C - Chemistry – Metallurgy – 12 – N
Patent
C - Chemistry, Metallurgy
12
N
C12N 15/12 (2006.01) A01K 67/027 (2006.01) C07K 14/705 (2006.01) C12N 15/00 (2006.01) C12N 15/11 (2006.01) C12Q 1/68 (2006.01) A61K 38/00 (2006.01)
Patent
CA 2376666
Described are general means and methods of diagnosing and treating the phenotypic spectrum as well as the overlapping clinical characteristics with several forms of inherited abnormal expression and/or function of the Multi Drug Resistance-1 (MDR-1) gene. In particular, polynucleotides of molecular variant MDR-1 genes which, for example, are associated with unsufficient and/or altered uptake of drugs by a target cell, and vectors comprising such polynucleotides are provided. Furthermore, host cells comprising such polynucleotides or vectors and their use for the production of variant MDR-1 proteins are described. In addition, variant MDR-1 proteins and antibodies specifically recognizing such proteins as well as concerns transgenic non- human animals comprising the above-described polynucleotide or vectors are provided. Described are also methods for identifying and obtaining inhibitors for therapy of disorders related to the malfunction of the MDR-1 gene as well as methods of diagnosing the status of such disorders. Pharmaceutical and diagnostic compositions comprising the above-described polynucleotides, vectors, proteins, antibodies and inhibitors by the above-described method are provided. Said compositions are particularly useful for diagnosing and treating various diseases with drugs that are substrates, inhibitors or modulators of the MDR-1 gene product.
L'invention concerne des moyens généraux et des procédés de diagnostic et de traitement du spectre phénotypique et des caractéristiques cliniques de chevauchement, au moyen de plusieurs formes d'expression et/ou de fonction anormales héréditaires du gène de résistance aux antibiotiques-1 (MDR-1). L'invention concerne en particulier des polynucléotides de variantes moléculaires de gènes MDR-1, associés à une absorption insuffisante et/ou altérée de substances pharmaceutiques par une cellule cible, et des vecteurs contenant de tels polynucléotides. L'invention concerne en outre des cellules hôtes contenant de tels polynucléotides ou vecteurs, leur utilisation pour la production de variantes de protéines MDR-1, des variantes de protéines MDR-1 et des anticorps reconnaissant spécifiquement ces protéines, des animaux transgéniques contenant les polynucléotides ou vecteurs décrits ci-dessus, des procédés destinés à identifier et obtenir des agents inhibiteurs pour la thérapie de maladies liées au dysfonctionnement du gène MDR-1, des procédés de diagnostic du statut de tels maladies, et des compositions pharmaceutiques et diagnostiques contenant les polynucléotides, vecteurs, protéines, anticorps et agents inhibiteurs décrits ci-dessus obtenus au moyen du procédé décrit ci-dessus. Lesdites compositions sont particulièrement utiles pour le diagnostic et le traitement de différentes maladies par des substances pharmaceutiques du type substrats, agents inhibiteurs ou modulateurs du produit du gène MDR-1.
Brinkmann Ulrich
Eichelbaum Michel
Hoffmeyer Sven
Roots Ivar
Epidauros
Goudreau Gage Dubuc
Pgxhealth Llc
LandOfFree
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