Modulating apolipoprotein (a) expression
Provided herein are oligomeric compounds with conjugate groups targeting apoplipoprotein (a). In certain embodiments, the apo(a) targeting oligomeric compounds are conjugated to N-Acetylgalactosamine. Also disclosed herein are conjugated oligomeric compounds targeting apo(a) for use in decreasing apo(a) to treat, prevent, or ameliorate diseases, disorders or conditions related to apo(a) and/or Lp(a). Certain diseases, disorders or conditions related to apo(a) and/or Lp(a) include inflammatory, cardiovascular and/or metabolic diseases, disorders or conditions. The conjugated oligomeric compounds disclosed herein can be used to treat such diseases, disorders or conditions in an individual in need thereof.
1. A pharmaceutical composition comprising an oligomeric compound, or a pharmaceutically acceptable salt thereof and one or more pharmaceutically acceptable carriers or diluents, wherein the oligomeric compound has the following structure:
and wherein the pharmaceutical composition contains 75 mg to 85 mg of the oligomeric compound, or a pharmaceutically acceptable salt thereof.
2. The pharmaceutical composition according to claim 1 , wherein the pharmaceutical composition contains about 80 mg of the oligomeric compound.
3. The pharmaceutical composition according to claim 1 , wherein the pharmaceutical composition contains 80 mg of the oligomeric compound, or a pharmaceutically acceptable salt thereof.
4. The pharmaceutical composition according to claim 1 , wherein the oligomeric compound is administered as a sodium salt.
5. The pharmaceutical composition according to claim 4 , wherein the oligomeric compound has the following structure:
6. The pharmaceutical composition according to claim 1 , wherein the pharmaceutical composition is formulated for administration to a human by injection.
7. The pharmaceutical composition according to claim 1 , wherein the oligomeric compound, or the pharmaceutically acceptable salt thereof, is formulated in a sterile liquid and optionally the composition is not more than 1 mL of the sterile liquid.
8. The pharmaceutical composition according to claim 7 , wherein the pharmaceutical composition is not more than 0.8 mL of the sterile liquid.
9. The pharmaceutical composition according to claim 7 , wherein the pharmaceutical composition is not more than 0.5 mL of the sterile liquid.
10. The pharmaceutical composition according to claim 7 , wherein the pharmaceutical composition is not more than 0.4 mL of the sterile liquid.
11. The pharmaceutical composition according to claim 7 , wherein the pharmaceutical composition is not more than 0.25 mL of the sterile liquid.
12. The pharmaceutical composition according to claim 7 , wherein the pharmaceutical composition is not more than 0.2 mL of the sterile liquid.
13. The pharmaceutical composition according to claim 7 , wherein the sterile liquid is water.
14. The pharmaceutical composition according to claim 7 , wherein the sterile liquid is water with a sodium phosphate buffer.
15. The pharmaceutical composition according to claim 7 , wherein the sterile liquid is water with a sodium phosphate buffer and sodium chloride.
16. The pharmaceutical composition according to claim 1 , wherein administering the pharmaceutical composition to a human reduces the fasting plasma Lp(a) concentration in the human by at least 50%, when the fasting plasma Lp(a) concentration in the human is measured at the start and end of the dosing period.
17. The pharmaceutical composition according to claim 1 , wherein administering the pharmaceutical composition to a human reduces the fasting plasma Lp(a) concentration in the human by at least 75%, when the fasting plasma Lp(a) concentration in the human is measured at the start and end of the dosing period.
18. The pharmaceutical composition according to claim 1 , wherein administering the pharmaceutical composition to a human reduces the fasting plasma Lp(a) concentration in the human by at least 80%, when the fasting plasma Lp(a) concentration in the human is measured at the start and end of the dosing period.
19. The pharmaceutical composition according to claim 1 , wherein administering the pharmaceutical composition to a human reduces the fasting plasma Lp(a) concentration in the human by at least 85%, when the fasting plasma Lp(a) concentration in the human is measured at the start and end of the dosing period.
20. A method for producing the pharmaceutical composition according to claim 1 , wherein the method comprises combining 75 mg to 85 mg of the oligomeric compound, or a pharmaceutically acceptable salt thereof with one or more pharmaceutically acceptable diluents or carriers.