Compositions as adjuvants to improve immune responses to vaccines and methods of use

• US 20050276756A1
• Filed: 03/22/2005
• Published: 12/15/2005
• Est. Priority Date: 03/24/2004
• Status: Abandoned Application

• Current Assignee: Telios Pharmaceuticals, Inc. (Integra LifeSciences Holdings Corporation), Telos Pharmaceuticals LLC
• Original Assignee: Telos Pharmaceuticals LLC
• Inventors: Jensen, Eric R., Helmich, Brian K., Carlo, Dennis J., Thatte, Jayant, Yei, Soonpin, Hoo, William Soo, Moll, Thomas
• Application Number:
  US11/087,177
• Publication Number:
  US 20050276756A1
• Time in Patent Office: Days
• US Class Current: 424/1.490
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: A61K 2039/55516 Proteins; Peptides
• CPC Class Codes: A61K 2039/55561 CpG containing adjuvants; Oligonucleotide containing adjuvants
• CPC Class Codes: A61K 2039/6056 Antibodies
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/704 attached to a condensed carbocyclic ring system, e.g. sennosides, thiocolchicosides, escin, daunorubicin digitoxin A61K31/7048
• CPC Class Codes: A61K 31/7048 having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin , digitoxin or digoxin
• CPC Class Codes: A61K 31/7076 containing purines, e.g. adenosine, adenylic acid
• CPC Class Codes: A61K 33/24 Heavy metals; Compounds thereof
• CPC Class Codes: A61K 33/243 Platinum; Compounds thereof
• CPC Class Codes: A61K 39/385 Haptens or antigens, bound to carriers
• CPC Class Codes: A61K 39/39 characterised by the immunostimulating additives, e.g. chemical adjuvants
• CPC Class Codes: A61K 39/395 Antibodies agglutinins A61K38/36 ; as drug carriers A61K47/50; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61K 47/6849 the antibody targeting a receptor, a cell surface antigen or a cell surface determinant
• CPC Class Codes: A61K 51/00 Preparations containing radioactive substances for use in therapy or testing in vivo
• CPC Class Codes: A61K 51/1039 against T-cell receptors
• CPC Class Codes: A61P 1/04 for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
• CPC Class Codes: A61P 1/16 for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
• CPC Class Codes: A61P 11/06 Antiasthmatics
• CPC Class Codes: A61P 13/12 : of the kidneys
• CPC Class Codes: A61P 15/08 : for gonadal disorders or for enhancing fertility, e.g. inducers of ovulation or of spermatogenesis
• CPC Class Codes: A61P 17/00 : Drugs for dermatological disorders
• CPC Class Codes: A61P 19/02 : for joint disorders, e.g. arthritis, arthrosis
• CPC Class Codes: A61P 19/04 : for non-specific disorders of the connective tissue
• CPC Class Codes: A61P 21/00 : Drugs for disorders of the muscular or neuromuscular system
• CPC Class Codes: A61P 21/04 : for myasthenia gravis
• CPC Class Codes: A61P 25/00 : Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/28 : for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
• CPC Class Codes: A61P 27/02 : Ophthalmic agents
• CPC Class Codes: A61P 29/00 : Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 3/10 : for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 31/00 : Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
• CPC Class Codes: A61P 31/04 : Antibacterial agents
• CPC Class Codes: A61P 31/06 : for tuberculosis
• CPC Class Codes: A61P 31/10 : Antimycotics
• CPC Class Codes: A61P 31/12 : Antivirals
• CPC Class Codes: A61P 31/18 : for HIV
• CPC Class Codes: A61P 31/20 : for DNA viruses
• CPC Class Codes: A61P 33/00 : Antiparasitic agents
• CPC Class Codes: A61P 35/00 : Antineoplastic agents
• CPC Class Codes: A61P 35/02 : specific for leukemia
• CPC Class Codes: A61P 35/04 : specific for metastasis
• CPC Class Codes: A61P 37/00 : Drugs for immunological or allergic disorders
• CPC Class Codes: A61P 37/02 : Immunomodulators
• CPC Class Codes: A61P 37/04 : Immunostimulants
• CPC Class Codes: A61P 37/08 : Antiallergic agents antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14
• CPC Class Codes: A61P 43/00 : Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 5/14 : of the thyroid hormones, e.g. T3, T4
• CPC Class Codes: A61P 7/06 : Antianaemics
• CPC Class Codes: A61P 9/10 : for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
• CPC Class Codes: C07K 16/2803 : against the immunoglobulin superfamily
• CPC Class Codes: C07K 2319/00 : Fusion polypeptide
• CPC Class Codes: C07K 2319/30 : Non-immunoglobulin-derived peptide or protein having an immunoglobulin constant or Fc region, or a fragment thereof, attached thereto

Abstract

The invention provides compositions containing an antigen and a TIM targeting molecule. The invention additionally provides a TIM targeting molecule conjugate, for example, a TIM targeting molecule targeted to a therapeutic or diagnostic moiety. The invention additionally provides methods of using such compositions. In one embodiment, the invention provides a method of stimulating an immune response in an individual by administering a composition comprising an antigen and a TIM targeting molecule in a pharmaceutically acceptable carrier. In another embodiment, the invention provides a method of stimulating an immune response in an individual by administering an antigen and a TIM targeting molecule, which can be administered together in a single composition or separately.

Claims

1. A composition comprising an antigen and a TIM targeting molecule in a pharmaceutically acceptable carrier.

2. The composition of claim 1, wherein said TIM targeting molecule is a TIM antibody.

3. The composition of claim 2, wherein said TIM antibody is specific for a TIM selected from TIM-1, TIM-2, TIM-3 and TIM-4.

4. The composition of claim 1, wherein said TIM targeting molecule is a TIM-Fc fusion polypeptide.

5. The composition of claim 4, wherein the Fc portion of said TIM-Fc fusion polypeptide is target-cell depleting.

6. The composition of claim 4, wherein the Fc portion of said TIM-Fc fusion polypeptide is non target-cell depleting.

7. The composition of claim 4, wherein the TIM portion of said TIM-Fc fusion polypeptide is selected from TIM-1, TIM-2, TIM-3 and TIM-4.

8. The composition of claim 1, wherein said antigen is selected from a viral, bacterial, parasitic, and tumor associated antigen.

9. A composition comprising a TIM targeting molecule conjugated to a therapeutic or diagnostic moiety.

10. The composition of claim 9, wherein the therapeutic moiety is selected from a chemotherapeutic agent, cytotoxic agent and toxin.

11. The composition of claim 10, wherein the cytotoxic agent is a radionuclide or chemical compound.

12. The composition of claim 11, wherein the chemical compound is selected from calicheamicin, esperamicin, duocarmycin, doxorubicin, melphalan, methotrexate, chlorambucil, cytarabine, vindesine, cis-platinum, etoposide, bleomycin, mitomycin C and 5-fluorouracil.

13. The composition of claim 11, wherein the radionuclide is Iodine-131 or Yttrium-90.

14. The composition of claim 10, wherein the toxin is a plant or bacterial toxin.

15. The composition of claim 14, wherein the plant toxin is selected from ricin, abrin, pokeweed antiviral protein, saporin and gelonin.

16. The composition of claim 14, wherein the bacterial toxin is selected from Pseudomonas exotoxin, and diphtheria toxin.

17. The composition of claim 9, wherein said TIM targeting molecule is a TIM antibody.

18. The composition of claim 17, wherein said TIM antibody is specific for a TIM selected from TIM-1, TIM-2, TIM-3 and TIM-4.

19. The composition of claim 9, wherein said TIM targeting molecule is a TIM-Fc fusion polypeptide.

20. The composition of claim 19, wherein the Fc portion of said TIM-Fc fusion polypeptide is target-cell depleting.

21. The composition of claim 19, wherein the Fc portion of said TIM-Fc fusion polypeptide is non target-cell depleting.

22. The composition of claim 19, wherein the TIM portion of said TIM-Fc fusion polypeptide is selected from TIM-1, TIM-2, TIM-3 and TIM-4.

116. The method of claim 14, wherein the bacterial toxin is selected from Pseudomonas exotoxin, and diphtheria toxin.

23. A method of stimulating an immune response in an individual, comprising administering a composition comprising an antigen and a TIM targeting molecule in a pharmaceutically acceptable carrier.

24. The method of claim 23, wherein said TIM targeting molecule is a TIM antibody.

25. The method of claim 24, wherein said TIM antibody is specific for a TIM selected from TIM-1, TIM-2, TIM-3 and TIM-4.

26. The method of claim 23, wherein said TIM targeting molecule is a TIM-Fc fusion polypeptide.

27. The method of claim 26, wherein the TIM portion of said TIM-Fc fusion polypeptide is selected from TIM-1, TIM-2, TIM-3 and TIM-4.

28. The method of claim 23, wherein said antigen is selected from a viral, bacterial, parasitic, and tumor associated antigen.

29. The method of claim 28, wherein said antigen is a peptide.

30. A method of prophylactic treatment of a disease, comprising administering to an individual a composition comprising an antigen and a TIM targeting molecule in a pharmaceutically acceptable carrier.

31. The method of claim 30, wherein said TIM targeting molecule is a TIM antibody.

32. The method of claim 31, wherein said TIM antibody is specific for a TIM selected from TIM-1, TIM-2, TIM-3 and TIM-4.

33. The method of claim 30, wherein said TIM targeting molecule is a TIM-Fc fusion polypeptide.

34. The method of claim 33, wherein the TIM portion of said TIM-Fc fusion polypeptide is selected from TIM-1, TIM-2, TIM-3 and TIM-4.

35. The method of claim 30, wherein the disease is an infectious disease.

36. The method of claim 35, wherein said antigen is selected from a viral, bacterial, and parasitic antigen.

37. The method of claim 30, wherein the disease is cancer.

38. The method of claim 37, wherein said antigen is a tumor associated antigen.

39. A method of ameliorating a sign or symptom associated with a disease, comprising administering to an individual a composition comprising an antigen and a TIM targeting molecule in a pharmaceutically acceptable carrier.

40. The method of claim 39, wherein said TIM targeting molecule is a TIM antibody.

41. The method of claim 39, wherein said TIM antibody is specific for a TIM selected from TIM-1, TIM-2, TIM-3 and TIM-4.

42. The method of claim 39, wherein said TIM targeting molecule is a TIM-Fc fusion polypeptide.

43. The method of claim 42, wherein the TIM portion of said TIM-Fc fusion polypeptide is selected from TIM-1, TIM-2, TIM-3 and TIM-4.

44. The method of claim 39, wherein the disease is an infectious disease.

45. The method of claim 44, wherein said antigen is selected from a viral, bacterial, and parasitic antigen.

46. The method of claim 39, wherein the disease is cancer.

47. The method of claim 46, wherein said antigen is a tumor associated antigen.

48. A method of targeting a tumor, comprising administering a TIM targeting molecule to a subject, wherein said tumor expresses a TIM or TIM ligand.

49. The method of claim 48, wherein said TIM targeting molecule is administered with an antigen.

50. The method of claim 49, wherein said antigen is a tumor associated antigen.

51. The method of claim 48, wherein said TIM targeting molecule is a TIM antibody.

52. The method of claim 51, wherein said TIM antibody is specific for a TIM selected from TIM-1, TIM-2, TIM-3 and TIM-4.

53. The method of claim 48, wherein said TIM targeting molecule is a TIM-Fc fusion polypeptide.

54. The method of claim 53, wherein the Fc portion of said TIM-Fc fusion polypeptide is target-cell depleting.

55. The method of claim 53, wherein the Fc portion of said TIM-Fc fusion polypeptide is non target-cell depleting.

56. The method of claim 53, wherein the TIM portion of said TIM-Fc fusion polypeptide is selected from TIM-1, TIM-2, TIM-3 and TIM-4.

57. The method of claim 48, wherein the tumor is selected from a carcinoma, sarcoma and lymphoma.

58. The method of claim 48, wherein said TIM targeting molecule is conjugated to a therapeutic moiety.

59. The method of claim 58, wherein the therapeutic moiety is selected from a chemotherapeutic agent, cytotoxic agent and toxin.

60. The method of claim 59, wherein the cytotoxic agent is a radionuclide or chemical compound.

61. The method of claim 60, wherein the chemical compound is selected from calicheamicin, esperamicin, duocarmycin, doxorubicin, melphalan, methotrexate, chlorambucil, cytarabine, vindesine, cis-platinum, etoposide, bleomycin, mitomycin C and 5-fluorouracil.

62. The method of claim 60, wherein the radionuclide is Iodine-131 or Yttrium-90.

63. The method of claim 59, wherein the toxin is a plant or bacterial toxin.

64. The method of claim 63, wherein the plant toxin is selected from ricin, abrin, pokeweed antiviral protein, saporin and gelonin.

65. The method of claim 63, wherein the bacterial toxin is selected from Pseudomonas exotoxin, and diphtheria toxin.

66. The method of claim 58, wherein said TIM targeting molecule is a TIM antibody.

67. The method of claim 66, wherein said TIM antibody is specific for a TIM selected from TIM-1, TIM-2, TIM-3 and TIM-4.

68. The method of claim 58, wherein said TIM targeting molecule is a TIM-Fc fusion polypeptide.

69. The method of claim 68, wherein the Fc portion of said TIM-Fc fusion polypeptide is target-cell depleting.

70. The method of claim 68, wherein the Fc portion of said TIM-Fc fusion polypeptide is non target-cell depleting.

71. The method of claim 68, wherein the TIM portion of said TIM-Fc fusion polypeptide is selected from TIM-1, TIM-2, TIM-3 and TIM-4.

72. A method of inhibiting tumor growth, comprising administering a TIM targeting molecule to a subject, wherein said tumor expresses a TIM or TIM ligand.

73. The method of claim 72, wherein said TIM targeting molecule is administered with an antigen.

74. The method of claim 72, wherein said TIM targeting molecule is a TIM antibody.

75. The method of claim 74, wherein said TIM antibody is specific for a TIM selected from TIM-1, TIM-2, TIM-3 and TIM-4.

76. The method of claim 72, wherein said TIM targeting molecule is a TIM-Fc fusion polypeptide.

77. The method of claim 76, wherein the Fc portion of said TIM-Fc fusion polypeptide is target-cell depleting.

78. The method of claim 76, wherein the Fc portion of said TIM-Fc fusion polypeptide is non target-cell depleting.

79. The method of claim 76, wherein the TIM portion of said TIM-Fc fusion polypeptide is selected from TIM-1, TIM-2, TIM-3 and TIM-4.

80. The method of claim 72, wherein the tumor is selected from a carcinoma, sarcoma and lymphoma.

81. The method of claim 72, wherein said TIM targeting molecule is conjugated to a therapeutic moiety.

82. The method of claim 81, wherein the therapeutic moiety is selected from a chemotherapeutic agent, cytotoxic agent and toxin.

83. The method of claim 82, wherein the cytotoxic agent is a radionuclide or chemical compound.

84. The method of claim 83, wherein the chemical compound is selected from calicheamicin, esperamicin, duocarmycin, doxorubicin, melphalan, methotrexate, chlorambucil, cytarabine, vindesine, cis-platinum, etoposide, bleomycin, mitomycin C and 5-fluorouracil.

85. The method of claim 83, wherein the radionuclide is Iodine-131 or Yttrium-90.

86. The method of claim 82, wherein the toxin is a plant or bacterial toxin.

87. The method of claim 86, wherein the plant toxin is selected from ricin, abrin, pokeweed antiviral protein, saporin and gelonin.

88. The method of claim 86, wherein the bacterial toxin is selected from Pseudomonas exotoxin, and diphtheria toxin.

89. The method of claim 81, wherein said TIM targeting molecule is a TIM antibody.

90. The method of claim 89, wherein said TIM antibody is specific for a TIM selected from TIM-1, TIM-2, TIM-3 and TIM-4.

91. The method of claim 81, wherein said TIM targeting molecule is a TIM-Fc fusion polypeptide.

92. The method of claim 91, wherein the Fc portion of said TIM-Fc fusion polypeptide is target-cell depleting.

93. The method of claim 91, wherein the Fc portion of said TIM-Fc fusion polypeptide is non target-cell depleting.

94. The method of claim 91, wherein the TIM portion of said TIM-Fc fusion polypeptide is selected from TIM-1, TIM-2, TIM-3 and TIM-4.

95. A method of detecting a tumor, comprising administering a TIM targeting molecule conjugated to a diagnostic moiety to a subject, wherein said tumor expresses a TIM or TIM ligand.

96. The method of claim 95, wherein said TIM targeting molecule is a TIM antibody.

97. The method of claim 96, wherein said TIM antibody is specific for a TIM selected from TIM-1, TIM-2, TIM-3 and TIM-4.

98. The method of claim 95, wherein said TIM targeting molecule is a TIM-Fc fusion polypeptide.

99. The method of claim 98, wherein the TIM portion of said TIM-Fc fusion polypeptide is selected from TIM-1, TIM-2, TIM-3 and TIM-4.

100. A method of ameliorating a sign or symptom associated with an autoimmune disease, comprising administering a TIM targeting molecule to a subject.

101. The method of claim 100, wherein said autoimmune disease is selected from rheumatoid arthritis, multiple sclerosis, autoimmune diabetes mellitus, systemic lupus erythematosus, and autoimmune lymphoproliferative syndrome (ALPS).

102. The method of claim 100, wherein said TIM targeting molecule is administered with an antigen.

103. The method of claim 100, wherein said TIM targeting molecule is a TIM antibody.

104. The method of claim 103, wherein said TIM antibody is specific for a TIM selected from TIM-1, TIM-2, TIM-3 and TIM-4.

105. The method of claim 100, wherein said TIM targeting molecule is a TIM-Fc fusion polypeptide.

106. The method of claim 105, wherein the Fc portion of said TIM-Fc fusion polypeptide is target-cell depleting.

107. The method of claim 105, wherein the Fc portion of said TIM-Fc fusion polypeptide is non target-cell depleting.

108. The method of claim 105, wherein the TIM portion of said TIM-Fc fusion polypeptide is selected from TIM-1, TIM-2, TIM-3 and TIM-4.

109. The method of claim 100, wherein said TIM targeting molecule is conjugated to a therapeutic moiety.

110. The method of claim 109, wherein the therapeutic moiety is selected from a chemotherapeutic agent, cytotoxic agent and toxin.

111. The method of claim 110, wherein the cytotoxic agent is a radionuclide or chemical compound.

112. The method of claim 111, wherein the chemical compound is selected from calicheamicin, esperamicin, duocarmycin, doxorubicin, melphalan, methotrexate, chlorambucil, cytarabine, vindesine, cis-platinum, etoposide, bleomycin, mitomycin C and 5-fluorouracil.

113. The method of claim 111, wherein the radionuclide is Iodine-131 or Yttrium-90.

114. The method of claim 110, wherein the toxin is a plant or bacterial toxin.

115. The method of claim 114, wherein the plant toxin is selected from ricin, abrin, pokeweed antiviral protein, saporin and gelonin.

117. The method of claim 109, wherein said TIM targeting molecule is a TIM antibody.

118. The method of claim 117, wherein said TIM antibody is specific for a TIM selected from TIM-1, TIM-2, TIM-3 and TIM-4.

119. The method of claim 109, wherein said TIM targeting molecule is a TIM-Fc fusion polypeptide.

120. The method of claim 119, wherein the Fc portion of said TIM-Fc fusion polypeptide is target-cell depleting.

121. The method of claim 119, wherein the Fc portion of said TIM-Fc fusion polypeptide is non target-cell depleting.

122. The method of claim 119, wherein the TIM portion of said TIM-Fc fusion polypeptide is selected from TIM-1, TIM-2, TIM-3 and TIM-4.