IP Library Granted Patent US 9,333,232
Granted Patent B2
US 9,333,232 · App. 12/534,666 · Granted May 10, 2016

Methods for treating papilloma virus infection

Inventors: James K. Bashkin (St. Louis, MO); Terri Grace Edwards (Kalamazoo, MI); Christopher Fisher (Kalamazoo, MI); Kevin J. Koeller (Richmond Heights, MO)
Assignees: NanoVir LLC; THE CURATORS OF THE UNIVERSITY OF MISSOURI
A61K38/02C07D403/14
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Quick Facts
Patent No.
US 9,333,232
App. No.
12/534,666
Granted
May 10, 2016
Kind
B2
Abstract

The present invention relates to polyamide compositions and therapies for treating cells infected with papilloma virus (PV).

Claims (58)

1. A method of treating papilloma virus infected cells in a patient, the method comprising administering to a patient in need thereof an effective amount of a compound of formula:

Z-(X) n -γ q -(X) m —Y-A

or a pharmaceutically acceptable salt thereof, wherein

m is an integer between 8 and 11;

n is an integer between 6 and 10;

Z is desamino-imidazole (Formula V, Im);

each X is independently selected from 4-amino-2-carbonyl-N-methylimidazole (I), 4-amino-2-carbonyl-N-methylpyrrole (P) or β-alanine (β);

γ q is γ-amino butyric acid (γ), (R)-2,4-diaminobutyric acid (formula VI), (R)-2-(acetylamino)-4-aminobutyric acid (γ-NH[C(O)CH 3 ]);

Y is β-alanine or 4-amino-2-carbonyl-N-methylpyrrole (P); and

A is 3,3′-diamino-N-methyldipropylamine (Ta) or dimethylaminopropylamine (Dp).

2. A method according to claim 1 , wherein the compound has an IC 50 of less than about 1.0 μM in inhibiting papilloma virus growth in culture.

3. A method according to claim 2 , wherein the compound has an IC 50 of less than about 0.1 μM in inhibiting papilloma virus growth in culture.

4. A method according to claim 1 , wherein the compound is designed to bind to papilloma virus.

5. A method according to claim 4 , wherein the compound is designed to bind to papilloma virus DNA.

6. A method according to claim 5 , wherein the compound is designed to bind to a double stranded DNA comprising SEQ ID NO: 1 and SEQ ID NO: 2.

7. A method of treating papilloma virus infected cells in a patient, the method comprising administering to a patient in need thereof an effective amount of a pharmaceutical composition for treating papilloma virus, the pharmaceutical composition comprising a pharmaceutically acceptable carrier and a compound of formula:

Z-(X) n -γ q -(X) m —Y-A

or a pharmaceutically acceptable salt thereof, wherein

m is an integer between 8 and 11;

n is an integer between 6 and 10;

Z is desamino-imidazole (Formula V, Im);

each X is independently selected from 4-amino-2-carbonyl-N-methylimidazole (I), 4-amino-2-carbonyl-N-methylpyrrole (P) or β-alanine (β);

γ q is γ-amino butyric acid (γ), (R)-2,4-diaminobutyric acid (formula VI), or (R)-2-(acetylamino)-4-aminobutyric acid (γ-NH[C(O)CH 3 ]);

Y is β-alanine or 4-amino-2-carbonyl-N-methylpyrrole (P); and

A is 3,3′-diamino-N-methyldipropylamine (Ta) or dimethylaminopropylamine (Dp).

8. A method according to claim 7 , wherein the compound has an IC 50 of less than about 1.0 μM in inhibiting papilloma virus growth in culture.

9. A method according to claim 8 , wherein the compound has an IC 50 of less than about 0.1 μM in inhibiting papilloma virus growth in culture.

10. A method according to claim 7 , wherein the compound is designed to bind to papilloma virus.

11. A method according to claim 10 , wherein the compound is designed to bind to papilloma virus DNA.

12. A method according to claim 11 , wherein the compound is designed to bind to a double stranded DNA comprising SEQ ID NO: 1 and SEQ ID NO: 2.

13. A method of treating HPV-16 infected cells in a patient, the method comprising administering to a subject in need thereof an effective amount of a compound of formula:

Z-(X) n -γ q -(X) m -Y-A

or a pharmaceutically acceptable salt thereof, wherein

m is an integer between 8 and 11;

n is an integer between 6 and 10;

Z is desamino-imidazole (Formula V, Im);

each X is independently selected from 4-amino-2-carbonyl-N-methylimidazole (I), 4-amino-2-carbonyl-N-methylpyrrole (P) or β-alanine (β);

γ q is γ-amino butyric acid (γ), (R)-2,4-diaminobutyric acid (formula VI), or (R)-2-(acetylamino)-4-aminobutyric acid (γ-NH[C(O)CH 3 ]);

Y is β-alanine or 4-amino-2-carbonyl-N-methylpyrrole (P); and

A is 3,3′-diamino-N-methyldipropylamine (Ta) or dimethylaminopropylamine (Dp).

14. A method according to claim 13 , wherein the compound has an IC 50 of less than about 1.0 μM in inhibiting HPV-16 growth in culture.

15. A method according to claim 14 , wherein the compound has an IC 50 of less than about 0.1 μM in inhibiting HPV-16 growth in culture.

16. A method according to claim 13 , wherein the compound is designed to bind to HPV-16.

17. A method according to claim 16 , wherein the compound is designed to bind to HPV-16 DNA.

18. A method according to claim 17 , wherein the compound is designed to bind to a double stranded DNA comprising SEQ ID NO: 1 and SEQ ID NO: 2.

19. A method according to claim 1 , wherein any β-alanine (β) unit in the compound is adjacent to at least three contiguous units of 4-amino-2-carbonyl-N-methylpyrrole (P), at least three contiguous units of 4-amino-2-carbonyl-N-methylimidazole (I), or at least three contiguous units of any combination of 4-amino-2-carbonyl-N-methylpyrrole (P) and 4-amino-2-carbonyl-N-methylimidazole (I).

20. A method according to claim 1 , wherein the total number of 4-amino-2-carbonyl-N-methylimidazole units in the compound is less than 0.10(m+n+2).

21. A method of treating papilloma virus infected cells in a patient, the method comprising administering to a patient in need thereof an effective amount of a compound selected from the group consisting of:

ImPPβPIPβPPγ(NH 2 )PPβPPPβPPPβTa;

ImPPβPPPγ(NH 2 )PPβPPPPβTa;

ImPPPβPPβγPPβPPPβPβTa;

ImPPPβPPβγ(NH 2 )PPβPPPβPβTa;

ImPPPβPPPγPPPβPPPββTa;

ImPPβPPPγPPβPPPPβTa;

ImPPPβPPβγ(NH 2 )PPβPPPβPβDp;

ImPPPβPPβPPPγ(NH 2 )PPPβPPPβPPPβDp; and

ImPPPβPPβPPPγPPPβPPPβPPPβDp;

or a pharmaceutically acceptable salt thereof.

Assignments (2)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Mar 26, 2014
From: BASHKIN, JAMES K; KOELLER, KEVIN J; EDWARDS, TERRI GRACE; FISHER, CHRISTOPHER
To: NANOVIR, LLC; THE CURATORS OF THE UNIVERSITY OF MISSOURI
Reel/Frame 032533/0292 →
CONFIRMATORY LICENSE Recorded Sep 5, 2013
From: NANOVIR, LLC
To: NATIONAL INSTITUTES OF HEALTH (NIH), U.S. DEPT. OF HEALTH AND HUMAN SERVICES (DHHS), U.S. GOVERNMENT
Reel/Frame 031163/0293 →
Continuity (4)
Division 11800105 · May 4, 2007
Continuation PCTUS2007006133 · Mar 9, 2007
Provisional Application 60797426 · May 4, 2006
Related Publication 20090306164A1 · Dec 10, 2009