definiens: means the oligonucleotide known as ISIS 681257 ( a lso known as IONIS - APO(a)-L Rx ) having the following sequence and chemistry : 5'-THA -AH P = O Me UG P = O Me CP = O Me UP = O Me CP = O Me CGTTGGTG Me CT Me UP = O GP = O Me UMe UMe C-3′. The underlined residues are 2'-O-(2 - methoxyethyl ) nucleosides ( 2'-MOE nucleosides ) . The residues are arranged so that there are five 2'-MO E nucleosides at the 5 ' and 3 ' ends of the oligonucle otide flanking a gap of ten 2'-deoxynucleosides . Th e cytosine and uracil bases are methylated at the 5 - position . Me U and T have the same structure and the choice for the symbol depends on whether the sugar is 2′-deoxy - D - ribose o r D - ribose . The P = O designates the location of a phosphate diester linkage . Each of the other internucleoside linkages is a phosphorothioate diester linkage . AH designates the location of the aminohexyl linker and THA is 5- N-{tris[(6-(2 - acetamido-3,4,6 - tri - O - acetyl - β - D - galactopyranosyloxy)hexylamino)-3 - oxopropoxymethyl ] methyl}amino-5 - oxopentanoyl