# US 2018/0021441 A1 · Hyperbranched polymers and polyplexes and dna or rna delivery systems including the same

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- Number: US 2018/0021441 A1
- Document ID: US20180021441A1
- Status: Published application
- Kind: A1
- Application number: 15/720,542
- Filed: 2017-09-29
- Published: 2018-01-25
- Earliest claimed: 2015-04-02
- Assignees: The Regents of the University of Michigan
- Applicants: The Regents of the University of Michigan
- Inventors: Peter X. Ma; Xiaojin Zhang
- Web page: https://patentgrep.com/patent/US20180021441A1

## CPC

- A61K 47/593: {Polyesters, e.g. PLGA or polylactide-co-glycolide}
- A61K 47/50: the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K 47/60: the organic macromolecular compound being a polyoxyalkylene oligomer, polymer or dendrimer, e.g. PEG, PPG, PEO or polyglycerol
- A61K 47/6937: {the polymer being PLGA, PLA or polyglycolic acid}
- A61L 27/18: obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
- A61L 27/26: Mixtures of macromolecular compounds
- A61L 27/44: having a macromolecular matrix
- A61L 27/52: Hydrogels or hydrocolloids
- A61L 27/54: Biologically active materials, e.g. therapeutic substances {(A61L27/227 takes precedence)}
- A61L 27/56: Porous materials, {e.g. foams or sponges}
- A61L 27/58: Materials at least partially resorbable by the body
- A61P 3/10: for hyperglycaemia, e.g. antidiabetics
- A61P 7/00: Drugs for disorders of the blood or the extracellular fluid
- A61P 9/00: Drugs for disorders of the cardiovascular system
- A61P 35/00: Antineoplastic agents
- C08F 210/02: Ethene
- C08G 63/66: Polyesters containing oxygen in the form of ether groups (C08G63/42, C08G63/58 take precedence)
- C08G 73/0206: {Polyalkylene(poly)amines}
- C08G 73/024: {Polyamines containing oxygen in the form of ether bonds in the main chain}
- C08G 81/00: Macromolecular compounds obtained by interreacting polymers in the absence of monomers, e.g. block polymers (involving only carbon-to-carbon unsaturated bond reactions C08F299/00 {; polyester-amides C08G69/44; polyester-imides C08G73/16; polyamides-imides C08G73/14; block- or graft polymers containing polysiloxane sequences C08G77/42})
- C08G 83/00: Macromolecular compounds not provided for in groups C08G2/00 - C08G81/00
- C08G 83/005: {Hyperbranched macromolecules}
- C12N 15/111: {General methods applicable to biologically active non-coding nucleic acids}
- 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)}
- A61K 48/0041: {the non-active part being polymeric}
- A61L 2300/258: Genetic materials, DNA, RNA, genes, vectors, e.g. plasmids
- A61L 2300/604: Biodegradation
- A61L 2430/02: for reconstruction of bones; weight-bearing implants
- C08G 2210/00: Compositions for preparing hydrogels
- C08G 2230/00: Compositions for preparing biodegradable polymers
- C12N 2310/113: targeting other non-coding nucleic acids, e.g. antagomirs
- C12N 2310/14: interfering nucleic acids [NA]
- C12N 2310/141: MicroRNAs, miRNAs
- C12N 2310/351: Conjugate
- C12N 2310/51: in polymeric form, e.g. multimers, concatemers
- C12N 2310/52: branched
- C12N 2320/32: Special delivery means, e.g. tissue-specific
- 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
- C08F: MACROMOLECULAR COMPOUNDS OBTAINED BY REACTIONS ONLY INVOLVING CARBON-TO-CARBON UNSATURATED BONDS
- 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

A hyperbranched polymer includes a hyperbranched, hydrophobic molecular core, respective low molecular weight polyethyleneimine chains attached to at least three branches of the hyperbranched, hydrophobic molecular core, and respective polyethylene glycol chains attached to at least two other branches of the hyperbranched, hydrophobic molecular core. Examples of the hyperbranched polymer may be used to form hyperbranched polyplexes, and may be included in DNA or RNA delivery systems.

## Claims

### Claim 1

A hyperbranched polymer, comprising:
a hyperbranched, hydrophobic molecular core;
respective low molecular weight polyethyleneimine chains attached to two or more branches of the hyperbranched, hydrophobic molecular core; and
respective polyethylene glycol chains attached to two or more other branches of the hyperbranched, hydrophobic molecular core.

### Claim 2 (depends on 1)

The hyperbranched polymer as defined in claim 1 wherein the hyperbranched, hydrophobic molecular core is a hyperbranched polyester including at least 4 terminal hydroxyl groups.

### Claim 3 (depends on 1)

The hyperbranched polymer as defined in claim 1 wherein the low molecular weight polyethyleneimine chains each have a molecular weight ranging from about 400 g/mol to about 5,000 g/mol.

### Claim 4

A linear polymer, comprising:
a polyethylene glycol chain;
a polyester chain attached to an end of the polyethylene glycol chain; and
respective low molecular weight polyethyleneimine chains attached as side chains to the polyester chain.

### Claim 5 (depends on 4)

The linear polymer as defined in claim 4 wherein the polyester chain is selected from the group consisting of polylactide, polycaprolactone, polycarbonate, poly(phosphoesters), polyanhydrides, and polyglycolic acid.

### Claim 6 (depends on 4)

The linear polymer as defined in claim 4 wherein the low molecular weight polyethyleneimine chains each have a molecular weight ranging from about 400 g/mol to about 5,000 g/mol.

### Claim 7

A hyperbranched polyplex, comprising:
a hydrophilic inner section formed of a first plurality of polyethylene glycol chains;
a hydrophilic outer section formed of a second plurality of polyethylene glycol chains; and
a central section formed of:
a hyperbranched, hydrophobic molecular core attached to each of the first and second pluralities of polyethylene glycol chains;
respective low molecular weight polyethyleneimine chains attached to two or more branches of the hyperbranched, hydrophobic molecular core; and
any of DNA or RNA biomolecules complexed with the low molecular weight polyethyleneimine chains.

### Claim 8 (depends on 7)

The hyperbranched polyplex as defined in claim 7 wherein the RNA biomolecules are selected from the group consisting of miRNA, mRNA, and siRNA.

### Claim 9 (depends on 7)

The hyperbranched polyplex as defined in claim 7 wherein the hyperbranched, hydrophobic molecular core is a hyperbranched polyester including at least 4 terminal hydroxyl groups.

### Claim 10 (depends on 7)

The hyperbranched polyplex as defined in claim 7 wherein the low molecular weight polyethyleneimine chains each have a molecular weight ranging from about 400 g/mol to about 5,000 g/mol.

### Claim 11 (depends on 7)

The hyperbranched polyplex as defined in claim 7 wherein the DNA biomolecules are selected from the group consisting of pDNA, cDNA, cpDNA, gDNA, msDNA, mtDNA, and rDNA.

### Claim 12 (depends on 7)

A biodegradable sphere, comprising;
a biodegradable polymer matrix; and
a plurality of the hyperbranched polyplexes of claim 7 embedded in the biodegradable polymer matrix.

### Claim 13 (depends on 12)

A biodegradable or erodible structure, comprising:
a scaffold or hydrogel; and
a plurality of the biodegradable spheres of claim 12 attached to the scaffold or hydrogel.

### Claim 14 (depends on 13)

The biodegradable or erodible structure as defined in claim 13 wherein the scaffold is formed of a porous material including a plurality of nano-fibers aggregated together and pores defined between at least some of the plurality of nano-fibers.

### Claim 15

A method for making a hyperbranched polyplex, the method comprising:
forming a hyperbranched polymer by:
converting hydroxyl groups of a hyperbranched polyester to carboxyl groups, thereby forming a first modified hyperbranched polyester;
introducing polyethylene glycol chains and azido groups onto the first modified hyperbranched polyester to form a second modified hyperbranched polyester; and
conjugating the respective low molecular weight polyethyleneimine chains to the second modified hyperbranched polyester;
forming a solution of the hyperbranched polymer;
mixing the solution of the hyperbranched polymer with any of a DNA solution or an RNA solution to form a mixture; and
incubating the mixture, thereby forming the hyperbranched polyplex.