# US 8,785,382 B2 · Lipid therapy

> Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt

- Number: US 8,785,382 B2
- Document ID: US8785382B2
- Status: Granted
- Kind: B2
- Application number: 11/694,793
- Filed: 2007-03-30
- Published: 2007-10-04
- Granted: 2014-07-22
- Earliest claimed: 2006-04-03
- Assignees: Abbott Cardiovascular Systems Inc.
- Applicants: Deborah Kilpatrick; Syed Faiyaz Ahmed Hossainy; Irina Astafieva; Florian N. Ludwig; Paul M. Consigny; Jeffrey T. Ellis; Florencia Lim
- Inventors: Deborah Kilpatrick; Syed Faiyaz Ahmed Hossainy; Irina Astafieva; Florian N. Ludwig; Paul M. Consigny; Jeffrey T. Ellis; Florencia Lim
- Web page: https://patentgrep.com/patent/US8785382B2

## CPC

- A61K 38/1709: {from mammals}
- A61K 9/0019: {Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner (non-active ingredients are additionally classified in A61K47/00)}
- A61K 9/1275: Lipoproteins or protein-free species thereof, e.g. chylomicrons; Artificial high-density lipoproteins [HDL], low-density lipoproteins [LDL] or very-low-density lipoproteins [VLDL]; Precursors thereof
- A61K 9/1617: {Organic compounds, e.g. phospholipids, fats}
- A61K 9/1658: {Proteins, e.g. albumin, gelatin}
- A61M 1/3472: {with treatment of the filtrate}
- A61M 1/3486: {Biological, chemical treatment, e.g. chemical precipitation; treatment by absorbents}
- A61P 9/10: for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
- A61M 2202/0456: Lipoprotein
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- A61M: DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY (introducing media into or onto the bodies of animals A61D7/00; means for inserting tampons A61F13/26; devices for administering food or medicines orally A61J; containers for collecting, storing or administering blood or medical fluids A61J1/05); DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY (surgery A61B; chemical aspects of surgical articles A61L); DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR {(Electrotherapy, e.g. producing anaesthesia by the use of alternating or intermittent currents A61N1/36021)}
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

A method including introducing into a blood stream a delipidated high density lipoprotein (HDL) and a bioactive agent. A composition including a delipidated high density lipoprotein (HDL) and an auxiliary agent in a form suitable for delivery into a blood vessel. A composition including Apo A1 comprising a hydrophobic ligand suitable to interact with cell surface binding sites. A composition including Apo A1 and an agent selected to one of increase the ATP-binding cassette protein 1 (ABCA1) transporter expression in macrophages and protect ABCA1 from thiol-mediated degradation.

## Claims

### Claim 1

A method for treating a subject comprising:
withdrawing an amount of blood from the subject using a catheter assembly;
delipidating high density lipoprotein (HDL) present in the amount of blood, wherein delipidating comprises combining the amount of blood with a solvent and a surfactant;
adding a surface coating to the delipidated HDL for increasing a partition coefficient of the delipidated HDL; and
after delipidating, (1) combining an exogenous bioactive agent having a hydrophobic ligand bound thereto with the delipidated HDL with the surface coating, wherein the exogenous bioactive agent includes at least one of an apolipoprotein A1 (Apo A1), a functional Apo A1 mutant, and a functional Apo A1 mimetic peptide, and (2) forming a composition comprising (i) the delipidated HDL with the surface coating combined with the exogenous bioactive agent having a hydrophobic ligand bound thereto, and (ii) a viscosifier including at least one of hyaluronic acid, polyvinylpyrrolidone (PVP), a hydroxypropylmethacrylate (HPMA) copolymer system, and carboxymethyl cellulose (CMC); and
introducing the composition into a blood stream or tissue of the subject, using the catheter assembly.

### Claim 2 (depends on 1)

The method of claim 1, wherein introducing comprises systemically introducing.

### Claim 3 (depends on 1)

The method of claim 1, wherein introducing comprises locally introducing.

### Claim 4 (depends on 1)

The method of claim 1, wherein introducing comprises locally introducing to an ischemic area.

### Claim 5 (depends on 1)

The method of claim 1, wherein introducing comprises introducing the delipidated HDL upstream from a treatment site.

### Claim 6 (depends on 1)

The method of claim 1, wherein introducing comprises introducing to a periadventitial area.

### Claim 7 (depends on 6)

The method of claim 6, further comprising introducing a gel-forming biomaterial to the periadventitial area.

### Claim 8 (depends on 1)

The method of claim 1, wherein withdrawing, delipidating and introducing comprise a closed loop system.

### Claim 9 (depends on 1)

The method of claim 1, wherein the hydrophobic ligand is selected from the group consisting of an elastin pentapeptide, leucine-rich oligopeptide, stearoyl, olyeol and palmitoyl.

### Claim 10 (depends on 1)

The method of claim 1 wherein the surfactant is selected from the group consisting of a sulfate, a sulfonate, a phosphate, a carboxylate and a sulfosuccinate.

### Claim 11

A method for treating a subject comprising:
delivering to a treatment site within a lumen of a blood vessel of the subject, in a wall of the blood vessel of the subject, or periadvential area beyond the blood vessel by a percutaneous transluminal route, a composition comprising (i) a delipidated HDL and an exogenous bioactive agent having a hydrophobic ligand bound thereto, the delipidated HDL comprising an added surface coating having a property that increases a partition coefficient of the delipidated HDL into the treatment site, and (ii) a viscosifier,
wherein the delivering step comprises locally delivering by placing a stent within the blood vessel of the subject, wherein the stent comprises the composition as a coating on a body of the stent or as a portion of the body of the stent, and
wherein the viscosifier comprises at least one of hyaluronic acid, polyvinylpyrrolidone (PVP), a hydroxypropylmethacrylate (HPMA) copolymer system, and carboxymethyl cellulose (CMC), and
wherein the exogenous bioactive agent includes at least one of an apolipoprotein A1 (Apo A1), a functional Apo A1 mutant, and a functional Apo A1 mimetic peptide.

### Claim 12 (depends on 11)

The method of claim 11, wherein prior to delivering the agent, the method comprises:
occluding the blood vessel at a point upstream of a treatment site and a point downstream of the treatment site.

### Claim 13 (depends on 11)

The method of claim 11, wherein prior to delivering the delipidated HDL, the method further comprises at least partially occluding the blood vessel at a treatment site with a porous occlusion device, and delivering comprises delivering the agent through the porous occlusion device.

### Claim 14 (depends on 11)

The method of claim 11, wherein prior to delivering the agent, the method comprises inserting an occlusion device into the blood vessel that at least partially occludes the blood vessel, and delivering comprises delivering the agent through the occlusion device.

### Claim 15 (depends on 14)

The method of claim 14, wherein the occlusion device comprises a balloon assembly comprising a porous portion and delivering comprises delivering the one of the agent through the porous portion.

### Claim 16 (depends on 14)

The method of claim 14, wherein the occlusion device comprises a sponge.

### Claim 17 (depends on 11)

The method of claim 11, wherein the treatment site comprises a periadventitial area.

### Claim 18 (depends on 17)

The method of claim 17, further comprising introducing a gel biomaterial to the periadvential area.