IP Library Granted Patent US 8,846,363
Granted Patent B2
US 8,846,363 · App. 12/910,767 · Granted Sep 30, 2014

Compositions of and methods of using sulfatases from

Inventors: James R. Myette (Waltham, MA); Ram Sasisekharan (Bedford, MA)
C12Q1/34G01N33/5011A61K38/00C12N9/16G01N2400/40
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Quick Facts
Patent No.
US 8,846,363
App. No.
12/910,767
Granted
Sep 30, 2014
Kind
B2
Abstract

This invention is related, in part, to sulfatase enzymes and methods of their use.

Claims (31)

1. A method, comprising contacting a glycosaminoglycan with a glycosaminoglycan-degrading enzyme in an amount effective to cleave the glycosaminoglycan, thereby producing a cleavage product, wherein the glycosaminoglycan-degrading enzyme is an isolated sulfatase comprising the amino acid sequence of SEQ ID NO: 2 or 4.

2. The method of claim 1 , wherein the isolated sulfatase comprises the amino acid sequence of SEQ ID NO:2.

3. The method of claim 1 , wherein the isolated sulfatase comprises the amino acid sequence of SEQ ID NO:4.

4. The method of claim 1 , wherein the glycosaminoglycan is further contacted with at least one additional glycosaminoglycan-degrading enzyme.

5. The method of claim 4 , wherein the at least one additional glycosaminoglycan-degrading enzyme is used prior to, subsequent to, or concurrently with the sulfatase.

6. The method of claim 4 , wherein the at least one additional glycosaminoglycan-degrading enzyme is heparinase I, heparinse II, heparinase III, 2-O sulfatase, or Δ4,5 glycuronidase.

7. The method of claim 4 , wherein the at least one additional glycosaminoglycan-degrading enzyme is another sulfatase, glycosyl hydrolase, endoglucuronidase, or lyase.

8. The method of claim 6 , wherein the at least one additional glycosaminoglycan-degrading enzyme is Δ4,5 glycuronidase.

9. The method of claim 8 , wherein the Δ4,5 glycuronidase is contacted with the glycosaminoglycan prior to the sulfatase.

10. The method of claim 9 , wherein the glycosaminoglycan is further contacted with a 2-O sulfatase and the contact with the 2-O sulfatase is prior to the contact with the Δ4,5 glycuronidase.

11. The method of claim 10 , wherein the glycosaminoglycan is further contacted with a heparinase and the contact with the heparinase is prior to the contact with the 2-O sulfatase.

12. The method of claim 4 , wherein the sulfatase comprises the amino acid sequence of SEQ ID NO:2; wherein the glycosaminoglycan is also contacted with N-sulfamidase, and wherein the glycosaminoglycan is contacted with the sulfatase prior to the N-sulfamidase.

13. The method of claim 11 , wherein the sulfatase comprises the amino acid sequence of SEQ ID NO:2; wherein the glycosaminoglycan is also contacted with N-sulfamidase; and wherein the glycosaminoglycan is contacted with the sulfatase prior to the N-sulfamidase.

14. The method of claim 1 , wherein the glycosaminoglycan is 3-O desulfated prior to contact with the sulfatase.

15. The method of claim 1 , further comprising analyzing the cleavage product.

16. The method of claim 15 , wherein the glycosaminoglycan is also contacted with at least one additional glycosaminoglycan-degrading enzyme.

17. The method of claim 16 , wherein the at least one additional glycosaminoglycan-degrading enzyme is used prior to, subsequent to, or concurrently with the sulfatase.

18. The method of claim 16 , wherein the at least one additional glycosaminoglycan-degrading enzyme is heparinase I, heparinse II, heparinase III, 2-O sulfatase, or Δ4,5 glycuronidase.

19. The method of claim 16 , wherein the at least one additional glycosaminoglycan-degrading enzyme is another sulfatase, glycosyl hydrolase, endoglucuronidase, or lyase.

20. The method of claim 18 , wherein the at least one additional glycosaminoglycan-degrading enzyme is Δ4,5 glycuronidase.

21. The method of claim 20 , wherein the Δ4,5 glycuronidase is contacted with the glycosaminoglycan prior to the sulfatase.

22. The method of claim 21 , wherein the glycosaminoglycan is further contacted with a 2-O sulfatase and the contact with the 2-O sulfatase is prior to the contact with the Δ4,5 glycuronidase.

23. The method of claim 22 , wherein the glycosaminoglycan is further contacted with a heparinase and the contact with the heparinase is prior to the contact with the 2-O sulfatase.

24. The method of claim 16 , wherein the sulfatase comprises the amino acid sequence of SEQ ID NO:2; wherein the glycosaminoglycan is also contacted with an N-sulfamidase; and wherein the glycosaminoglycan is contacted with the sulfatase prior to the N-sulfamidase.

25. The method of claim 23 , wherein the sulfatase comprises the amino acid sequence of SEQ ID NO:2; wherein the glycosaminoglycan is also contacted with an N-sulfamidase; and wherein the glycosaminoglycan is contacted with the sulfatase prior to the N-sulfamidase.

26. The method of claim 15 , wherein the glycosaminoglycan is 3-O desulfated prior to contact with the sulfatase.

27. The method of claim 15 , wherein the presence of a particular glycosaminoglycan in a sample is determined based on the result from the analyzing step.

28. The method of claim 15 , wherein the purity of a glycosaminoglycan in a sample is determined based on the result from the analyzing step.

29. The method of claim 15 , wherein the composition of a glycosaminoglycan in a sample is determined based on the result from the analyzing step.

30. The method of claim 15 , wherein the sequence of saccharide units in a glycosaminoglycan is determined based on the result from the analyzing step.

31. The method of claim 15 , wherein the analyzing step is performed by subjecting the cleavage product to mass spectrometry, NMR spectroscopy, gel electrophoresis, capillary electrophoresis, or HPLC.

Assignments (3)
CONFIRMATORY LICENSE Recorded Dec 9, 2011
From: MASSACHUSETTS INSTITUTE OF TECHNOLOGY
To: NATIONAL INSTITUTES OF HEALTH (NIH), U.S. DEPT. OF HEALTH AND HUMAN SERVICES (DHHS), U.S. GOVERNMENT
Reel/Frame 027358/0976 →
CONFIRMATORY LICENSE Recorded Mar 10, 2011
From: MASSACHUSETTS INSTITUTE OF TECHNOLOGY
To: NATIONAL INSTITUTES OF HEALTH (NIH), U.S. DEPT. OF HEALTH AND HUMAN SERVICES (DHHS), U.S. GOVERNMENT
Reel/Frame 025920/0978 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Dec 8, 2010
From: MYETTE, JAMES R.; SASISEKHARAN, RAM
To: MASSACHUSETTS INSTITUTE OF TECHNOLOGY
Reel/Frame 025480/0083 →
Continuity (3)
Division 12006794 · Jan 4, 2008
Provisional Application 60879272 · Jan 5, 2007
Related Publication 20110033901A1 · Feb 10, 2011