# US 2019/0167795 A1 · Conjugated lipomers 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 2019/0167795 A1
- Document ID: US20190167795A1
- Status: Published application
- Kind: A1
- Application number: 16/181,109
- Filed: 2018-11-05
- Published: 2019-06-06
- 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/US20190167795A1

## 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 at position 1

1-21. (canceled)

### Claim 22

A conjugated lipomer of the Formula (IV):
or salt thereof; wherein:
each instance of L3 is independently:
provided that the conjugated lipomer contains at least one group (vi), (vii) or (viii);
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 at least one group of the formula (iii′);
each instance of R3 is independently 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 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 independently 0, 1 or 2;
q is an integer 2, 3, or 4; and
the dashed curved line, together with G and Y, is a covalent bond or a group of the formula:
wherein s is 0, 1, or 2.

### Claim 23 (depends on 22)

The conjugated lipomer of claim 22, wherein each instance of R8 is independently hydrogen or a group of the formula (iii′).

### Claim 24 (depends on 22)

The conjugated lipomer of claim 22, wherein each instance of R3 is independently substituted or unsubstituted alkyl; substituted or unsubstituted heteroalkyl; or a hydrophilic polymer.

### Claim at position 5

25-28. (canceled)

### Claim 29 (depends on 22)

The conjugated lipomer of claim 22, wherein the dashed curved line, together with G and Y, is a covalent bond.

### Claim 30 (depends on 22)

The conjugated lipomer of claim 22, wherein the dashed curved line, together with G and Y, a group of the formula:
wherein s is 0, 1, or 2.

### Claim 31 (depends on 22)

The conjugated lipomer of claim 22, wherein the dashed curved line, together with G and Y, a group of the formula:
wherein s is 0, 1, or 2.

### Claim 32 (depends on 22)

The conjugated lipomer of claim 22, wherein the lipomer comprises at least one instance of the group of the formula (vi).

### Claim 33 (depends on 32)

The conjugated lipomer of claim 32, wherein the lipomer is of the Formula (VI), or (VII):
or salt thereof.

### Claim 34 (depends on 22)

The conjugated lipomer of claim 22, wherein the lipomer comprises at least one instance of the group of the formula (vii), (viii), or (ix).

### Claim 35 (depends on 34)

The conjugated lipomer of claim 34, wherein the lipomer is of the Formula (VII) or (IX):
or salt thereof.

### Claim 36 (depends on 33)

The conjugated lipomer of claim 33, wherein the conjugated lipomer is selected from the group consisting of:
and salts thereof.

### Claim 37 (depends on 35)

A conjugated lipomer of claim 35, wherein the conjugated lipomer is selected from the group consisting of:
and salts thereof.)

### Claim 38 (depends on 22)

A composition comprising one or more conjugated lipomers of claim 22, and, optionally, an excipient.

### Claim 39 (depends on 38)

The composition of claim 38, wherein the composition is a pharmaceutical composition or a cosmetic composition.

### Claim 40 (depends on 38)

The composition of claim 38, wherein the composition further comprises an agent.

### Claim 41 (depends on 40)

The composition of claim 40, wherein the agent is an organic molecule, inorganic molecule, nucleic acid, protein, peptide, polynucleotide, targeting agent, an isotopically labeled chemical compound, vaccine, or an immunological agent.

### Claim 42 (depends on 41)

The composition of claim 41, wherein the agent is a polynucleotide, and the polynucleotide is DNA or RNA.

### Claim 43 (depends on 42)

The composition of claim 42, wherein the RNA is RNAi, dsRNA, siRNA, shRNA, miRNA, or antisense RNA.

### Claim at position 21

44-49. (canceled)

### Claim 50 (depends on 22)

A method of preparing a conjugated lipomer of claim 22, or salt thereof, the method comprising contacting a compound of the Formula (III), or salt thereof, with an epoxide of the formula (xii):
wherein each instance of L2 is independently:
provided that the compound of Formula (III) contains at least one group (vi), (vii) or (viii); and
further provided that at least one R8 group is hydrogen;
to provide the conjugated lipomer of the Formula (IV), or salt thereof.

### Claim at position 23

51-53. (canceled)

### Claim 54 (depends on 22)

A method of treating cancer comprising administering to a subject in need thereof an effective amount of a conjugated lipomer, or salt thereof, of claim 22.