C - Chemistry – Metallurgy – 12 – N
Patent
C - Chemistry, Metallurgy
12
N
C12N 15/12 (2006.01) A61K 38/39 (2006.01) C07K 14/78 (2006.01) C07K 16/18 (2006.01) C12N 15/62 (2006.01) C12Q 1/68 (2006.01) A61K 38/00 (2006.01)
Patent
CA 2313251
Described herein are novel mutants of endostatin, one of which, designated "EM 1", has anti-angiogenic activity similar or superior to that of wild type endostatin. The invention relates to the discovery of an isolated anti- angiogenic peptide, wherein the C-terminal end of the peptide comprises the amino acid sequence SYIVLCIE, which has anti-angiogenic properties. Designated "EM 1", this protein comprises a mutated endostatin protein, where the mutation comprises a deletion of nine consecutive amino acids from the C- terminus of the mutated endostatin protein (e.g., NSFMTSFSK). EM 1 terminates in the amino acid sequence SYIVLCIE. The invention also comprises isolated polynucleotides encoding EM 1, operably linked to expression sequence, and host cells transformed with such a construct. Antibodies to EM 1 are also disclosed. The invention also relates to processes for producing EM 1, fusion proteins containing EM 1, and compositions comprising EM 1 or fusion products thereof. The invention also discloses methods of producing polypeptides encoding EM 1.
L'invention concerne de nouveaux mutants d'endostatine, l'un de ces mutants, ci-après dénommé "EM 1", présentant une activité anti-angiogénique identique ou supérieure à celle de l'endostatine de phénotype sauvage. L'invention concerne également la découverte d'un peptide anti-angiogénique isolé, l'extrémité C-terminale de ce peptide comprenant la séquence d'acide aminé SYIVLCIE, laquelle présente des propriétés anti-angiogéniques. Cette protéine ci-après dénommée "EM 1" renferme une protéine d'endostatine mutée, la mutation consistant en une délétion de quatre acides aminés consécutifs de l'extrémité carboxylique de ladite protéine d'endostatine mutée (par exemple NSFMTSFSK), EM 1 se terminant dans la séquence d'acide aminé SYIVLCIE. L'invention concerne en outre des polynucléotides isolés codant pour EM 1, ces polynucléotides étant liés de manière opérationnelle à une séquence d'expression, et des cellules hôtes transformées à l'aide de ce produit de recombinaison. L'invention concerne par ailleurs des anticorps de EM 1, des procédés de production de EM 1, des protéines de fusion renfermant EM 1, et des compositions contenant EM 1 ou des produits de fusion de EM 1. L'invention concerne enfin des procédés de production des polypeptides codant pour EM 1.
Beth Israel Deaconess Medical Center
Ogilvy Renault Llp/s.e.n.c.r.l.,s.r.l.
LandOfFree
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