Organic compounds -- part of the class 532-570 series – Organic compounds – Carbohydrates or derivatives
Reexamination Certificate
1998-09-30
2001-10-09
Schwartzman, Robert A. (Department: 1635)
Organic compounds -- part of the class 532-570 series
Organic compounds
Carbohydrates or derivatives
Reexamination Certificate
active
06300484
ABSTRACT:
FIELD OF THE INVENTION
The present invention is in the field of molecular biology. More specifically, the present invention relates to a DNA sequence and corresponding protein.
BACKGROUND OF THE INVENTION
A family of GTP binding proteins and related proteins has been implicated in tumorgenicity of hyperproliferative cells. These proteins include dbl, eci2, lbc, ost, and TIM. See, respectively, Ron et al.,
EMBO J
7: 2465-2473 (1988); Miki el al.,
Nature
362: 462-465 (1993); Toksoz et al.,
Oncogene
9(2): 641-628 (1994); Horii et al.,
EMBO J
13(20): 4776-4786 (1994); Chan et al.,
Oncogene
9(4) 1057-1063 (1994). Also, included in this family is the Tiam-1 protein. This protein has been shown to modulate the invasive potential of a cell. See Habets et al.,
Cell
77: 537-549 (1994); Habets et al.,
Oncogene
10(7): 1371-1376 (1995); and Gaston et al.,
Nature
375: 338-340 (1995). Tiam-1 also has been identified as a member of a family of GDP dissociation stimulators (GDSs). These proteins activate Rho4like and Rac-like GTPases.
SUMMARY
The present invention is a novel nucleic acid sequence which hybridizes to the DP-75 sequence of SEQ ID NO:6 or fragments thereof under stringent conditions. The invention also includes diagnostic assays, expression vectors, control sequences, antisense molecules, ribozymes, and host cells to express the polypeptide encoded by the nucleic acid sequence. The present invention also includes claims to the polypeptide sequence coded by the nucleic acid sequences.
The present invention is also related to pharmaceutical compositions comprising at least one 15- to 40-mer antisense oligonucleotide which is complementary to a region in DP-75; and a pharmaceutically acceptable carrier. The invention is also related to a method for treating cancer by suppressing cancer cell growth using a molecule that can inhibit DP-75, one example is by administering a growth suppressing amount of a DP-75 antisense oligonucleotide.
REFERENCES:
patent: 5482835 (1996-01-01), King et al.
patent: WO 92/10571 (1992-06-01), None
patent: WO97/46680 (1997-12-01), None
Chiu et al., “Cloning and Characterization of T-Cell Lymphoma Invasion and Metastasis 2 (TIAM2), a Novel Guanine Nucleotide Exchange Factor Related to TIAMI,”Genomics61:66-73, 1999.
Hoshino et al., “Identification of the stef Gene That Encodes a Novel Guanine Nucleotide Exchange Factor Specific for Racl *,”The Journal of Biological Chemistry 274(25):17837-17844, Jun. 18, 1999.
Leeuwen et al., “The Guanine Nucleotide Exchange Factor Tiam 1 Affects Neuronal Morphology; Opposing Roles for the Small GTPases Rac and Rho,”The Journal of Cell Biology 139(3):797-807, Nov. 3, 1997.
GenBank Accession No. AB022915, “Identification of the stef gene that encodes a novel guanine nucleotide exchange factor specific for Rac1,” Jun. 30, 1999, located at http://www.ncbi.nlm.nih.gov.
Boguski and McCormick, “Proteins regulating Ras and its relatives,”Nature 366:643-654, 1993.
Chan et al., “Expression cDNA cloning of a novel oncogene with sequence similarity to regulators of small GTP-binding proteins,”Oncogene 9(4):1057-1063, 1994.
Fantl et al., “Signalling By Receptor Tyrosine Kinases,”Annu. Rev. Biochem. 62:453-481, 1993.
Habets et al., “Identification of an Invasion-Inducing Gene,Tiam-1,That Encodes a Protein with Homology to GDP-GTP Exchangers for Rho-Like Proteins,”Cell 77:537-549, 1994.
Habets et al., “Sequence of the human invasion-inducing Tiami gene, its conservation in evolution and its expression in tumor cell lines of different tissue origin,” Oncogene 10(7) : 1371-1376, 1995.
Hart et al., “Cellular Transformation and Guanine Nucleotide Exchange Activity Are Catalyzed by a Common Domain on the dbl Oncogene Product,”The Journal of Biological Chemistry269(1) :62-65, 1994.
Hillier et al., EMBL Sequence Database Accession No. W21217, May 8, 1996.
Horii et al., “A novel oncogene, ost, encodes a guanine nucleotide exchange factor that potentially links Rho and Rac signaling pathways,”The EMBO Journal 13(20): 4776-4786, 1994.
Michiels et al., “A role for Rac in Tiam 1-induced membrane ruffling and invasion,”Nature 375:338-340, 1995.
Miki et al., “Oncogene ect2 is related to regulators of small GTP-binding proteins,”Nature 362:462-465, 1993.
Ron et al., “Molecular cloning and characterization of the human dbl proto-oncogene: evidence that its overexpression is sufficient to transform NIH/3T3 cells,”The EMBO Journal 7(8): 2465-2473, 1988.
Toksoz and Williams, “Novel human oncogene lbc detected by transfection with distinct homology regions to signal transduction products,”Oncogene 9(2): 621-628, 1994.
Blackburn Robert P.
Chiron Corporation
Morley Kimberlin L.
Potter Jane E. R.
Schmidt Mary M.
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