IP Library Granted Patent US 6,977,248
Granted Patent B1
US 6,977,248 · App. 10/069,280 · Granted Dec 20, 2005

Pharmaceutical preparations for the inhibition of herpes simplex virus 1 entry

Assignee: Massachusetts Institute of Technology
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Quick Facts
Patent No.
US 6,977,248
App. No.
10/069,280
Granted
Dec 20, 2005
Kind
B1
Abstract

Disclosed herein are polysaccharide preparations enriched in 3-OST-3 modified heparan sulfate. Also disclosed are methods of treating herpes simplex viral type-1 infection using the pharmaceutical preparations of the invention.

Claims (28)

1. A pharmaceutical preparation for inhibiting herpes simplex virus type-1 (HSV-1) infection in a mammal comprising a substantially pure heparan sulfate polysaccharide preparation enriched to comprise at least 5% for 3-O-sulfated glucosamine residues, wherein said substantially pure heparan sulfate polysaccharide preparation enriched for 3-O-sulfated glucosamine residues is obtained by the process comprising the step of contacting a heparan sulfate polysaccharide with a 3-OST-3 enzyme and a sulfate donor so as to produce a substantially pure heparan sulfate polysaccharide preparation enriched for 3-O-sulfated glucosamine residues.

2. The pharmaceutical preparation of claim 1 , wherein said polysaccharide preparation is enriched for GlcN3S6S.

3. The pharmaceutical preparation of claim 1 , wherein said 3-OST-3 enzyme is selected from the group consisting of 3-OST-3A and 3-OST-3B.

4. The pharmaceutical preparation of claim 1 , wherein the preparation comprises the disaccharide sequence-IdoA2S-GlcN3S6S.

5. The pharmaceutical preparation of claim 1 , wherein the preparation comprises the trisaccharide sequence GlcNS-IdoA2S-GlcNH 2 3S6S.

6. The pharmaceutical preparation of claim 1 , wherein the preparation comprises the tetrasaccharide sequence UA2S-GlcNS-IdoA2S-GlcNH 2 3S6S.

7. The pharmaceutical preparation of claim 1 , wherein the preparation comprises the pentasaccharide sequence GlcNS6S-UA2S-GlcNS-IdoA2S-GlcNH 2 3S6S.

8. The pharmaceutical preparation of claim 1 , wherein the preparation comprises the hexasaccharide sequence UA-GlcNS6S-UA2S-GlcNS-IdoA2S-GlcNH 2 3S6S.

9. The pharmaceutical preparation of claim 1 , wherein the preparation comprises the heptasaccharide sequence GlcNAc-UA-GlcNS6S-UA2S-GlcNS-IdoA2S-GlcNH 2 3S6S.

10. The pharmaceutical preparation of claim 1 , wherein the preparation comprises the octasaccharide sequence UA-GlcNAc-UA-GlcNS6S-UA2S-GlcNS-IdoA2S-GlcNH 2 3S6S.

11. The pharmaceutical preparation of claim 1 , wherein said pharmaceutical preparation comprises pharmaceutically acceptable carriers selected from the group consisting of lotions, creams, jellies, liniments, ointments, salves, oils, foams, gels, washes, suppositories, slow-releasing polymers, and coatings.

12. The pharmaceutical preparation of claim 1 , wherein said pharmaceutical preparation further comprises at least one skin penetrating enhancer.

13. The pharmaceutical preparation of claim 12 , wherein said skin penetrating enhancer is selected from the group consisting of dimethylsulfoxide (DMSO), propylene glycol, isopropanol, ethanol, oleic acid, and N-methylpyrrolidone.

14. A method of inhibiting herpes simplex virus type-1 (HSV-1) viral infection in mammal comprising administering to a mammal at risk of HSV-1 infection a therapeutically effective amount of a pharmaceutical composition comprising a substantially pure heparan sulfate polysaccharide preparation enriched to comprise at least 5% for 3-O-sulfated glucosamine residues, wherein said substantially pure heparan sulfate polysaccharide preparation enriched for 3-O-sulfated glucosamine residues is obtained by the process comprising the step of contacting a heparan sulfate polysaccharide with a 3-OST-3 enzyme and a sulfate donor.

15. A method of inhibiting herpes simplex virus type-1 (HSV-1) viral infection in mammal comprising administering to a mammal diagnosed with HSV-1 infection a therapeutically effective amount of a pharmaceutical composition comprising a substantially pure heparan sulfate polysaccharide preparation enriched to comprise at least 5% for 3-O-sulfated glucosamine residues, wherein said substantially pure heparan sulfate polysaccharide preparation enriched for 3-O-sulfated glucosamine residues is obtained by the process comprising the step of contacting a heparan sulfate polysaccharide with a 3-OST-3 enzyme and a sulfate donor.

16. The method of claim 14 or 15 , wherein said polysaccharide preparation is enriched for structures capable of specific binding with HSV-1 gD viral glycoprotein.

17. The method of claim 14 or 15 , wherein said 3-OST-3 enzyme is selected from the group consisting of 3-OST-3A and 3-OST-3B.

18. The method of claim 14 or 15 , wherein said polysaccharide preparation comprises the disaccharide sequence -IdoA2S-GlcN3S6S.

19. The method of claim 14 or 15 , wherein said polysaccharide preparation comprises the trisaccharide sequence GlcNS-IdoA2S-GIcNH23S6S.

20. The method of claim 14 or 15 , wherein said polysaccharide preparation comprises the trisaccharide sequence UA2S-GIcNS-IdoA2S.

21. The method of claim 14 or 15 , wherein said polysaccharide preparation comprises the pentasaccharide sequence GlcNS6S-UA2S-GIcNS-IdoA2S-GIcNH23S6S.

22. The method of claim 14 or 15 , wherein said polysaccharide preparation comprises the hexasaccharide sequence UA-GlcNS6S-UA2S-GlcNS-IdoA2S-GIcNH23S6S.

23. The method of claim 14 or 15 , wherein said polysaccharide preparation comprises the hexasaccharide sequence UA-GlcNS6S-UA2S-GIcNS-IdoA2S-GlcNH23S6S.

24. The method of claim 14 or 15 , wherein said polysaccharide preparation comprises the heptasaccharide sequence GIcNAc-UA-GIcNS6S-UA2S-GIcNS-IdoA2S-GIcNH23S6S.

25. The method of claim 14 or 15 , wherein said polysaccharide preparation comprises the octasaccharide sequence UA-GIcNAc-UA-GIcNS6S-UA2S-GIcNS-IdoA2SGlcNH23S6S.

26. The method of claim 14 or 15 , wherein said pharmaceutical preparation comprises pharmaceutically acceptable carrier selected from the group consisting of lotions, creams, jellies, liniments, ointments, salves, oils, foams, gels, washes, suppositories, slow-releasing polymers, and coatings.

27. The method of claim 14 or 15 , wherein said pharmaceutical preparation further comprises at least one skin penetrating enhancer.

28. The method of claim 14 or 15 , wherein said skin penetrating enhancer is selected from the group consisting of dimethylsulfoxide (DMSO), propylene glycol, isopropanol, ethanol, oleic acid, and N-methylpyrrolidone.

Assignments (3)
CONFIRMATORY LICENSE Recorded Dec 26, 2021
From: NORTHWESTERN UNIVERSITY
To: NATIONAL INSITUTES OF HEALTH - DIRECTOR DEITR
Reel/Frame 058477/0489 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Mar 30, 2005
From: ROSENBERG, ROBERT D.
To: MASSACHUSETTS INSTITUTE OF TECHNOLOGY
Reel/Frame 015837/0803 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jul 30, 2002
From: SHUKLA, DEEPAK; SPEAR, PATRICIA G.
To: NORTHWESTERN UNIVERSITY
Reel/Frame 013135/0689 →
Continuity (2)
Provisional Application 6017534700 · Jan 10, 2000
Provisional Application 6015074300 · Aug 25, 1999