IP Library › Granted Patent US 12,274,731
Granted Patent B1
US 12,274,731 · App. 16/509,812 · Granted Apr 15, 2025

Polybasic antimalarial agents and methods of use thereof

Inventors: Sergej Djuranovic (St. Louis, MO); Slavica Pavlovic Djuranovic (St. Louis, MO); Jessey Lee Erath (St. Louis, MO)
Assignee: Washington University
A61K38/02A61K47/60A61P33/06
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Quick Facts
Patent No.
US 12,274,731
App. No.
16/509,812
Granted
Apr 15, 2025
Kind
B1
Abstract

Among the various aspects of the present disclosure is the provision of methods of suppressing Plasmodium parasite growth or infectivity or treating malaria comprising administering a polybasic antimalarial agent. The polybasic peptides and polymers provided can be used for the treatment of Plasmodium falciparum and other plasmodium species that cause human malaria.

Claims (29)

1. A method of suppressing Plasmodium parasite growth or infectivity in a subject in need thereof, the method comprising:

administering to the subject a therapeutically effective amount of a composition consisting of a biologically active polybasic antimalarial agent to target a Plasmodium parasite-infected cell in an amount sufficient to suppress the Plasmodium parasite growth or infectivity;

wherein the biologically active polybasic antimalarial agent is poly-ornithine; and

wherein the biologically active polybasic antimalarial agent does not include epsilon poly-lysine.

2. The method of claim 1 , wherein the therapeutically effective amount of the biologically active polybasic antimalarial agent is an amount sufficient to inhibit cellular adhesion of the Plasmodium parasite or inhibit interaction of the Plasmodium parasite with an erythrocyte.

3. The method of claim 1 , wherein the biologically active polybasic antimalarial agent has a net positive charge.

4. The method of claim 1 , wherein the subject is a human or a mosquito.

5. The method of claim 1 , wherein the subject has malaria, is suspected of having malaria, or is at risk for contracting malaria.

6. The method of claim 1 , wherein the biologically active polybasic antimalarial agent:

has a molecular weight between 1 kDa and 15 kDa or has a distribution of molecular weights having an average molecular weight between 1 kDa and 15 kDa;

is greater than 10 polybasic amino acids or between 10 polybasic amino acids and 50 amino acids; or

is greater than 50 polybasic amino acids.

7. The method of claim 1 , wherein the Plasmodium parasite is selected from the group consisting of Plasmodium falciparum, Plasmodium yoelii, Plasmodium knowlesi, Plasmodium vivax, Plasmodium berghei, Plasmodium chabaudi , and Plasmodium cynomolgi.

8. The method of claim 1 , wherein the biologically active polybasic antimalarial agent blocks Plasmodium adhesion to cells.

9. The method of claim 1 , wherein the biologically active polybasic antimalarial agent substantially targets malaria parasite-infected erythrocytes and does not detectably bind to uninfected cells.

10. A method of treating malaria in a subject, the method comprising:

administering to the subject a therapeutically effective amount of a composition consisting of a biologically active polybasic antimalarial agent conjugated to a polyethylene glycol (PEG), a dextran, a rhodamine dextran, or a dendrimer,

wherein the biologically active polybasic antimalarial agent is poly-ornithine; and

wherein the biologically active polybasic antimalarial agent does not include epsilon poly-lysine.

11. The method of claim 10 , wherein the therapeutically effective amount of the biologically active polybasic antimalarial agent is an amount sufficient to inhibit cellular adhesion of a Plasmodium parasite or inhibit interaction of the Plasmodium parasite with an erythrocyte.

12. The method of claim 10 , wherein the biologically active polybasic antimalarial agent has a net positive charge.

13. The method of claim 10 , wherein the subject is a human or a mosquito.

14. The method of claim 10 , wherein the subject has malaria, is suspected of having malaria, or is at risk for contracting malaria.

15. The method of claim 10 , wherein the biologically active polybasic antimalarial agent:

has a molecular weight between 1 kDa and 15 kDa or has a distribution of molecular weights having an average molecular weight between 1 kDa and 15 kDa;

is greater than 10 polybasic amino acids or between 10 polybasic amino acids and 50 amino acids; or

is greater than 50 polybasic amino acids.

16. The method of claim 11 , wherein the Plasmodium parasite is selected from the group consisting of Plasmodium falciparum, Plasmodium yoelii, Plasmodium knowlesi, Plasmodium vivax, Plasmodium berghei, Plasmodium chabaudi , and Plasmodium cynomolgi.

17. The method of claim 10 , wherein the biologically active polybasic antimalarial agent competes with endogenous poly-lysine and polybasic proteins for cell binding or the biologically active polybasic antimalarial agent blocks Plasmodium adhesion to cells.

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jul 24, 2019
From: DJURANOVIC, SERGEJ; PAVLOVIC-DJURANOVIC, SLAVICA; ERATH, JESSEY LEE
To: WASHINGTON UNIVERSITY
Reel/Frame 049848/0109 →
Continuity (1)
Provisional Application 62696868 · Jul 12, 2018
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