# US 12,180,255 B2 · Compositions and methods for derepressing RE1 silencing transcription factor target genes

> Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt

- Number: US 12,180,255 B2
- Document ID: US12180255B2
- Status: Granted
- Kind: B2
- Application number: 17/778,738
- Filed: 2020-11-20
- Published: 2023-02-23
- Granted: 2024-12-31
- Earliest claimed: 2019-11-22
- Assignees: Alcamena Stem Cell Therapeutics, LLC
- Applicants: Alcamena Stem Cell Therapeutics, LLC
- Inventors: Edmund Nesti; Alexander Pisarchik
- Web page: https://patentgrep.com/patent/US12180255B2

## CPC

- C07K 14/4703: {Inhibitors; Suppressors}
- C12N 9/16: acting on ester bonds (3.1)
- A61P 25/00: Drugs for disorders of the nervous system
- C07K 14/47: from mammals
- A61K 38/00: Medicinal preparations containing peptides (peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00)
- C07K 2319/06: containing a lysosomal/endosomal localisation signal
- 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)
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- 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

The invention relates to compounds, compositions, and methods for derepressing RE1 silencing transcription factor (REST) target genes are provided. In particular, a peptide having the sequence TEDLEPPEPPLPKEN (SEQ. ID NO: 1) and EDLEPPEPPLPK (SEQ. ID NO: 15), or the reversed sequences made of D-amino acids (retro inverted, RI) nekplppeppeldet (SEQ ID NO: 16) and kplppeppelde (SEQ ID NO: 17), are disclosed for inhibiting REST activity. The peptides are useful to treat, prevent, or ameliorate conditions such as traumatic brain injury, epilepsy, dementia, Huntington's Disease (HD), chronic pain, brain cancer (including glioblastoma multiforme), pancreatic cancer; diabetes, and peripheral nerve injury.

## Claims

### Claim 1

An isolate peptide comprising an amino acid sequence, wherein the amino acid sequence is selected from the group consisting of SEQ ID NOS: 1, 15-17, 18, 22, 25, 31, 35, 60, 63, 64, 66, 68, 75, 81, 85, 110, 113, 114, and 116.

### Claim 2 (depends on 1)

The peptide of claim 1, wherein the amino acid sequence is a fusion peptide.

### Claim 3 (depends on 2)

The peptide of claim 2, wherein the amino acid sequence is fused to a cell penetrating peptide or an endosomal release sequence.

### Claim 4 (depends on 3)

The peptide of claim 3, wherein the cell penetrating peptide or the endosomal release sequence is selected from the group consisting of SEQ ID NOS: 118-137 or 140-159.

### Claim 5 (depends on 3)

The peptide of claim 3, wherein a linker connects the amino acid sequence to the cell penetrating peptide or the endosomal release sequence.

### Claim 6 (depends on 5)

The peptide of claim 5, wherein the linker is selected from the group consisting of SEQ ID NOS: 138, 139, 160, and 161.

### Claim 7 (depends on 3)

The peptide of claim 3, wherein the cell penetrating peptide or the endosomal release sequence is fused to the amino acid sequence at an N- or a C-terminus.

### Claim 8 (depends on 1)

A pharmaceutical composition comprising the peptide of claim 1.

### Claim 9 (depends on 8)

The composition of claim 8, wherein the peptide is contained in an oral solution, a caplet, a capsule, an injectable, an infusible, a suppository, a lozenge, a tablet, a cream, a salve, or an inhalant.

### Claim 10 (depends on 8)

The composition of claim 8, further comprising an excipient.

### Claim 11

An isolate peptide comprising an amino acid sequence, wherein the amino acid sequence is a cyclized fusion peptide selected from the group consisting of SEQ ID NOS: 2, 5, 12, 13 and 14.

### Claim 12 (depends on 11)

The peptide of claim 11, wherein the amino acid sequence is fused to a cell penetrating peptide or an endosomal release sequence.

### Claim 13 (depends on 12)

The peptide of claim 12, wherein the cell penetrating peptide or the endosomal release sequence is fused to the amino acid sequence at an N- or a C-terminus.

### Claim 14 (depends on 11)

A pharmaceutical composition comprising the peptide of claim 11.

### Claim 15 (depends on 14)

The composition of claim 14, wherein the peptide is contained in an oral solution, a caplet, a capsule, an injectable, an infusible, a suppository, a lozenge, a tablet, a cream, a salve, or an inhalant.

### Claim 16 (depends on 14)

The composition of claim 14, further comprising an excipient.

### Claim 17

An isolate peptide comprising an amino acid sequence, wherein the amino acid sequence is a fusion peptide selected from the group consisting of SEQ ID NOS: 2 and 4-14.

### Claim 18 (depends on 17)

A pharmaceutical composition comprising the peptide of claim 17.

### Claim 19 (depends on 18)

The composition of claim 18, wherein the peptide is contained in an oral solution, a caplet, a capsule, an injectable, an infusible, a suppository, a lozenge, a tablet, a cream, a salve, or an inhalant.

### Claim 20 (depends on 18)

The composition of claim 18, further comprising an excipient.