Chemistry: molecular biology and microbiology – Measuring or testing process involving enzymes or... – Involving nucleic acid
Reexamination Certificate
1999-10-15
2002-09-17
Jones, W. Gary (Department: 1655)
Chemistry: molecular biology and microbiology
Measuring or testing process involving enzymes or...
Involving nucleic acid
C435S091100, C435S091200
Reexamination Certificate
active
06451532
ABSTRACT:
BACKGROUND OF THE INVENTION
Throughout this application, various publications are referenced by arabic numbers in parentheses. Full citations for these publications may be found listed at the end of the specification immediately preceding the Sequence Listing and the claims. The disclosures of these publications in their entireties are hereby incorporated by reference in order to more fully describe the state of the art as known to those skilled therein as of the date of the invention described and claimed herein.
For several forms of solid tumors, the process of tumor detection and staging has been greatly improved by the development of assays that detect and measure tumor-specific markers in specimens of patient tissues or body fluids. As exemplified by the use of prostate specific antigen (PSA) screening for prostate cancer (1), such assays have the potential of revolutionizing the clinical approach to diagnosis, staging and monitoring the effect of therapeutic intervention in human malignancies. Many of these tumor marker assays are based on immunologic detection of the tumor marker protein. Increasingly, tumor detection methods that involve DNA- and RNA-based assays of patient specimens are being used (2,3,4). With the use of polymerase chain reaction (PCR) technology to amplify unique genetic sequences which are markers for malignancy, these assays can now detect small numbers of cancer cells in patient blood specimens (5,6).
With regard to kidney cancer, it is estimated that 28,800 new cases will be diagnosed in 1997, resulting in approximately 11,700 deaths (8). The majority of deaths will be caused by renal cell carcinoma. If renal cell carcinoma tumors are detected while still confined to the kidney, radical nephrectomy results in excellent long term survival. Unfortunately, symptoms of disease rarely occur prior to metastatic spread. Once renal cell carcinoma has metastasized, survival rates are less than 10% at five years (9). Until now, no suitable diagnostic marker existed for renal cell carcinoma detection, staging or for monitoring the effect of therapy.
This invention provides a PCR-based technique to detect the malignant renal cell marker MN in a peripheral blood sample. The MN protein was first detected on the cell surface of the highly-malignant cervical cancer cell line, HeLa (10). MN expression has also been detected in human cervical and ovarian tumor specimens, but not in normal cervical or ovarian tissue. These results suggested that MN might be a useful marker for screening certain gynecological malignancies (11). In these early studies, MN expression was also detected in normal epithelial cells of the gastric mucosa. Its restricted expression in this normal tissue was viewed as unlikely to interfere with tumor-specific detection in tissues outside of the gastrointestinal tract (11,12).
The availability of the complete cDNA sequence for the MN gene product (10) allowed the design of specific PCR primers that amplify a portion of the MN cDNA in a reverse transcriptase-PCR (RT-PCR) assay. The assay is useful for-the diagnosis and molecular staging of renal cell carcinoma. The assay is also useful for the follow-up of renal cell carcinoma therapy. The assay is particularly sensitive for detection of a subset of renal cell carcinoma known as clear cell carcinoma. Quite importantly, the assay is capable of detecting the renal cell carcinoma marker MN in a peripheral blood test.
SUMMARY OF THE INVENTION
This invention provides methods of: (a) diagnosing; (b) determining the stage of; and (c) monitoring the effect of a therapeutic intervention for a renal cell carcinoma in a human subject which comprises detecting the expression of the MN gene. In one embodiment, the method is directed to detection of the renal cell carcinoma known as clear cell carcinoma. In another embodiment, the method is used as a peripheral blood assay. In another embodiment, the method is a polymerase chain reaction assay for amplifying and detecting the presence of the cDNA molecule encoding the MN protein.
REFERENCES:
patent: 4935344 (1990-06-01), Bander et al.
patent: 5387676 (1995-02-01), Zavada et al.
Bander et al. (1989) “Analysis of a Mouse Monoclonal Antibody That Reacts with a Specific Region of the Human Proximal Tubule and Subsets Renal Cell Carcinoma,”Cancer Research49:6774-6780.
Brewer et al. (1996) “A Study of Biomarkers in Cervical Carcinoma and Clinical Correlation of the Novel Biomarker MN,”Gynecol. Oncol.63(3): 337-344.
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Kusama et al. (1991) “Tumor Markers in Human Renal Cell Carcinoma,”Tumor Biol12:189-197.
Liao et al. (1994) “Identification of the MN Antigen as a Diagnostic Biomarker of Cervical Intraepithelial Squamous and Glandular Neoplasia and Cervical Carcinomas,”Am. J. Pathol.145 (23):598-609.
McKiernan, J.M. et al., (1997) “Expression of Tumor-associated Gene MN: A potential biomarker for human renal cell carcinoma”,Cancer Research, 57:2362-2365.
Olive et al. (1997) “Characterisation of &ggr;&dgr;T cells in renal cell carcinoma patients by polymerase chain reaction analysis of T cell receptor transcripts,”Cancer Immunology Immunotherapy.44:27-34.
Oosterwijk et al. (1993) “Antibody Localization in Human Renal Cell Carcinoma: A Phase I Study of Monoclonal Antibody G250,”J. Clin. Oncol.11(4):738-750.
Oosterwijk et al. (1986) “Monoclonal Antibody G 250 Recognizes a Determinant Present in Renal-Cell Carcinoma and Absent from Normal Kidney,”Intl. J. Cancer38:489-494.
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Oosterwijk et al. (1995) “Radiolabled Monoclonal Antibody G250 in Renal-Cell Carcinoma,”World J. Urol.13(3):186-190.
Oosterwijk et al. (1995) “The Use of Monoclonal Antibody G250 in the Therapy of Renal-Cell Carcinoma,”Semin. Oncol.22(1):34-41.
Opavský et al. (1996) “Human Mn/ca9 Gene, a Novel Member of the Carbonic Anhydrase Family:Structure and Exon to Protein Domain Relationships,”Genomics33:480-487.
Pastorek et al. (1994) “Cloning and Characterization of MN, a Human Tumor-associated Protein with a Domain Homologous to Carbonic Anhydrase and a Putative Helix-loop-helix Dna Binding Segment,”Oncogene9:2877-2888.
Pastorekova et al. (1997) “Carbonic Anhydrase IX, MN/CA IX: Analysis of Stomach Complementary DNA Sequence and Expression in Human and Rat Alimentary Tracts,”Gastroenterology112(2):398-408.
Steffens et al. (1997) “Targeting of Renal Cell Carcinoma with Iodine-131-Labeled Chimeric Monoclonal Antibody G250,”J. Clin. Oncol.15(4):1529-37.
Surfus et al. (1996) “Anti-Renal-Cell Carcinoma Chimeric Antibody G250 Facilitates Antibody-Dependent Cellular Cytotoxicity with In Vitro and In Vivo Interleukin-2-Activated Effectors,”J. Immunother Emphasis Tumor Immunol.19(3):184-191.
Uemura et al. (1994) “Immunization with Anti-Idiotype Monoclonal Antibodies Bearing the Internal Image of the Renal-Cell Carcinoma-Associated Antigen G250 Induces Specific Cellular Immune Responses,”Int. J. Cancer59(6):802-807.
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Uemura et al. (1994) “Vaccination with Anti-Idiotype Antibodies Mimicking a Renal Cell Carcinoma-Associated Antigen Induces Tumor Immunity,”Int. J. Cancer58(4): 555-561.
Van Dijk et al. (1994) “Therapeutic Effects of Monoclonal Antibody G250, Interferons and Tumor Necrosis Factor, In Mice with Renal-Cell Carcinoma Xenografts,”Int. J. Cancer56(2): 262-268.
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Bander Neil H.
Buttyan Ralph
McKiernan James M.
Sawczuk Ihor S.
Cooper & Dunham LLP
Jones W. Gary
Souaya Jehanne
The Trustees of Columbia University in the City of New York
White John P.
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