# US 9,040,019 B2 · Methods of detecting myelin basic protein

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- Number: US 9,040,019 B2
- Document ID: US9040019B2
- Status: Granted
- Kind: B2
- Application number: 13/689,819
- Filed: 2012-11-30
- Published: 2014-06-05
- Granted: 2015-05-26
- Earliest claimed: 2012-11-30
- Assignees: General Electric Company
- Applicants: General Electric Company
- Inventors: Tiberiu Mircea Siclovan; Cristina Abucay Tan Hehir; Rong Zhang; Victoria Eugenia Cotero; Anshika Bajaj
- Web page: https://patentgrep.com/patent/US9040019B2

## CPC

- A61K 49/0021: {the fluorescent group being a small organic molecule}
- A61K 49/0002: {General or multifunctional contrast agents, e.g. chelated agents}
- G01N 33/6893: {related to diseases not provided for elsewhere}
- G01N 2800/285: Demyelinating diseases; Multipel sclerosis
- 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)
- 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

A method and a kit for detecting myelin basic protein are provided. The method comprises administering an agent, which binds to myelin basic protein (MBP), to a subject at risk of or diagnosed with a myelin-associated neuropathy, and determining myelination by detecting the agent resided in the subject. The amount of the agent present in the subject is indicative of a myelin-associated neuropathy. A method of quantifying an amount of MBP present in a tissue sample is also provided, wherein the method comprises contacting the tissue sample with the same agent, detecting the agent present in the tissue sample; and quantifying an amount of the agent present in the tissue sample.

## Claims

### Claim 1

A method of detecting myelin-associated neuropathy, comprising:
administering an agent to a subject at risk of or diagnosed with a myelin-associated neuropathy, wherein said agent;
binds to myelin basic protein (MBP); and
comprises a compound of Formula I, a 13C enriched compound of Formula I, a 19F-labeled derivative of Formula I, or a radioisotope derivative of Formula I or combinations thereof;
wherein R1 and R2 are independently at each occurrence a hydrogen, hydroxyl group, C1-C30 aliphatic radicals, C3-C30 cycloaliphatic radicals, or C2-C30 aromatic radicals with the proviso that R1 and R2 are not both equal to a hydroxyl group;
R3 is hydrogen, a hydroxyl group, an alkoxy group, a C1-C6 hydroxyalkyl group, a C1-C6 alkyl group or a substituted alkyl group; and
the summation of alkyl groups of R1, R2 and R3 is less than or equal to 16 carbon atoms; and
determining myelination by detecting the agent resided in the subject,
quantifying an amount of the agent resided in the subject, and
comparing the amount of the agent resided in the subject with an amount of the agent resided in a control sample administered with the same agent, whereby the amount of the agent resided in the subject compared to the control sample is indicative of a myelin-associated neuropathy.

### Claim 2 (depends on 1)

The method of claim 1, wherein R3 is hydrogen, an alkyl group of from 1 to 6 carbon atoms, or an alkoxy group.

### Claim 3 (depends on 1)

The method of claim 1, wherein at least one of the R1 and R2 is hydrogen, C1-C30 aliphatic radicals, and C2-C30 aromatic radicals.

### Claim 4 (depends on 1)

The method of claim 1, wherein the R1 is hydrogen and R2 is a 4-aminobenzyl group.

### Claim 5 (depends on 1)

The method of claim 1, wherein R1 is hydrogen and R2 is a hydroxyethyl group.

### Claim 6 (depends on 1)

The method of claim 1, wherein R1 and R2 are hydroxyethyl groups.

### Claim 7 (depends on 1)

The method of claim 1, wherein both R1 and R2 are hydrogen.

### Claim 8 (depends on 1)

The method of claim 1, wherein the agent crosses the blood brain barrier (BBB).

### Claim 9 (depends on 1)

The method of claim 1, wherein the agent crosses the blood nerve barrier (BNB).

### Claim 10 (depends on 1)

The method of claim 1, wherein a molecular weight of the compound of Formula I is less than or equal to 500 Da.

### Claim 11 (depends on 1)

The method of claim 1, wherein a Log P value of the compound of Formula I is less than or equal to 5.

### Claim 12 (depends on 1)

The method of claim 1, wherein the compound of Formula I is

### Claim 13 (depends on 1)

The method of claim 1, wherein the compound of Formula I is

### Claim 14 (depends on 1)

The method of claim 1, wherein the compound of Formula I is

### Claim 15 (depends on 1)

The method of claim 1, wherein the compound of Formula I is

### Claim 16 (depends on 1)

The method of claim 1, wherein the compound of Formula I is

### Claim 17 (depends on 1)

The method of claim 1, wherein the compound of Formula I is
wherein R1 is a hydrogen, a hydroxyl group, a C1-C30 aliphatic radical, a C3-C30 cycloaliphatic radical, or a C2-C30 aromatic radical; and
n is an integer between 0 and 4.

### Claim 18 (depends on 1)

The method of claim 1, wherein the compound of Formula I is
and wherein m and n are integers such that m+n is less than or equal to 4.

### Claim 19 (depends on 1)

The method of claim 1, wherein the administering comprises intravenous injection, intraperitoneal injection, subcutaneous injection, intramuscular injection, intrathecal injection, intracerebral injection, intracerebroventricular injection, intraspinal injection, or combinations thereof.

### Claim 20 (depends on 1)

The method of claim 1, wherein the detecting is effected by gamma imaging, fluorescence microscopy, laser-confocal microscopy, cross-polarization microscopy, autoradiography, magnetic resonance imaging, magnetic resonance spectroscopy, or combinations thereof.

### Claim 21 (depends on 1)

The method of claim 1, wherein the detecting is effected by:
applying a light source on the subject, wherein the light source is tuned to the spectral excitation characteristics of the compound of Formula I; and
observing the subject through an optical filter tuned to the spectral emission characteristics of the compound of Formula I.

### Claim 22 (depends on 1)

The method of claim 1, wherein the quantifying step comprises measuring a radioactivity of the agent present in the subject and wherein the agent comprises the radioactive derivative of Formula I.

### Claim 23 (depends on 1)

The method of claim 1, wherein the myelin-associated neuropathy comprises multiple sclerosis, Alzheimer's disease, Guillain-Barré syndrome, leukodystrophies, metachromatic leukodystrophy, Refsum's disease, adrenoleukodystrophy, Krabbe's disease, phenylketonuria, Canavan disease, Pelizaeus-Merzbacher disease, Alexander's disease, diabetic neuropathy, chemotherapy-induced neuropathy, or a combination thereof.
