# US 10,117,934 B2 · Conjugated lipomers and uses thereof

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- Number: US 10,117,934 B2
- Document ID: US10117934B2
- Status: Granted
- Kind: B2
- Application number: 14/995,842
- Filed: 2016-01-14
- Published: 2016-07-21
- Granted: 2018-11-06
- Earliest claimed: 2011-03-28
- Assignees: Massachusetts Institute of Technology
- Applicants: Massachusetts Institute of Technology
- Inventors: James E. Dahlman; Avraham D. Schroeder; Daniel Griffith Anderson; Robert S. Langer; Christopher G. Levins
- Web page: https://patentgrep.com/patent/US10117934B2

## CPC

- A61K 47/22: Heterocyclic compounds, e.g. ascorbic acid, tocopherol or pyrrolidones
- 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 9/1272: comprising non-phosphatidyl surfactants as bilayer-forming substances, e.g. cationic lipids or non-phosphatidyl liposomes coated or grafted with polymers (lipids as modifying agents {A61K47/543})
- 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 47/543: {Lipids, e.g. triglycerides; Polyamines, e.g. spermine or spermidine}
- A61K 47/59: obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes
- A61K 47/6907: {the form being a microemulsion, nanoemulsion or micelle}
- A61K 47/6911: {the form being a liposome}
- A61K 47/6921: {the form being a particulate, a powder, an adsorbate, a bead or a sphere}
- A61P 35/00: Antineoplastic agents
- A61P 37/04: Immunostimulants
- C07D 257/02: not condensed with other rings
- C07D 273/00: Heterocyclic compounds containing rings having nitrogen and oxygen atoms as the only ring hetero atoms, not provided for by groups C07D261/00 - C07D271/00
- C07D 273/08: having two nitrogen atoms and more than one oxygen atom
- C07D 295/084: with the ring nitrogen atoms and the oxygen or sulfur atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings
- C08G 73/10: Polyimides; Polyester-imides; Polyamide-imides; Polyamide acids or similar polyimide precursors
- C12N 15/1137: {against enzymes (viral enzymes C12N15/1131; receptors C12N15/1138)}
- C12N 15/1138: {against receptors or cell surface proteins}
- C12N 2310/14: interfering nucleic acids [NA]
- 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)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)
- 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

The present invention provides inventive conjugated polyethyleneimine (PEI) polymers and conjugated aza-macrocycles (collectively referred to herein as “conjugated lipomers” or “lipomers”) containing one or more groups of the formula (iii): wherein R3 and R4 are as defined herein. Also provided are compositions comprising the inventive conjugated lipomers, and methods of preparation and use.

## Claims

### Claim 1

A conjugated lipomer of Formula (IV):
or salt thereof; wherein:
each instance of L3 is independently:
each instance of R8 is independently hydrogen; acyl; silyl; sulfonyl; an amino protecting group; substituted or unsubstituted alkyl; substituted or unsubstituted alkenyl; substituted or unsubstituted alkynyl; substituted or unsubstituted heteroalkyl; substituted or unsubstituted heteroalkenyl; substituted or unsubstituted heteroalkynyl; substituted or unsubstituted carbocyclyl; substituted or unsubstituted heterocyclyl; substituted or unsubstituted aryl; substituted or unsubstituted heteroaryl; or
provided the conjugated lipomer contains two, three, or four groups of Formula (iii′);
each instance of R3 is independently substituted or unsubstituted C5-20 alkyl; substituted or unsubstituted alkenyl; substituted or unsubstituted alkynyl; substituted or unsubstituted heteroalkenyl; substituted or unsubstituted heteroalkynyl; substituted or unsubstituted carbocyclyl; substituted or unsubstituted heterocyclyl; substituted or unsubstituted heteroaryl; or a hydrophilic polymer;
each instance of R4 is independently hydrogen, acyl; silyl; a hydroxyl protecting group; substituted or unsubstituted alkyl; substituted or unsubstituted alkenyl; substituted or unsubstituted alkynyl; substituted or unsubstituted heteroalkyl; substituted or unsubstituted heteroalkenyl; substituted or unsubstituted heteroalkynyl; substituted or unsubstituted carbocyclyl; substituted or unsubstituted heterocyclyl; substituted or unsubstituted aryl; or substituted or unsubstituted heteroaryl;
each instance of m and p is 1;
q is 2; and
the dashed curved line, together with G and Y, is a covalent bond.

### Claim 2 (depends on 1)

The conjugated lipomer of claim 1, wherein each instance of R8 is independently hydrogen or a group of Formula (iii′).

### Claim 3 (depends on 1)

The conjugated lipomer of claim 1, wherein each instance of R3 is independently substituted or unsubstituted C5-20 alkyl or a hydrophilic polymer.

### Claim 4 (depends on 1)

The conjugated lipomer of claim 1, wherein at least one instance of R3 is substituted or unsubstituted C5-20 alkyl.

### Claim 5 (depends on 1)

The conjugated lipomer of claim 1, wherein the lipomer is of Formula (V):
or salt thereof.

### Claim 6 (depends on 1)

The conjugated lipomer of claim 1, wherein the conjugated lipomer is selected from the group consisting of:
and salts thereof.

### Claim 7 (depends on 1)

A composition comprising one or more conjugated lipomers of claim 1, and, optionally, an excipient.

### Claim 8 (depends on 7)

The composition of claim 7, wherein the composition is a pharmaceutical composition or a cosmetic composition.

### Claim 9 (depends on 7)

The composition of claim 7, wherein the composition further comprises an agent.

### Claim 10 (depends on 9)

The composition of claim 9, wherein the agent is an organic molecule, inorganic molecule, protein, peptide, polynucleotide, targeting agent, isotopically labeled chemical compound, vaccine, or immunological agent.

### Claim 11 (depends on 10)

The composition of claim 10, wherein the agent is a polynucleotide.

### Claim 12 (depends on 7)

The composition of claim 7, wherein the one or more conjugated lipomers are in the form of a particle.

### Claim 13 (depends on 9)

The composition of claim 9, wherein the agent is a polynucleotide that encodes a protein or peptide.

### Claim 14 (depends on 11)

The composition of claim 11, wherein the polynucleotide is DNA.

### Claim 15 (depends on 11)

The composition of claim 11, wherein the polynucleotide is RNA.

### Claim 16 (depends on 15)

The composition of claim 15, wherein the RNA is RNAi, dsRNA, siRNA, shRNA, miRNA, or antisense RNA.

### Claim 17 (depends on 1)

A method of preparing a conjugated lipomer of claim 1, the method comprising contacting a compound of Formula (III), or salt thereof, with an epoxide of Formula (xii):
wherein each instance of L2 is independently:
provided that at least one R8 group is hydrogen;
to provide the conjugated lipomer of claim 1.