# US 9,517,270 B2 · Lipocationic polymers and uses thereof

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

- Number: US 9,517,270 B2
- Document ID: US9517270B2
- Status: Granted
- Kind: B2
- Application number: 14/962,422
- Filed: 2015-12-08
- Published: 2016-08-04
- Granted: 2016-12-13
- Earliest claimed: 2014-12-08
- Assignees: Board of Regents, The University of Texas System
- Applicants: The Board of Regents of the University of Texas System
- Inventors: Daniel J. Siegwart; Jing Hao; Kejin Zhou; Jason Miller; Petra Kos; Lian Xue
- Web page: https://patentgrep.com/patent/US9517270B2

## CPC

- 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 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 9/5153: {Polyesters, e.g. poly(lactide-co-glycolide)}
- A61K 31/713: Double-stranded nucleic acids or oligonucleotides
- A61K 47/22: Heterocyclic compounds, e.g. ascorbic acid, tocopherol or pyrrolidones
- A61K 47/24: containing atoms other than carbon, hydrogen, oxygen, halogen, nitrogen or sulfur, e.g. cyclomethicone or phospholipids
- A61K 47/28: Steroids, e.g. cholesterol, bile acids or glycyrrhetinic acid
- C08G 63/688: containing sulfur
- C08G 63/912: {derived from hydroxycarboxylic acids}
- C08G 65/48: Polymers modified by chemical after-treatment
- C12N 15/113: Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; {Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing (when used in plants C12N15/8218)}
- C12N 2310/14: interfering nucleic acids [NA]
- 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)
- C08G: MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)

## Abstract

Polymers produced by ring opening polymerization which comprises an amino group that can be used in compositions to deliver a nucleic acid such as a miRNA or a siRNA. In some embodiments, compositions which comprise the polymers described herein and a nucleic acid are also provided herein. In some embodiments, these compositions are used to silence one or more genes in vivo or treat a disease or disorder.

## Claims

### Claim 1

A polymer comprising a formula:
wherein:
X1 is alkyl(C≦18) or substituted alkyl(C≦18);
X2 is hydrogen, alkyl(C≦18), or substituted alkyl(C≦18);
R1 is -A-Z;
wherein:
A is an alkanediyl(C≦18) or substituted alkanediyl(C≦18);
Z is —NR3R4;
wherein:
R3 and R4 are each independently selected from hydrogen, alkyl(C≦18), substituted alkyl(C≦18); or R3 and R4 are taken together and are alkanediyl(C≦18) or substituted alkanediyl(C≦18);
R2 is alkyl(C≦24), alkenyl(C≦24), substituted alkyl(C≦24), or substituted alkenyl(C≦24);
x and y are each independently 0, 1, 2, 3, 4, or 5;
m and n are each independently an integer between 0 and 250, provided that at least one of m and n is greater than 1; and
the repeating units defined by m and n are randomly distributed throughout the polymer;
or a pharmaceutically acceptable salt thereof.

### Claim 2 (depends on 1)

The polymer of claim 1, wherein Z is —NR3R4; wherein: R3 and R4 are each independently alkyl(C≦18) or substituted alkyl(C≦18).

### Claim 3 (depends on 1)

The polymer of claim 1, wherein Z is —NR3R4; wherein: R3 and R4 are taken together and are alkanediyl(C≦18) or substituted alkanediyl(C≦18).

### Claim 4 (depends on 1)

The polymer of claim 1, wherein R2 is alkyl(C≦24).

### Claim 5 (depends on 1)

The polymer of claim 1, wherein m is an integer between 1 and 100.

### Claim 6 (depends on 1)

The polymer of claim 1, wherein n is an integer between 1 and 100.

### Claim 7 (depends on 1)

The polymer of claim 1, wherein the polymer comprises a molar ratio of the m repeating unit and the n repeating unit between about 10:1 to about 1:10.

### Claim 8 (depends on 1)

A nanoparticle composition comprising:
(A) a polymer of claim 1; and
(B) a nucleic acid.

### Claim 9 (depends on 8)

The composition of claim 8, wherein the nucleic acid is a short (small) interfering RNA (siRNA), a microRNA (miRNA), a messenger RNA (mRNA), a clustered regularly interspaced short palindromic repeats (CRISPR) nucleic acid, a plasmid DNA (pDNA), a double stranded DNA (dsDNA), a single stranded DNA (ssDNA), a single stranded RNA (ssRNA), a double stranded RNA (dsRNA), a locked nucleic acid (LNA), a peptide nucleic acid (PNA), a miRNA mimic, or a anti-miRNA.

### Claim 10 (depends on 9)

The composition of claim 9, wherein the nucleic acid is a siRNA.

### Claim 11 (depends on 8)

The composition of claim 8, wherein the composition further comprises a steroid or steroid derivative.

### Claim 12 (depends on 11)

The composition of claim 11, wherein steroid derivative is a sterol.

### Claim 13 (depends on 8)

The composition of claim 8, wherein the composition further comprises a phospholipid.

### Claim 14 (depends on 13)

The composition of claim 13, wherein the phospholipid is a phosphatidylcholine.

### Claim 15 (depends on 8)

The composition of claim 8, wherein the composition further comprises a PEG lipid.

### Claim 16 (depends on 15)

The composition of claim 15, wherein the PEG lipid is a PEGylated diacylglycerol.

### Claim 17 (depends on 15)

The composition of claim 15, wherein the PEG lipid is:
wherein:
n1 is an integer from 1 to 250; and
n2 and n3 are each independently selected from 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, or 23.

### Claim 18 (depends on 8)

The composition of claim 8, wherein the composition comprises a molar ratio of polymer to steroid to phospholipid to PEG lipid from about 25:15:57:3 to about 75:5:19:1.

### Claim 19 (depends on 8)

The composition of claim 8, wherein the composition comprises a weight ratio of polymer to nucleic acid from about 5:1 to about 500:1.

### Claim 20 (depends on 8)

A pharmaceutical composition composing a composition of claim 8 and an excipient.