Chemistry: molecular biology and microbiology – Measuring or testing process involving enzymes or... – Involving antigen-antibody binding – specific binding protein...
Reexamination Certificate
2001-04-05
2003-12-30
Eyler, Yvonne (Department: 1646)
Chemistry: molecular biology and microbiology
Measuring or testing process involving enzymes or...
Involving antigen-antibody binding, specific binding protein...
C530S324000, C530S350000, C530S388100, C530S389100
Reexamination Certificate
active
06670136
ABSTRACT:
Throughout this application, various publications are referenced by author and date within the text. Full citations for these publications may be found listed alphabetically at the end of the experimental details sections for each experiment. The disclosures of these publications in their entireties are hereby incorporated by reference into this application in order to more fully describe the state of the art as known to those skilled therein as of the date of the invention described and claimed herein.
BACKGROUND OF THE INVENTION
The Receptor for AGE (RAGE) is a member of the immunoglobulin superfamily of cell-surface molecules (1-2). originally identified and characterized as a cellular receptor for glucose (aldose sugar)-modified proteins, or Advanced Glycation Endproducts (AGEs) (3-13), RAGE has subsequently been reported to interact with other ligands, in both settings of normal development and in Alzheimer's disease (14-16). In normal development, RAGE interacts with amphoterin, a polypeptide which mediates neurite outgrowth in cultured embryonic neurons. In those studies, either anti-RAGE F(ab′)
2
or soluble RAGE (sRAGE) inhibited neurite outgrowth on amphoterin-coated matrices, but not on matrices coated with other substrates such as laminin or poly-l-lysine (3). In later studies, RAGE was identified as a receptor on neurons and microglia for amyloid-&bgr;-peptide, a polypeptide linked to the pathogenesis of neuronal toxicity and death in Alzheimer's disease.
SUMMARY OF THE INVENTION
The present invention provides for an isolated human EN-RAGE peptide. The present invention also provides for a method for determining whether a compound is capable of inhibiting the interaction c an EN-RAGE peptide with a RAGE peptide, which comprises: (a) admixing: (i) a RAGE peptide or an sRAGE peptide or a fragment of either thereof, (ii) an EN-RAGE peptide or a fragment thereof, and (iii) the compound; (b) measuring the level of interaction between the peptide of step (a) (i) and the peptide of step (a) (ii), and (c) comparing the amount of interaction measured in step (b) with the amount measured between the peptide of step (a) (i) and the peptide of step (a) (ii) in the absence of the compound thereby determining whether the compound is capable of inhibiting the interaction of the EN-RAGE peptide with the RAGE peptide, wherein a reduction in the amount of interaction in the presence of the compound indicates that the compound is capable of inhibiting the interaction. The present invention also provides for a method for inhibiting inflammation in a subject which comprises administering to the subject a compound capable of interfering with the interaction between EN-RAGE peptide and receptor for advanced glycation endproduct (RAGE) in the subject thereby inhibiting inflammation in the subject.
REFERENCES:
Schmidt, A.M., SD Yan, and D. Stern. (1995). The Dark Side of Glucose (News and Views). Nature Medicine 1:1002-1004,.
Wu J, Rogers L, Stern D, Schmidt AM and Chiu DTW. (1997). The soluble Receptor for Advanced Glycation Endproducts (sRAGE) ameliorates impaired wound healing in diabetic mice. Plastic Surgery Research Council, Abstract #77, p. 43,.
Schmidt, A.M., Wautier, J-1., Stern D., and Yan S.D. (1998). RAGE: a receptor with a taste for multiple ligands and varied pathophysiologic states. Hormones and Signaling 1, 41-63.
Schmidt, A.M., Vianna,M., Gerlach, M., Brett, J., Ryan, J., Kao, J., Esposito, C., Hegarty, H., Hurley, W., Clauss, M., Wang, F., Pan, Y.C., Tsang, T.C., and Stern, D. (1992). Isolation and characterization of binding proteins for Advanced Glycosylation Endproducts from lung tissue which are present on the endothelial cell surface. J. Biol. Chem. 267,14987-14997.
Brett, J, et al., (1993). Survey of the distribution of a newly-characterized receptor for AGEs in tissues.Am. J. Pathol, 143:1699-1712.
Schmidt, A-M, et al. (1994). Receptor for Advanced Glycation Endproducts (AGEs) has a central role in vessel wall interactions and gene activation in response to circulating AGE proteins.Proc. Natl. Acad. Sci.(USA), 91:8807-8811.
Sell, D., and Monnier, V. (1989). Structure elucidation of a senescene cross-link from human extracellular matrix; implication of pentoses in the aging process.J.Biol. Chem. 10 264, 21597-21602.
Vlassara, H., et al. (1995). Identification of Galectin-3 as a high affinity binding protein for Advanced Glycation Endproducts (AGE): a new member of the AGE-Receptor complex.Molecular Medicine, 1:634-646.
Schmidt, A-M, et al. (1994). Cellular receptors for Advanced Glycation Endproducts.Arterioscler. Thromb., 14:1521-1528.
Hori, O., Brett, J., Slattery, T., Cao, R., Zhang, J., Chen, J., Nagashima, M., Nitecki, D., Morser, J., Stern, D., and Schmidt, A.M. (1995). The receptor for Advanced Glycation Endproducts (RAGE) is a cellular binding site for amphoterin: mediation of neurite outgrowth and coexpression of RAGE and amphoterin in the developing nervous system. J.Biol.Chem. 270, 25752-25761.
Wautier, J.-L., et al. (1996). Interaction of diabetic erythrocytes bearing advanced glycation endproducts with the endothelial receptor AGE induces generation of reactive oxygen intermediates and cellular dysfunction. Circulation Supplement 94 (8) :4139.
Schmidt Ann Marie
Stern David
Andres Janet L.
Cooper & Dunham LLP
Eyler Yvonne
The Trustees of Columbia University in the City of New York
White John P.
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