Monoclonal antibody specific for advanced glycosylation endproducts in biological samples

Abstract

The present invention relates to monoclonal antibodies to advanced glycosylation endproducts formed in vivo and cross-reactive with advanced glycosylation endproducts formed in vitro, and to methods of diagnosis and therapy based thereon. More particularly, the invention is directed to a monoclonal antibody, or an antigen-binding fragment thereof, reactive with in vivo produced advanced glycosylation endproducts (AGEs), which monoclonal antibody or antigen binding fragment thereof demonstrates an immunological binding characteristic of monoclonal antibody 4G9 as produced by hybridoma 4G9, deposited with the American Type Culture Collection (ATCC) and assigned Accession Number CRL 11626, on Apr. 27, 1994. In a specific embodiment, the 4G9 antibody is used in a sandwich ELISA to detect ApoB-AGE, IgG-AGE, collagen-AGE, serum-AGE peptides and proteins and urinary-AGE peptides and proteins.

1. Monoclonal antibody 4G9 produced by hybridoma 4G9, deposited with the American Type Culture Collection (ATCC) and assigned Accession Number CRL 11626, or an antigen binding fragment thereof reactive with in vivo produced advanced glycosylation endproducts (AGEs). 
     
     
       2. The monoclonal antibody or antigen binding fragment thereof of  claim 1 , which specifically binds to serum-AGE proteins, serum-AGE lipids, serum-AGE peptides, LDL-AGE, Hb-AGE, or collagen-AGE. 
     
     
       3. A humanized or chimetic chimeric human-murine antibody of the monoclonal antibody of  claim 1 . 
     
     
       4. The antigen-binding fragment of the monoclonal antibody of  claim 1 , selected from the group consisting of a single chain Fv fragment, an F(ab′) fragment, an F(ab) fragment, and an F(ab′) 2  fragment. 
     
     
       5. The monoclonal antibody or fragment thereof of  claim 1  which is a murine IgG isotype antibody. 
     
     
       6. A labeled antibody wherein the antibody is the antibody of  claim 1 . 
     
     
       7. A hybridoma deposited with the American Type Culture Collection (ATCC) and assigned Accession Number CRL 11626. 
     
     
       8. A pharmaceutical composition containing an anti-AGE antibody in combination with a pharmaceutically acceptable carrier;
 wherein said anti-AGE antibody is the monoclonal antibody in accordance with any of claims  1 - 3  or  4 .  
 
     
     
       9. A monoclonal antibody, or an antigen binding fragment thereof reactive with in vivo produced advanced glycosylation endproducts ( AGEs ) , wherein the antibody or fragment is selected such that antigen binding measured by binding competition by  6   - aminocaproic acid browned with glucose matches that of      a reference binding moiety which is monoclonal antibody  4 G 9  produced by hybridoma  4 G 9 , deposited with the American Type Culture Collection  ( ATCC )  and assigned Accession Number CRL  11626  or a fragment thereof corresponding to the antigen binding fragment.     
     
     
       10. The monoclonal antibody or antigen binding fragment thereof of  claim 9 , which specifically binds to serum- AGE proteins, serum - AGE lipids, serum - AGE peptides, LDL - AGE, Hb - AGE, or collagen - AGE.   
     
     
       11. A humanized or chimeric human- murine antibody of the monoclonal antibody of    claim 9   .   
     
     
       12. The antigen- binding fragment of the monoclonal antibody of    claim 9   , selected from the group consisting of a single chain Fv fragment, an F ( ab ′)  fragment, an F ( ab )  fragment, and an F ( ab ′) 2    fragment.   
     
     
       13. The monoclonal antibody or fragment thereof of  claim 9 , which is a murine IgG isotype antibody. 
     
     
       14. A labeled antibody wherein the antibody is the antibody of  claim 9 . 
     
     
       15. A pharmaceutical composition containing an anti- AGE antibody in combination with a pharmaceutically acceptable carrier; wherein said anti - AGE antibody is the monoclonal antibody in accordance with any of claims  9 ,  11 - 12  or  13 .