Patent FR-2843753-A1 (FR)
Title: Antisense nucleic molecule useful as inhibitor of angiogenesis in the treatment of angiogenic disorders, e.g., rheumatoid arthritis, atherosclerosis and endometriosis
Inventor: COLIN SYLVIE
IPC: A61K48/00
Filed: 2003-06-20
Abstract: Inhibitor of angiogenesis (C) comprising an active substance chosen from at least one of a nucleic acid molecule, an antisense nucleic acid molecule, a polypeptide or an antibody, is new. Inhibitor of angiogenesis (C) comprising an active substance chosen from at least one of the following: (a) a gene comprising a nucleic acid molecule from an endothelial cell, whose expression is induced by an angiogenic factor and is inhibited by an angiostatic agent, chosen from any of the sequences of SEQ ID NO. 1 to SEQ ID NO. 5, SEQ ID NO. 7, SEQ ID NO. 9, SEQ ID NO. 11 to SEQ ID NO. 15, SEQ ID NO. 17 to SEQ ID NO. 53, SEQ ID NO. 225 and SEQ ID NO.284 to SEQ ID NO. 290 and/or a sequence complementary to any of these and/or a fragment of any of these sequences; (b) a polypeptide sequence encoded by any of the above nucleic acid molecules, chosen from any of the sequences of SEQ ID NO. 54 to SEQ ID NO. 58, SEQ ID NO. 60, SEQ ID NO. 62, SEQ ID NO. 64 to SEQ ID NO. 67, SEQ ID NO. 68 to SEQ ID NO. 102 and SEQ ID NO. 291 to SEQ ID NO. 297 and/or a fragment of any of these sequences; (c) an antisense nucleic acid molecule chosen from any of the sequences of SEQ ID NO. 6 , comprising at least 10 residues of a nucleic acid sequence chosen from SEQ ID NO. 108, SEQ ID NO. 110 and SEQ ID NO. 112; or (d) an antibody specific for a polypeptide encoded by the nucleic acid sequences chosen from SEQ ID NO. 6, SEQ ID NO. 8, SEQ ID NO. 10 and SEQ ID NO. 16; Independent claims are also included for: (1) antisense nucleic acid sequence (I) chosen from any of the sequences of SEQ ID NO. 1 to SEQ ID NO. 5, SEQ ID NO. 7, SEQ ID NO. 9, SEQ ID NO. 11 to SEQ ID NO. 15, SEQ ID NO. 17 to SEQ ID NO. 53, SEQ ID NO. 225 and SEQ ID NO. 284 to SEQ ID NO. 290, comprising at least ten residues chosen from any of the sequences of SEQ ID NO. 103 to SEQ ID NO. 107, SEQ ID NO.  109, SEQ ID NO. 111 and SEQ ID NO. 113 to SEQ ID NO. 148 and/or a sequence having at least 85%, preferably 95% sequence identity with a sequence chosen from any of SEQ ID NO. 103 to SEQ ID NO. 107, SEQ ID NO. 109, SEQ ID NO. 111 and SEQ ID NO. 113 to SEQ ID NO. 148; (2) antibody (II) specific for any of the polypeptide sequences comprising any of the sequences of SEQ ID NO. 54 to SEQ ID NO. 56, SEQ ID NO. 60, SEQ ID NO. 62, SEQ ID NO. 64 to SEQ ID NO. 67, SEQ ID NO. 68 to SEQ ID NO. 102 and SEQ ID NO. 291 to SEQ ID NO. 297; (3) preparation of the antibody (II) comprising in vivo or in vitro immunization of an immunocompetent animal cell, preferably of a vertebrate and most preferably of a mammal, with at least one of the polypeptide sequences chosen from any of SEQ ID NO. 54 to SEQ ID NO. 58, SEQ ID NO. 60, SEQ ID NO. 62, SEQ ID NO. 64 to SEQ ID NO. 67, SEQ ID NO. 68 to SEQ ID NO. 102 and SEQ ID NO. 291 to SEQ ID NO. 297 (4) mammalian expression vector (III) comprising at least one antisense sequence chosen from above (1) and/or from SEQ ID NO. 149 to SEQ ID NO. 153, SEQ ID NO. 157, SEQ ID NO. 159 to SEQ ID NO. 163, SEQ ID NO. 164 to SEQ ID NO. 194; (5) preparation of a genetically modified cell, that over- or under-expresses a gene implicated in an angiogenic disorder, comprising inserting into a mammalian cell a vector (III); (6) genetically modified cell (IV) that over-expresses or under-expresses at least one gene involved in angiogenesis by a nucleic acid sequence chosen from any of SEQ ID NO. 1 to SEQ ID NO. 290 as in (1) or a fragment of any of these; (7) preparation of a cell line that stably expresses an expression vector (III) comprises: (a) introducing a gene offering resistance to at least an antibiotic into a genetically modified cell (IV); (b) cultivating the cells obtained in step (a) in the presence of the antibiotic to which the transformed cells are resistant; and (c) selecting viable cells. (8) therapeutic composition useful to treat or diagnose an angiogenic disorder in mammals, preferably in humans, comprising (IV) or a cell line prepared as above in (7); (9) preparation of a recombinant protein comprising: (a) construction of an expression vector (III)