Organic compounds -- part of the class 532-570 series – Organic compounds – Carbohydrates or derivatives
Reexamination Certificate
1997-03-14
2002-10-01
Bansal, Geetha P. (Department: 1642)
Organic compounds -- part of the class 532-570 series
Organic compounds
Carbohydrates or derivatives
C536S023500, C536S024310, C435S430100, C435S252300, C435S320100, C435S325000, C435S091400, C435S091100
Reexamination Certificate
active
06458939
ABSTRACT:
1. BACKGROUND OF THE INVENTION
The present invention relates to methods and compositions for the diagnosis, prevention, and treatment of neoplastic cell growth and proliferation, i.e., tumors and cancers (e.g., colon cancer) in mammals, for example, humans. Specifically, genes which are differentially expressed in tumor cells relative to normal cells are identified. Among these are certain novel genes.
Malignant tumors, i.e., cancers, are the second leading cause of death in the United States, after heart disease (Boring, et al.,
CA Cancer J. Clin
., 43:7, 1993), and develop in one in three Americans. One of every four Americans dies of cancer. Cancer is characterized primarily by an increase in the number of abnormal, or neoplastic, cells derived from a normal tissue which proliferate to form a tumor mass, the invasion of adjacent tissues by these neoplastic tumor cells, and the generation of malignant cells which spread via the blood or lymphatic system to regional lymph nodes and to distant sites. The latter progression to malignancy is referred to as metastasis.
Cancer can result from a breakdown in the communication between neoplastic cells and their environment, including their normal neighboring cells. Signals, both growth-stimulatory and growth-inhibitory, are routinely exchanged between cells within a tissue. Normally, cells do not divide in the absence of stimulatory signals, and, likewise, will cease dividing in the presence of inhibitory signals. In a cancerous, or neoplastic, state, a cell acquires the ability to “override” these signals and to proliferate under conditions in which normal cells would not grow.
Tumor cells must acquire a number of distinct aberrant traits to proliferate. Reflecting this requirement is the fact that the genomes of certain well-studied tumors carry several different independently altered genes, including activated oncogenes and inactivated tumor suppressor genes. Each of these genetic changes appears to be responsible for imparting some of the traits that, in aggregate, represent the full neoplastic phenotype (Land et al.,
Science
, 222:771, 1983; Ruley,
Nature
, 304:602, 1983; Hunter,
Cell
, 64:249, 1991).
Differential expression of the following suppressor genes has been demonstrated in human cancers: a retinoblastoma gene, RB; the Wilms' tumor gene, WT1 (11p); a gene deleted in colon carcinoma, DCC (18q); the neurofibromatosis type 1 gene, NF1 (17q); and a gene involved in familial adenomatous polyposis coli, APC (5q) (Vogelstein, B. and Kinzler, K. W.,
Trends Genet
., 9:138-141, 1993).
2. SUMMARY OF THE INVENTION
The present invention relates to methods and compositions for the diagnosis, prevention, and treatment of tumors and cancers, e.g., colon or lung cancer, in mammals, e.g., humans. The invention is based on the discovery of genes that are differentially expressed in tumor cells relative to normal cells of the same tissue. The genes identified can be used diagnostically or as targets for therapy, and can be used to identify compounds useful in the diagnosis, prevention, and therapy of tumors and cancers (e.g., colon cancer). The genes also can be used in gene therapy, protein synthesis, and to develop antisense nucleic acids.
In general, the invention features an isolated nucleic acid including the nucleotide sequence of any one of SEQ ID NOS: 1, 3 to 7, 9 to 13, 16, 17, or 19 to 23, or an isolated nucleic acid that hybridizes under stringent hybridization conditions to one of these nucleic acids or their complements. The invention also features a genetically engineered host cell containing one of these nucleotide sequences, and an expression vector containing one of these nucleotide sequences operably linked to a nucleotide sequence regulatory element that controls expression of the nucleotide sequence in a host cell.
The invention further features a substantially pure gene product encoded by one of these nucleic acids, e.g., having the amino acid sequence of SEQ ID NO:18. The invention also features an antibody that immunospecifically binds to this gene product.
In another embodiment, the invention features a method of diagnosing a tumor in a mammal by obtaining a test sample of tissue cells, e.g., colon cells, from the mammal; obtaining a control sample of known normal cells from the same type of tissue; and detecting in both the test sample and the control sample the level of expression of any one or more of genes 048, 083, 090, 093, and 097, wherein a level of expression higher in the test sample than in the control sample indicates a tumor in the test sample.
The method of diagnosing a tumor can also be carried out using any one or more of genes 029, 030, 036, 038, 056, 075, 082, 092, 096, or 101, wherein a level of expression lower in the test sample than in the control sample indicates a tumor in the test sample.
The invention further features a method of treating a tumor, e.g., a colon tumor, in a patient, e.g., a mammal such as a human, by administering to the mammal a compound in an amount effective to decrease the level of expression or activity of the gene transcript or gene product of any one or more of genes 048, 083, 090, 093, and 097, to a level effective to treat the tumor.
In this method, the compound can be an antisense or ribozyme molecule that blocks translation of the gene transcript, or a nucleic acid complementary to the 5′ region of any one or more of genes 048, 083, 090, 093, and 097, and blocks formation of a gene transcript via triple helix formation. The compound also can be an antibody that neutralizes the activity of the gene product.
In another method of treating a tumor in a mammal, a compound is administered in an amount effective to increase the level of expression or activity of the gene transcript or gene product of any one or more of genes 029, 030, 036, 038, 056, 075, 082, 092, 096, and 101, to a level effective to treat the tumor, e.g., colon tumor. In this method, the compound can be a nucleic acid whose administration results in an increase in the level of expression of any one of genes 029, 030, 036, 038, 056, 075, 082, 092, 096, and 101, thereby ameliorating symptoms of the tumor.
In another aspect, the invention features a method for inhibiting tumors in a mammal by administering to the mammal a normal allele of one or more of genes 029, 030, 036, 038, 056, 075, 082, 092, 096, and 101, so that a gene product is expressed, thereby inhibiting tumors. The invention also covers a method for treating tumors in a mammal by administering to the mammal an effective amount of a gene product of any one or more of genes 029, 030, 036, 038, 056, 075, 082, 092, 096, and 101.
The invention also features a method of monitoring the efficacy of a compound in clinical trials for inhibition of tumors, e.g., colon tumors, in a patient by obtaining a first sample of tumor tissue cells from the patient; administering the compound to the patient; after a time sufficient for the compound to inhibit the tumor, obtaining a second sample of tumor tissue cells from the patient; and detecting in the first and second samples the level of expression of any one or more of genes 048, 083, 090, 093, and 097, wherein a level of expression lower in the second sample than in the first sample indicates that the compound is effective to inhibit a tumor in the patient.
This method can also be carried out using any one or more of genes 029, 030, 036, 038, 056, 075, 082, 092, 096, or 101, wherein a level of expression higher in the second sample than in the first sample indicates that the compound is effective to inhibit a tumor in the patient.
A “tumor,” as used herein, refers to all neoplastic cell growth and proliferation, whether malignant or benign, and all precancerous and cancerous cells and tissues.
A “differentially expressed” gene transcript, as used herein, refers to a gene transcript that is found in different numbers of copies, or in activated versus inactivated states, in different cell or tissue types of an organism having a tumor or cancer, e.g., colon cancer, compared to the numbers of
Bansal Geetha P.
Fish & Richardson P.C.
Millennium Pharmaceuticals Inc.
LandOfFree
Compositions and methods for the diagnosis, prevention, and... does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Compositions and methods for the diagnosis, prevention, and..., we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Compositions and methods for the diagnosis, prevention, and... will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-2991512