Nucleic acid encoding angiogenesis inhibitor

Details Nucleic acid encoding angiogenesis inhibitor Nucleic acid encoding angiogenesis inhibitor

2006-10-10

2006-10-10

Haddad, Maher M. (Department: 1644)

Chemistry: molecular biology and microbiology

Micro-organism, per se ; compositions thereof; proces of...

Bacteria or actinomycetales; media therefor

C435S320100, C536S023500

Reexamination Certificate

active

07118905

ABSTRACT:
The present invention provides a novel angiogenesis inhibitor, LK68 whose amino acid sequence is identical with the human apolipoprotein (a) kringle domains IV36, IV37 and V38, a cDNA sequence encoding the LK68, a recombinant expression vector comprising the cDNA, a recombinant microorganism transformed with the recombinant expression vector and a novel use of the LK68 as an anticancer agent and a method for treating angiogenesis-mediated disease. LK68, LK6, LK7 and LK8 exhibit inhibitory activities on the cultured endothelial cell proliferation as well as on the endothelial cell migration. LK68 and its single kringles also inhibit the normal development of capillaries in the chick embryo chorioallantoic membrane (CAM). It was also showed that systemic administration of LK68 causes the inhibition of primary tumor growth, which is correlated with a suppression of tumor-induced angiogenesis. Accordingly, LK68 protein, its single kringles or their functional equivalents may be applied for the development of a potent anti-cancer agent, which is highly effective for angiogenesis-mediated diseases covering cancer, rheumatoid arthritis, psoriasis, ocular angiogenic disease, etc.

REFERENCES:
patent: 5639725 (1997-06-01), O'Reilly et al.
patent: 5801012 (1998-09-01), Soff et al.
patent: 5945403 (1999-08-01), Folkman et al.
patent: 6743428 (2004-06-01), Chang et al.
Lou, X. J. et al., 1998, Despite Its Homology to Angiostatin Apolipoprotein(a) Does Not Affect Angiogenesis,Exp. Mol. Pathol., 65:53-63.
LoGrasso, P. V. et al., 1994, Cloning, Expression, and Characterization of Human Apolipoprotein (a) Kringle IV37,J. Biol. Chem., 269(34):21820-21827.
Scanu, A. M. and Edelstein, C., 1994, Apolipoprotein(a): structural and functional consequences of mutations in kringle type 10 (or kringle 4-37),Clinical Genetics, 46:42-45.
Scanu, A. M. et al., 1994, A single point mutation (Trp72→Arg) in human apo (a) kringle 4-37 associated with a lysine binding defect in Lp(a), Biochimica et Biophysica Acta, 1227:41-45.
Gabel, B. R. and Koschinsky, M. L., 1998, Sequences within Apolipoprotein(a) Kringle IV Types 6-8 Bind Directly to Low-Density Lipoprotein and Mediate Noncovalent Association of Apolipoprotein(a) and Apolipoprotein B-100, Biochemistry, 37:7892-7898.
Mikol V, et al., 1996, Crystal structures of apolipoprotein(a) kringle IV37 free and complexed with 6-aminohexanoic acid and with p-aminomethylebenzoid acid: existence of novel and expected binding modes. J Mol Biol. 256(4):751-61.
Burgess et al., 1990, Possible dissociation of the heparin-binding and mitogenic activities of heparin-binding growth factor-1 from its receptor-binding activites by site-directed mutagenesis of a single lysine residue. J Cell Biol. 111:2129-2138.
Bowie JU et al., 1990, Deciphering the message in protein sequences: tolerance to amino acid substitutions. Science. 247(4948):1306-1310.
Fogarty M., 2002, Learning from Angiogenesis Trial Failures. The Scientist 16:33.
Fan TP et al., 1995, Controlling the vasculature: angiogenesis, anti-angiogenesis and vascular targeting of gene therapy. Trends Pharmacol Sci. 16:57-66.
Wallace RW, 1998, Media hype and drug discovery Drug Discovery Today, 3(10):433-434.
Cao Y et al., 1997, Kringle 5 of plasminogen is a novel inhibitor of endothelial cell growth. J Biol Chem. 272:22924-22928.
Kraft HG et al., 1995, Sequence polymorphism in kringle IV 37 in linkage disequilibrium with the aopolipoprotein (a) size polymorphism Hum Genet. 95(3):275-282.
McLean et al., 1987, cDNA sequence of human apolipoprotein(a) is homologous to plaminogen. Nature 330(6144):132-7.

Affiliated with

Also associated with

Rating

Nucleic acid encoding angiogenesis inhibitor does not yet have a rating. At this time, there are no reviews or comments for this patent.

If you have personal experience with Nucleic acid encoding angiogenesis inhibitor, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Nucleic acid encoding angiogenesis inhibitor will most certainly appreciate the feedback.

Rate now

Comments { 0 }

Profile ID: LFUS-PAI-O-3703663