Methods and Apparatus for Creating Particle Derivatives of HDL with Reduced Lipid Content
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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.
105 Citations
72 Claims
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1-24. -24. (canceled)
- 25. A particle derivative of a pre-beta form of high density lipoprotein comprising a protein shell and a lipid bilayer substantially devoid of cholesterol wherein the particle derivative is discoidal in shape and is formed by first removing low density lipoprotein from a mixture of the high density lipoprotein and the low density lipoprotein and subsequently exposing the mixture to a lipid removing agent.
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29. A particle derivative of a pre-beta form of high density lipoprotein comprising a protein shell and a lipid bilayer substantially devoid of cholesterol wherein said particle derivative is discoidal in shape and 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.
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30-48. -48. (canceled)
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49. A method for modifying at least one form of high density lipoprotein contained in plasma, serum, or other suitable blood fraction of a patient, comprising the steps of:
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a. obtaining a blood fraction containing high density lipoprotein and low density lipoprotein from the patient; b. separating the low density lipoprotein from the blood fraction; c. mixing the blood fraction with a lipid removing agent which removes lipids from the high density lipoprotein to yield a mixture of lipid, lipid removing agent, and modified high density lipoprotein; d. separating the modified high density lipoprotein from the lipid and the lipid removing agent; and
,e. delivering the modified high density lipoprotein to the patient. - View Dependent Claims (59, 61)
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50. A method for modifying at least one form of high density lipoprotein contained in plasma, serum, or other suitable blood fraction of a patient, comprising the steps of:
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a. obtaining a blood fraction containing high density lipoprotein and low density lipoprotein from the patient; b. mixing the blood fraction with a lipid removing agent which removes lipids associated with the high density lipoprotein without substantially modifying the low density lipoprotein to yield a mixture of lipid, the lipid removing agent, modified high density lipoprotein, and the low density lipoprotein; c. separating the modified high density lipoprotein and the low density lipoprotein from the lipid and the lipid removing agent; and
,d. delivering the modified high density lipoprotein and the low density lipoprotein to the patient. - View Dependent Claims (60, 62)
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51. A method of modifying a protein distribution in a fluid wherein the protein distribution has a first state, the first state having alpha high density lipoproteins and pre-beta high density lipoproteins, comprising the steps of:
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exposing the fluid to a lipid removing agent wherein the exposure modifies the protein distribution from the first state into a second state, the second state having an increased concentration of pre-beta high density lipoprotein relative to the first state; and
,removing the lipid removing agent from the biological fluid. - View Dependent Claims (52)
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- 53. A method of enhancing an ABCA1 pathway of a patient with a first protein distribution, the first protein distribution having a concentration of pre-beta high density lipoproteins relative to total protein, comprising the step of modifying a fluid containing the first protein distribution by exposing the fluid to a lipid removing agent, wherein the modification increases the concentration of pre-beta high density lipoprotein relative to the total protein, and introducing the fluid into the patient.
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55. A method of modifying a protein distribution in a fluid wherein the protein distribution has a first state, the first state having more alpha high density lipoprotein than pre-beta high density lipoprotein, comprising the steps of:
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exposing the fluid to a lipid removing agent wherein the exposure modifies the protein distribution from the first state into a second state, the second state having more pre-beta high density lipoprotein than alpha high density lipoprotein; and
,removing the lipid removing agent from the biological fluid. - View Dependent Claims (56, 57, 58)
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63-64. -64. (canceled)
- 65. A method of enhancing cellular cholesterol efflux comprising administration of a modified HDL particle to a patient.
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67. 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.
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68. A particle comprising a modified HDL particle, wherein the modified HDL particle has a relatively normal complement of Apo A-1 and substantially reduced cholesterol and phospholipid compared to an HDL particle before modification.
- 69. A biological fluid capable of enhancing an ABCA1 pathway of a patient wherein said biological fluid is made by modifying a fluid having a first concentration of pre-beta high density lipoprotein relative to total protein wherein the modification increases the concentration of pre-beta high density lipoprotein relative to total protein.
- 71. A biological fluid comprising a modified protein distribution wherein the biological fluid had a first state, the first state having alpha high density lipoproteins and pre-beta high density lipoproteins, and wherein the biological fluid has a second state after being exposed to a lipid removing agent, the second state having an increased concentration of pre-beta high density lipoprotein relative to the first state.
Specification