# US 10,245,271 B2 · Treatment of impaired cognitive flexibility with TrkB receptor antagonists

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- Number: US 10,245,271 B2
- Document ID: US10245271B2
- Status: Granted
- Kind: B2
- Application number: 15/215,327
- Filed: 2016-07-20
- Published: 2017-01-26
- Granted: 2019-04-02
- Earliest claimed: 2015-07-20
- Assignees: The Florida State University Research Foundation, Inc.; The General Hospital Corporation
- Applicants: Florida State University Research Foundation, Inc.; The General Hospital Corporation
- Inventors: Pradeep G. Bhide; Dierdre M. McCarthy; Joseph Biederman; Thomas J. Spencer
- Web page: https://patentgrep.com/patent/US10245271B2

## CPC

- A61K 31/551: having two nitrogen atoms, e.g. dilazep
- A61K 31/37: Coumarins, e.g. psoralen
- A61K 31/55: having seven-membered rings, e.g. azelastine, pentylenetetrazole
- A61K 38/06: Tripeptides
- A61K 38/12: Cyclic peptides {, e.g. bacitracins; Polymyxins; Gramicidins S, C; Tyrocidins A, B or C (A61K38/043 - A61K38/046 take precedence)}
- 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 cognitive flexibility of a subject may be improved by administering a therapeutically effective amount of a TrkB receptor antagonist to the subject in need thereof. The TrkB receptor antagonist compound may be administered in a pharmaceutical dosage form.

## Claims

### Claim 1

A method of treating impaired cognitive flexibility, the method comprising administering to a subject having impaired cognitive flexibility a therapeutically effective amount of a selective tyrosine kinase B (TrkB) receptor antagonist compound, the therapeutically effective amount being sufficient to improve cognitive flexibility in the subject;
wherein the selective TrkB receptor antagonist compound does not inhibit tyrosine kinase A (TrkA) or tyrosine kinase C (TrkC) receptors;
wherein the subject is identified as having at least one of attention deficit hyperactivity disorder (ADHD), autism spectrum disorder, and Asperger's syndrome; and
wherein the TrkB receptor antagonist compound is at least one compound selected from (a) ANA-12, (b) an ANA-12 based compound, and (c) a pharmaceutically acceptable salt of compound (a) or (b), wherein ANA-12 comprises the formula

### Claim 2 (depends on 1)

The method of claim 1, wherein the subject is identified as having impaired reversal learning.

### Claim 3 (depends on 1)

The method of claim 1, wherein the compound is in a pharmaceutical composition including 0.1 to 100 mg of the compound.

### Claim 4 (depends on 1)

The method of claim 1, wherein the therapeutically effective amount is 0.001 mg to 20 mg per kg of body weight of the subject.

### Claim 5 (depends on 1)

The method of claim 1, further comprising administering a stimulant to the subject.

### Claim 6 (depends on 1)

The method of claim 1, wherein the compound is in at least one pharmaceutical dosage form selected from an oral, transdermal, and an injectable dosage form.

### Claim 7 (depends on 1)

The method of claim 1, further comprising, prior to administering to the subject having impaired cognitive flexibility the therapeutically effective amount of the selective tyrosine kinase B (TrkB) receptor antagonist compound, conducting a psychiatric evaluation of the patient that determines whether the patient has impaired cognitive flexibility.