# US 10,946,061 B2 · Peptide inhibitors of twist

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- Number: US 10,946,061 B2
- Document ID: US10946061B2
- Status: Granted
- Kind: B2
- Application number: 16/843,718
- Filed: 2020-04-08
- Published: 2020-07-23
- Granted: 2021-03-16
- Earliest claimed: 2016-11-18
- Assignees: City of Hope
- Applicants: City of Hope
- Inventors: Carlotta A. Glackin
- Web page: https://patentgrep.com/patent/US10946061B2

## CPC

- A61K 38/10: Peptides having 12 to 20 amino acids {(A61K38/043 - A61K38/046 take precedence)}
- A61K 31/337: having four-membered rings, e.g. taxol
- A61K 31/4745: condensed with ring systems having nitrogen as a ring hetero atom, e.g. phenantrolines (yohimbine derivatives, vinblastine A61K31/475; ergoline derivatives A61K31/48)
- A61K 31/555: containing heavy metals, e.g. hemin, hematin, melarsoprol
- A61K 33/243: Platinum; Compounds thereof
- A61K 38/1709: {from mammals}
- A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- 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}
- C07K 7/08: having 12 to 20 amino acids (gastrins C07K14/595; somatostatins C07K14/655; melanotropins C07K14/68)
- C07K 14/4702: {Regulators; Modulating activity}
- C07K 2319/10: containing a tag for extracellular membrane crossing, e.g. TAT or VP22
- C07K 2319/60: containing spectroscopic/fluorescent detection, e.g. green fluorescent protein [GFP]
- C07K 2319/70: containing domain for protein-protein interaction
- 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)
- C07K: PEPTIDES (peptides in foodstuffs A23; obtaining protein compositions for foodstuffs, working-up proteins for foodstuffs A23J; preparations for medicinal purposes A61K; peptides containing beta-lactam rings C07D; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, C07D; ergot alkaloids of the cyclic peptide type C07D519/02; macromolecular compounds having statistically distributed amino acid units in their molecules, i.e. when the preparation does not provide for a specific; but for a random sequence of the amino acid units, homopolyamides and block copolyamides derived from amino acids C08G69/00; macromolecular products derived from proteins C08H1/00; preparation of glue or gelatine C09H; single cell proteins, enzymes C12N; genetic engineering processes for obtaining peptides C12N15/00; compositions for measuring or testing processes involving enzymes C12Q; investigation or analysis of biological material G01N33/00)

## Abstract

The disclosure provides, inter alia, compositions comprising TWIST peptide inhibitors and optionally one or more anti-cancer agents, and methods of using the compositions for the treatment of cancer.

## Claims

### Claim 1

A composition comprising a TWIST peptide or a nucleic acid encoding said TWIST peptide covalently bound to a delivery vehicle, wherein said TWIST peptide comprises a WR domain of TWIST1.

### Claim 2

A fusion protein comprising a TWIST peptide covalently attached to a cell-penetrating peptide, wherein said TWIST peptide comprises a WR domain of TWIST1.

### Claim 3 (depends on 2)

A nucleic acid sequence encoding said fusion protein of claim 2.

### Claim 4 (depends on 3)

The nucleic acid sequence of claim 3, wherein said nucleic acid sequence is part of a vector sequence.

### Claim 5 (depends on 1)

The composition of claim 1, wherein the TWIST peptide comprises an amino acid sequence comprising at least 80% sequence identity to SEQ ID NO: 1.

### Claim 6 (depends on 5)

The composition of claim 5, wherein the TWIST peptide comprises an amino acid sequence of SEQ ID NO: 1.

### Claim 7 (depends on 1)

The composition of claim 1, wherein the delivery vehicle is a nanoparticle, a vector, a virus capsid, a liposome, a liposomal vesicle, a lipoplex, a polyplex, a dendrimer, a macrophage, a polymer, a hybrid particle, or a lipid vehicle.

### Claim 8 (depends on 2)

The fusion protein of claim 2, wherein the cell-penetrating peptide comprises an amino acid sequence of SEQ ID NO:4.

### Claim 9 (depends on 2)

The fusion protein of claim 2, wherein the cell penetrating peptide comprises an amino acid sequence of SEQ ID NO:5, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23.

### Claim 10 (depends on 2)

The fusion protein of claim 2, wherein the cell penetrating peptide comprises an amino acid sequence of SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, or SEQ ID NO:11.

### Claim 11 (depends on 1)

The composition of claim 1, further comprising an anti-cancer agent.

### Claim 12 (depends on 11)

The composition of claim 11, wherein the anti-cancer agent is doxorubicin, cisplatin, carboplatin, a taxane, camptothecin, or a combination of two or more thereof.

### Claim 13 (depends on 1)

The composition of claim 1, further comprising a pharmaceutically acceptable excipient.

### Claim 14 (depends on 4)

The nucleic acid sequence of claim 4, wherein the vector sequence is a plasmid vector sequence or a viral vector sequence.

### Claim 15

A composition comprising a TWIST peptide or a nucleic acid encoding said TWIST peptide bound to a delivery vehicle, wherein
said TWIST peptide comprises a WR domain of TWIST1, and wherein
said delivery vehicle is a nanoparticle, a vector, a virus capsid, a liposome, a liposomal vesicle, a lipoplex, a polyplex, a dendrimer, a macrophage, a polymer, a hybrid particle, or a lipid vehicle.

### Claim 16 (depends on 15)

The composition of claim 15, wherein said TWIST peptide comprises an amino acid sequence comprising at least 80% sequence identity to SEQ ID NO: 1.

### Claim 17 (depends on 16)

The composition of claim 16, wherein said TWIST peptide comprises an amino acid sequence of SEQ ID NO: 1.

### Claim 18 (depends on 15)

The composition of claim 15, further comprising an anti-cancer agent.

### Claim 19 (depends on 18)

The composition of claim 18, wherein the anti-cancer agent is doxorubicin, cisplatin, carboplatin, a taxane, camptothecin, or a combination of two or more thereof.

### Claim 20 (depends on 15)

The composition of claim 15, further comprising a pharmaceutically acceptable excipient.