Patent owned by the University of British Columbia

Technology overview

A team lead by Dr Edward P. Candido at the Department of Biochemistry, University of British Columbia conducted research on stress response using Caenorhabditis elegans as a model organism.  Major research interests of Dr Candido’s laboratory include the ubiquitin-conjugation system and heat shock protein (hsp) biology, one study of which concerned the creation of transgenic C. elegans having the promoter of hsp fused to the lacZ gene of E. coli that was evaluated for the potential to be used as a biosensor to detect environmental pollutants.  The following three related scientific articles were published by the research team:

  1. Stringham et al. (1992).  Temporal and spatial expression patterns of the small heat shock (hsp16) genes in transgenic Caenorhabditis elegans.  Mol Biol Cell. 3(2):221-33.
  2. Stringham and Candido (1993).  Transgenic strains of the nematode Caenorhabditis elegans as biological monitors of environmental stress.  FASEB J. 7(7): A1222-A1222.
  3. Stringham and Candido (1994).  Transgenic hsp16-lacZ strains of the soil nematode Caenorhabditis elegans as biological monitors of environmental stress.  Environ Toxicol Chem. 13(8): 1211-1220.

Details of the patent document

Patent or Publication no. Title, Independent Claims and Summary Assignee and licensing information
US 5877398

  • Earliest priority – 29 Jan 1993
  • Filed – 7 Apr 1995
  • Granted – 2 Mar 1999
  • Patent expired – 2 Apr 2003
Title – Biological systems incorporating stress-inducible genes and reporter constructs for environmental biomonitoring and toxicology

Claim 1
A transgenic nematode

  • selected from the group consisting of PC71, deposited as ATCC Accession Designation No. 209318, PC72, deposited as ATCC Accession Designation No. 209319, and PC73, deposited as ATCC Accession Designation No. 209320,
  • said nematode having a gene construct stably integrated into its genome, and gene construct comprising the nematode hsp16promoter operably linked to the lacZ gene, wherein the lacZ gene is expressed when said nematode is exposed to a toxin.
Claim 5
A kit comprising:

(a) a test chamber containing a liquid growth medium and at least one transgenic nematode selected from the group consisting of PC71, deposited as ATCC Accession Designation No. 209318, PC72, deposited as ATCC Accession Designation No. 209319, and PC73, deposited as ATCC Accession Designation No. 209320, said nematode having a gene construct stably integrated into its genome, said gene construct comprising a nematode hsp16 promoter operably linked to the lacZ gene, wherein the lacZ gene is expressed when said nematode is exposed to a toxin; and

(b) means for detecting expression of the lacZ gene.

The claims are generally drawn towards:

  • a transgenic nematode having the nematode hsp16 promoter operably linked to the lacZ gene (claim 1)
  • a kit comprising a test chamber containing at least one transgenic nematode having the nematode hsp16 promoter operably linked to the lacZ gene (claim 5)

Definitions extracted from the description are:

  • Nematode – there is no definition for this term. All ATCC accessions are transgenic Caenorhabditis elegans lines.
  • hsp16 (heat shock protein 16) – of the nematode Caenorhabditis elegans
  • lacZ gene – of the E. coli gene… encodes the enzyme, β-galactosidase
  • Toxin – there is no definition/limitation for this term. The examples report β-galactosidase activity upon exposure of a transgenic nematode to Pb(NO3)2, ZnCl2, NaAsO2, HgCl2, CuCl2, CdCl2, and a herbicide ‘paraquat’ (see Figure 5 in the specification). Note that heat (33 ˚C is the temperature given in the example and in Figure 6) also induces β-galactosidase activity for these transgenic nematodes.
  • Means (for detecting lacZ gene expression) – this term is not defined.  The specification provides the following two methods of detection:
  1. qualitative histochemical assay – indicates which tissues have undergone the stress response
  2. quantitative soluble assay – provides a colour change reflecting the level of stress-induced enzyme in the whole animal
  • PC71 and PC72 – C. elegans strains containing the complete translational fusion of hsp16::lacZ
  • PC73 – C. elegans strain containing the hsp16-48/1 translational exon 1::lacZ fusion

Comments:

Granted US 5877398 has expired due to non-payment of maintenance fees.

Although not recited in the claims (and therefore are not enforceable), the specification provides other possible reporter systems by potentially using a bacterial or firefly luciferase gene as the reporter gene, and other promoters that ‘respond to different classes of stressors or conditions…, e.g. metallothionein or cytochrome P450 promoters, or other heat shock promoters’.

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Search strategy

Search details
Date of search 28 Apr 2006
Database searched Patent Lens
Type of search Simple
Collections searched AU-B, US-A, US-B, EP-B, WO
Search terms biomonitor and cadmium
Results 22
Comments Of the 22 results identified using these search terms, 3 results were identified as being of particular interest based on their abstracts and a review of their claims.