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The General Hospital Corporation’s patents

The General Hospital Corporation has granted patents in Canada and Australia and filed an application in Europe. However, this patent family was obviously abandoned.

The disclosed inventions are mainly related to:

  • A method for the production of a polypeptide or protein whose structural gene is under the control of an inducible heat shock promoter.

    The structural gene and the heat inducible promoter are transformed in a host cell, which is not limited to a particular host organism.
    A gene amplification system under the control of a constitutive promoter is used to increase the copy number of the structural gene.

  • A method for increasing the production of a protein in a dihydrofolate reductase deficient mammalian cell. The structural gene of the protein of interest is placed under the control of a heat shock promoter and a dihydrofolate reductase gene is under the control of a constitutive promoter.
  • A host cell co-transformed with a gene amplification system as mentioned before and a structural gene driven by an inducible heat shock promoter.

Dihydrofolate reductase is a small enzyme that plays a supporting role in the building of DNA and other processes. It manages the concentration of folate, an organic molecule that shuttles carbon atoms to enzymes that need them in their reactions. Dihydrofolate reductase recycles folate after the release of its carbon atoms.

The dihydrofolate reductase gene is used by the inventors as a gene amplification system. Dihydrofolate reductase deficient mammalian cells transformed with this gene are able to grow in the presence of methotrexate, which is an inhibitor of dihydrofolate reductase. Growing in increasing concentrations of methotrexate leads the cells to overproduce dihydrofolate reductase. If a structural gene controlled by an inducible heat shock promoter is co-transformed with the dihydrofolate reductase gene system, both genes are amplified together under the selection pressure.

Title, Independent Claims and Summary of Claims Assignee
CA 1324097

  • Earliest priority – 6 February 1986
  • Filed – 4 February 1987
  • Granted -9 November 1993
  • Lapsed – 11 May 1996
 Title – Inducible heat shock and amplification system

Claim 1
A method for high level production of a polypeptide or protein in a transformed host cell comprising:
(a) transforming a host cell with a structural gene encoding for a polypeptide or protein, under the control of an inducible heat shock promoter;
(b) amplifying the copy number of said structural gene in said transformed host cells using an amplification system urder the control of a promoter other than an inducie e heat shock promoter;
(c) inducing said inducible promoter by heat shock to said transformedost cells at a temperature and for a time sufficient to transcribe said structural gene;;
(d) allowing said heat shocked cells to recover at a lower temperature than said heat shock temperature and for a time sufficient to translate said transcribed structural gene, producing said polypeptide or protein.
Claim 10
A method for increasing the production of a structural polypeptide or protein in a transformed mammalian cell comprising the steps of:
(a) culturing a dihydrofolate reductase (DHFR) deficient mammalian cell transformed with
(i) a DHFR gene under the control of a constitutive promoter. and
(ii) astructural gene encoding for a polypeptide or protein under the control of an inducible heat shock promoter, in a culture medium containing methotrexate, for a time sufficient to permit growth of said transformed mammalian cells;
(b) inducing said heat shock promoter at a temperature and for a time sufficient to transcribe said structural gene; and
(c) allowing said heat shocked cells to recover from said heat shock at a lower temperature and for a time sufficient to translate said transcribed structural gene, producing said polypeptide or protein.
Claim 17
A host cell cotransformed with:
(a) a gene amplification system under the control of a constitutive promoter, and
(b) a structural gene encoding for a polypeptide or protein under control of an inducible heat shock promoter.

General Hospital Corporation

Remarks

 The related Australian granted patent AU 606049 B2, granted on January 31, 1991, ceased on September 21, 1995. Similarly, the related European patent application EP 232845 A2 was withdrawn on October 23, 1991.

Note: Patent information on this page was last updated on 4 May 2006.

Search terms: “inducible heat shock” in abstract.

Patent database: Patent Lens and esp@cenet in combinaton with INPADOC.