Rhone-poulenc Rorer S.a.

Exonhit Therapeutics, Sa

Aventis Pharma S.a.

University of Texas System

Institut National De La Sante Et De La Recherche Medicale

Rhone Poulenc Rorer

Diaxonhit

Bruno Tocque

Fabien J Schweighoffer

Laurent Bracco

Marc Duchesne

Jack A Roth

Fabienne Parker

Bohdan Wasylyk

Didier Faucher

Moussa Alkhalaf

Wei Wei Zhang

Fabien Schweighoffer

The invention concerns a method for identifying and/or cloning nucleic acid regions representing qualitative differences associated with alternative splicing events and/or with insertions, deletions located in RNA transcribed genome regions, between two physiological situations, comprising either hybridization of RNA derived from the test situation with cDNA's derived from the reference situation and/or reciprocally, or double-strand hybridization of cDNA derived from the test situation with cDNA's derived from the reference situation; and identifying and/or cloning nucleic acids representing qualitative differences. The invention also concerns compositions or banks of nucleic acids representing qualitative differences between two physiological situations, obtainable by the above method, and their use as probe, for identifying genes or molecules of interest, or still for example in methods of pharmacogenomics, and profiling of molecules relative to their therapeutic and/or toxic effects. The invention further concerns the use of dysregulation of splicing RNA as markers for predicting molecule toxicity and/or efficacy, and as markers in pharmacogenomics.

Qualitative differential screening

A medicinal combination of one or more nucleic acids that at least partially inhibit oncogenic cell signalling pathways, and a therapeutic anticancer agent, for use simultaneous, separate or over a period of time to treat hyperproliferative diseases.

Combined therapeutical treatment of hyperproliferative diseases

A polypeptide derivative of p62 having at least one deletion of at least one amino acid between amino acids 145 to 247 of p62, where the derivative inhibits signals transduced by ras.

&Dgr;P62, variants thereof, amino acid sequences coding therefor and their uses in gene therapy for cancer

The present invention describes new methods for the determination of the potential toxicity of test compounds, as well as the kits and tools for the implementation of these methods. The invention also describes methods for generating nucleic acid sequences that can be used as genetic markers of toxicity. The invention is based in particular on the creation of differential nucleic acid banks characteristic of situations in which cell viability and/or proliferation are deregulated, and on the demonstration that these banks can be used to evaluate the toxicity profile of compounds with reliability and high sensitivity. The invention is of special utility in the pharmaceutical industry for analysis of the toxicity profile of compounds involved in drug development and/or in pharmaceutical compositions.

Genetic markers of toxicity preparation and uses

The present invention concerns new compositions and methods for the detection of pathological events. It more specifically concerns methods for the detection in vitro of the presence of a pathology or a pathological event in a subject, comprising taking a sample of blood cells from the subject and determining, in this sample, the presence of blood cells presenting a physiological state characteristic of the pathology. The invention also concerns the tools, kits and compositions for the implementation of such methods, as well as their uses in the field of human and animal health, or in experimental research for example.

Methods and composition for the detection of pathologic events

Method of destroying hyperproliferative cells by combined p53 and taxoid treatment

The present invention is directed to a method for identifying and/or cloning within a biological sample alternatively spliced nucleic acid regions ocurring between two physiological conditions, comprising hybridizing RNA derived from a test condition with cDNA derived from the standard condition and further identifying and/or cloning nucleic acids corresponding to alternative forms of splicing.

Differential Qualitative screening

Peptides capable of inhibiting the transforming activity of activated p21 proteins, their preparation and compositions containing them are disclosed. Particular regions of the GAP protein have been identified and characterized that are involved in the transduction of activation signals of p21 proteins. Peptides derived from GAP protein but carrying an effector region rendered non-functional have been shown to inhibit the p21 signaling route. The products according to the invention are useful in pharmaceutical compositions to inhibit the transformation activity of ras genes whose transformation proceeds by a functional p21-GAP interaction.

Peptides which inhibit ras protein activity, their preparation and use

Anti-RAS intracellular binding proteins and use thereof

The present invention relates to transgenic, non-human animals overexpressing a MDM2 gene. These animals model MDM2 over-expression associated with human tumors, display a major phenotype characterized by the severe skin disorder ichthyosis, and are useful for identifying compounds for the treatment of human disease. Therefore, the invention also relates to methods of using the animals for identifying compounds effective for the treatment of diseases of the skin and respiratory tract, and to the compounds themselves.

Transgenic animals overexpressing MDM2

Peptides capable of binding to the GAP protein SH3 domain, nucleotide

Grb3-3 cDNA and polypeptides

Peptides having GDP exchange factor activity, nucleic acid sequences

The present invention relates generally to the area of quality control for recombinant agents to be used in gene therapy. Specifically, the invention concerns an assay used to identify the percentage of defective or therapeutically inactive vector in a vector stock.

Growing community of inventors

Courbevoie, France

Bruno Tocque