In 1998, Professor Paul Holvoet, University of Leuven, Belgium demonstrated for the first time that elevated levels of oxidized LDL were found in patients with both chronic and acute coronary artery syndromes, and that elevated levels of malondialdehyde (MDA)-modified LDL were found in patients with acute syndromes (unstable angina and acute myocardial infarction).
Oxidized LDL levels were determined using an enzyme-linked immunosorbent assay (ELISA) based on monoclonal antibody 4E6. MDA-modified LDL levels were determined using an ELISA based on monoclonal antibody 1H11. It should be noted that National Screening Institute (NSI) has the sole right to antibodies 4E6 and 1H11; including all sublicensing rights. For example, Mercodia AB, Sweden uses the 4E6 antibody, licensed from NSI, for its commercial test kits.
The 4E6 antibody is directed against a conformational epitope in the ApoB-100 moiety of LDL generated as a consequence of substitution of at least 60 lysine residues of ApoB-100 with aldehydes. This number of substituted lysines corresponds to the minimal number required for scavenger-mediated uptake of LDL.
A detailed description of the antibodies is contained in US patent 7,390,627 B2 dated June 24, 2008 is presented in the following pages.