Methods for the early diagnosis of ovarian cancer

• US 6,268,165 B1
• Filed: 02/22/2000
• Issued: 07/31/2001
• Est. Priority Date: 03/19/1997
• Status: Expired due to Term

• Current Assignee: Bioventures, LLC
• Original Assignee: The Board of Trustees of the University of Arkansas (University of Arkansas System)
• Inventors: OʼBrien, Timothy L.
• Primary Examiner(s): Myers, Carla J.
• Application Number:
  US09/510,738
• Time in Patent Office: 525 Days
• Field of Search: 435/6, 435/7.1, 435/7.4, 435/23, 536/23.5, 536/23.2, 536/24.31, 530/350
• US Class Current: 435/23
• CPC Class Codes: A61K 2039/5154 Antigen presenting cells [APCs], e.g. dendritic cells or macrophages
• CPC Class Codes: A61K 2039/53 DNA (RNA) vaccination
• CPC Class Codes: A61K 38/00 Medicinal preparations containing peptides peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00
• CPC Class Codes: A61K 39/00 Medicinal preparations containing antigens or antibodies materials for immunoassay G01N33/53
• CPC Class Codes: A61K 48/00 Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
• CPC Class Codes: C07K 14/435 from animals; from humans
• CPC Class Codes: C12N 9/6424 Serine endopeptidases (3.4.21)
• CPC Class Codes: C12N 9/6472 Cysteine endopeptidases (3.4.22)
• CPC Class Codes: C12Q 1/37 involving peptidase or proteinase
• CPC Class Codes: C12Q 1/686 Polymerase chain reaction [PCR]
• CPC Class Codes: C12Q 1/6886 for cancer immunoassay for cancer G01N33/574
• CPC Class Codes: C12Q 2600/136 Screening for pharmacological compounds
• CPC Class Codes: C12Q 2600/158 Expression markers
• CPC Class Codes: G01N 2333/96433 Serine endopeptidases (3.4.21)
• CPC Class Codes: G01N 2333/96486 Metalloendopeptidases (3.4.24)
• CPC Class Codes: G01N 2333/976 Trypsin; Chymotrypsin
• CPC Class Codes: G01N 2500/20 cell-free systems
• CPC Class Codes: G01N 33/573 for enzymes or isoenzymes
• CPC Class Codes: G01N 33/574 for cancer
• CPC Class Codes: G01N 33/57449 of ovaries
• CPC Class Codes: G01N 33/57492 : involving compounds localized on the membrane of tumor or cancer cells

Abstract

The disclosed nucleic acid primer sets, used in combination with quantitative amplification (PCR) of tissue cDNA, can indicate the presence of specific proteases in a tissue sample. The detected proteases are themselves specifically overexpressed in certain cancers, and the presence of their genetic precursors may serve for early detection of associated ovarian and other malignancies, and for the design of interactive therapies for cancer treatment.

Claims

1. A method of diagnosing ovarian cancer in an individual, comprising the steps of:

(a) obtaining a biological sample from an individual; and

(b) detecting hepsin in said sample, wherein over-expression of hepsin in said sample compared to normal ovarian tissue sample is indicative of the presence of ovarian cancer in said individual.

2. The method of claim 1, wherein said biological sample is selected from the group consisting of blood, interstitial fluid, ascites fluid, tumor tissue biopsy and circulating tumor cells.

3. The method of claim 1, wherein said detection of said hepsin is by means selected from the group consisting of Western blot, dot blot, ELISA sandwich assay, radioimmunoassay, and flow cytometry.

4. A method for detecting malignant ovarian hyperplasia in a biological sample, comprising the steps of:

(a) isolating protein from said sample; and

(b) detecting hepsin protein in said sample, wherein over-expression of said hepsin protein in said sample compared to normal ovarian tissue sample is indicative of the presence of malignant ovarian hyperplasia.

5. The method of claim 4, wherein said detection is by immunoaffinity to an antibody, wherein said antibody is specific for hepsin.

6. The method of claim 4, wherein said biological sample is selected from the group consisting of blood, interstitial fluid, ascites fluid, tumor tissue biopsy and circulating tumor cells.