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1. WO2011033391 - METHODS OF TREATING A PATIENT RECEIVING A CARDIAC STENT IMPLANT

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CLAIMS

1. A method of treating a patient receiving a cardiac stent implant comprising the steps of:

(i) monitoring the circulating level of Troponin I (Tnl) in said patient; and

(ii) administering SERP-1 to said patient in an amount sufficient to prevent said circulating level of Tnl from exceeding a threshold of 0.5 ng/ml for the first 24 hours following implantation of said stent in said patient.

2. The method of claim 1, wherein said amount of said SERP-1 is not more than three times the minimum dose of SERP-1 that is sufficient to prevent said circulating level of Tnl from exceeding a threshold of 0.5 ng/ml for the first 24 hours following implantation of said stent in said patient.

3. A method of treating a patient receiving a cardiac stent implant comprising the steps of:

(i) monitoring the circulating level of Tnl in said patient; and

(ii) administering SERP-1 to said patient in an amount sufficient to achieve an exposure of SERP-1 of at least 8.5 ng»h/ml during the first 24 hours following implantation of said stent in said patient.

4. The method of claim 3, wherein said amount of said SERP-1 is not more than three times the minimum dose of SERP-1 that is sufficient to achieve the exposure of SERP-1 of at least 8.5 ng»h/ml during the first 24 hours following implantation of said stent in said patient.

5. A method of treating a patient receiving a cardiac stent implant comprising the steps of:

(i) monitoring the circulating level of Tnl in said patient; and

(ii) administering SERP-1 to said patient in an amount of greater than 5 μg/kg/day within 24 hours of implantation of said stent in said patient.

6. The method of claim 5, wherein said amount of said SERP-1 is from about 15 μg/kg/day to about 250 μg/kg/day.

7. The method of claim 6, wherein said amount of said SERP-1 is from about 15 μg/kg/day to about 150 μg/kg/day.

8. The method of claim 7, wherein said amount of said SERP-1 is about 15 μg/kg/day.

9. The method of any one of claims 1-8, wherein step (i) is performed subsequent to step (ii) during the first 24 hours following stent implantation, and wherein, if said circulating level of Tnl exceeds 0.40 ng/ml, step (ii) is repeated.

10. A method of treating a patient receiving a cardiac stent implant comprising the steps of:

(i) monitoring the circulating level of creatinine kinase MB fraction (CKMB) in said patient; and

(ii) administering SERP-1 to said patient in an amount sufficient to prevent said circulating level of CK-MB from exceeding a threshold of 5.0 ng/ml for the first 24 hours following implantation of said stent in said patient.

1 1. The method of claim 10, wherein said amount of said SERP-1 is not more than three times the minimum dose of SERP-1 that is sufficient to prevent said circulating level of CK-MB from exceeding a threshold of 5.0 ng/ml for the first 24 hours following implantation of said stent in said patient.

12. A method of treating a patient receiving a cardiac stent implant comprising the steps of:

(i) monitoring the circulating level of CK-MB in said patient; and

(ii) administering SERP-1 to said patient in an amount sufficient to achieve an exposure of SERP-1 of at least 8.5 ng-h/ml during the first 24 hours following implantation of said stent in said patient.

13. The method of claim 12, wherein said amount of said SERP-1 is not more than three times the minimum dose of SERP-1 that is sufficient to achieve the exposure of SERP-1 of at least 8.5 ng»h/ml during the first 24 hours following implantation of said stent in said patient.

14. A method of treating a patient receiving a cardiac stent implant comprising the steps of:

(i) monitoring the circulating level of CK-MB in said patient; and

(ii) administering SERP- 1 to said patient in an amount of greater than 5 μg/kg/day within 24 hours of implantation of said stent in said patient.

15. The method of claim 14, wherein said amount of said SERP-1 is from about 15 μg/kg/day to about 250 μg/kg/day.

16. The method of claim 15, wherein said amount of said SERP-1 is from about 15 μg/kg/day to about 150 μg/kg/day.

17. The method of claim 16, wherein said amount of said SERP-1 is about 15 μg/kg/day.

18. The method of any one of claims 10-17, wherein step (i) is performed subsequent to step (ii) and during the first 24 hours following stent implantation, and wherein, if said circulating level of CK-MB exceeds 4.0 ng/ml, step (ii) is repeated.

19. The method of any one of claims 1-8 or 10-17, wherein said SERP-1 is administered prior to implantation of said stent in said patient.

20. The method of claim 19, wherein said SERP-1 is administered less than 6 hours prior to implantation of said stent in said patient.

21. The method of claims 19 or 20, wherein SERP-1 is not administered during the first 24 hours following implantation of said stent in said patient.

22. The method of any one of claims 1-21, wherein said SERP-1 is administered once about every 24 hours.

23. The method of claim 22, wherein said SERP-1 is administered once about every 24 hours for three days.

24. The method of any one of claims 1-23, wherein said stent is a bare metal stent.

25. The method of any one of claims 1-23, wherein said stent is a drug-eluting stent.

26. The method of any one of claims 1-25, wherein said SERP-1 is administered intravenously.

27. The method of any one of claims 1-26, wherein said SERP-1 comprises an amino acid sequence that is at least 90% identical to amino acids 16-369 of SEQ ID NO: 2.

28. The method of claim 27, wherein said SERP-1 comprises an amino acid sequence that is at least 95% identical to amino acids 16-369 of SEQ ID NO: 2.

29. The method of claim 28, wherein said SERP-1 comprises amino acids 16-369 of SEQ ID NO: 2.

30. The method of claim 27, wherein the amino acid sequence of said SERP-1 consists of an amino acid sequence that is at least 90% identical to amino acids 16-369 of SEQ ID NO: 2.

31. The method of claim 30, wherein the amino acid sequence of said SERP-1 consists of an amino acid sequence that is at least 95% identical to amino acids 16-369 of SEQ ID NO: 2.

32. The method of claim 31, wherein the amino acid sequence of said SERP-1 consists of amino acids 16-369 of SEQ ID NO: 2.

33. The method of any one of claims 1-32, wherein said SERP-1 is encoded by a nucleic acid molecule that hybridizes under high stringency conditions to at least a portion of a nucleic acid molecule comprising SEQ ID NO: 1.

34. The method of any one of claims 1-33, wherein said SERP-1 is at least 90% pure.

35. The method of claim 34, wherein said SERP-1 is at least 99% pure.

36. The method of any one of claims 1-35, wherein said SERP-1 is glycosylated.

37. The method of any one of claims 1-36, wherein said patient is human.

38. The method of any one of claims 1-37, wherein said method reduces the likelihood of occurrence of a major adverse cardiac event (MACE) for the first 6 months following implantation of said stent in said patient.

39. The method of claim 38, wherein said method reduces the likelihood of occurrence of a MACE in said patient by at least 25%.

40. The method of claim 38 or 39, wherein said MACE is

cardiovascular death.

41. The method of claim 38 or 39, wherein said MACE is myocardial infarction.

42. The method of claim 38 or 39, wherein said MACE is target lesion revascularization.

43. The method of claim 42, wherein said target lesion revascularization comprises percutaneous coronary intervention.

44. The method of claim 38 or 39, wherein said MACE is coronary artery bypass graft (CABG).

45. The methods of any of claims 1-44, wherein said SERP-1 is formulated in a pharmaceutical composition comprising a pharmaceutically acceptable excipient.

46. A method of treating a patient receiving a cardiac stent implant comprising the steps of:

(i) monitoring the circulating level of Troponin I (Tnl) in said patient; and

(ii) administering a first dosage of SERP-1 to said patient prior to implantation of said stent in an amount sufficient to prevent said circulating level of Tnl from exceeding a threshold of 0.5 ng/ml for the first 24 hours following implantation of said stent in said patient.

47. A method of treating a patient receiving a cardiac stent implant comprising the steps of:

(i) monitoring the circulating level of Tnl in said patient; and

(ii) administering a first dosage of SERP- 1 to said patient prior to implantation of said stent in an amount sufficient to achieve an exposure of SERPl of at least 8.5 ng»h/ml during the first 24 hours following implantation of said stent in said patient.

48. A method of treating a patient receiving a cardiac stent implant comprising the steps of:

(i) monitoring the circulating level of Tnl in said patient; and

(ii) administering a first dosage of SERP- 1 to said patient prior to implantation of said stent in an amount of greater than 5 μg/kg/day.

49. The method of any one of claims 46 to 48, wherein said method reduces the likelihood of occurrence of a major adverse cardiac event (MACE) for the first 6 months following implantation of said stent in said patient.

50. The method of any one of claims 46 to 49, wherein said method further comprises administering a second dosage of said SERP-1 to said patient after 24 hours following implantation of said stent in said patient.

51. SERP-1 for use in a method of preventing the circulating level of Troponin I (Tnl) in a patient receiving a cardiac stent implant from exceeding a threshold of 0.5 ng/ml for the first 24 hours following implantation of said stent in said patient, wherein said method comprises administering to said patient SERP-1 in an amount sufficient to prevent said circulating level of Tnl from exceeding said threshold.

52. SERP-1 for use of claim 51, wherein said method further comprises monitoring the circulating level of Tnl in said patient.

53. SERP-1 for use of claim 51 or 52, wherein said amount of said SERP-1 is not more than three times the minimum dose of SERP-1 that is sufficient to prevent said circulating level of Tnl from exceeding a threshold of 0.5 ng/ml for the first 24 hours following implantation of said stent in said patient.

54. SERP-1 for use in a method of preventing the circulating level of creatinine kinase MB fraction (CK-MB) in a patient receiving a cardiac stent implant from exceeding a threshold of 5.0 ng/ml for the first 24 hours following implantation of said stent in said patient, wherein said method comprises administering to said patient SERP- 1 in an amount sufficient to prevent said circulating level of CK-MB from exceeding said threshold.

55. SERP-1 for use of claim 54, wherein said method further comprises monitoring the circulating level of CK-MB in said patient.

56. SERP-1 for use of claim 54 or 55, wherein said amount of said SERP-1 is not more than three times the minimum dose of SERP-1 that is sufficient to prevent said circulating level of CK-MB from exceeding a threshold of 5.0 ng/ml for the first 24 hours following implantation of said stent in said patient.

57. SERP-1 for use in a method of achieving an exposure of SERP-1 in a patient receiving a cardiac stent implant of at least 8.5 ng»h/ml during the first 24 hours following implantation of said stent in said patient, wherein said method comprises administering to said patient SERP-1 in an amount sufficient to achieve said exposure of SERP-1.

58. SERP-1 for use of claim 57, wherein said method further comprises monitoring the circulating level of Tnl in said patient.

59. SERP-1 for use of claim 57, wherein said method further comprises monitoring the circulating level of CK-MB in said patient.

60. SERP-1 for use of any one of claims 57-59, wherein said amount of said SERP-1 is not more than three times the minimum dose of SERP-1 that is sufficient to achieve the exposure of SERP-1 of at least 8.5 ng»h/ml during the first 24 hours following implantation of said stent in said patient.

61. SERP- 1 for use in a method of treating a patient receiving a cardiac stent implant, wherein said method comprises administering SERP-1 to said patient in an amount of greater than 5 μg/kg/day within 24 hours of

implantation of said stent in said patient.

62. SERP-1 for use of claim 61, wherein said method further comprises monitoring the circulating level of Tnl in said patient.

63. SERP-1 for use of claim 61, wherein said method further comprises monitoring the circulating level of CK-MB in said patient.

64. SERP-1 for use of any one of claims 61-63, wherein said amount of said SERP-1 is from about 15 μg/kg/day to about 250 μg/kg/day.

65. SERP-1 for use of claim 64, wherein said amount of said SERP-1 is from about 15 μg/kg/day to about 150 μg/kg/day.

66. SERP-1 for use of claim 65, wherein said amount of said SERP-1 is about 15 μg/kg/day.

67. SERP-1 for use of any one of claims 51-53, 57-58, 60-62, or 64-66, wherein a step of monitoring the circulating level of Tnl in said patient is performed subsequent to said administering step and during the first 24 hours following stent implantation, and wherein, if said circulating level of Tnl exceeds 0.40 ng/ml, said administering step is repeated.

68. SERP-1 for use of any one of claims 54-56, 57, 59-61, or 63-66, wherein a step of monitoring the circulating level of CK-MB in said patient is performed subsequent to said administering step and during the first 24 hours following stent implantation, and wherein, if said circulating level of CK-MB exceeds 4.0 ng/ml, said administering step is repeated.

69. SERP-1 for use of any one of claims 51-68, wherein said SERP-1 is administered prior to implantation of said stent in said patient.

70. SERP-1 for use of claim 69, wherein said SERP-1 is administered less than 6 hours prior to implantation of said stent in said patient.

71. SERP-1 for use of claim 69 or 70, wherein SERP-1 is not administered during the first 24 hours following implantation of said stent in said patient.

72. SERP-1 for use of any one of claims 51-71, wherein said SERP-1 is administered once about every 24 hours.

73. SERP-1 for use of claim 72, wherein said SERP-1 is administered once about every 24 hours for three days.

74. SERP-1 for use of any one of claims 51-73, wherein said stent is a bare metal stent.

75. SERP-1 for use of any one of claims 51-73, wherein said stent is a drug-eluting stent.

76. SERP-1 for use of any one of claims 51-75, wherein said SERP-1 is administered intravenously.

77. SERP-1 for use of any one of claims 51-76, wherein said SERP-1 comprises an amino acid sequence that is at least 90% identical to amino acids 16-369 of SEQ ID NO: 2.

78. SERP-1 for use of claim 77, wherein said SERP-1 comprises an amino acid sequence that is at least 95% identical to amino acids 16-369 of SEQ ID NO: 2.

79. SERP-1 for use of claim 78, wherein said SERP-1 comprises amino acids 16-369 of SEQ ID NO: 2.

80. SERP-1 for use of claim 77, wherein the amino acid sequence of said SERP- 1 consists of an amino acid sequence that is at least 90% identical to amino acids 16-369 of SEQ ID NO: 2.

81. SERP-1 for use of claim 80, wherein the amino acid sequence of said SERP-1 consists of an amino acid sequence that is at least 95% identical to amino acids 16-369 of SEQ ID NO: 2.

82. SERP-1 for use of claim 81, wherein the amino acid sequence of said SERP-1 consists of amino acids 16-369 of SEQ ID NO: 2.

83. SERP-1 for use of any one of claims 51-82, wherein said SERP-1 is encoded by a nucleic acid molecule that hybridizes under high stringency conditions to at least a portion of a nucleic acid molecule comprising SEQ ID NO: 1.

84. SERP-1 for use of any one of claims 51-83, wherein said SERP-1 is at least 90% pure.

85. SERP-1 for use of claim 84, wherein said SERP-1 is at least 99% pure.

86. SERP-1 for use of any one of claims 51-85, wherein said SERP-1 is glycosylated.

87. SERP-1 for use of any one of claims 51-86, wherein said patient is human.

88. SERP-1 for use of any one of claims 51-87, wherein said method reduces the likelihood of occurrence of a major adverse cardiac event (MACE) for the first 6 months following implantation of said stent in said patient.

89. SERP-1 for use of claim 88, wherein said method reduces the likelihood of occurrence of a MACE in said patient by at least 25%.

90. SERP-1 for use of claim 88 or 89, wherein said MACE is cardiovascular death.

91. SERP-1 for use of claim 88 or 89, wherein said MACE is

myocardial infarction.

92. SERP-1 for use of claim 88 or 89, wherein said MACE is target lesion revascularization.

93. SERP-1 for use of claim 92, wherein said target lesion

revascularization comprises percutaneous coronary intervention.

94. SERP-1 for use of claim 88 or 89, wherein said MACE is coronary artery bypass graft (CABG).

95. SERP-1 for use of any of claims 51-94, wherein said SERP-1 is formulated in a pharmaceutical composition comprising a pharmaceutically acceptable excipient.

96. SERP-1 for use in a method of preventing the circulating level of Troponin I (Tnl) in a patient receiving a cardiac stent implant from exceeding a threshold of 0.5 ng/ml for the first 24 hours following implantation of said stent in said patient, wherein said method comprises administering a first dosage of SERP-1 to said patient prior to implantation of said stent in an amount sufficient to prevent said circulating level of Tnl from exceeding said threshold.

97. SERP-1 for use of claim 96, wherein said method further comprises monitoring the circulating level of Tnl in said patient.

98. SERP-1 for use in a method of achieving an exposure of SERP-1 in a patient receiving a cardiac stent implant of at least 8.5 ng*h/ml during the first 24 hours following implantation of said stent in said patient, wherein said method comprises administering a first dosage of SERP-1 to said patient prior

to implantation of said stent in an amount sufficient to achieve said exposure of SERP-1.

99. SERP-1 for use of claim 98, wherein said method further comprises monitoring the circulating level of Tnl in said patient.

100. SERP-1 for use in a method of treating a patient receiving a cardiac stent implant, wherein said method comprises administering a first dosage of SERP-1 to said patient prior to implantation of said stent in an amount of greater than 5 g/kg/day within 24 hours of implantation of said stent in said patient.

101. SERP-1 for use of claim 100, wherein said method further comprises monitoring the circulating level of Tnl in said patient.

102. SERP-1 for use of any one of claims 96-101, wherein said method reduces the likelihood of occurrence of a major adverse cardiac event (MACE) for the first 6 months following implantation of said stent in said patient.

103. SERP-1 for use of any one of claims 96-102, wherein said method further comprises administering a second dosage of said SERP- 1 to said patient after 24 hours following implantation of said stent in said patient.