Halogenated xanthene composition and method for treating hematologic cancers

Patent metadata

Field	Value
Publication number	US-12133840-B2
Application number	US-202217890659-A
Country	US
Kind code	B2
Filing date	Aug 18, 2022
Priority date	Nov 19, 2019
Publication date	Nov 5, 2024
Grant date	Nov 5, 2024

Abstract

A method of treating a mammalian subject having hematologic, non-tumorous cancer cells is disclosed. The method comprises the steps of: (A) administering to such a mammalian subject a therapeutically effective amount of a halogenated xanthene, a pharmaceutically acceptable salt or a C 1 -C 4 alkyl ester thereof as a first cancer cytotoxic agent dissolved or dispersed in a pharmaceutically acceptable aqueous medium. The mammalian subject is maintained for a period of time sufficient to induce death of hematologic, non-tumorous cancer cells. A contemplated administration is typically repeated. A contemplated treatment method can also be carried out in conjunction with administration to said mammalian subject of a second therapeutically effective amount of a second, differently-acting cancer cytotoxic agent dissolved or dispersed in a pharmaceutically acceptable medium. The second cancer cytotoxic agent can be a small molecule or an intact antibody or paratope-containing portion thereof.

First claim

The invention claimed is:

1. A method of treating a mammalian subject having multiple myeloma comprising the steps of:
(A) administering a therapeutically effective amount of a halogenated xanthene, a pharmaceutically acceptable salt or a C 1 -C 4 alkyl ester thereof as a first cancer cytotoxic agent dissolved or dispersed in a pharmaceutically acceptable aqueous medium to a mammalian subject having multiple myeloma; and
(B) maintaining said mammalian subject for a period of time sufficient to induce death of said multiple myeloma cells,
wherein said first cancer cytotoxic agent halogenated xanthene, pharmaceutically acceptable salt or C 1 -C 4 alkyl ester thereof is rose bengal disodium salt.

2. The method according to claim 1 , wherein said steps are repeated.

3. The method according to claim 1 , wherein said contacting is carried out in vivo in said mammalian subject.

4. The method according to claim 3 , wherein said mammalian subject is selected from the group consisting of a human, an ape, a monkey, a laboratory animal, a companion animal and a food animal.

5. The method according to claim 1 , wherein said administration of step (A) is carried out in conjunction with administration to said mammalian subject of a second therapeutically effective amount of a second, differently-acting cancer cytotoxic agent dissolved or dispersed in a pharmaceutically acceptable medium.

6. The method according to claim 5 , wherein said second cancer cytotoxic agent is dissolved or dispersed in a pharmaceutically acceptable solid medium.

7. The method according to claim 5 , wherein the pharmaceutically acceptable solid medium containing the second cancer cytotoxic agent is administered per os.

8. The method according to claim 5 , wherein second cancer cytotoxic agent is a small molecule having a molecular weight of about 200 to about 1000 Da.

9. The method according to claim 5 , wherein said small molecule exhibits synergy with said first cancer cytotoxic agent.

10. The method according to claim 5 , wherein said second cancer cytotoxic agent is dissolved or dispersed in a pharmaceutically acceptable aqueous medium.

11. The method according to claim 10 , wherein the pharmaceutically acceptable aqueous medium containing the second cancer cytotoxic agent is administered intravenously.

12. The method according to claim 11 , wherein the second cancer cytotoxic agent comprises intact monoclonal antibodies or paratope-containing portions thereof.

13. The method according to claim 12 , wherein said intact monoclonal antibodies or paratope-containing portions thereof are immune checkpoint protein inhibitors.

14. The method according to claim 13 , wherein said immune checkpoint protein inhibitors bind to one or more proteinaceous materials selected from one or more of the group consisting of CTLA-4, PD-1, PD-L1, PD-L2, and OX40.

15. The method according to claim 5 , wherein said first and said second cancer cytotoxic agents are administered simultaneously to within about 3 hours of each other.

Assignees

• Provectus Pharmatech Inc
• Uti Lp

Inventors

• Wachter Eric A
• Rodrigues Dominic
• Thakur Satbir
• Swift Lucy
• Zhang Chunfen
• Jain Mohit
• Narendran Aru

Classifications

• A61K31/365 Primary

  Lactones · CPC title

• A61K31/21

  Esters, e.g. nitroglycerine, selenocyanates · CPC title

• A61K9/0019

  Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner (non-active ingredients are additionally classified in A61K47/00) · CPC title

• C07K16/2818

  against CD28 or CD152 · CPC title

• C07K16/2827

  against B7 molecules, e.g. CD80, CD86 · CPC title