# US 5,702,704 A · Antibodies to in vivo advanced glycosylation endproducts > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 5,702,704 A - Document ID: US5702704A - Status: Granted - Kind: A - Application number: 08/486,513 - Filed: 1995-06-07 - Granted: 1997-12-30 - Earliest claimed: 1991-12-20 - Assignees: The Rockefeller University - Inventors: Richard J. Bucala - Web page: https://patentgrep.com/patent/US5702704A ## CPC - G01N 33/6842: {Proteomic analysis of subsets of protein mixtures with reduced complexity, e.g. membrane proteins, phosphoproteins, organelle proteins} - C07K 1/1077: {by covalent attachment of residues other than amino acids or peptide residues, e.g. sugars, polyols, fatty acids} - C07K 1/22: Affinity chromatography or related techniques based upon selective absorption processes - C07K 16/18: against material from animals or humans - C07K 16/44: against material not provided for elsewhere {, e.g. haptens, metals, DNA, RNA, amino acids} - G01N 33/68: involving proteins, peptides or amino acids {(involving lipoproteins G01N33/92)} - G01N 33/723: {Glycosylated haemoglobin} - 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) - Y10S 435/975: Kit - 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) - C07K: PEPTIDES (peptides in foodstuffs A23; obtaining protein compositions for foodstuffs, working-up proteins for foodstuffs A23J; preparations for medicinal purposes A61K; peptides containing beta-lactam rings C07D; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, C07D; ergot alkaloids of the cyclic peptide type C07D519/02; macromolecular compounds having statistically distributed amino acid units in their molecules, i.e. when the preparation does not provide for a specific; but for a random sequence of the amino acid units, homopolyamides and block copolyamides derived from amino acids C08G69/00; macromolecular products derived from proteins C08H1/00; preparation of glue or gelatine C09H; single cell proteins, enzymes C12N; genetic engineering processes for obtaining peptides C12N15/00; compositions for measuring or testing processes involving enzymes C12Q; investigation or analysis of biological material G01N33/00) - 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) - Y10S: TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS ## 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 ### Claim 1 A pharmaceutical composition containing an anti-AGE antibody in combination with a pharmaceutically acceptable carrier; wherein said anti-AGE antibody is reactive with in vivo-produced advanced glycosylation endproducts and has the following characteristics: i. it reacts with an immunological epitope common to said in vivo-formed advanced glycosylation endproducts; ii. it is cross reactive with advanced glycosylation endproducts formed in vitro; and iii. 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), carboxymethyllysine, and pentosidine, wherein reactivity is detected in a competitive immunosorbent assay format, wherein bovine serum albumin (BSA)-AGE obtained by incubation of BSA with glucose is adsorbed to said solid phase, and said model AGE is tested as the inhibitor of binding of said antibody to said BSA-AGE. ### Claim 2 (depends on 1) The pharmaceutical composition of claim 1 wherein said in vivo-produced advanced glycosylation endproducts are selected from the group consisting of Hb-AGE, AGE-HSA, serum AGE-peptides, urinary AGE-peptides, and combinations thereof. ### Claim 3 An 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; and 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), carboxymethyllysine, and pentosidine, wherein reactivity is detected in a competitive immunosorbent assay format, wherein bovine serum albumin (BSA)-AGE obtained by incubation of BSA with glucose is adsorbed to said solid phase, and said model AGE is tested as the inhibitor of binding of said antibody to said BSA-AGE. ### Claim 4 (depends on 3) The antibody of claim 3 wherein the advanced glycosylation endproducts formed in vitro and reactive with said antiserum are selected from the group consisting of AGE-RNAse, AGE-hemoglobin, AGE-albumin, AGE-LDL, AGE-collagen Type IV, AGE-BSA reduced with NaBH.sub.4, and mixtures. ### Claim 5 (depends on 3) The antibody of claim 3 prepared by hyperimmunizing a mammal with a foreign protein or the reaction product of a protein incubated with a reducing sugar. ### Claim 6 (depends on 5) The antibody of claim 5 wherein said reaction product of a protein incubated with a reducing sugar is AGE-RNAse. ### Claim 7 (depends on 3) The antibody of claim 3 wherein said epitope is formed by the incubation of a reducing sugar with a proteinaceous material selected from the group consisting of RNAse, hemoglobin, lysine, collagen Type IV, LDL, BSA and HSA. ### Claim 8 (depends on 7) The antibody of claim 7 wherein the reducing sugar is selected from the group consisting of glucose, glucose-6-phosphate, fructose, and ribose. ### Claim 9 (depends on 3) The antibody of claim 3 wherein said epitope is formed by the incubation of glucose with RNAse. ### Claim 10 (depends on 3) The antibody of claim 3 which is polyclonal. ### Claim 11 (depends on 3) The antibody of claim 3 which is monoclonal. ### Claim 12 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; and C. it is not cross reactive with the following model advanced glyeosylation 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), carboxymethyllysine, and pentosidine, wherein reactivity is detected in a competitive immunosorbent assay format, wherein bovine serum albumin (BSA)-AGE obtained by incubation of BSA with glucose is adsorbed to said solid phase, and said model AGE is tested as the inhibitor of binding of said antibody to said BSA-AGE. ### Claim 13 (depends on 12) The labeled antibody of claim 12 wherein said label is selected from the group consisting of an enzyme, a chemical which fluoresces, and a radioactive element. ### Claim 14 (depends on 12) The labeled antibody of claim 12 which is polyclonal. ### Claim 15 (depends on 13) The labeled antibody of claim 13 which is monocional.