Chemistry: molecular biology and microbiology – Measuring or testing process involving enzymes or... – Involving antigen-antibody binding – specific binding protein...
Reexamination Certificate
1999-02-22
2001-09-18
Caputa, Anthony C. (Department: 1642)
Chemistry: molecular biology and microbiology
Measuring or testing process involving enzymes or...
Involving antigen-antibody binding, specific binding protein...
C435S007100, C530S300000, C530S387700
Reexamination Certificate
active
06291196
ABSTRACT:
FIELD OF INVENTION
The subject invention is related to the use of antibodies, which bind to a unique peptide obtainable from a Xiphophorus melanoma mrk-receptor tyrosine kinase for the diagnosis and therapy of melanoma and prostate cancer.
BACKGROUND
The ability to detect and diagnose cancer through the identification of tumor markers is an area of widespread interest. Tumor markers are substances, typically proteins, glycoproteins, polysaccharides, and the like which are produced by tumor cells and are characteristic thereof. Often, a tumor marker is produced by normal cells as well as by tumor cells. In the tumor cells, however, the production is in some way atypical. For example, production of a tumor marker may be greatly increased in the cancer cell. Additionally, the tumor marker may be released or shed into the circulation. Detection of such secreted substances in serum may be diagnostic of the malignancy. Therefore, it is desirable to identify previously unrecognized tumor markers, particularly, tumor markers which are secreted into the circulation and which may be identified by serum assays. It Is also desirable to develop methods and compositions which allow determination of the cellular origin of a particular tumor or other proliferative disease, for example by radioimaging techniques. The location of the tumor markers on the surface of the cells, particularly where there is all extracellular domain that is accessible to antibodies (i.e., the domain acts as a receptor for the antibodies), provides a basis for targeting cytotoxic compositions to the receptor. Examples of compositions of interest in such a method include complement fixing antibodies or immunotoxins which bind to the receptor as a means of specifically killing those cells which express the receptor on the cell surface.
Human malignant melanoma arises from a series of stages starting with the harmless mole, going through intermediate states of radial to invasive growth and ending in the destructive final stage of metastatic melanoma. Melanoma usually resists chemotherapy as well as radiotherapy. Surgery is the most effective treatment. However, for it to be effective, surgery requires early diagnosis which is unfortunately hampered by the lack of accurate markers for melanoma. Melanoma associated antigens have been found, but they are of little diagnostic value. For example, the nerve growth factor receptor is found in high density on melanoma cells. However, monoclonal anti-nerve growth receptor antibodies are specific for neural crest cell diseases rather than for melanoma alone. Likewise, other melanoma associated antigens against which antibodies have been raised are nonspecific for melanoma cells. Examples are the monoclonal antibodies raised against in vitro grown melanoma cells which are directed against gangliosides or glycoproteins present on the melanoma cells. Both antigens are also found on other cells.
Adenocarcinoma of the prostate is one of the most common tumors in men and accounts for 10% of deaths from malignant disease in males in the United States. Only a small proportion of these cases becomes clinically apparent prior to death, the remainder being latent carcinoma. Radical prostatectomy remains the treatment of choice for tumors confined to the gland but this is applicable to only a tiny fraction of cases. Orchiectomy and hormone therapy (usually estrogen therapy) together appear to be the most effective palliative treatment in patients with symptomatic cancer of the prostate and are also used as an adjunct to surgery. However, there are significant side effects to the use of estrogens, including an increase in mortality from cardiovascular disease.
Three-fourths of the tumors arise in the posterior lobe, and urinary symptoms therefore tend to occur late in the disease. The identification and isolation of cancer genes, most notably demonstrated for colon carcinoma, has been a major breakthrough for our understanding of tumorigenesis. Cancer is basically a disease of multiple genetic changes resulting in stages of progression of a normal cell into a highly malignant, metastasizing cell.
However, very little is known about the development and clinical progression of prostatic carcinoma at the genetic level. Studies of familial clustering of prostate cancer have provided evidence for a rare, high risk autosomal dominant allele which may be responsible for early onset of prostate cancer (Carter B. S., et al.,
Proc. Natl. Acad. Sci USA
89:3367-3371, 1992; Carter B.S., et al.,
J. Urol.
150:797-802, 1993). Indeed a consortium of several research groups has recently localized a major prostate cancer susceptibility locus on the long arm of chromosome 1 (1q24-25) (Smith R. J. et al.,
Science
274:1371-1373, 1996). In addition, several chromosomal alterations such as gain of 8q and loss of 8p (Visakorpi T. et al.,
Cancer Res.
55:342-347, 1995; cher M. L. et al.,
Cancer Res.
56:3091-3102, 1996) as well as loss of 10q, 13q, 16q, 17p (Isaacs W. B., et al.,
Cancer Surveys
23:19-32, 1995; Cher M. L. et al.,
Cancer Res.
56:3091-3102, 1996) and 11p11.2 (Dong, J. T., et al.,
Science
268:884-886, 1995) have been identified. Similarly, the group at the Mayo Clinic (Qian et al., 1995) using fluorescence in situ hybridization has shown gains of chromosome 7, 8, 10 and 12 and detected similar proportions of anomalies in PIN and carcinoma supporting the notion that PIN is the supposed precursor lesion. This study showed also that the gain of chromosome 8 was the most common alteration and mostly correlated with the cancer grade. This amplification of chromosome 8 genes may lead to overexpression and could play a key role in progression of prostatic carcinoma.
A significant number of patients come into the physician with symptoms due to distant metastases. Cancer of the prostate arises through a continuum from normal luminal secretory cells which progress through a dysplastic stage of mild to severe prostatic intraepithelial neoplasia (PIN) to carcinoma in situ and invasive carcinoma cells. PIN is considered the precursor stage; however, once grade 3 is reached, the cancer enters a malignant stage which is characterized by cells breaking loose from the epithelium and invading the neighboring stromal component of the prostate gland. This invasion takes place where the basal cell layer is disrupted and the basement membrane is fragmented. The cancer cells then progress from well, to moderately and finally poorly differentiated cells. These cells, staged according to Gleason grades 1-5, are believed to reflect the increasing aggressiveness of the cancer of the prostate.
Frequent routine rectal examinations are the best means of demonstrating early and operable prostatic tumors. Measurement of prostate specific antigen as a screening test for prostate cancer has been used but presents both technical difficulties and a high false positive rate. Prostatic acid phosphatase also has been used as a marker for prostate cancer but does not detect all cancers. The most successful detection of prostate cancer is from the combined use of a digital rectal exam, transrectal ultrasound and detection of prostate specific antigen. The sensitivities of the three tests individually vary from 50% to 85% but the positive predictive value fluctuates around 30%. When these three investigations are summated, the detection rate is approximately twice as high as when a single parameter is used. The only reliable procedure for definitive diagnosis of prostatic carcinoma is by open perineal biopsy. Needle biopsies and cytologic studies of prostatic fluid are unreliable for the diagnosis of early cancer but are useful methods of obtaining a histological diagnosis in the more advanced cases. It therefore is of interest to identify in particular, early stage prostatic cancer and to identify non-invasive methods of treating prostatic cancer. It also is of interest to identify a melanoma-associated antigen which is specific for melanoma as compared to normal melanocytes as well as other normal and malignant cells. An antibody
Caputa Anthony C.
Davis Minh-Tam
Research Corporation Technologies Inc.
Scully Scott Murphy & Presser
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