Methods and apparatus for creating particle derivatives of HDL with reduced lipid content

• US 20060172939A1
• Filed: 10/26/2005
• Published: 08/03/2006
• Est. Priority Date: 07/03/2003
• Status: Active Grant

• Current Assignee: HDL Therapeutics, LLC, Lipid Sciences, Inc.
• Original Assignee: Lipid Sciences, Inc.
• Inventors: Bellotti, Marc, Perlman, Timothy Jon, Brewer, H. Bryan Jr., Conner, Adam Paul, Akeefe, Hassibullah
• Granted Patent: US 7,393,826 B2
• Time in Patent Office: Days
• US Class Current: 424/529
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/685 one of the hydroxy compounds having nitrogen atoms, e.g. phosphatidylserine, lecithin
• CPC Class Codes: A61K 38/1709 from mammals
• CPC Class Codes: A61K 9/1275 Lipoproteins; Chylomicrons; Artificial HDL, LDL, VLDL, protein-free species thereof; Precursors thereof
• CPC Class Codes: A61P 3/06 Antihyperlipidemics
• CPC Class Codes: A61P 9/10 for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
• CPC Class Codes: B01D 11/0492 Applications, solvents used
• CPC Class Codes: B01D 15/00 Separating processes involving the treatment of liquids with solid sorbents using liquid sorbents B01D11/00; ion exchange processes or materials, sorbent materials in general B01J, e.g. sorbents for chromatography B01J20/281; for investigating or analysing materials G01N30/00; Apparatus therefor
• CPC Class Codes: B01D 15/426 Specific type of solvent
• CPC Class Codes: C07K 14/775 Apolipopeptides
• CPC Class Codes: G01N 33/92 involving lipids, e.g. cholesterol , lipoproteins, or their receptors steroid hormones G01N33/743

Abstract

The present invention is directed to systems, apparatus and methods for creating derivatives of at least one form of HDL without substantially affecting LDL. These derivatives of HDL are particles with reduced lipid content, particularly reduced cholesterol content. These particles have the capacity to bind cholesterol and are administered to a patient to enhance cellular cholesterol efflux and reduce cholesterol levels in cells, tissues, organs, and blood vessels. The present method is useful for treating atherogenic vascular disease and may be combined with other therapies such as statins, inhibitors of cholesterol absorption, niacin, anti-inflammatories, exercise and dietary restriction.

Claims

1. A particle derivative of at least one form of high density lipoprotein comprising apolipoprotein A-1 and phospholipids wherein the particle derivative is formed by exposing a mixture of the high density lipoprotein and low density lipoprotein to a lipid removing agent, wherein the exposure does not substantially modify the low density lipoprotein.

2. A particle comprising a modified HDL particle, wherein the modified HDL particle has a relatively normal complement of Apo A-1 and phospholipid and substantially reduced cholesterol compared to an HDL particle before modification.

3. A method for making a particle derivative of at least one form of high density lipoprotein wherein the particle derivative comprises a protein shell and a lipid bilayer comprising the steps of:

a. connecting a patient to a device for withdrawing blood;

b. withdrawing blood containing blood cells from the patient;

c. separating the blood cells from the blood to yield a blood fraction containing high density lipoprotein and low density lipoprotein;

d. separating the low density lipoprotein from the blood fraction;

e. mixing the blood fraction with a lipid removing agent which removes lipids associated with the lipid bilayer of the high density lipoprotein to yield a mixture of lipid, the lipid removing agent, and the particle derivative;

f. separating the particle derivative from the lipid and the lipid removing agent; and

,

delivering the particle derivative to the patient.