1) a protein and (2) an oligosaccharide of Formula 3:
wherein k is selected from α, β, and a mixture of α and β.
3. The oligosaccharide-protein conjugate of claim 1 , wherein the protein is a glycoprotein.
4. The oligosaccharide-protein conjugate of claim 3 , wherein the glycoprotein is a lysosomal enzyme.
5. The oligosaccharide-protein conjugate of claim 4 , wherein the lysosomal enzyme is acid α-glucosidase, α-galactosidase A, acid sphingomyelinase, α-L-iduronidase, iduronate-2-sulfatase, or N-acetylgalactosamine-4-sulfatase.
6. The oligosaccharide-protein conjugate of claim 4 , wherein the lysosomal enzyme is acid α-glucosidase.
7. A pharmaceutical composition comprising the oligosaccharide-protein conjugate of claim 1 and an excipient.
8. A method of treating a lysosomal storage disorder, comprising administering to a mammal an oligosaccharide-glycoprotein conjugate comprising (1) a lysosomal enzyme and (2) an oligosaccharide of any one of Formulae 1-3:
wherein:
k is selected from α, β, and a mixture of α and β.
9. The method of claim 8 , wherein the lysosomal storage disorder is chosen from Fabry disease, Pompe disease, Niemann-Pick A disease, Niemann-Pick B disease, mucopolysaccharidosis I, mucopolysaccharidosis II, and mucopolysaccharidosis VI.
10. The method of claim 9 , wherein the lysosomal storage disorder is Pompe disease.
11. The method of claim 8 , further comprising administering methotrexate to the mammal before, after, or during treatment with the oligosaccharide-glycoprotein conjugate.
12. The method of claim 8 , wherein the oligosaccharide is an oligosaccharide of Formula 1, wherein k is selected from α, β, and a mixture of α and β.
13. The method of claim 8 , wherein the oligosaccharide is an oligosaccharide of Formula 2, wherein k is selected from α, β, and a mixture of α and β.
14. The method of claim 8 , wherein the oligosaccharide is an oligosaccharide of Formula 3, wherein k is selected from α, β, and a mixture of α and β.
15. The oligosaccharide-protein conjugate of claim 2 , wherein the protein is a glycoprotein.
16. The oligosaccharide-protein conjugate of claim 15 , wherein the glycoprotein is a lysosomal enzyme.
17. The oligosaccharide-protein conjugate of claim 16 , wherein the lysosomal enzyme is acid α-glucosidase, α-galactosidase A, acid sphingomyelinase, α-L-iduronidase, iduronate-2-sulfatase, or N-acetylgalactosamine-4-sulfatase.
18. The oligosaccharide-protein conjugate of claim 16 , wherein the lysosomal enzyme is acid α-glucosidase.
19. A pharmaceutical composition comprising the oligosaccharide-protein conjugate of claim 2 and an excipient.