Diagnosis of carcinomas

• US 20090104684A1
• Filed: 08/08/2007
• Published: 04/23/2009
• Est. Priority Date: 08/29/2001
• Status: Abandoned Application

• Current Assignee: Pacific Northwest Research Institute
• Original Assignee: Pacific Northwest Research Institute, University of Washington
• Inventors: Schummer, Michel, HELLSTROM, INGEGERD, HAYDEN-LEDBETTER, MARTHA, LEDBETTER, JEFFREY A., Hellstrom, Karl Erik
• Application Number:
  US11/890,896
• Publication Number:
  US 20090104684A1
• Time in Patent Office: Days
• US Class Current: 435/255.100
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: A61P 1/18 for pancreatic disorders, e.g. pancreatic enzymes
• CPC Class Codes: A61P 15/00 Drugs for genital or sexual disorders for disorders of sex hormones A61P5/24; Contraceptives
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 35/02 specific for leukemia
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07K 14/811 Serine protease (E.C. 3.4.21) inhibitors
• CPC Class Codes: C07K 16/18 against material from animals or humans
• CPC Class Codes: C07K 16/30 from tumour cells
• CPC Class Codes: C07K 16/3069 Reproductive system, e.g. ovaria, uterus, testes, prostate
• CPC Class Codes: C07K 16/40 against enzymes
• 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
• CPC Class Codes: G01N 2333/705 Assays involving receptors, cell surface antigens or cell surface determinants
• CPC Class Codes: G01N 33/57449 of ovaries
• CPC Class Codes: G01N 33/57488 involving compounds identifable in body fluids

Abstract

The invention is directed to compositions and methods for the detection of a malignant condition, and relates to the discovery of soluble and cell surface forms of HE4a polypeptides, including HE4a that is overexpressed in ovarian carcinomas. In particular the invention provides a nucleic acid sequence encoding HE4a, and also provides a method of screening for the presence of a malignant condition in a subject by detecting reactivity of an antibody specific for a HE4a polypeptide with a molecule naturally occurring in soluble and/or cell surface form in a sample from such a subject, and by hybridization screening using an HE4a nucleotide sequence, as well as other related advantages.

Claims

1-72. -72. (canceled)

73. A polypeptide that specifically binds with HE4a, the polypeptide comprising an immunoglobulin variable region that specifically binds with an HE4a polypeptide having an amino acid sequence comprising the sequence set forth in SEQ ID NO:

11.

74. The polypeptide of claim 73, wherein the immunoglobulin variable region does not specifically bind with an HE4 polypeptide having the amino acid sequence SEQ ID NO:

9.

75. The polypeptide of claim 73, further comprising an immunoglobulin Fc domain.

76. The polypeptide of claim 73, being an antibody.

77. The polypeptide of claim 76, being a single chain antibody.

78. The polypeptide of claim 76, being an F(ab′

)₂ fragment of an antibody.

79. The polypeptide of claim 76, wherein the antibody is a recombinant antibody.

80. The polypeptide of claim 76, wherein the polypeptide is biotinylated.

81. The polypeptide of claim 73, further comprising a detectable protein domain fused with the immunoglobulin variable region.

82. The polypeptide of claim 81, wherein the detectable protein domain comprises a biotin mimetic sequence.

83. The polypeptide of claim 81, wherein the detectable protein domain comprises a site that is covalently modifiable with a detectable labeling moiety.

84. The polypeptide of claim 81, wherein the detectable labeling moiety is biotin.

85. The polypeptide of claim 81, wherein the detectable protein domain exhibits enzymatic modification of a detectable substrate.

86. The polypeptide of claim 81, wherein the detectable protein domain binds with a solid-phase support.

87. The polypeptide of claim 81, wherein the detectable protein domain is bound with a solid-phase support.

88. A monoclonal antibody preparation comprising the polypeptide of claim 76.

89. A hybridoma that secretes the polypeptide of claim 76.

90. A yeast two-hybrid system, the system comprising a first yeast that produces the polypeptide of claim 83 and a second yeast that produces an enzyme that covalently modifies the detectable protein domain with the detectable labeling moiety.

91. The polypeptide of claim 73, wherein the immunoglobulin variable region binds with the HE4a polypeptide with a K_a not less than 10⁵M⁻

1.

92. An antibody that specifically binds with an HE4a polypeptide having an amino acid sequence comprising the sequence set forth in SEQ ID NO:

11.

93. The antibody of claim 92, wherein the antibody does not specifically bind with an HE4 polypeptide having the amino acid sequence SEQ ID NO:

9.

94. The antibody of claim 92, having a detectable protein domain fused with the variable region of the antibody.

95. The antibody of claim 94, wherein the detectable protein domain is biotinylated.