# US 9,517,203 B2 · Polymer particle delivery compositions and methods of use

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- Number: US 9,517,203 B2
- Document ID: US9517203B2
- Status: Granted
- Kind: B2
- Application number: 13/477,832
- Filed: 2012-05-22
- Published: 2012-12-27
- Granted: 2016-12-13
- Earliest claimed: 2000-08-30
- Assignees: Mediv AS, LLC
- Applicants: William G. Turnell; Hong Li; Zaza D. Gomurashvili; Ramaz Katsarava
- Inventors: William G. Turnell; Hong Li; Zaza D. Gomurashvili; Ramaz Katsarava
- Web page: https://patentgrep.com/patent/US9517203B2

## CPC

- A61K 9/1075: {Microemulsions or submicron emulsions; Preconcentrates or solids thereof; Micelles, e.g. made of phospholipids or block copolymers (A61K9/0026 takes precedence)}
- A61K 9/1647: {Polyesters, e.g. poly(lactide-co-glycolide)}
- A61K 9/5031: {obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, poly(lactide-co-glycolide)}
- A61K 9/5153: {Polyesters, e.g. poly(lactide-co-glycolide)}
- A61K 47/34: Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers (A61K47/10 takes precedence)
- A61K 47/59: obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes
- A61K 47/593: {Polyesters, e.g. PLGA or polylactide-co-glycolide}
- A61K 47/595: {Polyamides, e.g. nylon (polyamino acids A61K47/62)}
- A61P 1/00: Drugs for disorders of the alimentary tract or the digestive system
- A61P 19/06: Antigout agents, e.g. antihyperuricemic or uricosuric agents
- A61P 27/02: Ophthalmic agents
- A61P 27/16: Otologicals
- A61P 29/00: Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- A61P 31/00: Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- C07K 16/2821: {against ICAM molecules, e.g. CD50, CD54, CD102}
- C08L 77/12: Polyester-amides
- C12N 15/88: using microencapsulation, e.g. using {amphiphile} liposome vesicle
- Y10S 977/773: Nanoparticle, i.e. structure having three dimensions of 100 nm or less
- Y10S 977/788: Of specified organic or carbon-based composition
- Y10S 977/906: Drug delivery
- 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)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- C07K: PEPTIDES (peptides in foodstuffs A23; obtaining protein compositions for foodstuffs, working-up proteins for foodstuffs A23J; preparations for medicinal purposes A61K; peptides containing beta-lactam rings C07D; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, C07D; ergot alkaloids of the cyclic peptide type C07D519/02; macromolecular compounds having statistically distributed amino acid units in their molecules, i.e. when the preparation does not provide for a specific; but for a random sequence of the amino acid units, homopolyamides and block copolyamides derived from amino acids C08G69/00; macromolecular products derived from proteins C08H1/00; preparation of glue or gelatine C09H; single cell proteins, enzymes C12N; genetic engineering processes for obtaining peptides C12N15/00; compositions for measuring or testing processes involving enzymes C12Q; investigation or analysis of biological material G01N33/00)
- C08L: COMPOSITIONS OF MACROMOLECULAR COMPOUNDS (compositions based on polymerisable monomers C08F, C08G; artificial filaments or fibres D01F; textile treating compositions D06)
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)
- Y10S: TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS

## Abstract

The present invention provides biodegradable polymer particle delivery compositions based on polymers, such as polyester amide (PEA) and polyester urethane (PEUR) polymers, that contain amino acids in the polymer. The polymer particle delivery compositions can be formulated as a liquid dispersion of polymer particles with the bioactive agents dispersed in the particle or conjugated attached to polymer molecules or particle surfaces. The bioactive agents can include drugs, polypeptides, DNA and cells for cell-based therapies using particles sized for local, mucosal or circulatory delivery. Methods of treating a disease by administering to a subject the polymer particle delivery composition, which incorporates a bioactive agent suitable for treatment of the disease, or its symptoms, are also included.

## Claims

### Claim 1

A polymer particle delivery composition comprising a therapeutically effective amount of at least one bioactive agent dispersed in a biodegradable polymer, wherein the polymer is
a polyester amide having a chemical formula described by structural Formula III:
wherein
n ranges from about 5 to about 150;
m ranges about 0.1 to 0.9;
p ranges from about 0.9 to 0.1;
R1 is independently selected from residues of α,ω-bis(4-carboxyphenoxy)-(C1-C8) alkane, 3,3′-(alkanedioyldioxy)dicinnamic acid or 4,4′-(alkanedioyldioxy)dicinnamic acid, (C2-C20) alkylene, (C2-C20) alkenylene
each R2 is independently hydrogen, (C1-C12) alkyl or (C6-C10) aryl or a protecting group;
the R3s within an individual m monomer are independently selected from the group consisting of hydrogen, (C1-C6) alkyl, (C2-C6) alkenyl, (C2-C6) alkynyl, (C6-C10) aryl (C1-C6) alkyl; and
R4 is independently selected from the group consisting of (C2-C20) alkylene, (C2-C20) alkenylene, (C2-C8) alkyloxy, bicyclic-fragments of 1,4:3,6-dianhydrohexitols of structural Formula(II)
and combinations thereof.

### Claim 2 (depends on 1)

The polymer particle delivery composition of claim 1, wherein the composition is Formulated for administration in the form of a liquid dispersion of the polymer particles.

### Claim 3 (depends on 1)

The polymer particle delivery composition of claim 1, wherein R1 is selected from the group consisting of: —(CH2)4—, —(CH2)6—, and —(CH2)8—.

### Claim 4 (depends on 1)

The polymer particle delivery composition of claim 1, wherein the composition forms a time release polymer depot when administered in vivo.

### Claim 5 (depends on 1)

The polymer particle delivery composition of claim 1, wherein the composition is sized such that it is capable of passing through a syringe needle ranging in size from about 19 to about 27 Gauge.

### Claim 6 (depends on 1)

The polymer particle delivery composition of claim 1, wherein the particles have an average diameter in the range from about 1 micron to about 1000 microns.

### Claim 7 (depends on 1)

The polymer particle delivery composition of claim 1, wherein the particles have a size in the range from about 10 nanometers to about 500 nanometers.

### Claim 8 (depends on 1)

The polymer particle delivery composition of claim 1, wherein the composition further comprises a pharmaceutically acceptable vehicle.

### Claim 9 (depends on 1)

The polymer particle delivery composition of claim 1, wherein the composition is in the form of disperse droplets containing the particles in a mist.

### Claim 10 (depends on 9)

The polymer particle delivery composition of claim 9, wherein the mist is produced by a nebulizer.

### Claim 11 (depends on 1)

The polymer particle delivery composition of claim 1, wherein the bioactive agent is selected from the group consisting of a drug, peptide, protein, lipid, sugar, RNA and DNA.

### Claim 12 (depends on 1)

A method for treating a disease in a subject in need thereof, the method comprising:
administering to the subject a polymer particle delivery composition according to claim 1 in the form of a liquid dispersion of polymer particles that incorporate at least one bioactive agent selected to treat the disease of interest, which particles biodegrade by enzymatic action to release the bioactive agent over time.

### Claim 13 (depends on 1)

A method for delivering the polymer particles according to claim 1 to a local site in the body of a subject in need thereof, said method comprising:
injecting a dispersion of the polymer particles to an in vivo site in the subject whereby the injected particles agglomerate to form a polymer depot of particles of increased size, wherein the particles comprise a polymer containing at least one amino acid and a non-amino acid moiety per repeat unit of the polymer.