METHODS FOR TREATING ATHEROSCLEROTIC CARDIOVASCULAR DISEASE WITH LPA-TARGETED RNAi CONSTRUCTS

A method for reducing serum or plasma Lp(a) levels in a patient in need thereof comprising administering to the patient an LPA RNAi construct at a dose from about 9 mg to about 675 mg at a dosing interval of at least 8 weeks, wherein the LPA RNAi construct comprises a sense strand comprising the sequence of SEQ ID NO:

• 1, an antisense strand comprising the sequence of SEQ ID NO:
• 2, and a targeting moiety comprising an asialoglycoprotein receptor ligand, wherein the targeting moiety is covalently attached to the 5′ end of the sense strand.

A method for treating, reducing, or preventing a cardiovascular disease in a patient in need thereof comprising administering to the patient an LPA RNAi construct at a dose from about 9 mg to about 675 mg at a dosing interval of at least 8 weeks, wherein the LPA RNAi construct comprises a sense strand comprising the sequence of SEQ ID NO:

• 1, an antisense strand comprising the sequence of SEQ ID NO:
• 2, and a targeting moiety comprising an asialoglycoprotein receptor ligand, wherein the targeting moiety is covalently attached to the 5′ end of the sense strand.

A method for reducing the risk of a cardiovascular event in a patient with atherosclerotic cardiovascular disease comprising administering to the patient an LPA RNAi construct at a dose from about 9 mg to about 675 mg at a dosing interval of at least 8 weeks, wherein the LPA RNAi construct comprises a sense strand comprising the sequence of SEQ ID NO:

• 1, an antisense strand comprising the sequence of SEQ ID NO:
• 2, and a targeting moiety comprising an asialoglycoprotein receptor ligand, wherein the targeting moiety is covalently attached to the 5′ end of the sense strand.

An LPA RNAi construct for use in a method for treating, reducing, or preventing atherosclerosis in a patient in need thereof, wherein the method comprises administering to the patient the LPA RNAi construct at a dose from about 9 mg to about 675 mg at a dosing interval of at least 8 weeks, wherein the LPA RNAi construct comprises a sense strand comprising the sequence of SEQ ID NO:

• 1, an antisense strand comprising the sequence of SEQ ID NO:
• 2, and a targeting moiety comprising an asialoglycoprotein receptor ligand, wherein the targeting moiety is covalently attached to the 5′ end of the sense strand.

An LPA RNAi construct for use in a method for reducing serum or plasma Lp(a) levels in a patient in need thereof, wherein the method comprises administering to the patient the LPA RNAi construct at a dose from about 9 mg to about 675 mg at a dosing interval of at least 8 weeks, wherein the LPA RNAi construct comprises a sense strand comprising the sequence of SEQ ID NO:

• 1, an antisense strand comprising the sequence of SEQ ID NO:
• 2, and a targeting moiety comprising an asialoglycoprotein receptor ligand, wherein the targeting moiety is covalently attached to the 5′ end of the sense strand.

An LPA RNAi construct for use in a method for treating, reducing, or preventing a cardiovascular disease in a patient in need thereof, wherein the method comprises administering to the patient the LPA RNAi construct at a dose from about 9 mg to about 675 mg at a dosing interval of at least 8 weeks, wherein the LPA RNAi construct comprises a sense strand comprising the sequence of SEQ ID NO:

• 1, an antisense strand comprising the sequence of SEQ ID NO:
• 2, and a targeting moiety comprising an asialoglycoprotein receptor ligand, wherein the targeting moiety is covalently attached to the 5′ end of the sense strand.

An LPA RNAi construct for use in a method for reducing the risk of a cardiovascular event in a patient with atherosclerotic cardiovascular disease, wherein the method comprises administering to the patient the LPA RNAi construct at a dose from about 9 mg to about 675 mg at a dosing interval of at least 8 weeks, wherein the LPA RNAi construct comprises a sense strand comprising the sequence of SEQ ID NO:

• 1, an antisense strand comprising the sequence of SEQ ID NO:
• 2, and a targeting moiety comprising an asialoglycoprotein receptor ligand, wherein the targeting moiety is covalently attached to the 5′ end of the sense strand.

Use of an LPA RNAi construct for preparation of a medicament for treating, reducing, or preventing atherosclerosis in a patient in need thereof, wherein the medicament is administered or formulated for administration at a dose from about 9 mg to about 675 mg at a dosing interval of at least 8 weeks, wherein the LPA RNAi construct comprises a sense strand comprising the sequence of SEQ ID NO:

• 1, an antisense strand comprising the sequence of SEQ ID NO:
• 2, and a targeting moiety comprising an asialoglycoprotein receptor ligand, wherein the targeting moiety is covalently attached to the 5′ end of the sense strand.

Use of an LPA RNAi construct for preparation of a medicament for reducing serum or plasma Lp(a) levels in a patient in need thereof, wherein the medicament is administered or formulated for administration at a dose from about 9 mg to about 675 mg at a dosing interval of at least 8 weeks, wherein the LPA RNAi construct comprises a sense strand comprising the sequence of SEQ ID NO:

• 1, an antisense strand comprising the sequence of SEQ ID NO:
• 2, and a targeting moiety comprising an asialoglycoprotein receptor ligand, wherein the targeting moiety is covalently attached to the 5′ end of the sense strand.

Use of an LPA RNAi construct for preparation of a medicament for treating, reducing, or preventing a cardiovascular disease in a patient in need thereof, wherein the medicament is administered or formulated for administration at a dose from about 9 mg to about 675 mg at a dosing interval of at least 8 weeks, wherein the LPA RNAi construct comprises a sense strand comprising the sequence of SEQ ID NO:

• 1, an antisense strand comprising the sequence of SEQ ID NO:
• 2, and a targeting moiety comprising an asialoglycoprotein receptor ligand, wherein the targeting moiety is covalently attached to the 5′ end of the sense strand.

Use of an LPA RNAi construct for preparation of a medicament for reducing the risk of a cardiovascular event in a patient with atherosclerotic cardiovascular disease, wherein the medicament is administered or formulated for administration at a dose from about 9 mg to about 675 mg at a dosing interval of at least 8 weeks, wherein the LPA RNAi construct comprises a sense strand comprising the sequence of SEQ ID NO:

• 1, an antisense strand comprising the sequence of SEQ ID NO:
• 2, and a targeting moiety comprising an asialoglycoprotein receptor ligand, wherein the targeting moiety is covalently attached to the 5′ end of the sense strand.