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1. (WO2010071934) MODULATION OF PLATELET ACTIVATION
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CLAIMS:

1. A method for inhibiting platelet activation in a subject, said method comprising administering to said subject an agent which inhibits binding of a staphylococcal superantigen-like protein (SSL) to a molecule expressed on the surface of a platelet, thereby inhibiting platelet activation.

2. The method of Claim 1 , wherein the agent is selected from the group consisting of:

(a) an agent that binds to a staphylococcal superantigen-like protein (SSL), thereby inhibiting binding of the SSL to the molecule expressed on the surface of the platelet;

(b) an agent that binds to a molecule expressed on the surface of a platelet, thereby competing with a SSL in binding to the molecule expressed on the surface of a platelet;

(c) an agent that down-regulates the amount of a SSL available to bind to a molecule expressed on the surface of a platelet; or

(d) an agent that down-regulates the ability of a SSL to bind to a molecule expressed on the surface of a platelet.

3. The method of Claim 1 or Claim 2, wherein the agent is selected from the group comprising sialyl Lewis X or a mimetic thereof, sLacNac or a mimetic thereof, an anti-SSL antibody, an anti-platelet glycoprotein antibody, a regulator of SSL transcription or translation, soluble SSL receptor or mimetic thereof or any precursor, modulator or combination thereof.

4. The method of Claim 3, wherein the sLacNac mimetic is selected from the group comprising a monosaccharide sialyllactosamine (sLacNac) mimetic, a disaccharide sialyllactosamine (sLacNac) mimetic, a trisaccharide sialyllactosamine (sLacNac) mimetic, CGP77175A, CGP69669A and a compound selected from Formulae 1 through 64.

5. The method of Claim 3, wherein the sialyl Lewis X mimetic is selected from the group comprising a monosaccharide sialyl Lewis X (sLX) mimetic, a disaccharide sLX mimetic, a trisaccharide sLX mimetic or a tetrasaccharide sLX mimetic.

6. The method of Claim 3, wherein the agent is bimosiamose or derivative thereof.

7. The method of Claim 3, wherein the anti-SSL antibody is the monoclonal antibody designated herein 5E3.

8. The method of any one of Claims 1 to 7, wherein the SSL is selected from the group comprising SSL2, SSL3, SSL4, SSL5, SSL6 and SSLl 1.

9. The method of Claim 3 or 8, wherein the SSL is SSL5.

10. The method of any one of Claims 1 to 9, wherein the molecule expressed on the surface of the platelet is a glycoprotein.

1 1. The method of Claim 10, wherein the glycoprotein is selected from the group comprising GPIbα and GPVl.

12. A method for inhibiting formation of a thrombis involving platelet activation in a subject, said method comprising administering to said subject an agent which inhibits binding of a staphylococcal superantigen-like protein (SSL) to a platelet glycoprotein, thereby inhibiting platelet activation.

13. The method of Claim 12, wherein the agent is selected from the group consisting of:

(a) an agent that binds to a staphylococcal superantigen-like protein (SSL), thereby inhibiting binding of the SSL to a platelet glycoprotein;

(b) an agent that binds to a platelet glycoprotein, thereby competing with a SSL in binding to a platelet glycoprotein;

(c) an agent that down-regulates the amount of a SSL available to bind to a platelet glycoprotein; or

(d) an agent that down-regulates the ability of a SSL to bind to a platelet glycoprotein.

14. The method of Claim 12 or 13, wherein the agent is selected from the group comprising sialyl Lewis X or a mimetic thereof, sLacNac or a mimetic thereof including a compound selected from Formulae 1 through 64, an anti-SSL antibody, an anti-platelet glycoprotein antibody, a regulator of SSL transcription or translation, a soluble SSL receptor or any precursor, modulator or combination thereof.

15. The method of Claim 14, wherein the sLacNac mimetic is selected from the group comprising a monosaccharide sialyllactosamine (sLacNac) mimetic, a disaccharide sialyllactosamine (sLacNac) mimetic, a trisaccharide sialyllactosamine (sLacNac) mimetic, CGP77175A and CGP69669A.

16. The method of Claim 14, wherein the sialyl Lewis X mimetic is selected from the group comprising a monosaccharide sialyl Lewis X (sLX) mimetic, a disaccharide sLX mimetic, a trisaccharide sLX mimetic or a tetrasaccharide sLX mimetic.

17. The method of Claim 14 wherein the agent is Bimosiamose or a derivative thereof.

18. The method of Claim 14, wherein the anti-SSL antibody is the monoclonal antibody designated herein 5E3.

19. The method of any one of Claims 12 to 18, wherein the SSL is selected from the group comprising SSL2, SSL3, SSL4, SSL5, SSL6 and SSLI l .

20. The method of Claim 14 or 19, wherein the SSL is SSL5.

21. The method of any one of Claims 12 to 20, wherein the platelet glycoprotein is selected from the group comprising GPIbα and GPVI.

22. A method for treating or preventing a disease involving platelet activation in a subject, wherein said method comprises administering to the subject the agent wherein the agent is selected from the group consisting of

(a) an agent that binds to a staphylococcal superantigen-like protein (SSL), thereby inhibiting binding of the SSL to a platelet glycoprotein;

(b) an agent that binds to a platelet glycoprotein, thereby competing with a SSL in binding to a platelet glycoprotein;

(c) an agent that down-regulates the amount of a SSL available to bind to a platelet glycoprotein; or

(d) an agent that down-regulates the ability of a SSL to bind to a platelet glycoprotein thereby inhibiting platelet activation and preventing the disease.

23. The method of Claim 22, wherein the disease is selected from the group comprising venous thrombosis, arterial thrombosis, embolisation, gangrene, diabetes, disseminated intravascular coagulopathy (DIC), pneumonia, sepsis, septicaemia and infection by Staphylococcus aureus.

24. The method of Claim 23, wherein the venous thrombosis is selected from the group comprising deep vein thrombosis, portal vein thrombosis, renal vein thrombosis, jugular vein thrombosis, Budd-Chiari syndrome, Paget-Schroetter disease and cerebral venous sinus thrombosis.

25. The method of Claim 23, wherein the arterial thrombosis is selected from stroke and myocardial infarction.

26. The method of Claims 23, wherein the embolisation is selected from pyemia, a septic embolus, sepsis and septicaemia.

27. A method for

(a) diagnosing platelet activation in a subject;

(b) diagnosing formation of a thrombus involving platelet activation in a subject; or

(c) diagnosing a disease involving platelet activation in a subject wherein said method comprises:

(d) administering to the subject; or

(e) contacting ex vivo a biological sample of the subject with an anti-SSL antibody, wherein binding of the anti-SSL antibody to a SSL is indicative of platelet activation, or a predisposition thereto, and wherein binding of the anti-SSL antibody to a SSL is indicative of a Staphylococcus aureus infection.

28. The method of Claim 27, wherein the biological sample of the subject is a fluid.

29. The method of Claim 28, wherein the fluid is selected from the group comprising blood, serum, plasma or lymph.

30. The method of any one of Claims 27 to 29, wherein the disease involving platelet activation is selected from the group comprising venous thrombosis, arterial thrombosis, embolisation, gangrene, diabetes, pneumonia sepsis, septicaemia, DIC and a Staphylococcus aureus infection.

31. The method of any one of Claims 27 to 30, wherein the anti-SSL antibody is the monoclonal antibody designated 5E3.

32. A method for:

(a) inhibiting platelet activation in a subject;

(b) inhibiting formation of a thrombus involving platelet activation in a subject; or

(c) treating or preventing a disease involving platelet activation in a subject wherein said method comprises administering to the subject an agent that inhibits binding of Staphylococcal superantigen-like protein-5 (SSL5) to a platelet glycoprotein.

33. The method of Claim 32, wherein the agent is an anti-SSL5 monoclonal antibody.

34. The method of Claim 32 or 33, wherein the disease is selected from the group comprising venous thrombosis, arterial thrombosis, embolisation, gangrene, diabetes, pneumonia, sepsis, septicaemia, DIC and infection by Staphylococcus aureus.

35. A method for diagnosing a Staphylococcus aureus infection in a subject, wherein said method comprises:

(a) administering to the subject; or

(b) contacting ex vivo a biological sample of the subject with an anti-SSL antibody, wherein binding of the anti-SSL antibody to a SSL is indicative of platelet activation, or a predisposition thereto, and wherein binding of the anti-SSL antibody to a SSL is indicative of a Staphylococcus aureus infection.

36. The method of Claim 35 wherein the fluid is selected from the group comprising blood, serum, plasma, lymph, urine, abscess, cerebral, pericardial and pleuritic fluid.

37. The method of Claim 35 or Claim 36, wherein the anti-SSL antibody is the monoclonal antibody designated herein 5E3.

38. An agent for inhibiting platelet activation in a subject, said method comprising administering to said subject an agent which inhibits binding of a staphylococcal superantigen-like protein (SSL) to a molecule expressed on the surface of a platelet, thereby inhibiting platelet activation.

39. The agent of Claim 38, wherein the agent is selected from the group consisting of:

(a) an agent that binds to a staphylococcal superantigen-like protein (SSL), thereby inhibiting binding of the SSL to the molecule expressed on the surface of the platelet;

(b) an agent that binds to a molecule expressed on the surface of a platelet, thereby competing with a SSL in binding to the molecule expressed on the surface of a platelet;

(c) an agent that down-regulates the amount of a SSL available to bind to a molecule expressed on the surface of a platelet; or

(d) an agent that down-regulates the ability of a SSL to bind to a molecule expressed on the surface of a platelet.

40. The agent of Claim 38 or Claim 39, wherein the agent is selected from the group comprising sialyl Lewis X or a mimetic thereof, sLacNac or a mimetic thereof including a compound selected from Formulae 1 through 64, an anti-SSL antibody, an anti-platelet glycoprotein antibody, a regulator of SSL transcription or translation, a soluble SSL receptor or any precursor, modulator or combination thereof.

41. The agent of Claim 40, wherein the sLacNac mimetic is selected from the group comprising a monosaccharide sialyllactosamine (sLacNac) mimetic, a disaccharide sialyllactosamine (sLacNac) mimetic, a trisaccharide sialyllactosamine (sLacNac) mimetic, CGP77175A and CGP69669A.

42. The agent of Claim 40, wherein the sialyl Lewis X mimetic is selected from the group comprising a monosaccharide sialyl Lewis X (sLX) mimetic, a disaccharide sLX mimetic, a trisaccharide sLX mimetic or a tetrasaccharide sLX mimetic.

43. The agent of Claim 40 wherein the agent is bimosiamose or a derivative thereof.

44. The agent of Claim 40, wherein the anti-SSL antibody is the monoclonal antibody designated 5E3.

45. The agent of any one of Claims 38 to 43, wherein the SSL is selected from the group comprising SSL2, SSL3, SSL4, SSL5, SSL6 and SSLl 1.

46. The agent of Claim 40 or 45, wherein the SSL is SSL5.

47. The agent of any one of Claims 38 to 45, wherein the molecule expressed on the surface of the platelet is a glycoprotein.

48. The agent of Claim 47, wherein the glycoprotein is selected from the group comprising GPIbα and GPVI.

49. Use of an SSL in the manufacture of a diagnostic agent to detect anti-SSL antibodies in a subject.

50. Use of Claim 49 wherein the SSL is SSL5.

51. Use of Claim 49 or 50 wherein the presence of anti-SSL antibodies is indicative of historical exposure to Staphylococcus aureus.