Chemistry: molecular biology and microbiology – Micro-organism – tissue cell culture or enzyme using process... – Recombinant dna technique included in method of making a...
Patent
1991-03-22
1993-11-16
Hill, Jr., Robert J.
Chemistry: molecular biology and microbiology
Micro-organism, tissue cell culture or enzyme using process...
Recombinant dna technique included in method of making a...
530351, 4351723, C12P 2106, C07K 1300, C12N 1500
Patent
active
052623092
DESCRIPTION:
BRIEF SUMMARY
TECHNOLOGICAL FIELD
This invention relates to a novel physiologically active polypeptide, a recombinant plasmid containing a DNA region encoding the polypeptide, a recombinant microorganism transformed with the plasmid, a method of producing the polypeptide using the microorganism cell, use of the polypeptide and a method of recovering the purified polypeptide.
More specifically, it relates to a series of technologies in regard to a novel antitumorally active polypeptide.
In the present specification, an amino acid and a polypeptide will be described abbreviatingly by the method accepted by Committee on Biochemical Nomenclature (CBN) of IUPAC-IUB, and for example, the following abbreviations are used.
A DNA sequence will be expressed by the bases contained in deoxyribonucleotides constituting it, and for example, the following abbreviations are used.
A: adenine (representing deoxyadenylic acid)
C: cytosine (representing deoxycytidylic acid)
G: guanine (representing deoxyguanylic acid)
T: thymine (representing deoxythymidylic acid)
(H.sub.2 N)- and -(COOH) respectively show the aminoterminus and carboxy-terminus of an amino acid sequence, 5 and (5')- and (3')- respectively show the 5'-terminus and the 3'-terminus of a DNA sequence.
TECHNOLOGICAL BACKGROUND
Carswell et al. found that a serum sample taken from a mouse stimulated with Bacillus Calmette-Guerin (BCG) and then given an endotoxin contains a substance which bleeds and necrotizes a solid tumor caused by a transplanted Meth A sarcoma; and named this substance tumor necrosis factor (abbreviated as "TNF") (E. A. Carswell et al., Proc. Natl. Acad. Sci., U. S. A. 72, 3666 (1975)). TNF is found in many animals such as mice, rabbits and humans. Since it acts specifically on tumor cells of any species, it is expected to be used as an antitumor agent.
Recently, Pennica et al. disclosed the primary structure of a human TNF protein by cloning cDNA of human TNF, and reported on the expression of the human TNF gene in Escherichia coli (D. Pennica et al.: Nature, 312, 724 (1984)). Later, Shirai et al. (T. Shirai et al.: Nature, 313, 803 (1985)), Somura et al. [Somura et al.: Cancer and Chemotherapy, 12, 160 (1985)), Wang et al. (A. M. Wang et al.: Science, 228, 149 (1985)), and Marmenout et al. (A. Marmenout et al.: Eur. J. Biochem., 152, 515 (1985)) reported the expression of human TNF genes in E. coli.
Thus, large quantities of pure human TNF proteins have become available by using the genetic manipulation technology, and physiological activities of TNF other than the antitumor activity have been elucidated in more detail. For example, it was suggested that cachectin, a substance which is one cause of inducing cachexia in patients in the terminal stage of cancer or patients with serious infections, is very similar to TNF (B. Beulter et al.: "Nature", 316, 552 (1985)), and since cachectin has lipoprotein lipase inhibitory activity, the administration of TNF increases the amount of triglycerides in the blood, and may possibly induce side-effects such as hyperlipemia. Elsewhere, the influence of TNF on vascular endothelial cells (J. R. Gamble et al.: J. Exp. Med., 162, 2163 (1985)), and its bone absorbing action (D. R. Beltolini et al.: "Nature", 319, 516 (1986)) have been reported.
On the other hand, the recent advance in genetic manipulation technology has enabled gene recombination to substitute an amino acid in a useful protein by another amino acid, to add an amino acid or to delete an amino acid from it. A number of research works have been conducted for modifying a naturally occurring protein and creating proteins which meet a specific purpose.
On the other hand, with regard to the modification of human TNF proteins, a number of research works have been made; there have been reported substitution of either or both of amino acid residues of CYs.sup.69 and Cys.sup.101 by other amino acid residues in the amino acid sequence of human TNF proteins shown in FIG. 1 ( see PCT Application Laid-Open Specification W086/04606 and Japanese Laid-Open Patent Publicati
REFERENCES:
patent: 4736020 (1988-04-01), Hillen et al.
Stryer 1981, Biochemistry, W. H. Freeman & Co., San Francisco, Chap. 2, pp. 18-20.
Creasey et al. 1987 Cancer Res. 47:145-149.
Kamijo et al. 1989 Biochem. Biophys. Res. Commun. 160(2):80-827.
Gase et al. 1990 Immunology 71:368-371.
Nakamura et al. 1991 Int. J. Cancer 48:744-748.
Somura et al., "Cancer and Chemotherapy", 12 160-162 (1985).
Fukuoka Masami
Ichikawa Yataro
Kato Arata
Kitai Kazuo
Masegi Tsukio
Carlson K. Cochrane
Hill Jr. Robert J.
Teijin Limited
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