Development of a highly efficient second generation fentanyl-conjugate vaccine to treat fentanyl addiction

Patent metadata

Field	Value
Publication number	US-2024307517-A1
Application number	US-202218560241-A
Country	US
Kind code	A1
Filing date	May 10, 2022
Priority date	May 10, 2021
Publication date	Sep 19, 2024
Grant date	—

Abstract

The invention is directed to fentanyl analogues and a conjugate comprising same, as well as a method of inducing an immune response against fentanyl.

First claim

1 . A fentanyl analogue having the structure of any of Formulae (1)-(7):

wherein
A is H or -alkyl-R 1 ;
R 1 , R 2 , and R 3 are each independently H or —(C 1 -C 12 alkyl)-COOH, provided that at least one of R 1 , R 2 , and R 3 is —(C 1 -C 12 alkyl)-COOH.

2 . The fentanyl analogue of claim 1 , having the following structure:

3 . The fentanyl analogue of claim 1 , wherein the fentanyl analogue is any one of Formulae (8)-(12):

wherein R 1 , R 2 , and R 3 are each —(C 1 -C 12 alkyl)-COOH.

4 . The fentanyl analogue of claim 1 having the following structure:

5 . A conjugate comprising the fentanyl analogue of claim 1 or carfentanil conjugated to an adenoviral capsid protein, optionally a hexon protein, a penton base protein, or a fiber protein.

6 . A conjugate comprising the fentanyl analogue of claim 2 conjugated to an adenoviral capsid protein, optionally a hexon protein, a penton base protein, or a fiber protein.

7 . A conjugate comprising the fentanyl analogue of claim 3 conjugated to an adenoviral capsid protein, optionally a hexon protein, a penton base protein, or a fiber protein.

8 . A conjugate comprising the fentanyl analogue of claim 4 conjugated to an adenoviral capsid protein, optionally a hexon protein, a penton base protein, or a fiber protein.

9 . The conjugate of claim 5 having the following structure of any of Formulae 1a-7a:

wherein
A is H or -alkyl-R 1 ;
R 1 , R 2 , and R 3 are each independently H, —(C 1 -C 12 alkyl)-COOH, or —(C 1 -C 12 alkyl)-C(O)NH—X, provided that at least one of R 1 , R 2 , and R 3 is —(C 1 -C 12 alkyl)-C(O)NH—X, and
X is an adenoviral capsid protein;

or having the structure of any one of Formulae 8a-10a:

wherein R 1 , R 2 , and R 3 are each —(C 1 -C 12 alkyl)-C(O)NH—X, and X is an adenoviral capsid protein;

or having the structure:

wherein X is an adenoviral capsid protein.

10 . (canceled)

11 . The conjugate of claim 5 , wherein the conjugate comprises carfentanil and has the formula:

wherein R 1 is —(C 1 -C 12 alkyl)-C(O)NH—X, and X is an adenoviral capsid protein.

12 . The conjugate of claim 5 , wherein the adenovirus capsid protein is isolated or purified.

13 . (canceled)

14 . The conjugate of claim 5 , wherein the adenovirus capsid protein is synthetic or recombinant.

15 . The conjugate of claim 5 , wherein the conjugate comprises a disrupted adenovirus, or one or more additional adenovirus capsid proteins.

16 . The conjugate of claim 5 , wherein the adenovirus is a human adenovirus, optionally a serotype 5 adenovirus.

17 . The conjugate of claim 5 , wherein the conjugate comprises an adenovirus disrupted by exposure to heat and/or detergents.

18 . A composition comprising the fentanyl analogue of claim 1 or conjugate comprising same and a pharmaceutically acceptable carrier.

19 . A method of inducing an immune response against fentanyl in a subject, and/or prevent or treat fentanyl addiction and/or reduce the likelihood of overdose in a subject, optionally a human, which method comprises administering to the subject the conjugate of claim 5 .

20 . (canceled)

21 . (canceled)

22 . (canceled)

23 . A method of preparing a conjugate comprising the fentanyl analogue of claim 1 or carfentinil and an adenovirus capsid protein, the method comprising combining the fentanyl analogue with an adenovirus capsid protein, whereby the fentanyl analogue is conjugated to the capsid protein.

24 . The method of claim 23 , wherein the fentanyl analogue and the capsid protein are combined in the presence of N-hydroxysulfosuccinimide (sulfo-NHS) and/or 1-ethyl-3-[3-dimethylaminopropyl]carbodiimide hydrochloride (EDC).

25 . The method of claim 23 , wherein the method comprises combining the fentanyl analogue with a disrupted adenovirus, and the fentanyl analogue conjugates with a capsid protein of the disrupted adenovirus.

Assignees

• Univ Cornell

Inventors

• Crystal Ronald G
• Kaminsky Stephen
• Lambert Tristan H
• Sondhi Dolan
• De Bishnu
• Leopold Philip L
• Holm Andrew Thomas

Classifications

• C12N2750/14134

  Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein · CPC title

• C07D471/04

  Ortho-condensed systems · CPC title

• C07D401/04

  directly linked by a ring-member-to-ring-member bond · CPC title

• C07D211/58 Primary

  attached in position 4 · CPC title

• A61K2039/6075

  Viral proteins · CPC title