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Genes involved in regulating angiogenesis, pharmac

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专利名称:Genes involved in regulating angiogenesis,

pharmaceutical preparations containingsame and applications thereof

发明人:AL-MAHMOOD, SALMAN,COLIN,

SYLVIE,SCHNEIDER, CHRISTOPHE

申请号:EP05290552.8申请日:20030304公开号:EP1566387A2公开日:20050824

摘要:A composition active on angiogenesis comprising an endothelial cell nucleic acidwhose expression is induced by an angiogenic factor and inhibited by an angiostatic agentor its complement or fragment, a polypeptide sequence encoded by the nucleic acid, anantisense nucleic acid capable of inhibiting expression of the nucleic acid or an antibodywhich binds to the polypeptide sequence, is new. A new pharmaceutical compositionactive on angiogenesis comprises an endothelial cell nucleic acid whose expression isinduced by an angiogenic factor and inhibited by an angiostatic agent or its complementor fragment, a polypeptide sequence encoded by the nucleic acid or its fragment, anantisense nucleic acid capable of inhibiting expression of the nucleic acid or an antibodywhich binds to the polypeptide sequence. Independent claims are also included for (1)monoclonal or polyclonal antibodies having affinity for one of the polypeptide sequences(P1) fully defined in the specification; (2) preparing the above antibodies, comprisingimmunizing an immunocompetent animal, particularly a mammal, with at least one P1; (3)nucleic acid antisense to one of the nucleic acid sequences (N1 sequences) fully defined in

the specification; (4) a mammalian expression vector comprising the above antisensesequence, preferably a GS-V1 - GS-46 vector; (5) preparing a genetically modified cellwhich under-expresses a gene implicated in an angiogenic disorder, comprising insertinginto a mammalian cell the above vector; (6) a genetically modified cell which under-expresses or over-expresses a gene implicated in angiogenesis comprising an N1sequence or its fragment; (7) preparing a cell line which stably expresses the claimedexpression vector comprising introducing an antibiotic resistance gene in the abovegenetically modified cell, cultivating the cell in antibiotic and selecting viable cells; (8)preparing a recombinant protein, comprising introducing an expression vector containingan N1 sequence into a host cell, culturing the cell and purifying the expressed protein; (9)a recombinant protein obtained by the above method; (10) diagnosing or prognosing anangiogenic pathology in a mammal, particularly human, comprising detecting over-expression or under-expression of an N1 sequence; (11) determining efficacy of

angiogenic treatment to a mammal, comprising identifying in vitroa cell population of themammal that overexpresses or underexpresses a gene implicated in an angiogenicdisorder of an N1 sequence; (12) identifying a compound useful for treating an angiogenicdisorder, comprising detecting expression of an N1 sequence in a mammalian cellpopulation in the presence of a candidate compound and comparing it with expression ina reference cell population; (13) a device comprising a support containing probes specificfor N1 sequences ACTIVITY : Vasotropic; Antirheumatic; Antiarthritic; Hypotensive;Antianginal; Antiinflammatory; Cardiant; Ophthalmological; Antiarteriosclerotic;

Antipsoriatic; Cytostatic; Gynecological. MECHANISM OF ACTION : Angiogenesis inhibitor;Angiogenesis activator.

申请人:GENE SIGNAL INTERNATIONAL SA

地址:4 rue Pierre Fontaine 91000 Evry FR

国籍:FR

代理机构:Galup, Cédric Olivier Nicolas

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