Chemistry: molecular biology and microbiology – Micro-organism – tissue cell culture or enzyme using process... – Enzymatic production of a protein or polypeptide
Patent
1984-11-14
1989-03-28
Hazel, Blondel
Chemistry: molecular biology and microbiology
Micro-organism, tissue cell culture or enzyme using process...
Enzymatic production of a protein or polypeptide
4351723, 435243, 435255, 435320, 43525231, 43525233, C12P 2100, C12N 1500, C12N 100, C12N 120
Patent
active
048163970
DESCRIPTION:
BRIEF SUMMARY
This invention relates to multichain polypeptides or proteins and processes for their production in cells of host organisms which have been transformed by recombinant DNA techniques.
In recent years advances in molecular biology based on recombinant DNA techniques have provided processes for the production of heterologous (foreign) polypeptides or proteins in host cells which have been transformed with heterologous DNA sequences which code for the production of these products.
Theoretically, the recombinant DNA approach may be applied to the production of any heterologous polypeptide or protein in a suitable host cell, provided that appropriate DNA coding sequences can be identified and used to transform the host cell. In practice, when the recombinant DNA approach was first applied to the production of commercially useful products, its application for the production of any specified polypeptide or protein presented particular problems and difficulties, and the success of applying this approach to the production of any particular polypeptide or product was not readily predictable.
However, a large number of heterologous single chain polypeptides or proteins have now been produced by host cells transformed by recombinant DNA techniques. Examples of such heterologous single chain polypeptides or proteins include human interferons, the A and B chains of human insulin, human and bovine growth hormone, somatostatin, calf prochymosin and urokinase. Such transformed host cells provide a reproducible supply of authentic heterologous polypeptiede or protein which may be produced on an industrial scale using industrial fermentation technology.
It should be pointed out that some of these polypeptides, for instance urokinase, after secretion by a host cell appear as two chain molecules. However, in such cases, the molecule is synthesised by the host cell as a single chain polypeptide, coded for by a single DNA sequence, which is cleaved in the host cell subsequent to synthesis to form the two chain structure.
It is known that in both human and animal systems there are a number of polypeptides or proteins which have multichain structure in which the chains are not derived from the cleavage of a single chain polypeptide coded for by a single DNA sequence. In such cases, the gene for each of the chains may be located at different points on the same chromosome or even on different chromosomes. In these cases, the polypeptide chains are synthesised separately and then assembled into the complete molecule subsequent to synthesis. Heretofore, no such multichain polypeptide or protein has been produced by recombinant DNA techniques from a single host cell.
A particular example of a class of such multichain polypeptides or proteins is the immunoglobulins.
Immunoglobulins, commonly referred to as antibodies, are protein molecules produced in animals by B-lymphocyte cells in response to challenge with foreign antigenic agents, such as bacteria, viruses and foreign proteins. The immunoglobulins comprise a crucial part of the immune systems of humans and animals. The immunoglobulins recognise specific parts of the foreign agents and bind onto them. The specific parts are usually known as antigenic determinants or antibody binding sites. A given foreign agent is likely to have a number of different antigenic determinants.
A typical immunoglobulin (Ig) molecule is shown in FIG. 1 of the accompanying drawings, to which reference is now made. The Ig molecule comprises two identical polypeptide chains of about 600 amino acid residues (usually referred to as the heavy chains H), disulphide bonded to each other, and two identical shorter polypeptide chains of about 220 amino acid residues (usually referred to as the light chains L), each light chain being disulphide bonded to one end of each heavy chain as shown.
When the Ig molecule is correctly folded, each chain is formed into a number of distinct globular areas, usually known as domains, joined by a more linear polypeptide chain. The light chains have two such domains, one of which i
REFERENCES:
patent: 4403036 (1983-09-01), Hartley et al.
patent: 4642334 (1987-02-01), Moore et al.
Adams et al., Biochemistry, vol. 19, pp. 2711-2719, 1980.
Haley et al., DNA, vol. 1, pp. 155-162, 1982.
Gough et al., Biochemistry, vol. 19, pp. 2702-2710, 1980.
Iserentant et al., Gene, vol. 9, pp. 1-12, 1980.
Seidman et al: "Immunoglobulin light-chain structural gene sequences cloned in a bacterial plasmid," Nature, vol. 271, pp. 582-585, 1978.
Boss Michael A.
Emtage John S.
Kenten John H.
Wood Clive R.
Celltech Limited
Hazel Blondel
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