# US 5,700,447 A · Methods and materials for the diagnosis and treatment of conditions such as stroke > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 5,700,447 A - Document ID: US5700447A - Status: Granted - Kind: A - Application number: 08/319,747 - Filed: 1994-10-07 - Granted: 1997-12-23 - Earliest claimed: 1992-05-21 - Assignees: The Picowder Institute for Medical Research - Inventors: Richard J. Bucala; Helen Vlassara; Anthony Cerami; Kevin J. Tracey - Web page: https://patentgrep.com/patent/US5700447A ## CPC - A61K 31/155: Amidines ([IMAGE cpc-sch-A61K-1029.gif]), e.g. guanidine (H2N—C(=NH)—NH2), isourea (N=C(OH)—NH2), isothiourea (—N=C(SH)—NH2) - A61K 31/00: Medicinal preparations containing organic active ingredients - A61K 31/195: having an amino group - A61K 31/415: 1,2-Diazoles - A61K 31/70: Carbohydrates; Sugars; Derivatives thereof (sorbitol A61K31/047) - A61K 38/1709: {from mammals} - G01N 33/533: with fluorescent label - G01N 33/6893: {related to diseases not provided for elsewhere} - G01N 33/92: involving lipids, e.g. cholesterol {, lipoproteins, or their receptors (steroid hormones G01N33/743)} - G01N 2800/042: Disorders of carbohydrate metabolism, e.g. diabetes, glucose metabolism - G01N 2800/044: Hyperlipemia or hypolipemia, e.g. dyslipidaemia, obesity - G01N 2800/323: Arteriosclerosis, Stenosis - A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D) - G01N: INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES (measuring or testing apparatus or processes other than immunoassay, involving enzymes or microorganisms C12M, C12Q) ## Abstract The in vivo oxidation of lipids and lipid-containing molecules has been discovered to be initiated by the concurrent reaction of such lipid materials with reducing sugars such as glucose, advanced glycosylation endproducts such as AGE-peptides, or a compound which forms advanced glycosylation endproducts, to form materials or particles known as AGE-lipids. AGE-lipids have been implicated in the aging process, the abnormal formation of lipofuscin and in various disease states such as diabetes and atherosclerosis. Diagnostic methods are contemplated, extending in utility from the detection of the onset and course of conditions in which variations in lipid oxidation, AGE-lipid levels, LDL levels, apolipoprotein levels, apolipoprotein receptor binding the like, may be measured, to drug discovery assays. Corresponding methods of treatment and pharmaceutical compositions are disclosed that are based on an active ingredient or ingredients that demonstrates the ability to modulate the levels of all of the foregoing markers of lipid oxidation. A further aspect of the invention relates to the treatment of stroke and related maladies, and to agents and compositions that are prepared for such purpose. ## Claims ### Claim 1 A method for estimating the course and extent of in vivo lipid oxidation in a mammal comprising measuring the presence and amount of AGE-lipids in said mammal. ### Claim 2 (depends on 1) The method of claim 1, wherein said AGE-lipids are measured by an in vitro procedure. ### Claim 3 (depends on 1) The method of claim 1, comprising the steps of: A. preparing at least one biological sample taken from said mammal in which said AGE-lipids are suspected to be present; B. immobilizing the biological sample of Step A or a binding partner to AGE-lipid or AGE-lipid related material, on a suitable substrate, and labelling the other of the materials not immobilized; C. incubating said sample with said binding partner for a period of time sufficient for said binding partner to become bound to any AGE-lipid or AGE-bearing lipid-related material present in said sample; D. removing any unbound material from Step C, and E. comparing the amount of label bound to said sample to a standard. ### Claim 4 (depends on 3) The method of claim 3, wherein said binding partner is selected from the group consisting of a receptor for an AGE, and an antibody reactive with or capable of binding to said AGE-lipid. ### Claim 5 (depends on 4) The method of claim 4, wherein said antibody to said AGE-lipid is selected from the group consisting of polyclonal antibodies, monoclonal antibodies, and chimeric antibodies. ### Claim 6 (depends on 1) The method of claim 1 comprising a method for monitoring the level of low density lipoprotein in said mammal. ### Claim 7 (depends on 1) The method of claim 1, comprising a method for diagnosing the likelihood or onset, and/or for monitoring the course and severity of a pathology selected from atherosclerosis, vascular disease, diabetes, diabetic nephropathy, and hypercholesterolemia. ### Claim 8 A method of testing the ability of a drug or other entity to prevent blockade of the LDL receptor binding domain on apo B, which comprises disposing a quantity of apo B with unbound LDL receptor binding domain in a suitable medium, simultaneously adding a quantity of an material capable of forming an AGE on said binding domain, and the drug under test, and thereafter measuring the quantity of AGE-apo B, if any, that is formed.