# US 12,180,251 B2 · Nucleic acids encoding peptides that block binding of a2d-1 to glutamate receptors for treating diseases and disorders

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- Number: US 12,180,251 B2
- Document ID: US12180251B2
- Status: Granted
- Kind: B2
- Application number: 18/465,145
- Filed: 2023-09-11
- Published: 2024-03-14
- Granted: 2024-12-31
- Earliest claimed: 2017-08-14
- Assignees: Board of Regents, The University of Texas System
- Applicants: Board of Regents, The University of Texas System
- Inventors: Hui-Lin Pan
- Web page: https://patentgrep.com/patent/US12180251B2

## CPC

- C07K 14/00: Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- 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 31/485: Morphinan derivatives, e.g. morphine, codeine
- A61K 31/515: Barbituric acids; Derivatives thereof, e.g. sodium pentobarbital
- A61K 31/5513: 1,4-Benzodiazepines, e.g. diazepam {or clozapine}
- A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- A61P 23/00: Anaesthetics
- C07K 7/06: having 5 to 11 amino acids
- C07K 7/08: having 12 to 20 amino acids (gastrins C07K14/595; somatostatins C07K14/655; melanotropins C07K14/68)
- C07K 14/005: from viruses
- C07K 14/70571: {for neuromediators, e.g. serotonin receptor, dopamine receptor}
- C12N 7/00: Viruses; Bacteriophages; Compositions thereof; Preparation or purification thereof (preparing medicinal viral antigen or antibody compositions, e.g. virus vaccines, A61K39/00)
- C12N 15/1138: {against receptors or cell surface proteins}
- G01N 33/5041: {involving analysis of members of signalling pathways}
- 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 2319/10: containing a tag for extracellular membrane crossing, e.g. TAT or VP22
- C07K 2319/43: containing a FLAG-tag
- C07K 2319/60: containing spectroscopic/fluorescent detection, e.g. green fluorescent protein [GFP]
- C12N 2740/15043: viral genome or elements thereof as genetic vector
- 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)
- 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
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)
- G01N: INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES (measuring or testing apparatus or processes other than immunoassay, involving enzymes or microorganisms C12M, C12Q)

## Abstract

The present disclosure provides α2δ-1 C-terminal domain mimetics for the treatment of pain, epilepsy or other disorders in a subject. Further provided is an α2δ-1 C-terminal domain peptide which blocks binding of α2δ-1 to the glutamate receptors NMDAR and AMPAR.

## Claims

### Claim 1

An isolated nucleic acid encoding a peptide, the peptide comprising the amino acid sequence SEQ ID NO:1 and a cell-penetrating peptide, wherein said peptide blocks binding of α2δ-1 to a glutamate receptor.

### Claim 2 (depends on 1)

The isolated nucleic acid of claim 1, wherein the peptide comprises at least 30, 35, 40, 45 or 50 residues.

### Claim 3 (depends on 1)

The isolated nucleic acid of claim 1, wherein the peptide contains no more than 30, 35, 40, 45 or 50 residues.

### Claim 4 (depends on 1)

The isolated nucleic acid of claim 1, wherein the cell penetrating peptide is TAT.

### Claim 5 (depends on 1)

The isolated nucleic acid of claim 1, wherein the cell-penetrating peptide comprises the sequence of SEQ ID NO:2.

### Claim 6 (depends on 1)

The isolated nucleic acid of claim 1, wherein said peptide comprises the sequence of SEQ ID NO:4.

### Claim 7 (depends on 1)

The isolated nucleic acid of claim 1, wherein said peptide consists of the sequence of SEQ ID NO:4.

### Claim 8 (depends on 1)

A vector comprising a contiguous sequence consisting of the nucleic acid of claim 1.

### Claim 9 (depends on 8)

The vector of claim 8, wherein the vector is a viral vector.

### Claim 10 (depends on 9)

The vector of claim 9, wherein the viral vector is a lentiviral vector.

### Claim 11 (depends on 1)

A method for treating pain and/or epileptic seizures in a subject comprising administering an effective amount of a α2δ-1 C-terminal domain inhibitor comprising a vector comprising the nucleic acid of claim 1 to the subject, wherein the α2δ-1 C-terminal domain inhibitor blocks binding of α2δ-1 to a glutamate receptor.

### Claim 12 (depends on 11)

The method of claim 11, wherein the pain is neuropathic pain.

### Claim 13 (depends on 12)

The method of claim 12, wherein the neuropathic pain is chronic.

### Claim 14 (depends on 13)

The method of claim 13, wherein the chronic neuropathic pain is chemotherapy-induced neuropathic pain.

### Claim 15 (depends on 11)

The method of claim 11, wherein administering comprises intravenous, intra-arterial, intra-tumoral, subcutaneous, or intraperitoneal administration.

### Claim 16 (depends on 11)

The method of claim 11, further comprising administering to said subject a second therapy.

### Claim 17 (depends on 16)

The method of claim 16, wherein said second therapy is an anticonvulsant.

### Claim 18 (depends on 17)

The method of claim 17, wherein the anticonvulsant is a barbiturate, benzodiazepine, bromide, carbamate, or carboxamide.

### Claim 19 (depends on 1)

A method for treating brain injury comprising ischemia and/or reperfusion in a subject comprising administering an effective amount of a α2δ-1 C-terminal domain inhibitor comprising a vector comprising the nucleic acid of claim 1 to the subject, wherein the α2δ-1 C-terminal domain inhibitor blocks binding of α2δ-1 to a glutamate receptor.