SOLUBLE ErbB3 AND TREATMENT OF CANCER

• US 20080267961A1
• Filed: 06/23/2008
• Published: 10/30/2008
• Est. Priority Date: 05/31/2001
• Status: Active Grant

• Current Assignee: Tumor Biology Investment Group, Inc.
• Original Assignee: Tumor Biology Investment Group, Inc.
• Inventors: Lee, Hakjoo, Maihle, Nita J.
• Granted Patent: US 7,745,398 B2
• Time in Patent Office: Days
• US Class Current: 424/133.1
• CPC Class Codes: A61K 38/179 for growth factors; for growth regulators
• CPC Class Codes: A61P 31/00 Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
• CPC Class Codes: C07K 14/71 for growth factors; for growth regulators
• CPC Class Codes: C12N 15/1135 against oncogenes or tumor suppressor genes
• CPC Class Codes: C12N 2310/14 interfering N.A.
• CPC Class Codes: C12Q 1/6886 for cancer immunoassay for cancer G01N33/574
• CPC Class Codes: C12Q 2600/106 Pharmacogenomics, i.e. genetic variability in individual responses to drugs and drug metabolism
• CPC Class Codes: C12Q 2600/136 Screening for pharmacological compounds
• CPC Class Codes: G01N 2333/71 for growth factors; for growth regulators
• CPC Class Codes: G01N 2333/9121 with an alcohol group as acceptor (2.7.1), e.g. general tyrosine, serine or threonine kinases
• CPC Class Codes: G01N 2800/50 Determining the risk of developing a disease
• CPC Class Codes: G01N 2800/52 Predicting or monitoring the response to treatment, e.g. for selection of therapy based on assay results in personalised medicine; Prognosis
• CPC Class Codes: G01N 2800/54 Determining the risk of relapse
• CPC Class Codes: G01N 2800/56 Staging of a disease; Further complications associated with the disease
• CPC Class Codes: G01N 33/54306 Solid-phase reaction mechanisms
• CPC Class Codes: G01N 33/57407 Specifically defined cancers
• CPC Class Codes: G01N 33/57415 of breast
• CPC Class Codes: G01N 33/57434 of prostate
• CPC Class Codes: G01N 33/6872 Intracellular protein regulatory factors and their receptors, e.g. including ion channels

Abstract

Regulation of sErbB3 isoforms in methods of regulating heregulin activity or ErbB receptor activities is disclosed. Cancer therapeutics and methods of therapeutically treating cancer comprising sErbB3 are also disclosed. Detection of sErbB3 in biological samples for risk assessment and prevention, screening, diagnosis, prognosis, theragnosis, evaluation of responsiveness to treatment, and/or monitoring of disease progression, recurrence, or metastasis of a cancer is disclosed as well. In examples, sErbB3 nucleic acid sequences, polypeptides, molecular probes, and antibodies are useful agents for regulation, expression, detection, and cancer therapeutics related to sErbB3.

Claims

1. A method for regulating heregulin activity, said method comprising administering an effective amount of an sErbB3 agent.

2. The method of claim 1 wherein said regulating is upregulating.

3. The method of claim 1 wherein said regulating is downregulating.

4. The method of claim 1 wherein said sErbB3 agent comprises a polypeptide.

5. The method of claim 1 wherein said sErbB3 agent comprises a nucleic acid sequence.

6. The method of claim 1 wherein said sErbB3 agent comprises p85-sErbB3 or p45-sErbB3.

7. The method of claim 4 wherein said polypeptide consists essentially of SEQ ID NO:

2 or SEQ ID NO;

4.

8. The method of claim 5 wherein said nucleic acid sequence consists essentially of SEQ ID NO:

1 or SEQ ID NO;

3.

9. The method of claim 5 wherein the nucleic acid sequence is complementary to SEQ ID NO:

1 or SEQ ID NO;

3.

10. The method of claim 5 wherein the nucleic acid sequence is used for an RNAi mechanism.

11. The method of claim 5 wherein said sequence comprises a sense sequence or an antisense sequence.

12. The method of claim 1 wherein said sErbB3 agent comprises an expression vector, said expression vector comprising a promoter operably linked to a sequence for regulation or expression of an sErbB3.

13. The method of claim 12 wherein said vector is a plasmid or a virus.

14. The method of claim 12 wherein said promoter is inducible.

15. The method of claim 12 wherein said promoter is cell-type or tissue specific.

16. The method of claim 12 wherein said promoter is heterologous.

17. The method of claim 12 wherein said vector is inducible.

18. The method of claim 12 wherein said vector is suitable for in vivo gene therapy.

19. The method of claim 12 wherein said vector is suitable for ex vivo gene therapy.

20. The method of claim 1, wherein said sErbB3 agent comprises a lipid-based vehicle.

21. The method of claim 1, wherein said sErbB3 agent comprises a polymer-based carrier.

22. The method of claim 1 wherein said sErbB3 agent is an antibody that specifically binds an sErbB3.

23. The method of claim 22 wherein said antibody is polyclonal.

24. The method of claim 22 wherein said antibody is monoclonal.

25. The method of claim 22 wherein said antibody is humanized.

26. The method of claim 22 wherein said antibody is human.

27. The method of claim 22 wherein said antibody specifically binds p85-sErbB3 or p45-sErbB3.

28. The method of claim 22 wherein said antibody specifically binds p85-sErbB3 at its unique carboxy terminal sequence of amino acids:

Ser Lys Gly Ser Gln Ser Arg Met Gly Gly Gly Gly Ala Leu Gln Trp Asn Cys Ser Gly Gly Ile Gln.

29. The method of claim 1 wherein said sErbB3 agent is a polypeptide agonist or antagonist of an sErbB3 expression or activity.

30. The method of claim 1 wherein said sErbB3 agent is a small molecule that increases or decreases expression or activity of an sErbB3.

31. A method for regulating an activity of an ErbB receptor, the method comprising administering an effective amount of an sErbB3 agent.

32. The method of claim 31 wherein said ErbB receptor is selected from the group consisting of ErbB2, ErbB3, and ErbB4.

33. The method of claim 31 wherein said regulating is upregulating.

34. The method of claim 31 wherein said regulating is downregulating.

35. The method claim 31 wherein said sErbB3 agent comprises a polypeptide.

36. The method of claim 31 wherein said sErbB3 agent comprises a nucleic acid sequence.

37. The method of claim 31 wherein said sErbB3 agent comprises p85-sErbB3 or p45-sErbB3.

38. The method of claim 35 wherein said polypeptide consists essentially of SEQ ID NO:

2 or SEQ ID NO;

4.

39. The method of claim 36 wherein said nucleic acid sequence consists essentially of SEQ ID NO:

1 or SEQ ID NO;

3.

40. The method of claim 36 wherein said nucleic acid sequence is complementary to SEQ ID NO:

1 or SEQ ID NO;

3.

41. The method of claim 36 wherein said sequence is used for an RNAi mechanism.

42. The method of claim 36 wherein said sequence comprises a sense sequence or an antisense sequence.

43. The method of claim 31 wherein said sErbB3 agent comprises an expression vector, said expression vector comprising a promoter operably linked to a sequence for regulation or expression of an sErbB3.

44. The method of claim 43 wherein said vector is a plasmid or a virus.

45. The method of claim 43 wherein said promoter is inducible.

46. The method of claim 43 wherein said promoter is cell-type or tissue specific.

47. The method of claim 43 wherein said promoter is heterologous.

48. The method of claim 43 wherein said vector is inducible.

49. The method of claim 43 wherein said vector is suitable for in vivo gene therapy.

50. The method of claim 43 wherein said vector is suitable for ex vivo gene therapy.

51. The method of claim 31 wherein said sErbB3 agent comprises a lipid-based vehicle.

52. The method of claim 31 wherein said sErbB3 agent comprises a polymer-based carrier.

53. The method of claim 31 wherein said sErbB3 agent is an antibody which specifically binds an sErbB3.

54. The method of claim 53 wherein said antibody is polyclonal.

55. The method of claim 53 wherein said antibody is monoclonal.

56. The method of claim 53 wherein said antibody is humanized.

57. The method of claim 53 wherein said antibody is human.

58. The method of claim 53 wherein said antibody specifically binds p85-sErbB3 or p45-sErbB3.

59. The method of claim 53 wherein said antibody specifically binds p85-sErbB3 at its carboxy terminal sequence of amino acids:

Ser Lys Gly Ser Gln Ser Arg Met Gly Gly Gly Gly Ala Leu Gln Trp Asn Cys Ser Gly Gly Ile Gln.

60. The method of claim 31 wherein said sErbB3 agent is a polypeptide agonist or antagonist of an sErbB3 expression or activity.

61. The method of claim 31 wherein said sErbB3 agent is a small molecule that increases or decreases expression or activity of an sErbB3.

62. A method for therapeutically treating a cancer in a subject, the method comprising administering an effective amount of an sErbB3 agent.

63. The method of claim 62 wherein the subject is a human.

64. The method of claim 62 wherein said cancer is a carcinoma or a glioma.

65. The method of claim 62 wherein said cancer is at least one of breast, ovarian, colon, lung, prostate, skin, pancreatic, and thyroid.

66. The method of claim 62 wherein said cancer is breast.

67. The method of claim 62 wherein said cancer is prostate.

68. The method of claim 62 wherein said cancer is regulated by heregulin signaling.

69. The method of claim 68 wherein said heregulin signaling is increased or decreased activity.

70. The method of claim 62 wherein said cancer is regulated, in part, by an ErbB activity.

71. The method of claim 70 wherein said ErbB is selected from the group consisting of ErbB2, ErbB3, and ErbB4.

72. The method of claim 70 wherein said ErbB activity is increased or decreased activity.

73. The method of claim 62 wherein said effective amount is sufficient to substantially reduce or prevent at least one of carcinoma cell growth and metastasis.

74. The method claim 62 wherein said sErbB3 agent comprises a polypeptide.

75. The method of claim 62 wherein said sErbB3 agent comprises a nucleic acid sequence.

76. The method of claim 62 wherein said sErbB3 agent comprises p85-sErbB3 or p45-sErbB3.

77. The method of claim 74 wherein said polypeptide consists essentially of SEQ ID NO:

2 or SEQ ID NO;

4.

78. The method of claim 75 wherein said nucleic acid sequence consists essentially of SEQ ID NO:

1 or SEQ ID NO;

3.

79. The method of claim 75 wherein said nucleic acid sequence is complementary to SEQ ID NO:

1 or SEQ ID NO;

3.

80. The method of claim 75 wherein said sequence is used for an RNAi mechanism.

81. The method of claim 75 wherein said sequence comprises a sense sequence or an antisense sequence.

82. The method of claim 62 wherein said sErbB3 agent comprises an expression vector, said expression vector comprising a promoter operably linked to a sequence for regulation or expression of an sErbB3.

83. The method of claim 82 wherein said vector is a plasmid or a virus.

84. The method of claim 82 wherein said promoter is inducible.

85. The method of claim 82 wherein said promoter is cell or tissue specific.

86. The method of claim 82 wherein said promoter is heterologous.

87. The method of claim 82 wherein said vector is inducible.

88. The method of claim 82 wherein said vector is suitable for in vivo gene therapy.

89. The method of claim 82 wherein said vector is suitable for ex vivo gene therapy.

90. The method of claim 62 wherein said sErbB3 agent comprises a lipid-based vehicle.

91. The method of claim 62 wherein said sErbB3 agent comprises a polymer-based carrier.

92. The method of claim 62 wherein said sErbB3 agent is an antibody which specifically binds an sErbB3.

93. The method of claim 92 wherein said antibody is polyclonal.

94. The method of claim 92 wherein said antibody is monoclonal.

95. The method of claim 92 wherein said antibody is humanized.

96. The method of claim 92 wherein said antibody is human.

97. The method of claim 92 wherein said antibody specifically binds p85-sErbB3 or p45-sErbB3.

98. The method of claim 92 wherein said antibody specifically binds p85-sErbB3 at its carboxy terminal sequence of amino acids:

Ser Lys Gly Ser Gln Ser Arg Met Gly Gly Gly Gly Ala Leu Gln Trp Asn Cys Ser Gly Gly Ile Gln.

99. The method of claim 62 wherein said sErbB3 agent is a polypeptide agonist or antagonist of an sErbB3 expression or activity.

100. The method of claim 62 wherein said sErbB3 agent is a small molecule that increases or decreases expression or activity of an sErbB3.

101. A therapeutic composition for a cancer in a subject, said therapeutic composition comprising an effective amount of an sErbB3 agent.

102. The therapeutic composition of claim 101 wherein said subject is a human.

103. The therapeutic composition of claim 101 wherein said cancer is a carcinoma or a glioma.

104. The therapeutic composition of claim 101 wherein said cancer is at least one of breast, ovarian, colon, lung, prostate, skin, pancreatic, and thyroid.

105. The therapeutic composition of claim 101 wherein said cancer is breast.

106. The therapeutic composition of claim 101 wherein said cancer is prostate.

107. The therapeutic composition of claim 101 wherein said cancer is regulated by heregulin signaling.

108. The therapeutic composition of claim 107 wherein said heregulin signaling is increased or decreased activity.

109. The therapeutic composition of claim 101 wherein said cancer is regulated, in part, by an ErbB activity.

110. The therapeutic composition of claim 109 wherein said ErbB is selected from the group consisting of ErbB2, ErbB3, and ErbB4.

111. The therapeutic composition of claim 109 wherein said ErbB activity is increased or decreased ErbB activity.

112. The therapeutic composition of claim 101 wherein said effective amount is sufficient to substantially reduce or prevent at least one of carcinoma cell growth and metastasis in at least one dose.

113. The therapeutic composition claim 101 wherein said sErbB3 agent comprises a polypeptide.

114. The therapeutic composition of claim 101 wherein said sErbB3 agent comprises a nucleic acid sequence.

115. The therapeutic composition of claim 101 wherein said sErbB3 agent comprises p85-sErbB3 or p45-sErbB3.

116. The therapeutic composition of claim 113 wherein the polypeptide consists essentially of SEQ ID NO:

2 or SEQ ID NO;

4.

117. The therapeutic composition of claim 114 wherein said nucleic acid sequence consists essentially of SEQ ID NO:

1 or SEQ ID NO;

3.

118. The therapeutic composition of claim 114 wherein said nucleic acid sequence is complementary to SEQ ID NO:

1 or SEQ ID NO;

3.

119. The therapeutic composition of claim 114 wherein said sequence is used for an RNAi mechanism.

120. The therapeutic composition of claim 114 wherein said sequence comprises a sense sequence or an antisense sequence.

121. The therapeutic composition of claim 101 wherein said sErbB3 agent comprises an expression vector, said expression vector comprising a promoter operably linked to a sequence for regulation or expression of an sErbB3.

122. The therapeutic composition of claim 121 wherein said vector is a plasmid or a virus.

123. The therapeutic composition of claim 121 wherein said promoter is inducible.

124. The therapeutic composition of claim 121 wherein said promoter is cell or tissue specific.

125. The therapeutic composition of claim 121 wherein said promoter is heterologous.

126. The therapeutic composition of claim 121 wherein said vector is inducible.

127. The therapeutic composition of claim 121 wherein said vector is suitable for in vivo gene therapy.

128. The therapeutic composition of claim 121 wherein said vector is suitable for ex vivo gene therapy.

129. The therapeutic composition of claim 101 wherein said sErbB3 agent comprises a lipid-based vehicle.

130. The therapeutic composition of claim 101 wherein said sErbB3 agent comprises a polymer-based carrier.

131. The therapeutic composition of claim 101 wherein said sErbB3 agent is an antibody which specifically binds an sErbB3.

132. The therapeutic composition of claim 131 wherein said antibody is polyclonal.

133. The therapeutic composition of claim 131 wherein said antibody is monoclonal.

134. The therapeutic composition of claim 131 wherein said antibody is humanized.

135. The therapeutic composition of claim 131 wherein said antibody is human.

136. The therapeutic composition of claim 131 wherein said antibody specifically binds p85-sErbB3 or p45-sErbB3.

137. The therapeutic composition of claim 131 wherein said antibody specifically binds p85-sErbB3 at its carboxy terminal sequence of amino acids:

Ser Lys Gly Ser Gln Ser Arg Met Gly Gly Gly Gly Ala Leu Gln Trp Asn Cys Ser Gly Gly Ile Gln

138. The therapeutic composition of claim 131 wherein said antibody is conjugated to a therapeutic agent or drug moiety.

139. The therapeutic composition of claim 101 wherein said sErbB3 agent is a polypeptide agonist or antagonist of an sErbB3 expression or activity.

140. The therapeutic composition of claim 101 wherein said sErbB3 agent is a small molecule that increases or decreases expression or activity of an sErbB3.

141. The therapeutic composition of claim 101 further comprising at least one of pharmaceutically acceptable excipients, adjuvants, carriers, and diluents.

142. A kit comprising at least one dosage of a composition comprising an effective amount of an sErbB3 agent and an informational material.

143. The kit of claim 142 wherein said composition is a therapeutic further comprising at least one of pharmaceutically acceptable excipients, adjuvants, carriers, and diluents.