# US 11,998,589 B2 · PEGylated peptide amphiphile nanofibers and methods of use

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- Number: US 11,998,589 B2
- Document ID: US11998589B2
- Status: Granted
- Kind: B2
- Application number: 17/374,287
- Filed: 2021-07-13
- Published: 2022-01-13
- Granted: 2024-06-04
- Earliest claimed: 2020-07-13
- Assignees: Northwestern University
- Applicants: Northwestern University
- Inventors: Jacob A. Lewis; Ronit Freeman; Samuel I. Stupp
- Web page: https://patentgrep.com/patent/US11998589B2

## CPC

- A61K 38/1841: {Transforming growth factor [TGF]}
- 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 9/0092: {Hollow drug-filled fibres, tubes of the core-shell type, coated fibres, coated rods, microtubules or nanotubes}
- A61K 9/70: Web, sheet or filament bases {; Films; Fibres of the matrix type containing drug (hollow drug-filled fibres A61K9/0092)}
- A61K 47/54: the modifying agent being an organic compound
- A61K 47/542: {Carboxylic acids, e.g. a fatty acid or an amino acid}
- A61K 47/60: the organic macromolecular compound being a polyoxyalkylene oligomer, polymer or dendrimer, e.g. PEG, PPG, PEO or polyglycerol
- A61K 47/64: Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent (peptidic linkers A61K47/65)
- A61K 47/645: {Polycationic or polyanionic oligopeptides, polypeptides or polyamino acids, e.g. polylysine, polyarginine, polyglutamic acid or peptide TAT}
- A61K 47/6929: {the form being a nanoparticle, e.g. an immuno-nanoparticle}
- 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)

## Abstract

Provided herein are peptide amphiphiles (PAs). In some embodiments, provided herein are PEGylated PAs (e.g. nonionic PAs). In some embodiments, the peptide amphiphiles are assembled into nanofibers. The nanofibers may further comprise a growth factor protein, which may bind to a growth factor binding sequence presented on the nonionic PA. In some embodiments, the nanofibers further comprise a charged peptide amphiphile. The charged peptide amphiphile may be bound to a growth factor protein. Further provided herein are methods of use of the peptide amphiphiles and compositions comprising the same, such as for regenerative therapy.

## Claims

### Claim 1

A peptide amphiphile comprising a hydrophobic tail, a structural peptide segment, and a PEG domain, wherein the peptide amphiphile is nonionic.

### Claim 2 (depends on 1)

The peptide amphiphile of claim 1, wherein the hydrophobic tail comprises an 8-24 carbon alkyl chain (C8-24).

### Claim 3 (depends on 1)

The peptide amphiphile of claim 1, wherein the structural peptide segment has a propensity for forming (3-sheet conformations.

### Claim 4 (depends on 3)

The peptide amphiphile of claim 3, wherein the structural peptide segment comprises V2A2 or V3A3.

### Claim 5 (depends on 1)

The peptide amphiphile of claim 1, wherein the PEG domain comprises a PEG containing 1-20 repeating ethylene glycol subunits.

### Claim 6 (depends on 5)

The peptide amphiphile of claim 5, wherein the PEG contains 10 repeating ethylene glycol subunits.

### Claim 7 (depends on 1)

The peptide amphiphile of claim 1, further comprising a growth factor binding sequence.

### Claim 8 (depends on 7)

The peptide amphiphile of claim 7, wherein the growth factor binding sequence binds to a TGF-β family protein.

### Claim 9 (depends on 8)

The peptide amphiphile of claim 8, wherein the growth factor binding sequence comprises the peptide sequence HSNGLPL.

### Claim 10 (depends on 1)

A nanofiber comprising the peptide amphiphile of claim 1.

### Claim 11 (depends on 10)

The nanofiber of claim 10, further comprising one or more charged peptide amphiphiles, wherein the charged peptide amphiphiles comprise a hydrophobic tail, a structural peptide segment, and a charged peptide segment.

### Claim 12 (depends on 11)

The nanofiber of claim 11, wherein the charged segment is anionic.

### Claim 13 (depends on 12)

The nanofiber of claim 12, wherein the charged segment comprises E2-4.

### Claim 14 (depends on 11)

The nanofiber of claim 11, further comprising at least one growth factor protein or a mimetic thereof.

### Claim 15 (depends on 14)

The nanofiber of claim 14, wherein the growth factor protein or mimetic thereof is bound to the charged peptide amphiphile.

### Claim 16 (depends on 15)

The nanofiber of claim 15, wherein the growth factor protein is a TGF-β family protein.

### Claim 17 (depends on 10)

A composition comprising the nanofiber of claim 10.

### Claim 18 (depends on 17)

A method comprising contacting a cell with the composition of claim 17.

### Claim 19 (depends on 17)

A method comprising providing the composition of claim 17 to a subject in need thereof.

### Claim 20 (depends on 19)

The method of claim 19, wherein the composition promotes regeneration of one or more damaged bones or tissues in the subject.