Organic compounds -- part of the class 532-570 series – Organic compounds – Carbohydrates or derivatives
Reexamination Certificate
2000-08-03
2002-06-11
Wortman, Donna C. (Department: 1642)
Organic compounds -- part of the class 532-570 series
Organic compounds
Carbohydrates or derivatives
C530S350000, C435S006120, C435S091200, C536S023100, C536S024300, C536S024330
Reexamination Certificate
active
06403785
ABSTRACT:
TECHNICAL FIELD
The invention relates to a gene of use as an index in the prophylaxis, diagnosis and therapy of human diseases and more particularly to a novel lung-specific human gene which is homologous to human 1 amp-1 and -2 [lysosomal membrane glycoprotein; Saito, O. et al., J. Biol. Chem., 267, 5700-5711 (1992); Sawada, R. et al., J. Biol. Chem., 268, 12675-12681 (1993); Sawada, R. et al., J. Biol. Chem., 269, 1425-1431 (1994)] and suspected to act as an oncogene.
The invention further relates to a novel human gene which is analogous to the rat, mouse, yeast, nematode, known human and other genes and, through the cDNA analysis, chromosome mapping and functional analysis of its cDNA, can be utilized in gene diagnosis and for the development of new therapeutic drugs.
In addition, the invention relates to novel proteins encoded by said genes and to specific antibodies thereto.
BACKGROUND ART
The genetic information in organisms is accumulated as arrays (DNA) of four kinds of bases, viz. A, C, G and T, in the cell nucleus, and this genetic information is conserved for maintenance of lineage and ontogenesis. In a human being, the number of such bases is said to be approximately three-billion (3×10
9
) and it is estimated that this population includes 50-100 thousand genes. The genetic information is involved in the maintenance of vital phenomena through the creation of regulatory proteins, structural proteins, enzymes, etc. along the flow of transcription of mRNA from genes (DNA) and ensuing translation into proteins.
It is generally acknowledged that any abnormality of the above flow from a gene to its translation product protein leads to an error of the life maintenance system inclusive of the proliferation and differentiation of cells, and can becauses of various diseases. The results of gene analyses made to this day suggest that the genes of various receptors, such as the insulin, LDL and other receptors, and those of metabolic enzymes associated with the growth and differentiation of cells, such as protease, ATPase, superoxide dismutase, etc., are considered to be useful tools for the development of pharmaceuticals.
However, the analysis of human genes and the study of their functions and relationships to various diseases are still in the inchoate stage and much remains to be known. Therefore, analysis of new genes, analytical explorations into the functions and relationships to diseases of such genes, and studies for the establishment of gene diagnostics exploiting the genes so analyzed, and pharmaceutical application studies on such genes are subjects of immense interest to this industry.
Meanwhile, carcinoma of the pancreas is one of the malignant tumors of the digestive system with the poorest prognosis, ranking fourth and fifth on the list of causes for cancer-related death in Japan and Western counties, respectively (Poston, J. G., et al., Gut., 32, 800-812 (1991)). The most important goal in cancer research is to identify changes in the genes in the early phase of oncogenesis. Identification of such changes should lead to the development of genetic tools for early diagnosis and novel therapeutic modalities for effective treatment of this lethal disease.
Elucidation of the physiological roles of such genes and the resulting information are important to the explication of the mechanisms of genesis and onset of neoplastic diseases, and have been demanded not only in the field of fundamental scientific research but also from the standpoint of characterization and treatment of malignant tumors in the pharmaceutical field.
DISCLOSURE OF INVENTION
Thus, assuming that a novel human gene be provided, its expression levels in various cells as well as its structure and functions could be elucidated and through analysis of expression products of the gene, the clarification of pathology, diagnosis and therapy of the diseases associated with the gene, such as hereditary diseases and cancers, would become feasible. The object of the invention is to provide such novel human genes.
With the above object in mind, the inventors did intensive research as described below. Thus, to begin with, the inventors synthesized cDNAs from the mRNAs extracted from various human tissues such as human fetal brain, adult blood vessel and placenta, cloned them into vectors to construct libraries, cultured
Escherichia coli
cells transformed with each library on agar medium picked up transformant colonies at random and transferred them to microtiter plates to prepare and register
E. coli
clones containing various human genes. Then, each of these clones was cultured, the DNA extracted and purified, and using the cDNA thus obtained as a template, an amplification reaction with chain termination specific to said 4 bases is carried out by the deoxy terminator method, and using an automatic DNA sequencer, the sequence of about 400 nucleotides from the 5′ end of the human gene in each registered clone was determined. Based on the thus-obtained nucleotide sequence information on human genes, novel family genes similar to the known bacterial, yeast, nematoid, murine, human and other animal and plant genes were explored. The above technology for cDNA analysis is described in detail in the report of Fujiwara et al. [Fujiwara, Tsutomu, Saibo Kogaku (Cell Engineering), 14, 645-654 (1995)].
As a result, among the cDNA clones picked up arbitrarily from the human fetal brain cDNA library, the inventors found a clone harboring a novel gene which codes for an amino acid sequence having high homology to p33
ING1
which is considered to be a cancer-suppressive protein [GenBank A. C. No. AF001954, Garkavetsev, et al., Nature, Genet., 14, 415-420 (1996); Garkavetsev, et al., Mol. Cell. Biol., 17, 2014-2019 (1997); rewrote-GenBank A. C. No. AF0440767]. This invention has been developed on the basis of the above finding.
Furthermore, for the purpose of providing said information demanded by the industry, in particular a gene coding for a novel protein having homology to lamp-1 gene and lamp-2 gene, the inventors made an intensive exploration into the genes derived from various human tissues and succeeded in isolating and characterizing a novel lung-specific gene matching for the above purpose. This invention has been developed on the basis of the above finding.
Thus, in the first place, the invention provides a gene containing a nucleotide sequence coding for the amino acid sequence of SEQ ID NO:1 (hereinafter referred to TSC403 gene), in particular said gene which is a human gene.
In addition, the invention provides a novel protein encoded by said TSC403 gene (hereinafter referred to as TSC403 protein) and an antibody having a binding affinity for said protein.
Further, the invention provides a TSC403 gene which is any one of the following polynucleotides (a), (b) and (c), particularly said gene which is a human gene.
(a) a polynucleotide containing the nucleotide sequence of SEQ ID NO:2 or a complementary chain there; to
(b) a polynucleotide which hybridizes to a DNA having the nucleotide sequence of SEQ ID NO:2 under stringent conditions; and
(c) a polynucleotide having at least 95% homology to a polynucleotide coding for a polypeptide containing the amino acid sequence of SEQ ID NO:1
The invention further provides a TSC403 gene having the nucleotide sequence of SEQ ID NO:3.
The invention further provides an oligonucleotide having a sequence consisting of at least 15 consecutive nucleotides in the nucleotide sequence of SEQ ID NO:2 and a DNA fragment for use as a specific probe or primer for detecting genes having said oligonucleotide sequence.
Furthermore, in accordance with the invention, there is provided a human gene (hereinafter referred to as human ING1L gene) containing a nucleotide sequence coding for the amino acid sequence of SEQ ID NO:5.
This invention further provides a protein (hereinafter referred to as human ING1L protein) which is encoded by said human ING1L gene and an antibody binding said protein.
Further provided in accordance with this invention is a hu
Horie Masato
Nagata Masami
Ozaki Kouichi
Shimada Yoshikazu
Otsuka Pharmaceutical Co. Ltd.
Rawlings Stephen L.
Sughrue & Mion, PLLC
Wortman Donna C.
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