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1. (WO2019067984) COMPOSITIONS CIBLANT DES MACROPHAGES ASSOCIÉS À UNE TUMEUR ET LEURS MÉTHODES D'UTILISATION
Note: Texte fondé sur des processus automatiques de reconnaissance optique de caractères. Seule la version PDF a une valeur juridique

CLAIMS

What is claimed is:

1. An isolated peptide or peptidorn rnetic comprising the amino acid sequence

CSPGAK (SEQ ID NO: 6),

2. The isolated peptide or peptidornirnetic of claim 1, comprising the amino acid sequence CSPGAKVRC (SEQ ID NO: 1).

3. The isolated peptide or peptidornirnetic of claim 1 or 2, wherein the peptide is conformati onally con strained ,

4. The isolated peptide or peptidornirnetic of any one of claims 1-3, wherein the peptide is cyclic.

5. The isolated peptide or peptidornirnetic of any one of claims 1-2, wherein the peptide is linear.

6. The isolated peptide or peptidornirnetic of any one of claims 1-5, wherein the peptide is a modified peptide.

7. The isolated peptide or peptidornirnetic of any one of claims 1-6, wherein the peptide is a methylated peptide.

8. The isolated peptide or peptidornirnetic of any one of claims 1-7, wherein the peptide comprises a methylated ammo acid segment.

9. The isolated peptide or peptidornirnetic of any one of claims 1-8, wherein the peptide is N- or C-methylated in at least one position.

10. The isolated peptide or peptidornirnetic of any one of claims 1-9, which has a length of no more than 100 amino acid residues.

11. The isolated peptide or peptidornirnetic of any one of claims 1-9, which has a length of no more than 50 amino acid residues.

12. The isolated peptide or peptidornirnetic of any one of claims 1-9, which has a length of no more than 20 amino acid residues.

13. The isolated peptide or peptidornirnetic of any one of claims 1-9, which has a length of no more than 15 amino acid residues.

14. The isolated peptide or peptidornirnetic of any one of claims 1-9, which has a length of no more than 10 amino acid residues.

15. A composition comprising any one of claims 1-14.

16. The composition of claim 15, wherein the composition selectively homes to tumor tissue.

17. The composition of claim 15, wherein the composition selectively homes to

MRC1 -expressing tumor-associated macrophages (MEMs).

18. The composition of any one of claims 15-17, wherein the composition further comprises a detectable agent.

19. The composition of claim 18, wherein the detectable agent is a fluorescent molecule or a radionuclide.

20. The composition of claim 18, wherein the detectable agent is linked to the isolated peptide or peptidomimetic.

21. The composition of any one of claims 18-20, wherein the detectable agent is Feridex, a tantalum compound, iodine, radioactive iodine, an organic iodo acid, iron oxide, gadolinium, an enzyme, biotin, a metal, barium sulfate, diatrizoic acid sodium salt dehydrate, Lissamine Rhodamine PE, Rhodamine, a radioisotope, a ferromagnetic compound, a paramagnetic compound, a diamagnetic compound, indium- 111, technetium -99, carbon- 11, carbon- 13, or any combination thereof.

22. The composition of any one of claims 15-21 , wherein the composition further comprises a nanoparticle.

23. The composition of claim 22, wherein the nanoparticle is a polymersome.

24. The composition of claim. 23, wherein the polymersome is a polyethylene glycol-pol ycaprolactone pol ymersome .

25. The composition of claim 24, wherein the polyethylene glycol-polycaprolactone polymersome has a diameter of less than 1000 nanometers.

26. The composition of claim 24, wherein the polyethylene glycol-polycaprolactone polymersome has a diameter of less than 500 nanometers.

27. The composition of claim 24, wherein the polyethylene glycol-polycaprolactone polymersome has a diameter of about 120 nanometers.

28. The composition of claim. 24, wherein the isolated peptide or peptidomimetic is coated onto the polyethylene glycol-polycaprolactone polymersome.

29. The composition of any one of claims 24-28, wherein the polyethylene glycol-polycaprolactone polymersome is loaded with a therapeutic agent.

30. The composition of any one of claims 15-28, further comprising a therapeutic agent.

31. The composition of claim 30, wherein the therapeutic agent is linked to the isolated peptide or peptidomimetic.

32. The composition of any one of claims 29-3 i, wherein the therapeutic agent is a therapeutic protein, a therapeutic compound, a therapeutic composition, a chemotherapeutic agent, a cancer chemotherapeutic agent, a radiopharmaceutical, a toxin, a cytotoxic agent, Abraxane, paclitaxel, taxol, imatinib, a virus, a nucleic acid molecule, an antibody, a small interfering RNA, a microRNA, a polypeptide, a peptide, an anti -angiogenic agent, a pro-angiogenic agent, an anti-inflammatory agent, a TGF-β inhibitor, a β-2 agonist, an endothelin (ET- 1 ) receptor antagonist, interferon-o and tasquinimod, or any combination thereof.

33. A method for directing a moiety to a MRC1 -expressing tumor associated macrophage in a subject, comprising administering to the subject a composition comprising the moiety linked to an isolated peptide or peptidomimetic comprising the amino acid sequence CSPGAK (SEQ ID NO: 6} or a peptidomimetic thereof.

34. The method of claim 33, wherein the isolated peptide or peptidomimetic comprises the amino acid sequence CSPGAKVRC (SEQ ID NO: 1) or a peptidomimetic thereof.

35. The method of claim 33 or 34, wherein the peptide is conformationally constrained.

36. The method of any one of claims 33-35, wherein the peptide is cyclic.

37. The method of any one of claims 33-34, wherein the peptide is linear.

38. The method of any one of claims 33-37, wherein the peptide is a modified peptide.

39. The method of any one of claims 33-38, wherein the peptide is a methylated peptide.

40. The method of any one of claims 33-39, wherein the peptide comprises a methylated amino acid segment.

41. The method of any one of claims 33-40, wherein the peptide is N- or C -methylated in at least one position.

42. The method of any one of claims 33-41 , wherein the peptide or peptidomimetic has a length of no more than 100 amino acid residues.

43. The method of any one of claims 33-41, wherein the peptide or peptidomimetic has a length of no more than 50 amino acid residues.

44. The method of any one of claims 33-41, wherein the peptide or peptidomimetic has a length of no more than 20 amino acid residues.

45. The method of any one of claims 33-41, wherein the peptide or peptidomimetic has a length of no more than 15 amino acid residues.

46. The method of any one of claims 33-41 , wherein the peptide or peptidomimetic has a length of no more than 10 amino acid residues.

47. The method of any one of claims 33-46, wherein the moiety comprises a detectable agent.

48. The method of claim. 47, wherein the detectable agent is a fluorescent molecule or a radionuclide.

49. The method of claim 47 or 48, wherein the detectable agent is linked to the isolated peptide or peptidomimetic.

50. The method of any one of claims 47-49, wherein the detectable agent is Feridex, a tantalum compound, iodine, radioactive iodine, an organic iodo acid, iron oxide, gadolinium, an enzyme, biotin, a metal, barium sulfate, diatrizoic acid sodium salt dehydrate, Lissamine Rhodamine PE, Rhodamine, a radioisotope, a ferromagnetic compound, a paramagnetic compound, a diamagnetic compound, indium- 111, technetium -99, carbon- 11, carbon- 13, or any combination thereof.

51. The method of any one of claims 33-50, wherein the moiety further comprises a nanoparticle.

52. The method of claim. 51 , wherein the nanoparticle is a polymersome.

53. The method of claim 52, wherein the polymersome is a polyethylene glycol -poly caprolac tone polymersome.

54. The method of claim 53, wherein the polyethy lene glycol -polycaprolactone polymersome has a diameter of less than 1000 nanometers.

55. The method of claim 53, wherein the polyethylene glycol-polycaprolactone polymersome has a diameter of less than 500 nanometers.

56. The method of claim 53, wherein the polyethylene glycol-polycaprolactone polymersome has a diameter of about 120 nanometers.

57. The method of claim 53, wherein the isolated peptide or peptidomimetic is coated onto the polyethylene glycol-polycaprolactone polymersome.

58. The method of any one of claims 53-57, wherein the polyethylene glycol-polycaprolactone polymersome is loaded with a therapeutic agent.

59. The method of any one of claims 33-58, wherein the moiety comprises a therapeutic agent.

60. The method of claim 59, wherein the therapeutic agent is linked to the isolated peptide or peptidomimetic.

61 . The method of any one of claims 58-60, wherein the therapeutic agent is a therapeutic protein, a therapeutic compound, a therapeutic composition, a chemotherapeutic agent, a cancer chemotherapeutic agent, a radiopharmaceutical, a toxin, a cytotoxic agent, Abraxane, paclitaxel, taxoi, imatinib, a virus, a nucleic acid molecule, an antibody, a small interfering RNA, a microRNA, a polypeptide, a peptide, an anti -angiogenic agent, a pro-angiogenic agent, an anti-inflammatory agent, a TGF-β inhibitor, a β-2 agoni st, an endothelin (ET- 1 ) receptor antagonist, interferon-*? and tasquinimod, or any combination thereof.

62. The method of any one of claims 33-61, wherein the composition is administered intravenously, intraperitoneally, intramuscularly, subcutaneously, intracavitarally, or transdemiaily.

63. A method of diagnosing a subject with a disease or disorder comprising

administering to the subject a composition comprising a detectable agent linked to an

isolated peptide or peptidomimetic comprising the amino acid sequence CSPGAK (SEQ

ID NO: 6) or a peptidomimetic thereof.

64. The method of claim 63, wherein the isolated peptide or peptidomimetic comprises the amino acid sequence CSPGAKVRC (SEQ ID NO: 1) or a peptidomimetic thereof.

65. The method of claim 63 or 64, wherein the peptide is conformational^ constrained.

66. The method of any one of claims 63-65, wherein the peptide is cyclic.

67. The method of any one of claims 63-64, wherein the peptide is linear.

68. The method of any one of claims 63-67, wherein the peptide is a modified peptide.

69. The method of any one of claims 63-68, wherein the peptide is a methylated peptide.

70. The method of any one of claims 63-69, wherein the peptide comprises a methylated amino acid segment.

71. The method of any one of claims 63-70, wherein the peptide is N- or C-methylated in at least one position.

72. The method of any one of claims 63-71 , wherein the peptide or peptidomimetic has a length of no more than 100 amino acid residues.

73. The method of any one of claims 63-71, wherein the peptide or peptidomimetic has a length of no more than 50 amino acid residues.

74. The method of any one of claims 63-71, wherein the peptide or peptidomimetic has a length of no more than 20 amino acid residues.

75. The method of any one of claims 63-71, wherein the peptide or peptidomimetic has a length of no more than 15 amino acid residues.

76. The method of any one of claims 63-71 , wherein the peptide or peptidomimetic has a length of no more than 10 amino acid residues.

77. The method of any one of claims 63-76, wherein the detectable agent is a fluorescent molecule or a radionuclide.

78. The method of claim 77, wherein the detectable agent is linked to the isolated peptide or peptidomimetic.

79. The method of any one of claims 77-78, wherein the detectable agent is Feridex, a tantalum compound, iodine, radioactive iodine, an organic iodo acid, iron oxide, gadolinium, an enzyme, biotin, a metal, barium sulfate, diatrizoic acid sodium salt dehydrate, Lissamme Rhodamine PE, Rhodamine, a radioisotope, a ferromagnetic compound, a paramagnetic compound, a diamagnetic compound, indium- 1 11, technetium-99, carbon- 11, carbon- 13, or any combination thereof.

80. The method of any one of claims 63-79, wherein the composition further comprises a nanoparticle.

81 . The method of claim 80, wherein the nanoparticle is a polymersome.

82. The method of claim 81, wherein the polymersome is a polyethylene glycol -poly cap rolactone polymersome .

83. The method of claim 82, wherein the polyethylene glycol -polycaprolactone polymersome has a diameter of less than 1000 nanometers.

84. The method of claim 82, wherein the polyethylene glycol-polycaprolactone polymersome has a diameter of less than 500 nanometers.

85. The method of claim 82, wherein the polyethylene glycol-polycaprolactone polymersome has a diameter of about 120 nanometers.

86. The method of claim 82, wherein the isolated peptide or peptidomimetic is coated onto the polyethylene glycol-polycaprolactone polymersome.

87. The method of any one of claims 63-86, wherein the disease or disorder is

cancer, an inflammatory disorder, or an autoimmune disease.

88. The method of any one of claims 63-87, wherein the composition is administered intravenously, intraperitoneally, intramuscularly, subcutaneous!}', intracavitarally, or transdermal!}'.

89. A method of treating a subject with a disease or disorder comprising

administering to the subject a composition comprising a therapeutic agent linked to an

isolated peptide or peptidomimetic comprising the amino acid sequence CSPGAK

(SEQ ID NO: 6) or a peptidomimetic thereof.

90. The method of claim 89, wherein the isolated peptide or peptidomimetic comprises the amino acid sequence CSPGAKVRC (SEQ ID NO: 1) or a peptidomimetic thereof.

91. The method of claim 89 or 90, wherein the peptide is conformationally constrained.

92. The method of any one of claims 89-91 , wherein the peptide is cyclic.

93. The method of any one of claims 89-90, wherein the peptide is linear.

94. The method of any one of claims 89-93, wherein the peptide is a modified peptide.

95. The method of any one of claims 89-94, wherein the peptide is a methylated peptide.

96. The method of any one of claims 89-95, wherein the peptide comprises a methylated amino acid segment.

97. The method of any one of claims 89-96, wherein the peptide is N- or C -methylated in at least one position.

98. The method of any one of claims 89-97, wherein the peptide or peptidomimetic has a length of no more than 100 amino acid residues.

99. The method of any one of claims 89-97, wherein the peptide or peptidomimetic has a length of no more than 50 amino acid residues.

100. The method of any one of claims 89-97, wherein the peptide or peptidomimetic has a length of no more than 20 amino acid residues.

101. The method of any one of claims 89-97, wherein the peptide or peptidomimetic has a length of no more than 1 amino acid residues.

102. The method of any one of claims 89-97, wherein the peptide or peptidomimetic has a length of no more than 10 amino acid residues.

103. The method of any one of claims 89-102, wherein the composition further

comprises a nanoparticle.

104. The method of claim. 103, w herein the nanoparticle is a polymersome.

105. The method of claim 104, wherein the polymersome is a polyethylene glycol -pol ycaprolactone pol ymersome .

106. The method of claim 105, wherein the polyethylene glycol -poly caprolactone

polymersome has a diameter of less than 1000 nanometers.

107. The method of claim 105, wherein the polyethylene glycol -polycaprolactone

polymersome has a diameter of less than 500 nanometers.

108. The method of claim 105, wherein the polyethylene glycol -polycaprolactone

polymersome has a diameter of about 120 nanometers.

109. The method of claim 105, wherein the isolated peptide or peptidomimetic is coated onto the polyethylene glycol -polycaprolactone polymersome.

110. The method of any one of claims 105-109, wherein the polyethylene glycol-polycaprolactone polymersome is loaded with the therapeutic agent.

1 1 1 . The method of any one of claims 89-1 10, wherein the therapeutic agent is a therapeutic protein, a therapeutic compound, a therapeutic composition, a chemotherapeutic agent, a cancer chemotherapeutic agent, a radiopharmaceutical, a toxin, a cytotoxic agent, Abraxane, paciitaxei, taxoi, imatinib, a virus, a nucleic acid molecule, an antibody, a small interfering RNA, a microRNA, a polypeptide, a peptide, an anti -angiogenic agent, a pro-angiogenic agent, an anti-inflammatory agent, a TGF-β inhibitor, a β-2 agoni st, an endothelin (ET- 1 ) receptor antagonist, interferon-*? and tasquinimod, or any combination thereof.

112. The method of any one of claims 89-111, wherein the disease or disorder is

cancer, an inflammatory disorder, or an autoimmune disease .

113. The method of any one of claims 89-1 12, wherein the composition is administered intravenously, intraperitoneally, intramuscularly, subcutaneously, intracavitarally, or transdermals.