Patent applications filed and patents owned by VITO

Technology overview

VITO (Vlaamse instelling voor technologisch onderzoek, Flemish Institute for Technological Research) is a research organization in Belgium with a focus on contract research in the fields of energy, environment and materials technology.  A research team lead by Dr Luc PE Verschaeve has identified a method to enhance detection of genotoxic compounds by introducing a second ‘control’ transgenic microorganism along with the first transgenic microorganism that contains a stress-inducible promoter linked to a reporter gene.  The second transgenic microorganism contains a constitutive promoter linked to the same reporter gene as that of the first microorganism, which provides a background signal that can be used to adjust the signal from the first transgenic microorganism.

VITO has registered a genotoxicity test that uses this technology (and WO 1997/41251; see chapter 5 Detection of metal and other toxic compounds), which is called VITOTOX, containing two S. typhimuruim strains; one transformed with E. coli recN2-4 (recN promoter up mutation) and the other with a constitutive promoter with the sigma 70 consensus sequence, both promoters of which are linked to luxCDABE.  The related journal article of this technology is Verschaeve et al. (1999).  VITOTOX bacterial genotoxicity and toxicity test for the rapid screening of chemicals.  Environ. Mol. Mutagen. 33(3):240-8.

Details of patent documents

Patent or Publication no. Title, Independent Claims and Summary Assignee and licensing information
CA 2290354

  • Earliest priority – 14 Apr 1998
  • Filed – 12 Apr 1999
  • Application pending
  • Expected expiry – not applicable
Title – Diagnostic systems and method for determining the presence of a genotoxic and/or toxic compound in a sample

Claim 1
A diagnostic system made of:- a transformed micro-organism capable of an increased reporter activity upon exposure to an environmental insult, said micro-organism having a stress inducible promoter sequence being operatively linked to a reporter encoding nucleic acid sequence encoding a reporter molecule resulting in a signal that can be assayed, and of
– a transformed micro-organism having a constitutive and non stress inducible promoter sequence being operatively linked to a reporter encoding nucleic acid sequence encoding a reporter molecule resulting in a signal that can be assayed.
Claim 12
Method for determining the kinetics of genotoxicity of a compound into a sample, wherein the measuring of luminescence of both inducible and constitutive transformed micro-organisms occurs at multiple points in time, preferably continuously, and in addition carrying out the step of determining the signal-to-noise (S/N) ratio for the transformed micro-organisms at said point and time, dividing the S/N ratio of the inducible micro-organism by teat of the constitutive micro-organisms and plotting these data, said plotting representing the corrected kinetics ef genotoxicity of the genotoxic compound in the sample.

The claims are generally drawn towards:

  • a diagnostic system made of two transformed microorganisms , one with a stress inducible promoter and another with a constitutive and non-stress inducible promoter operably linked to a reporter (claim 1)
  • a method for determining the kinetics of genotoxicity of a compound into a sample (claim 12)

Definitions extracted from the description are provided in US 6472152.

Comments:

Since this is a published application and not a granted patent, currently there are no enforceable rights.

VITO

BOERETANG 200
B-2400
MOL BELGIUM

Ph + 32 14 33 55 11
Fax + 32 14 33 55 99

vito@vito.be

EP 950717

  • Earliest priority – 14 Apr 1998
  • Filed – 14 Apr 1998
  • Application deemed to be withdawn – 25 Oct 2000
  • Expected expiry – not applicable
Title – Diagnostic systems and method for determining the presence of a genotoxic and/or toxic compound in a sample

Claim 1
A diagnostic system made of :a transformed micro-organism capable of an increased reporter activity upon exposure to an environmental insult, said micro-organism having a stress inducible promoter sequence being operatively linked to a reporter encoding nucleic acid sequence encoding a reporter molecule resulting in a signal that can be assayed, and of
a transformed micro-organism having a constitutive and non stress inducible promoter sequence being operatively linked to a reporter encoding nucleic acid sequence encoding a reporter molecule resulting in a signal that can be assayed.
Claim 12
Method for determining the kinetics of genotoxicity of a compound into a sample, wherein the measuring of luminescence of both inducible and constitutive transformed micro-organisms occurs at multiple points in time, preferably continuously, and in addition carrying out the step of determining the signal-to-noise (S/N) ratio for the transformed micro-organisms at said point and time, dividing the S/N ratio of the inducible micro-organism by that of the constitutive micro-organisms and plotting these data, said plotting representing the corrected kinetics of genotoxicity of the genotoxic compound in the sample.

The claims are generally drawn towards:

  • a diagnostic system made of two transformed microorganisms , one with a stress inducible promoter and another with a constitutive and non-stress inducible promoter operably linked to a reporter (claim 1)
  • a method for determining the kinetics of genotoxicity of a compound into a sample (claim 12)

Definitions extracted from the description are provided in US 6472152.

Comments:

Since this is a published application and not a granted patent, currently there are no enforceable rights.

US 6472152

  • Earliest priority – 14 Apr 1998
  • Filed – 12 Apr 1999
  • Granted – 29 Oct 2002
  • Expected expiry – 12 Apr 2019
Title – Diagnostic systems and method for determining the presence of a genotoxic and/or toxic compound in a sample

Claim 1
A diagnostic system comprising:

  1. a first transformed micro-organism capable of an increased reporter activity upon exposure to an environmental insult, said micro-organism having a stress inducible promoter sequence being operatively linked to a nucleic acid sequence encoding a reporter molecule resulting in a signal that can be assayed, and
  1. a second transformed micro-organism having a constitutive and non-stress inducible promoter sequence being operatively linked to a nucleic acid sequence encoding a reporter molecule resulting in a signal that can be assayed, wherein

said second and first microorganisms are Salmonella typhimurium microorganisms selected from the group consisting of

  • Ames test micro-organism, micro-organism designated by deposit number LMG P-18318, transformed TA98, transformed TA100, transformed TA102, transformed TA104, transformed TA1538, transformed TA7001 to transformed TA7005, and transformed TA7041 to transformed TA7046,

said micro-organisms being suitable to cooperatively detect said environmental insult while eliminating false positive and false negative result.

The claims are generally drawn towards:

  • a diagnostic system comprising two transformed S. typhimurium strains, one with a stress inducible promoter and another with a constitutive and non-stress inducible promoter operably linked to a nucleic acid encoding a reporter molecule (claim 1)

Definitions extracted from the description are:

  • Environmental insult – this term is not defined in the specification. Dependent claim 7 recites this term as ‘the presence of a genotoxic and/or a toxic compound in a sample’
  • Stress inducible promoter – this term is not defined in the specification. Examples of promoters are provided in the following statement: ‘Advantageously, the stress inducible promoter sequence in the transformed bioluminescent micro-organism of the diagnostic system according to the invention is selected from the group consisting of groEL, dnaK, grpE, phoA, glnA, lon, lysU, rpoD, clpB, clpP, uspA, katG, uvrA, frda, micF, fabA, lac, his, sodA, sodB, soi-28, recA, xthA, narG, recF, recj, recN, recO, recQ, ruv, uvrD, ars, cad, mer, pco, and sfiA.’
  • Reporter – this term is not defined in the specification. Examples of reporters are provided in the following statement: ‘Preferably, both transformed micro-organisms are bioluminescent micro-organisms and the signal can be assayed as light production. Other possibilities are the peroxydase, alkaline phosphatase, β-gal and gus genetic sequence…’
  • LMG P-18318 – “pr1” strain, which is a transgenic S. typhimurium TA104 containing a constitutive promoter and luxCDABE

Comments:

Independent claim 1 of US 6472152 is relatively narrow in comparison to the other patent applications presented in this section (note: US 6472152 is the only granted patent presented in this section) in terms of the microorganism that can be used, which is limited to particular strains of S. typhimurium.

WO 1999/53092

  • Earliest priority – 14 Apr 1998
  • Filed – 12 Apr 1999
  • Published – 21 Oct 1999
  • Expected expiry – not applicable
Title – Diagnostic systems and method for determining the presence of a genotoxic and/or toxic compound in a sample

Claim 1
A diagnostic system made of- a transformed micro-organism capable of an increased reporter activity upon exposure to an environmental insult, said micro-organism having a stress inducible promoter sequence being operatively linked to a reporter encoding nucleic acid sequence encoding a reporter molecule resulting in a signal that can be assayed, and of
– a transformed micro-organism having a constitutive and non stress inducible promoter sequence being operatively linked  to  a reporter encoding nucleic acid sequence encoding a reporter molecule resulting in a signal that can be assayed.
Claim 12
Method for determining the kinetics of genotoxicity of a compound into a sample, wherein the measuring of luminescence of both inducible and constitutive transformed micro-organisms occurs at multiple points in time, preferably continuously, and in addition carrying out the step of determining the signal-to-noise (S/N) ratio for the transformed micro-organisms at said point and time, dividing the S/N ratio of the inducible micro-organism by that of the constitutive micro-organisms and plotting these data, said plotting representing the corrected kinetics of genotoxicity of the genotoxic compound in the sample.

The claims are generally drawn towards:

  • a diagnostic system made of two transformed microorganisms , one with a stress inducible promoter and another with a constitutive and non-stress inducible promoter operably linked to a reporter (claim 1)
  • a method for determining the kinetics of genotoxicity of a compound into a sample (claim 12)

Definitions extracted from the description are provided in US 6472152.

Comments:

Since this is a published application and not a granted patent, there are no enforceable rights.

Remarks
  1. National phase entry of WO 1999/53092 in China (CN 1227367) was granted on 16 Nov 2005.
  2. National phase entry of WO 1999/53092 in Europe (EP 977896) and Japan (JP 2002/509446) are pending.
  3. National phase entry of WO 1999/53092 in Australia (AU 36944/99) has lapsed on 22 May 2003.
  4. Other national phase entry of WO 1999/53092 includes Brazil (BR 9906356).

Search strategy

Search details
Date of search 17/05/2006
Database searched Patent Lens
Type of search Simple, stemming on
Collections searched AU-B, US-A, US-B, EP-B, WO
Search terms VITO in applicant
Results 3
Comments Of the 3 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.