# US 2019/0169583 A1 · STEP-Derived Peptide for Brain Injury Treatment

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

- Number: US 2019/0169583 A1
- Document ID: US20190169583A1
- Status: Published application
- Kind: A1
- Application number: 16/116,117
- Filed: 2018-08-29
- Published: 2019-06-06
- Earliest claimed: 2010-09-15
- Assignees: Stc.Unm
- Inventors: Surojit Paul
- Web page: https://patentgrep.com/patent/US20190169583A1

## CPC

- C12N 9/16: acting on ester bonds (3.1)
- A61K 38/465: {acting on ester bonds (3.1), e.g. lipases, ribonucleases}
- A61P 25/00: Drugs for disorders of the nervous system
- A61P 25/14: for treating abnormal movements, e.g. chorea, dyskinesia
- A61P 25/18: Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
- A61P 25/28: for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
- C12Y 301/03048: Protein-tyrosine-phosphatase (3.1.3.48)
- 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)
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)
- 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
- C12Y: ENZYMES

## Abstract

A novel peptide sequence that is a modified derivative of a neuron-specific tyrosine phosphatase is shown and described. Specifically, the novel peptide sequence is a modified derivative of striatal-enriched tyrosine phosphatase (STEP). The peptide sequence has been modified so as to be able to ameliorate and treat brain injury resulting from excessive glutamate release and/or oxidative stress. Examples of the types of brain injury which the presently disclosed peptide sequence is useful for treating includes acute brain injury resulting from stroke or traumatic brain injury and chronic disorders such as Huntington's chorea and schizophrenia. Furthermore, the presently described peptide sequence may further be useful in the treatment and amelioration of disorders associated with fear memory such as post-traumatic stress disorder.

## Claims

### Claim 1

An isolated peptide comprising a kinase interacting motif (KIM) domain and a kinase specificity sequence (KIS) domain of a striatal-enriched tyrosine phosphatase (STEP) protein, wherein a serine in the KIM domain is modified so as to prevent phosphorylation at that site and at least one of a threonine and a serine in the KIS domain is modified to a phospho-mimic so as to prevent phosphorylation at that site.

### Claim 2 (depends on 1)

The isolated peptide of claim 1, wherein the serine residue of the KIM domain is modified to an alanine, resulting in a constitutively active peptide.

### Claim 3 (depends on 2)

The isolated peptide of claim 2, wherein the serine residue is at position 49 using the numbering from SEQ ID NO: 1.

### Claim 4 (depends on 1)

The isolated peptide of claim 1, wherein the threonine residue of the KIS domain is modified to an aspartic acid residue or a glutamic acid residue.

### Claim 5 (depends on 1)

The isolated peptide of claim 1, wherein the serine residue of the KIS domain is modified to an aspartic acid residue or a glutamic acid residue.

### Claim 6 (depends on 1)

The isolated peptide of claim 1, wherein the threonine residue and the serine residues of the KIS domain are modified to a phospho-mimic amino acid residue.

### Claim 7 (depends on 5)

The isolated peptide of claim 5, wherein the serine residue of the KIS domain is at position 72 using the numbering from SEQ ID NO: 1.

### Claim 8 (depends on 1)

The isolated peptide of claim 1, further comprising a region configured to render the peptide cell permeable.

### Claim 9 (depends on 8)

The isolated peptide of claim 8, wherein the region configured to render the peptide cell permeable is a TAT domain.

### Claim 10 (depends on 1)

The isolated peptide of claim 1, further comprising a region configured to act as an observable marker.

### Claim 11 (depends on 10)

The isolated peptide of claim 10, wherein the region configured to act as an observable marker is a myc region.

### Claim 12 (depends on 4)

The isolated peptide of claim 4, wherein the threonine residue of the KIS domain is at position 59 using the numbering from SEQ ID NO: 1.

### Claim 13 (depends on 6)

The isolated peptide of claim 6, wherein the threonine residue of the KIS domain is replaced with an aspartic acid or a glutamic acid.

### Claim 14 (depends on 1)

The isolated peptide of claim 1, wherein the isolated peptide is SEQ ID: NO 4.

### Claim 15 (depends on 1)

The isolated peptide of claim 1, wherein the isolated peptide is SEQ ID: NO 8.

### Claim 16 (depends on 1)

The isolated peptide of claim 1, wherein the isolated peptide is SEQ ID: NO 10.

### Claim 17 (depends on 1)

The isolated peptide of claim 1, wherein the isolated peptide is SEQ ID: NO 11.

### Claim 18 (depends on 1)

A method of treating or ameliorating brain injury in a patient comprising delivering to the patient the isolated peptide of claim 1.

### Claim 19 (depends on 18)

The method of claim 18, wherein the brain injury is traumatic brain injury.

### Claim 20 (depends on 18)

The method of claim 18, wherein the brain injury is Huntington's Chorea or Schizophrenia.

### Claim 21 (depends on 18)

The method of claim 18, wherein the brain injury is ischemic stroke.
