# US 2013/0156792 A9 · Uniform field magnetization and targeting of therapeutic formulations

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- Number: US 2013/0156792 A9
- Document ID: US20130156792A9
- Status: Published application
- Kind: A9
- Application number: 12/653,465
- Filed: 2009-12-15
- Published: 2013-06-20
- Earliest claimed: 2004-02-20
- Assignees: The Trustees of the University of Pennsylvania; The Children's Hospital of Philadelphia
- Inventors: Robert J. Levy; Michael Chorny; Vladimir Muzykantov; Elizabeth Hood
- Web page: https://patentgrep.com/patent/US20130156792A9

## CPC

- A61K 9/5094: {Microcapsules containing magnetic carrier material, e.g. ferrite for drug targeting}
- A61K 9/5115: {Inorganic compounds}
- A61K 9/5123: {Organic compounds, e.g. fats, sugars}
- A61K 9/5146: {obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, polyamines, polyanhydrides}
- A61K 9/5153: {Polyesters, e.g. poly(lactide-co-glycolide)}
- A61K 9/5169: {Proteins, e.g. albumin, gelatin}
- A61K 9/5192: {Processes}
- A61K 47/42: Proteins; Polypeptides; Degradation products thereof; Derivatives thereof, e.g. albumin, gelatin or zein (oligopeptides having up to five amino acids {A61K47/183}; polyamino acids A61K47/34)
- A61K 47/59: obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes
- A61K 47/645: {Polycationic or polyanionic oligopeptides, polypeptides or polyamino acids, e.g. polylysine, polyarginine, polyglutamic acid or peptide TAT}
- A61K 47/6455: {Polycationic oligopeptides, polypeptides or polyamino acids, e.g. for complexing nucleic acids}
- A61K 47/6849: {the antibody targeting a receptor, a cell surface antigen or a cell surface determinant}
- A61K 47/6921: {the form being a particulate, a powder, an adsorbate, a bead or a sphere}
- A61K 47/6937: {the polymer being PLGA, PLA or polyglycolic acid}
- A61K 48/0008: {characterised by an aspect of the 'non-active' part of the composition delivered, e.g. wherein such 'non-active' part is not delivered simultaneously with the 'active' part of the composition}
- A61K 48/0041: {the non-active part being polymeric}
- A61K 48/0083: {characterised by an aspect of the administration regime}
- A61L 31/16: Biologically active materials, e.g. therapeutic substances {(A61L31/047 takes precedence)}
- A61P 9/00: Drugs for disorders of the cardiovascular system
- A61P 39/06: Free radical scavengers or antioxidants
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- C12N 15/111: {General methods applicable to biologically active non-coding nucleic acids}
- C12N 15/86: Viral vectors
- A61L 2300/416: Anti-neoplastic or anti-proliferative or anti-restenosis or anti-angiogenic agents, e.g. paclitaxel, sirolimus
- A61L 2300/60: characterised by a special physical form
- A61L 2300/624: Nanocapsules
- C12N 2320/32: Special delivery means, e.g. tissue-specific
- C12N 2710/10343: viral genome or elements thereof as genetic vector
- 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)
- A61L: METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES (preservation of bodies or disinfecting characterised by the agents employed A01N; preserving, e.g. sterilising, food or foodstuffs A23; preparations for medical, dental or toiletry purposes A61K)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)

## Abstract

Systems and methods for magnetic targeting of therapeutic particles are provided. Therapeutic particles comprise one or more magnetic or magnetizable materials and at least one therapeutic agent. Therapeutic particles are specifically targeted using uniform magnetic fields capable of magnetizing magnetizable materials, and can be targeted to particular locations in the body, or can be targeted for capture, containment, and removal. Therapeutic particles can comprise antioxidant enzymes, and can be targeted to cells to protect the cells from oxidative damage.

## Claims

### Claim 1

A therapeutic particle comprising a magnetic or magnetizable material, a stabilizer, a fatty acid or salt thereof, and a protein.

### Claim 2 (depends on 1)

The therapeutic particle of claim 1, wherein the magnetic or magnetizable material is a superparamagnetic material.

### Claim 3 (depends on 1)

The therapeutic particle of claim 1, wherein the fatty acid is oleic acid or a salt thereof.

### Claim 4 (depends on 1)

The therapeutic particle of claim 1, wherein the protein is an antioxidant enzyme.

### Claim 5 (depends on 4)

The therapeutic particle of claim 4, wherein the antioxidant enzyme is catalase, superoxide dismutase, or glutathione peroxidase.

### Claim 6 (depends on 1)

The therapeutic particle of claim 1, wherein the stabilizer is biotinylated.

### Claim 7 (depends on 1)

The therapeutic particle of claim 1, further comprising an antibody.

### Claim 8 (depends on 7)

The therapeutic particle of claim 7, wherein the antibody is joined to the stabilizer.

### Claim 9 (depends on 7)

The therapeutic particle of claim 7, wherein the antibody specifically binds to an antigen on the surface of an endothelial cell.

### Claim 10

A method for protecting a cell from oxidative damage, comprising contacting the cell with a particle comprising a magnetic or magnetizable material and at least one antioxidant enzyme, and generating a uniform magnetic field capable of magnetizing the magnetic or magnetizable material proximal to the cell for a period of time sufficient to permit the cell to internalize the particle.

### Claim 11 (depends on 10)

The method of claim 10, wherein the cell is an endothelial cell.

### Claim 12 (depends on 11)

The method of claim 11, wherein the endothelial cell is a vascular endothelium cell.

### Claim 13 (depends on 10)

The method of claim 10, wherein the antioxidant enzyme is catalase, superoxide dismutase, or glutathione peroxidase.

### Claim 14 (depends on 10)

The method of claim 10, wherein the particle further comprises an antibody that specifically binds to an antigen on the surface of the cell.

### Claim 15 (depends on 10)

The method of claim 10, wherein the cell is in the body of a mammal.

### Claim 16

A method for magnetically targeting a protein to an implanted device, comprising the steps of:
(a) administering to a subject having an implanted device a plurality of particles comprising a first magnetic or magnetizable material and the protein;
(b) generating a uniform magnetic field capable of magnetizing magnetizable materials, the uniform magnetic field generating a magnetic field gradient proximal to the implanted device, the implanted device comprising a second magnetic or magnetizable material, wherein the gradient targets one or more of the plurality of particles to the implanted device; and
(c) optionally removing one or more of the plurality of particles that are not delivered to the implanted device from the subject.

### Claim 17 (depends on 16)

The method of claim 16, further comprising the step of removing spent particles from the subject.

### Claim 18 (depends on 16)

The method of claim 16, wherein the protein is an antioxidant enzyme.

### Claim 19 (depends on 18)

The method of claim 18, wherein the antioxidant enzyme is catalase, superoxide dismutase, or glutathione peroxidase.

### Claim 20 (depends on 1, 16)

The method of claim 16, wherein each of the plurality of particles is the particle of claim 1.

### Claim 21 (depends on 16)

The method of claim 16, wherein the implanted device is a stent.

### Claim 22 (depends on 21)

The method of claim 21, wherein the stent is formed of 304 stainless steel.

### Claim 23 (depends on 16)

The method of claim 16, wherein the step of generating a uniform magnetic field comprises using a pair of electromagnets to generate the uniform magnetic field.

### Claim 24 (depends on 16)

The method of claim 16, wherein the step of generating a uniform magnetic field comprises using a permanent magnet to generate the uniform magnetic field.

### Claim 25 (depends on 16)

The method of claim 16, wherein the first magnetic or magnetizable material comprises a superparamagnetic material.

### Claim 26 (depends on 16)

The method of claim 16 further comprising the steps of:
(a) removing the uniform magnetic field and magnetic field gradient;
(b) administering to the subject another plurality of particles comprising the first magnetic or magnetizable material and the protein;
(c) repeating the step of generating a uniform magnetic field to generate a magnetic field gradient proximal to the implanted device to target one or more of the second plurality of particles to the implanted device and deliver an additional quantity of the protein to the device.

### Claim 27 (depends on 16)

The method of claim 16 further comprising the step of administering to the subject a plurality of particles comprising the first magnetic or magnetizable material and paclitaxel.

### Claim 28 (depends on 16)

The method of claim 16 wherein the plurality of particles comprising the first magnetic or magnetizable material further comprises paclitaxel.

### Claim 29 (depends on 1)

The therapeutic particle of claim 1, further comprising paclitaxel.