IP Library Granted Patent US 9,040,019
Granted Patent B2
US 9,040,019 · App. 13/689,819 · Granted May 26, 2015

Methods of detecting myelin basic protein

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Quick Facts
Patent No.
US 9,040,019
App. No.
13/689,819
Granted
May 26, 2015
Kind
B2
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 (37)

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 13 C enriched compound of Formula I, a 19 F-labeled derivative of Formula I, or a radioisotope derivative of Formula I or combinations thereof;

wherein R 1 and R 2 are independently at each occurrence a hydrogen, hydroxyl group, C 1 -C 30 aliphatic radicals, C 3 -C 30 cycloaliphatic radicals, or C 2 -C 30 aromatic radicals with the proviso that R 1 and R 2 are not both equal to a hydroxyl group;

R 3 is hydrogen, a hydroxyl group, an alkoxy group, a C 1 -C 6 hydroxyalkyl group, a C 1 -C 6 alkyl group or a substituted alkyl group; and

the summation of alkyl groups of R 1 , R 2 and R 3 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.

2. The method of claim 1 , wherein R 3 is hydrogen, an alkyl group of from 1 to 6 carbon atoms, or an alkoxy group.

3. The method of claim 1 , wherein at least one of the R 1 and R 2 is hydrogen, C 1 -C 30 aliphatic radicals, and C 2 -C 30 aromatic radicals.

4. The method of claim 1 , wherein the R 1 is hydrogen and R 2 is a 4-aminobenzyl group.

5. The method of claim 1 , wherein R 1 is hydrogen and R 2 is a hydroxyethyl group.

6. The method of claim 1 , wherein R 1 and R 2 are hydroxyethyl groups.

7. The method of claim 1 , wherein both R 1 and R 2 are hydrogen.

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

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

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

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

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

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

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

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

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

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

wherein R 1 is a hydrogen, a hydroxyl group, a C 1 -C 30 aliphatic radical, a C 3 -C 30 cycloaliphatic radical, or a C 2 -C 30 aromatic radical; and

n is an integer between 0 and 4.

18. 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.

19. 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.

20. 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.

21. 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.

22. 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.

23. 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.

Assignments (6)
QUITCLAIM ASSIGNMENT Recorded Sep 18, 2025
From: EDISON INNOVATIONS LLC
To: PLYMOUTH TECHNOLOGIES, LLC
Reel/Frame 072941/0328 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Mar 26, 2025
From: GENERAL ELECTRIC COMPANY
To: GE INTELLECTUAL PROPERTY LICENSING, LLC
Reel/Frame 070636/0815 →
CHANGE OF NAME Recorded Mar 26, 2025
From: GE INTELLECTUAL PROPERTY LICENSING, LLC
To: DOLBY INTELLECTUAL PROPERTY LICENSING, LLC
Reel/Frame 070643/0907 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Feb 20, 2025
From: DOLBY INTELLECTUAL PROPERTY LICENSING, LLC
To: EDISON INNOVATIONS, LLC
Reel/Frame 070293/0273 →
CONFIRMATORY LICENSE Recorded Jan 11, 2013
From: GENERAL ELECTRIC COMPANY
To: NATIONAL INSTITUTES OF HEALTH (NIH), U.S. DEPT. OF HEALTH AND HUMAN SERVICES (DHHS), U.S. GOVERNMENT
Reel/Frame 029610/0564 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Nov 30, 2012
From: SICLOVAN, TIBERIU MIRCEA; TAN HEHIR, CRISTINA ABUCAY; ZHANG, RONG; COTERO, VICTORIA EUGENIA; BAJAJ, ANSHIKA
To: GENERAL ELECTRIC COMPANY
Reel/Frame 029378/0755 →