Polypeptides and peptides, nucleic acids coding for them, and th

Details Polypeptides and peptides, nucleic acids coding for them, and th Polypeptides and peptides, nucleic acids coding for them, and th

1994-10-13

1999-11-09

Low, Christopher S. F.

Chemistry: molecular biology and microbiology

Animal cell, per se ; composition thereof; process of...

4353201, 435455, 435364, 435367, 4352523, 43525233, 43525411, 536 231, 536 235, 536 2433, 536 241, 935 9, 935 10, 935 11, 935 32, 935 66, C12N 502, C12N 506, C07N 2104

Patent

active

059812770

DESCRIPTION:

BRIEF SUMMARY
The invention relates to polypeptides and peptides, particularly recombinant polypeptides, which can be useful in the field of tumor therapy, inflammation or immunology.
The invention also relates to a process for preparing the above-said polypeptides and peptides.
It also relates to nucleic acids coding for said polypeptides and peptides.
Monocytes/macrophages are cells of great complexity accomplishing a multitude of different functions related to (i) responses to environmental challenges such as phagocytosis, antigen processing and presentation, (ii) enzyme production, (iii) to differentiation, (iv) to regulatory responses by the synthesis of macrophage-specific cytokines which function as metabolic or immunological regulatory proteins and (v) by the production of complement components, coagulation factors, enzymes, enzyme inhibitors, and oxygen radicals (reviewed by Adams and Hamilton (1984).
Several macrophage-derived cytokines have already been described: interleukin-1 (IL-1), tumor necrosis factor (TNF), interleukin-6 (IL-6), colony stimulating factor (CSF), interferon (IFN), macrophage inflammatory protein (MIP), and monocytic-derived neutrophil chemotactic factor (MDNCF or IL-8) (Old, 1985; Durum et al., 1986; Quesenberry, 1986; Billiau, 1987; Yoshimura et al., 1987; Davatelis et al., 1988; Kishimoto and Hirano, 1988;). In most instances, the production of these cytokines by the macrophages requires exposure to one or more signals present in the immediate microenvironment of the cells. These signals may consist of particulate matter which can be opsonized, invading parasites, bacterial infectants, or antibody-covered antigens (Unanue, (1989)). They invariably lead to a state of enhanced competence of the macrophage (termed activation), ultimately giving rise to the synthesis of some of the above-mentioned macrophage-specific cytokines (monokines).
A particular set of genes (some of which are specifically expressed by macrophages, hereafter termed monokine genes) may correspond to each individual activation process. Such genes can either be up- or down-regulated. Characterization of some of these genes is possible by measuring their corresponding biological function with appropriate bioassays (Ruff and Gifford, 1986; Van Snick et al., 1986; Van Damme et al., 1987), or using differential hybridization with cDNAs derived from either activated or nonactivated macrophages. This can result in the isolation of cDNAs that correspond to genes switched on during the process of differentiation of resting macrophages to activated cells.
It is an object of the invention to provide new polypeptides and their corresponding nucleic acids which can be used in immunology or in the field of tumor therapy.
It is another object of the invention to provide nucleic acids coding for the peptide chains of biologically pure, active recombinant peptides which enable their preparation on a large scale.
It is another aspect of the invention to provide nucleic sequences which can be used as antisense oligonucleotides.
It is another aspect of the invention to provide a chromosomal DNA fragment which can be used for producing a pathological model of a nonhuman animal such as a trangenic animal which can be used to study the effects of pharmacological compositions and to prepare different cell types from these trangenic animals which express the gene of the invention in a constitutive or inducible way.
It is another aspect of the invention to provide "knock-out" trangenic animals (Capecchi, 1989) in which the natural gene effectively homologous to the nucleotide sequences of the invention (definition of effectively homologous given hereafter) is rendered nonfunctional, for instance, by homologous recombination, with said animal being suitable for the study of the possible loss of functions or the possible restoration effects caused by the reintroduction of the polypeptides of the invention into the animals.
The polypeptide of the invention is characterized by the fact that it contains in its peptidic chain: liable to produce anti

REFERENCES:
patent: 5049659 (1991-09-01), Cantor et al.
Webster's II New Riverside University Dictionary, 1984, Soukhanov et al., eds., Houghton Mifflin Company, Boston, MA, p. 67.
Reeck et al. 1987 Cell 50: 667.
Watson et al. 1987 in: Molecular Biology Of The Gene, Fourth Edition, Benjamin/Cummings Publ. Co., Inc., Menlo Park Ca, p. 313.
Bosman et al. 1989 Downstream Processing in Biotechnol. II (2.29-2.36). (Abstract).

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