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1. WO2020232439 - METHODS AND MATERIALS FOR TREATING CANCER

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WHAT IS CLAIMED IS:

1. A method for treating a mammal having cancer, wherein said method comprises administering (a) an inhibitor of a chromosomal maintenance 1 (CRM1) polypeptide and (b) a salicylate to said mammal to reduce the number of cancer cells in said mammal.

2. The method of claim 1, wherein said mammal is a human.

3. The method of claim 1 or claim 2, wherein said cancer is a hematologic cancer.

4. The method of claim 3, wherein said cancer is selected from the group consisting of a diffuse large B-cell lymphoma (DLBCL), a T-cell lymphoma (TCL), a mantle cell lymphoma (MCL), a non-Hodgkin lymphoma (NHL), multiple myeloma (MM), Hodgkin lymphoma, small lymphocytic lymphoma, lymphoplasmacytic lymphoma, chronic lymphocytic leukemia, chronic lymphocytic leukemia, acute myelogenous leukemia, chronic

myelogenous leukemia, myeloproliferative syndromes, and myelodysplastic syndromes.

5. The method of any one of claims 1-4, wherein said inhibitor of a CRM1 polypeptide is selected from the group consisting of selinexor, leptomycin B, KPT- 185, KPT-276, eltanexor, piperlongumine, verdinexor, valtrate, and ratjadone C.

6. The method of claim 5, wherein said inhibitor of a CRM1 polypeptide results in a plasma concentration within said mammal of from about 0.01 nM to about 1.25 mM.

7. The method of any one of claims 1-6, wherein said salicylate is selected from the group consisting of aspirin, choline salicylate, sodium salicylate, acetyl salicylate, and choline magnesium trisalicylate.

8. The method of claim 7, wherein said salicylate results in a plasma concentration within said mammal of from about 0.1 mM to about 10 mM.

9. A method for treating a mammal having cancer, wherein said method comprises administering (a) an inhibitor of a CRM1 polypeptide and (b) a salicylate to said mammal to arrest the cell cycle of a cancer cell in said mammal.

10. The method of claim 9, wherein said cell cycle is arrested at a S phase.

11. The method of claim 9 or claim 10, wherein said mammal is a human.

12. The method of any one of claims 9-11, wherein said cancer is a hematologic cancer.

13. The method of claim 12, wherein said cancer is selected from the group consisting of a diffuse large B-cell lymphoma (DLBCL), a T-cell lymphoma (TCL), a mantle cell lymphoma (MCL), a non-Hodgkin lymphoma (NHL), multiple myeloma (MM), Hodgkin lymphoma, small lymphocytic lymphoma, lymphoplasmacytic lymphoma, chronic lymphocytic leukemia, chronic lymphocytic leukemia, acute myelogenous leukemia, chronic myelogenous leukemia, myeloproliferative syndromes, and myelodysplastic syndromes.

14. The method of any one of claims 9-13, wherein said inhibitor of a CRM1 polypeptide is CRM1 polypeptide is selected from the group consisting of selinexor, leptomycin B, KPT-185, KPT-276, eltanexor, piperlongumine, verdinexor, valtrate, and ratjadone C.

15. The method of claim 14, wherein said inhibitor of a CRM1 polypeptide results in a plasma concentration within said mammal of from about 0.01 nM to about 1.25 mM.

16. The method of any one of claims 9-15, wherein said salicylate is selected from the group consisting of aspirin, choline salicylate, sodium salicylate, acetyl salicylate, and choline magnesium trisalicylate.

17. The method of claim 16, wherein said salicylate results in a plasma concentration within said mammal of from about 0.1 mM to about 10 mM.

18. A method for treating a mammal having a viral infection, wherein said method comprises administering (a) an inhibitor of a chromosomal maintenance 1 (CRM1) polypeptide and (b) a salicylate to said mammal to reduce the number of viral particles in said mammal.

19. The method of claim 1, wherein said mammal is a human.

20. The method of claim 18 or claim 19, wherein said viral infection is caused by a coronavirus.

21. The method of claim 20, wherein said coronavirus is a betacoronavirus.

22. The method of claim 21, wherein said virus is SARS-CoV-2.

23. The method of any one of claims 18-22, wherein said inhibitor of a CRM1 polypeptide is selected from the group consisting of selinexor, leptomycin B, KPT- 185, KPT-276, eltanexor, piperlongumine, verdinexor, valtrate, and ratjadone C.

24. The method of claim 23, wherein said inhibitor of a CRM1 polypeptide results in a plasma concentration within said mammal of from about 0.01 nM to about 1.25 mM.

25. The method of any one of claims 18-24, wherein said salicylate is selected from the group consisting of aspirin, choline salicylate, sodium salicylate, acetyl salicylate, and choline magnesium trisalicylate.