# US 11,026,889 B2 · Polymeric drug delivery systems for treatment of disease

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- Number: US 11,026,889 B2
- Document ID: US11026889B2
- Status: Granted
- Kind: B2
- Application number: 15/780,799
- Filed: 2016-12-09
- Published: 2020-08-06
- Granted: 2021-06-08
- Earliest claimed: 2015-12-09
- Assignees: Board of Regents, The University of Texas System
- Applicants: Board of Regents, The University of Texas System
- Inventors: Chun Li; Jun Zhao; Jason Fleming
- Web page: https://patentgrep.com/patent/US11026889B2

## CPC

- A61K 9/107: Emulsions {; Emulsion preconcentrates; Micelles (composition of emulsions A61K47/00)}
- C08F 8/46: Reaction with unsaturated dicarboxylic acids or anhydrides thereof, e.g. maleinisation
- A61K 9/1273: Polymersomes; Liposomes with polymerisable or polymerised bilayer-forming substances
- A61K 31/337: having four-membered rings, e.g. taxol
- A61K 31/395: having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K 31/438: The ring being spiro-condensed with carbocyclic or heterocyclic ring systems
- A61K 31/59: Compounds containing 9, 10- seco- cyclopenta[a]hydrophenanthrene ring systems
- A61P 35/00: Antineoplastic agents
- C08F 293/005: {using free radical "living" or "controlled" polymerisation, e.g. using a complexing agent}
- C08F 2438/01: Atom Transfer Radical Polymerization [ATRP] or reverse ATRP
- 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)
- C08F: MACROMOLECULAR COMPOUNDS OBTAINED BY REACTIONS ONLY INVOLVING CARBON-TO-CARBON UNSATURATED BONDS
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

Provided are compositions and nanoparticle formulations that may be used, e.g., to deliver a therapeutic compound to a subject. In some embodiments, the nanoparticles may be used to deliver one or more chemotherapeutic agents to treat a cancer such, e.g., as a pancreatic ductal adenocarcinoma.

## Claims

### Claim 1

A polymer, wherein the polymer is a block copolymer comprising a polyacrylic acid backbone with a first plurality of PEG sidechains and a second plurality of ε-caprolactone sidechains, and wherein the ε-caprolactone sidechains terminates with carboxy, phosphonate, or hydroxysulfonyl.

### Claim 2 (depends on 1)

The polymer of claim 1, wherein the PEG sidechain component comprises from 5 ethylene glycol monomers to 50 ethylene glycol monomers.

### Claim 3 (depends on 1)

The polymer of claim 1, wherein the PEG sidechain is capped with a methyl group.

### Claim 4 (depends on 1)

The polymer of claim 1, wherein the ε-caprolactone sidechain comprises from 2 ε-caprolactone repeating units to 20 ε-caprolactone repeating units.

### Claim 5 (depends on 1)

The polymer of claim 1, wherein the ε-caprolactone sidechain is esterified with a succinate group.

### Claim 6 (depends on 1)

The polymer of claim 1, wherein the ε-caprolactone sidechain is linked to the polyacrylic acid backbone by an ethylene glycol linker.

### Claim 7 (depends on 1)

The polymer of claim 1, wherein the polyacrylic acid backbone is capped with an benzyl N-(2-hydroxylethyl)carbamate or ethanolamine group.

### Claim 8 (depends on 1)

The polymer of claim 1, wherein the polyacrylic acid backbone is terminated with a halogen group.

### Claim 9 (depends on 1)

The polymer of claim 1, wherein the polymer is further defined by the formula:
wherein:
R1 is alkyl(C1-18), cycloalkyl(C1-18), aryl(C1-18), or a substituted version of any of these groups; or an alkyl(C1-18) substituted with a protected amine group;
R2 is a group of the formula:
wherein:
R3 and R3′ are each independently hydrogen, alkyl(C1-6), or substituted alkyl(C1-6); and
x is 1-10;
m is 5-40;
n is 10-40;
p is 5-40;
q is 1-20;
y is 1-10; and
Y1 is carboxy, phosphonate, or hydroxysulfonyl;
or a pharmaceutically acceptable salt thereof.

### Claim 10 (depends on 9)

The polymer of claim 9, wherein m is 5-25.

### Claim 11 (depends on 1)

The polymer of claim 1Z wherein p is 5-25.

### Claim 12 (depends on 9)

The polymer according to claim 9, wherein R3 and R3′ are hydrogen.

### Claim 13 (depends on 1)

The polymer of claim 1, wherein the polymer has the structure:

### Claim 14 (depends on 1)

A composition comprising the polymer of claim 1, wherein the composition further comprises a second polymer of the formula:
wherein:
m is 5-40;
n is 10-40;
p is 5-30;
R1 and R2 are each independently alkanediyl(C1-8), arenediyl(6-12), or a substituted version of either of these groups;
R3, R3′, and, R3″ are each independently alkyl(C1-8), aryl(C3-12), or a substituted version of any of these groups; and
X1 and X2 are each independently a monovalent anion;
or a pharmaceutically salt thereof.

### Claim 15 (depends on 14)

The composition of claim 14, wherein R1 or R2 is ethylene.

### Claim 16 (depends on 14)

The composition of claim 14, wherein R3, R3′, and R3″ are each methyl.

### Claim 17 (depends on 14)

The composition of claim 14, wherein X1 or X2 is a halide.

### Claim 18 (depends on 14)

The composition of claim 14, wherein the second polymer has the structure:

### Claim 19 (depends on 1)

A pharmaceutical composition comprising:
(a) a micelle, liposome, or nanoparticle; and
(b) a therapeutic agent;
wherein the micelle, liposome, or nanoparticle comprises a first polymer of claim 1, and the micelle, liposome, or nanoparticle encapsulates the therapeutic agent.

### Claim 20 (depends on 19)

The pharmaceutical composition of claim 19, wherein the therapeutic agent is paclitaxel or cyclopamine.

### Claim 21 (depends on 20)

The pharmaceutical composition of claim 20, wherein the pharmaceutical composition comprises paclitaxel and cyclopamine.

### Claim 22 (depends on 19)

A method of treating a disease in a mammalian subject comprising administering a therapeutically effective amount of a pharmaceutical composition of claim 19 to the subject.