Antibodies against the tumor suppressor gene ING1

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Reexamination Certificate

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C530S387700, C530S387900, C530S387100, C530S389100, C530S389700, C424S130100, C424S138100, C424S139100, C424S141100

Reexamination Certificate

active

06747133

ABSTRACT:

FIELD OF THE INVENTION
This invention relates to a novel tumor suppressor gene, ING1, to methods for making and using this and related tumor suppressor genes and proteins and peptides, and to nucleic acids encoding this and related tumor suppressor proteins and peptides.
REFERENCES
The following references are cited in the application as numbers in brackets ([ ]) at the relevant portion of the application.
1. Levine, A. J., “The Tumor Suppressor Genes”,
Annu. Rev. Biochem
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J. Cell
79:573-582 (1994).
3. Gudkov, A. V. et al., “Isolation of genetic suppressor elements, inducing resistance to topoisomerase II-interactive cytotoxic drugs, from human topoisomerase II cDNA”,
Natl. Acad. Sc. USA
90:3231-3235 (1993).
4. Straus, D. et al., “Genomic subtraction for cloning DNA corresponding to deletion mutations”,
Proc. Natl. Acad. Sc. USA
87:1889-1893 (1990).
5. Lisitsyn, N. et al., “Cloning the Differences Between Two Complex Genomes”,
Science
259:946-951 (1993).
6. Yaswen, P. et al., “Down-regulation of a calmodulin-related gene during transformation of human mammary epithelial cells”,
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7:980-986 (1989).
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”, Nature
366:704-707 (1993).
9. Defeo-Jones, D., “Cloning of cDNAs for cellular proteins that bind to the retinoblastoma gene product”,
Nature
352:251-254 (1991).
10. Aharon, T. et al., “Selective Destabilization of Short-Lived mRNAs with the Granulocyte-Macrophage Colony-Stimulating Factor AU-Rich 3′ Noncoding Region is Mediated by a Cotranslational Mechanism”,
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11. Guan, K. et al., “Growth suppression by p18, a p16
INK4/MTS1
and p14
INK4B/MTS2
-related CDK6 inhibitor, correlates with wild-type pRb function”,
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12. Harper, J. W. et al., “The p21 Cdk-Interacting Protein Cip1 is a Potent Inhibitor of G1 Cyclin-Dependent Kinases”,
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264:436-440 (1994).
15. Nobori, T. et al., “Deletions of the cyclin-dependent kinase-4 inhibitor gene in multiple human cancers”,
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368:753-756 (1994).
16. Riabowol, K. et al., “The cdc2 Kinase Is a Nuclear Protein That Is Essential for Mitosis in Mammalian Cells”,
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57:393-401 (1989).
17. Sambrook, J. et al., “Molecular Cloning” (2nd.Ed.),
A Laboratory Manual, Cold Spring Harbor Laboratory Press
(1989).
18. Harlow, E. et al., “Antibodies”,
A Laboratory Manual, Cold Spring Harbor Laboratory
(1988).
19. Yang, Y. et al., “An approach for treating the hepatobiliary disease of cystic fibrosis by somatic gene transfer”
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90:4601-4605 (1993).
20. Atadja, P. et al., “Increased activity of p53 in senescing fibroblasts”
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92:8348-8352 (1995).
21. Demetrick, D. J. “Fluorescence in situ hybridization and human cell cycle genes” In the Cell Cycle—Materials and Methods M. Pagano (ed.) Springer Verlag Press, 29-45 (1995).
22. Motomura et al., “Loss of alleles at loci on chromosome 13 in human primary gastric cancers”
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2, 180-184 (1988).
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55:358-386 (1990).
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56:1146-1150 (1996).
25. Thompson, M. E. et al., “Decreased expression of BRCA-1 accelerates growth and is often present during sporadic breast cancer progression”
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9:444-450 (1995).
26. Pear, W. S. et al., “Production of high titer helper-free retroviruses by transient transfection”
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. 90:8392-8396 (1993).
27. Wong, H. et al., “Monitoring mRNA expression by polymerase chain reaction: the “primer-dropping” method”
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The disclosure of the above publications, patents and patent applications are herein incorporated by reference in their entirety to the same extent as if the language of each individual publication, patent and patent application were specifically and individually included herein.
BACKGROUND OF THE INVENTION
Many cancers originate and progress by accumulating mutations in one or more genes. Such mutations which result in cancer formation can be in proto-oncogenes or in tumor suppressor genes. Mutations in tumor suppressor genes result in loss of function, and therefore act in a recessive fashion to native genes. Oncogenes, in contrast, act in dominant fashion to native alleles and, therefore, are not usually inherited through the germ lines. The tumor suppressor genes, however, are found in inherited predispositions to cancer and are inherited as a dominant predisposition because of the high frequency of a second genetic event such as reduction in homozygosity[1].
Several tumor suppressor genes have been identified. Examples include the Rb gene, which is involved in retinoblastoma and osteosarcoma; p53, which is involved in osteosarcoma and adrenocortical, breast and brain cancers; WT-1, which is involved in Wilms′ tumor, nephroblastoma and neurofibromatosis; adenomatous polyposis coli (APC), which is involved in adenomatous polyposis; and deleted colorectal cancer (DCC), which is involved with a somatic mutation in the colon.
The negative regulation of cell growth is effected by tumor suppressor proteins that regulate the cell S cycle by different mechanisms[2]. The gene cloned and sequenced as described herein, ING1 (formerly called p33
IG1
), represents a new tumor suppressor gene which is expressed in normal mammary epithelial cells, but expressed only at lower levels in several cancerous mammary epithelial cell lines and is not expressed in many primary brain tumors.
Known applications of sequenced genes include use of the DNA sequence (or analogs thereof) or of RNA or amino acid sequences derived from these DNA sequences for diagnosis or treatment of the corresponding disease. Accordingly, the gene ING1 (previously designated p33
IG1
) is useful for the diagnosis and treatment of breast and brain cancers among others.
SUMMARY OF THE INVENTION
The present invention is directed to a novel DNA sequence for an isolated gene (designated ING1). The DNA sequence, an RNA sequence identical to or complementary to the DNA sequence; the protein the DNA sequence encodes, p33
ING1
, and/or fragments or analogs thereof and antibodies which bind to p33
ING1
which are useful for diagnosing and/or treating cancer.
One aspect provides a DNA sequence selected from the group consisting of a DNA isolate substantially identical to the p33
ING1
DNA sequence shown in
FIG. 2 and a
DNA sequence greater than about 10 base pair (bp) in length capable of hybridizing under stringent conditions to the complement of the p33
ING1
DNA sequence shown in FIG.
2
. Recombinant expression vectors comprising such DNA isolates and cells transformed with such recombinant expression vectors are also provided.
Another aspect of the invention provides peptide or protein encoded by the DNA sequence substantiall

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