Composition comprising PCSK9 peptide conjugated to a Qbeta carrier and methods of using the same

Patent metadata

Field	Value
Publication number	US-10925938-B2
Application number	US-201916250514-A
Country	US
Kind code	B2
Filing date	Jan 17, 2019
Priority date	Feb 11, 2014
Publication date	Feb 23, 2021
Grant date	Feb 23, 2021

Abstract

A vaccine construct comprising an antigenic PCSK9 peptide and an immunogenic carrier, and methods of using the same that are effective to lower blood cholesterol levels in a mammal and treat dyslipidemias and related disease states in a mammal without the frequency of administration required by passive immunity strategies.

First claim

What is claimed is:

1. A composition comprising:
a first antigenic proprotein convertase subtilisin-kexin type 9 (PCSK9) peptide linked to a bacteriophage virus-like particle (VLP) Qbeta immunogenic carrier, the first antigenic PCSK9 antigenic peptide comprising the amino acid sequence NVPEEDGTRFHRQASKC (SEQ ID NO:3); and
a second antigenic PCSK9 linked to a VLP Qbeta immunogenic carrier, the second antigenic PCSK9 peptide comprising:
the amino acid sequence SIPWNLERIIP (amino acids 150-160 of SEQ ID NO:1), or
the amino acid sequence SIPWNLERITP (amino acids 153-163 of SEQ ID NO:2).

2. The composition of claim 1 , wherein at least one amino acid is in the D -isomeric form.

3. The composition of claim 1 , wherein at least one immunogenic carrier is linked to the first PCSK9 peptide or the second PCSK9 peptide through a succinimidyl-6[β-maleimidopropionamido]hexanoate (SMPH) cross-linker molecule.

4. The composition of claim 1 , wherein the first PCSK9 antigenic peptide and the second PCSK9 antigenic peptide are linked to the same VLP Qbeta immunogenic carrier.

5. The composition of claim 1 , wherein:
at least one first antigenic PCSK9 peptide is linked to a first VLP Qbeta immunogenic carrier; and
at least one second antigenic PCSK peptide is linked to a second VLP Qbeta immunogenic carrier.

6. The composition of claim 1 , further comprising at least one adjuvant.

7. A method of preventing, alleviating, or treating a dyslipidemia in an individual, the method comprising administering a therapeutically effective amount of the composition of claim 1 to the individual.

8. The method according to claim 7 , wherein the dyslipidemia is selected from a group of hyperlipidemias consisting of type I, type II, type III, type IV, or type V hyperlipidemia, secondary hypertriglyceridemia, secondary hypercholesterolemia, hypercholesterolemia, familial hypercholesterolemia, familial combined hyperlipidemia xanthomatosis, and lecithin:cholesterol acetyltransferase deficiency.

9. The method of claim 7 , wherein the composition is administered in combination with at least one additional therapeutic agent selected from the group consisting of a statin, a bile acid sequestrant, niacin, a fibric acid derivative, and a long chain alpha, omego-dicarboxylic acid.

10. A method of preventing, alleviating, or treating a condition selected from atherosclerosis, coronary artery disease, cardiovascular disease, and acute coronary syndrome in an individual, the method comprising administering a therapeutically effective amount of the composition of claim 1 to the individual.

11. The method of claim 10 , wherein the composition is administered in combination with at least one additional therapeutic agent selected from the group consisting of a statin, a bile acid sequestrant, niacin, a fabric acid derivative, and a long chain alpha, omego-dicarboxylic acid.

12. A method of preventing, alleviating, or treating hypertriglyceridemia in an individual, the method comprising administering a therapeutically effective amount of the composition of claim 1 to the individual.

13. The method of claim 12 , wherein the composition is administered to the individual in combination with at least one adjuvant.

14. The method of claim 12 , wherein the composition is administered to the individual in combination with at least one of a statin and a fabric acid derivative.

Assignees

• The Usa As Represented By The Secretary Dept Of Health And Human Services
• Unm Rainforest Innovations

Inventors

• Remaley Alan
• Schiller John T
• Amar Marcelo
• Chackerian Bryce

Classifications

• A61K38/10

  Peptides having 12 to 20 amino acids {(A61K38/043 - A61K38/046 take precedence)} · CPC title

• C07K11/00

  Depsipeptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof · CPC title

• A61K2039/60

  characteristics by the carrier linked to the antigen · CPC title

• C12N2795/18141

  Use of virus, viral particle or viral elements as a vector · CPC title

• C12Y304/21061

  Kexin (3.4.21.61), i.e. proprotein convertase subtilisin/kexin type 9 · CPC title