Antiangiogenic composition, useful for treating e.g. tumors, comprises new angiogenesis-related nucleic acids or related polypeptides, antibodies or antisense sequences

摘要

Antiangiogenic pharmaceutical composition comprises, as active ingredient, one or more of: (i) nucleic acid (I) from an endothelial cell gene the expression of which is induced by an angiogenic agent, or its complement or fragment; (ii) polypeptide (II) encoded by (I), or its fragment; (iii) an antisense nucleic acid (III) able to inhibit expression of (I); or (iv) an antibody (Ab) that binds (II). Independent claims are also included for the following: (1) antibody (Ab1) with affinity for any of 9 specified protein sequences (A), reproduced or their fragments; (2) producing Ab1 by in vitro immunization of an immunocompetent cell, especially from a mammal, with any of (A) or their fragments; (3) composition for diagnosis, prognosis and/or treatment of angiogenesis-related diseases comprising Ab1 or its fragments; (4) antisense sequences (IIIa) containing at least 10 nucleotides (nt) from any of 9 nucleic acid sequences (B) reproduced; (5) mammalian expression vector containing at least one (IIIa); (6) mammalian expression vector containing any of (B) or their fragments; (7) preparing a cell that underexpresses a gene implicated in an angiogenic disease comprising inserting a vector of (5) or (6) into a mammalian cell; (8) genetically modified cell that under- or over-expresses a (B); (9) preparing a cell line that stably expresses a vector of (5) or (6); (10) composition for diagnosis, prognosis and/or treatment of angiogenic diseases in mammals containing a cell of (8) or (9); (11) preparing a recombinant protein by cloning a (B) into a vector and introducing the product into a host cell; (12) recombinant protein or its fragments, produced by method (11) and compositions containing it; (13) diagnosis and/or prognosis of angiogenic diseases by detecting over- or under-expression of (B), in vitro or in isolated cells; (14) verifying effect of angiogenic treatment by in vitro detection of cell populations that under- or over-express at least one (B); (15) screening compounds for use in treatment of angiogenic diseases; (16) device for method (15) comprising a support with one or more probes specific for (B) fixed to it; and (17) kit for detecting differential expression of genes implicated in angiogenesis comprising: (i) the device of (16), specific primers and reagents for amplification, hybridization and measurement; or (ii) a stable cell of (8), as reference population, gene-specific probes and reagents for detecting and measuring expression.