Immunochemical detection of in vivo advanced glycosylation endproducts

• US 5,712,101 A
• Filed: 06/07/1995
• Issued: 01/27/1998
• Est. Priority Date: 12/20/1991
• Status: Expired due to Fees

• Current Assignee: BBDX, Inc.
• Original Assignee: Rockefeller University
• Inventors: Bucala, Richard J.
• Primary Examiner(s): Chan, Christina Y.
• Assistant Examiner(s): Cech, Emma
• Application Number:
  US08/472,398
• Time in Patent Office: 965 Days
• Field of Search: 435/7.1, 436/67, 436/66
• US Class Current: 435/7.1
• CPC Class Codes: A61K 38/00 Medicinal preparations containing peptides peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00
• CPC Class Codes: C07K 1/1077 by covalent attachment of residues other than amino acids or peptide residues, e.g. sugars, polyols, fatty acids
• CPC Class Codes: C07K 1/22 Affinity chromatography or related techniques based upon selective absorption processes
• CPC Class Codes: C07K 16/18 against material from animals or humans
• CPC Class Codes: C07K 16/44 against material not provided for elsewhere , e.g. haptens, metals, DNA, RNA, amino acids
• CPC Class Codes: G01N 33/68 involving proteins, peptides or amino acids involving lipoproteins G01N33/92
• CPC Class Codes: G01N 33/6842 Proteomic analysis of subsets of protein mixtures with reduced complexity, e.g. membrane proteins, phosphoproteins, organelle proteins
• CPC Class Codes: G01N 33/723 Glycosylated haemoglobin
• CPC Class Codes: Y10S 435/975 Kit

Abstract

The circulating advanced glycosylation endproducts Hb-AGE, serum AGE-peptides and urinary AGE-peptides are disclosed as long term markers of diseases and dysfunctions having as a characteristic the presence of a measurable difference in AGE concentration. Diagnostic and therapeutic protocols taking advantage of the characteristics of these AGEs are disclosed. Antibodies which recognize and bind to in vivo-derived advanced glycosylation endproducts are also disclosed. Methods of using these antibodies as well as pharmaceutical compositions are also disclosed, along with numerous diagnostic applications, including methods for the measurement of the presence and amount of advanced glycosylation endproducts in both plants and animals, including humans, as well as in cultivated and systhesized protein material for therapeutic use.

Claims

1. A method for the long term measurement of the presence, extent or control of blood sugar in a mammal comprising:

obtaining a sample of hemoglobin from the mammal;

determining the level of advanced glycosylation of said hemoglobin by quantifying the formation of a reaction complex by measuring the extent of binding detected in said biological sample using a labeled antibody reactive with in vivo-formed advanced glycosylation endproducts and having the following characteristics;

A. it reacts with an immunological epitope, common to said in vivo-formed advanced glycosylation endproducts;

B. it is cross reactive with advanced glycosylation endproducts formed in vitro;

C. it is not cross reactive with the following model advanced glycosylation endproducts however formed;

2-(2-furoyl)-4(5)-(2-furanyl)-1H, imidazole (FFI), 1-alkyl-2-formyl-3,4-diglycosyl pyrrole (AFGP), 5-hydroxymethyl-1-alkylpyrrole-2-carbaldehyde(pyrraline) and pentosidine; and

comparing the level of advanced glycosylated hemoglobin to a level in said mammal obtained at an earlier time, wherein an increase indicates an increase in blood sugar, and a decrease indicates a decrease in blood sugar.