Drug – bio-affecting and body treating compositions – Immunoglobulin – antiserum – antibody – or antibody fragment,...
Reexamination Certificate
1996-11-22
2004-09-14
Navarro, Mark (Department: 1645)
Drug, bio-affecting and body treating compositions
Immunoglobulin, antiserum, antibody, or antibody fragment,...
C424S130100, C424S158100, C424S184100, C424S278100, C435S325000, C435S334000, C435S440000, C514S002600, C530S350000, C530S388220
Reexamination Certificate
active
06790443
ABSTRACT:
BACKGROUND OF THE INVENTION
Throughout this application, various publications are referenced by author and date. Full citations for these publications may be found listed alphabetically at the end of the specification immediately the claims. 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.
Ineffective healing of wounds is a serious problem in diabetes, contributing to increased morbidity (Reynolds, 1985; Galloway and Shuman, 1963; and Pearl and Kanat, 1988). The reparative response in wound healing is orchestrated by multiple cellular elements which work together in many ways, including infiltration of the lesion by inflammatory effector cells. Subsequent to this, fibroblastic elements together with inflammatory effector cells provide antibacterial mechanisms and promote removal of necrotic tissue, as well as laying down of new connective tissue. A fundamental disorder of glucose metabolism might perturb these complex and interactive protective processes. Previous work has suggested that cellular dysfunction in diabetic wound healing involves defective neutrophil function (Bagdade et al., 1978; Nolan et al., 1978; and Mowat and Baum, 1971), delayed infiltration of the wound with inflammatory cells (Greenhalgh et al., 1990 and Fahey et al., 1991), decreased production of collagen (Goodson and Hunt, 1977 and Goodson and Hunt, 1986), and diminished activity of endogenous growth factors, such as basic fibroblast growth factor (Giardino et al., 1994), which could provide a basis for the slower formation of granulation tissue and wound closure.
SUMMARY OF THE INVENTION
The present invention provides a method for treating symptoms of diabetes in a diabetic subject which comprises administering to the subject a therapeutic amount of an agent which inhibits binding of advanced glycation endproducts to any receptor for advanced glycation endproducts so as to treat symptoms of diabetes in the subject.
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Schmidt et al., “Regulation of Human Mononuclear Phagocyte Migration by Cell Surface-Binding Proteins for Advanced Glycosylation End Products,” Journal of Clinical Investigation, 91(5):2155-2168, 1993.*
Brownlee, M. Diab. Care 15(12): 1835-1842, (Exhibit 2); Dec. 1992.
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Schmidt, A. M. et al. (1993) Regulation of human mononuclear phagocyte migration by cell surface-binding proteins for advanced glycation end products.J. Clin. Invest. 92:2155-2168.
Schmidt, A. M., et al. (1994) “The endothelial cell binding site for advanced glycation endproducts consists of a complex: an integral membrane protein and a lactoferrin-like polypeptide”J. Biol. Chem., 269:9882-9888.
Schmidt, A-M, et al. (1992) “Isolation and characterization of binding proteins for advanced glycation endproducts from lung tissue which are present on the endothelial cell surface”J. Biol. Chem., 267:14987-14997.
Schmidt, A-M, et al. (1994) “Cellular receptors for advanced glycation end products”Arterioscler. Thromb., 14:1521-1528.
Schmidt, A. M., et al (1995) “The Dark Side of Glucose (News and Views)”Nature Medicine, 1:1002-1004.
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.
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Yang, Z., et al (1991) “Two novel rat liver membrane proteins that bind AGEs: relation to macrophage receptor for glucose-modified proteins”J. Exp. Med., 174:515-524.
Schmidt Ann Marie
Stern David M.
Cooper & Dunham LLP
Hines Ja'na
Navarro Mark
The Trustees of Columbia University in the City of New York
White John P.
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