Chemistry: molecular biology and microbiology – Measuring or testing process involving enzymes or... – Involving antigen-antibody binding – specific binding protein...
Reexamination Certificate
1999-01-15
2002-05-07
Huff, Sheela (Department: 1642)
Chemistry: molecular biology and microbiology
Measuring or testing process involving enzymes or...
Involving antigen-antibody binding, specific binding protein...
C435S007230, C435S006120, C435S007920, C530S388850, C530S389100
Reexamination Certificate
active
06383759
ABSTRACT:
1. FIELD OF THE INVENTION
The present invention is directed to methods for the detection of prostate cancer in an individual by assessing prostate cells in a body fluid. The present invention is also related to commercial kits for use in the detection of prostate cancer.
2. BACKGROUND OF THE INVENTION
In the United States prostate cancer is first in absolute incidence with an estimated 210,000 new cases in 1997, and second to lung cancer for deaths with an estimated 41,800 deaths in 1997. Parker et al., 1997, Cancer Abstracts 47(1):5-27. The incidence of prostate cancer has risen at an average annual rate of 3% per annum from 1960 to 1985. Boyle, 1997, Proceedings—First International Consultation on Prostate Cancer. Prostate cancer affects older men with the rates of incidence for men in their 40's being 1-2 per 100,000, the rates for Caucasian men in their 80's 1,200 per 100,000 and for African American men 1,600 per 100,000. In 1900 only 25% of the United States population lived to the age of 65. Currently that number is 70%. Brody, 1985, Nature 315:463-466.
The guidelines for diagnosis of new prostate cancer adopted by the American Cancer Society in June 1997 recommends an annual prostate specific antigen (PSA) exam as well as a digital rectal exam (DRE) for men over 50 years of age and in certain instances over the age of 45. Further action should be taken only if one or both screening methodologies are abnormal. An abnormal PSA is defined as a PSA greater than 4.0 ng/ml.
Patients suspected of having prostate cancer based on a PSA test and a DRE, would then undergo additional radiographic and/or surgical tests to confirm diagnosis. These additional tests may include urology consultation, ultrasound and tissue biopsy with pathological evaluation. The cost associated with these confirmatory tests typically exceeds $5000.
The PSA test and DRE are acceptable screening methods but one of the short comings of these screening methods is the large number of falsely identified patients. A PSA European screening study biopsied 976 men and detected 190 cases of prostate cancer. 767 of the 976 men had either of both a PSA value in the range of 4 to 10 ng/ml or a suspect DRE. Of these 767 patients, only 177 had prostate cancer. 77% of the population did not have prostate cancer. Schröder, 1997, First International Consultation on Prostate Cancer, 179-210.
Final determination of prostate cancer must be made with more expensive and invasive biopsy. However, even a single biopsy can miss prostate cancer. In one third of patients who underwent a serial biopsy study, multiple biopsies were required for the detection of prostate cancer. Keetch et al., 1994, J. Urol. 151:1571-1574.
A recent methodology attempted to further identify patients who are at risk for prostate cancer has been the determination of percent free PSA. Murphy et al., 1996, Cancer 78(4):809-818, report a difference in the ratio of free PSA to total PSA in 226 patients with benign prostatic hyperplasia and patients with no evidence of disease compared to the same ratio in patients with biopsy-proven prostate cancer. The ratio was 12.1% in patients with no evidence of prostate cancer and in the prostate cancer group the ratio was 7.1%. Despite the differences observed, the authors concluded that their data suggest that free PSA values do not provide additional diagnostic benefit compared to total PSA in screening populations in the presence of suspected cancer, post prostatectomy or in metastatic disease. Pronounced differences in the ability of available assays to detect free PSA have generated multiple cutoffs, ranging from 15-20%. Catalona et al., 1996, JAMA 274:1214-1220; Oesterling et al., 1995, J. Urol. 154:1090-1095; Toubert et al., 1996, Eur. J. Cancer 32A(12):2088-2093; Lilja, 1993, Urol. Clin. North Am. 20(4):681-686. Regardless of the potential sensitivity gained, prostate cancer will have to be confirmed with a cytological assessment. Clearly, the development of a non-invasive, cytologically based assay, able to compliment the traditional PSA and DRE, would assist the clinician in the early detection and treatment of prostate cancer without the necessity of relying on more expensive invasive means.
Citation or identification of any reference in Section 2 or any other section of this application shall not be construed as an admission that such reference is available as prior art to the present invention.
3. SUMMARY OF THE INVENTION
The present invention is directed to a method for the detection of prostate cancer comprising comparing the ratio of the number of prostate cells and the total number of epithelial cells in a body fluid sample, in which the ratio is elevated in individuals with prostate cancer as compared to individuals free of prostate cancer. The ratio is determined by (1) quantifying the number of prostate cells in a body fluid sample; (2) quantifying the total number of epithelial cells in the fluid sample; and (3) calculating the ratio of the number of prostate cells to the total number of epithelial cells. In an aspect of this embodiment of the present invention, the prostate cells are quantified by using an antibody which is specific for a prostate cell-specific marker, such as the prostate specific antigen (PSA) or the prostate specific membrane antigen (PSMA). In a preferred aspect, the prostate cell-specific marker is PSMA. The body fluid can be, but is not limited to, blood, urine or semen. In a preferred aspect, the body fluid is semen.
The present invention is also directed to a method for the detection of prostate cancer comprising comparing the ratio of the number of prostate cells which express a tumor associated marker and the total number of prostate cells in a body fluid sample, in which the ratio is elevated in individuals with prostate cancer as compared to individuals free of prostate cancer. The ratio is determined by (1) quantifying the total number of prostate cells in a body fluid sample; (2) quantifying the number of prostate cells in the fluid sample which express a tumor associated marker; and (3) calculating the ratio of the number of prostate cells which express the marker to the total number of prostate cells. In an aspect of this embodiment of the present invention, the prostate cells are quantified by using an antibody which is specific for a prostate cell-specific marker, such as the prostate specific antigen (PSA) or the prostate specific membrane antigen (PSMA). In a preferred aspect of this embodiment, the prostate cell-specific marker is PSMA. The body fluid can be, but is not limited to, blood, urine or semen. In a preferred aspect, the body fluid is semen.
The present invention is also directed to commercial kits for the detection of prostate cancer which comprise a prostate cell marker-specific antibody and an epithelial cell marker-specific antibody in one or more containers. Alternatively, the commercial kits comprise a prostate cell marker-specific antibody and a tumor associated marker-specific antibody in one or more containers.
As used herein, the term “epithelial cell marker” refers to an epithelial cell marker not present on sperm cells.
As used herein, the term “prostate cell-specific antibody” refers to any polyclonal or monoclonal antibody, or portion thereof, that can immunospecifically bind to an epitope present on or in a prostate cell. For example, such an antibody immunospecifically binds to PSMA or binds to an extracellular portion or to an intracellular portion of PSMA.
As used herein, the term “tumor associated marker-specific antibody” refers to any polyclonal or monoclonal antibody, or portion thereof, that can immunospecifically bind to a tumor associated marker, which when expressed in or on a cell is indicative that such cell is cancerous.
The invention may be understood more fully by reference to the following brief description of the figures, detailed description, illustrative, non-limiting examples and the appended figures.
4. BRIEF DESCRIPTION OF THE FIGURES
FIGS. 1A and 1B
are representative dot plots of cells binding ant
Barren, III Robert J.
Boynton Alton L.
Holmes Eric H.
Murphy Gerald P.
Gerald P. Murphy Cancer Foundation
Helms Larry
Huff Sheela
Pennie & Edmonds LLP
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