Administering antisense oligonucleotides complementary to human apolipoprotein b

Abstract

Methods for long-term lowering of lipid levels in human subjects and for the treatment of conditions associated with elevated LDL-cholesterol and elevated ApoB are provided.

1 . A method comprising administering to a subject a pharmaceutical composition comprising an antisense oligonucleotide complementary to a nucleic acid encoding human apolipoprotein B-100, wherein the administering comprises an induction phase, wherein a dose of the antisense oligonucleotide ranging from 100-300 mg is administered once per week for at least 13 weeks, followed by a maintenance phase, wherein a dose of the antisense oligonucleotide ranging from 80-200 mg is administered once per week or once every two weeks for as long as needed, effective, and/or tolerated. 
     
     
         2 . The method of  claim 1 , wherein the dose administered in the induction phase is a 100 mg dose and the dose administered in the maintenance phase is a 200 mg dose administered once per week. 
     
     
         3 . The method of  claim 1 , wherein the dose administered in the induction phase is a 200 mg dose, and the dose administered in the maintenance phase is a 300 mg dose administered once per week. 
     
     
         4 . The method of  claim 1 , wherein the dose administered in the induction phase is a 100 mg dose and the dose administered in the maintenance phase is a 200 mg dose administered once per week, and wherein the tolerability or the effectiveness of the antisense oligonucleotide are assessed during or at the end of the induction period, or a portion thereof once per week during the maintenance phase. 
     
     
         5 . The method of  claim 1 , wherein the dose administered in the induction phase is a 200 mg dose and the dose administered in the maintenance phase is a 300 mg dose administered once per week, and wherein the tolerability or the effectiveness of the antisense oligonucleotide are assessed during or at the end of the induction period, or a portion thereof. 
     
     
         6 . The method of  claim 1 , wherein the dose administered in the induction phase is a 100 mg dose and the dose administered in the maintenance phase is a 100 mg dose administered once every two weeks, and wherein the tolerability or the effectiveness of the antisense oligonucleotide are assessed during or at the end of the induction period, or a portion thereof. 
     
     
         7 . The method of  claim 1 , wherein the dose administered in the induction phase is a 200 mg dose and the dose administered in the maintenance phase is a 200 mg dose administered once every two weeks, and wherein the tolerability or the effectiveness of the antisense oligonucleotide are assessed during or at the end of the induction period, or a portion thereof. 
     
     
         8 . The method of  claim 1 , wherein the dose administered in the induction phase is from 100 mg to 200 mg and the dose administered in the maintenance phase is from 200 mg to 300 mg and is administered once per week. 
     
     
         9 . The method of  claim 1 , wherein said administering comprises parenteral administration. 
     
     
         10 . The method of  claim 1 , wherein said parenteral administration comprises subcutaneous administration. 
     
     
         11 . The method of  claim 1 , wherein each induction dose and each maintenance dose comprises a single injection. 
     
     
         12 . The method of  claim 1 , wherein each induction dose and each maintenance dose independently comprise two or more injections. 
     
     
         13 . The method of  claim 1 , further comprising assessing the tolerability or effectiveness of the antisense oligonucleotide during or at the end of the induction period, or a portion thereof. 
     
     
         14 . The method of  claim 13 , wherein the tolerability and the effectiveness of the antisense oligonucleotide are assessed. 
     
     
         15 - 144 . (canceled)