Genes involved in the regulation of angiogenesis, pharmaceutical preparations containing them and their applications

摘要

A composition active on angiogenesis comprising an endothelial cell nucleic acid whose expression is induced by an angiogenic factor and inhibited by an angiostatic agent or its complement or fragment, a polypeptide sequence encoded by the nucleic acid, an antisense nucleic acid capable of inhibiting expression of the nucleic acid or an antibody which binds to the polypeptide sequence, is new. A new pharmaceutical composition active on angiogenesis comprises an endothelial cell nucleic acid whose expression is induced by an angiogenic factor and inhibited by an angiostatic agent or its complement or fragment, a polypeptide sequence encoded by the nucleic acid or its fragment, an antisense nucleic acid capable of inhibiting expression of the nucleic acid or an antibody which 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, comprising immunizing 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 antisense sequence, preferably a GS-V1 - GS-46 vector; (5) preparing a genetically modified cell which under-expresses a gene implicated in an angiogenic disorder, comprising inserting into a mammalian cell the above vector; (6) a genetically modified cell which under-expresses or over-expresses a gene implicated in angiogenesis comprising an N1 sequence or its fragment; (7) preparing a cell line which stably expresses the claimed expression vector comprising introducing an antibiotic resistance gene in the above genetically modified cell, cultivating the cell in antibiotic and selecting viable cells; (8) preparing a recombinant protein, comprising introducing an expression vector containing an 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 an angiogenic 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 the mammal that overexpresses or underexpresses a gene implicated in an angiogenic disorder of an N1 sequence; (12) identifying a compound useful for treating an angiogenic disorder, comprising detecting expression of an N1 sequence in a mammalian cell population in the presence of a candidate compound and comparing it with expression in a reference cell population; (13) a device comprising a support containing probes specific for N1 sequences ACTIVITY : Vasotropic; Antirheumatic; Antiarthritic; Hypotensive; Antianginal; Antiinflammatory; Cardiant; Ophthalmological; Antiarteriosclerotic; Antipsoriatic; Cytostatic; Gynecological. MECHANISM OF ACTION : Angiogenesis inhibitor; Angiogenesis activator.