Claims for Patent: 12,076,319

Summary for Patent: 12,076,319

Title:	Therapeutic regimens for treatment of paroxysmal nocturnal hemoglobinuria
Abstract:	Provided herein are methods for treating a subject with PNH comprising administering to a subject a therapeutically effective amount of complement component C5 (C5) inhibitor, complement component C3 (C3) inhibitor, or complement factor B (CFB) inhibitor in combination with a therapeutically effective amount of small molecule complement factor D (CFD) inhibitor of Formula I or Formula II, or a pharmaceutically acceptable salt thereof.
Inventor(s):	Mingjun Huang, Dharaben Patel, Steven D. Podos
Assignee:	Achillion Pharmaceuticals Inc
Application Number:	US16/700,910
Patent Claims:	1. A method for treating paroxysmal nocturnal hemoglobinuria (PNH) in a human in need thereof comprising administering to the subject a therapeutically effective amount of an anti-C5 monoclonal antibody in combination with a therapeutically effective amount of orally administered Compound 1: or a pharmaceutically acceptable salt thereof; wherein the human at the time of the first administration of Compound 1 is experiencing extravascular hemolysis. 2. The method of claim 1, wherein the human has anemia at the time of the first administration of Compound 1. 3. The method of claim 1, wherein the human has a hemoglobin level of less than about 10 g/dL at the time of the first administration of Compound 1. 4. The method of claim 1, wherein the human has been receiving the C5 inhibitor for at least three months prior to the first administration of Compound 1, wherein the C5 inhibitor is an anti-C5 monoclonal antibody. 5. A method for treating paroxysmal nocturnal hemoglobinuria (PNH) in a human in need thereof comprising: a. orally administering to the human a therapeutically effective amount of Compound 1, which has the structure: or a pharmaceutically acceptable salt thereof; b. administering to the human a therapeutically effective amount of a complement 5 (C5) inhibitor, wherein the C5 inhibitor is an anti-C5 monoclonal antibody; wherein the human at the time of the first administration of Compound 1 has previously been receiving a therapeutic regimen comprising administration of the C5 inhibitor; and, wherein the human at the time of the first administration of Compound 1 is experiencing extravascular hemolysis. 6. The method of claim 5, wherein the human has a hemoglobin level of less than about 10 g/dL at the time of the first administration of Compound 1. 7. The method of claim 5, wherein the human has a LDH level of less than 250 U/L at the time of the first administration of Compound 1. 8. The method of claim 5, wherein the human has received one or more blood transfusions within the twelve months prior to the first administration of Compound 1. 9. The method of claim 5, wherein the human has been receiving a C5 inhibitor for at least three months prior to the first administration of Compound 1, wherein the C5 inhibitor is an anti-C5 monoclonal antibody. 10. A method for treating paroxysmal nocturnal hemoglobinuria (PNH) in a human in need thereof comprising: a. orally administering to the human a therapeutically effective amount of Compound 1, which has the structure: or a pharmaceutically acceptable salt thereof; b. administering to the human a therapeutically effective amount of a complement 5 (C5) inhibitor, wherein the C5 inhibitor is an anti-C5 monoclonal antibody; wherein the human at the time of the first administration of Compound 1 has previously been receiving a therapeutic regimen comprising administration of the C5 inhibitor; and, wherein the human at the time of the first administration of Compound 1 is experiencing residual intravascular hemolysis. 11. The method of claim 10, wherein the human has a hemoglobin level of less than about 10 g/dL at the time of the first administration of Compound 1. 12. The method of claim 10, wherein the human has a LDH level of greater than 250 U/L at the time of the first administration of Compound 1. 13. The method of claim 10, wherein the human has received one or more blood transfusions within the twelve months prior to the first administration of Compound 1. 14. The method of claim 10, wherein the human has been receiving a C5 inhibitor for at least three months prior to the first administration of Compound 1, wherein the C5 inhibitor is an anti-C5 monoclonal antibody. 15. A method for treating paroxysmal nocturnal hemoglobinuria (PNH) in a human in need thereof comprising a. orally administering to the human a therapeutically effective amount of Compound 1, which has the structure: or a pharmaceutically acceptable salt thereof; b. administering to the human a therapeutically effective amount of a complement 5 (C5) inhibitor, wherein the C5 inhibitor is an anti-C5 monoclonal antibody; wherein the human at the time of the first administration of Compound 1 has previously been receiving a therapeutic regimen comprising administration of the C5 inhibitor; and, wherein the human at the time of the first administration of Compound 1 has a hemoglobin level of less than about 10 g/dL. 16. The method of claim 15, wherein the human has a hemoglobin level of less than about 8 g/dL at the time of the first administration of Compound 1. 17. The method of claim 15, wherein the human has a LDH level of greater than about 250 U/L at the time of first administration of Compound 1. 18. The method of claim 15, wherein the human has a LDH level of less than about 250 U/L at the time of first administration of Compound 1. 19. The method of claim 15, wherein the human has received one or more blood transfusions within the twelve months prior to the first administration of Compound 1. 20. The method of claim 15, wherein the human has been receiving a C5 inhibitor for at least three months prior to the first administration of Compound 1, wherein the C5 inhibitor is an anti-C5 monoclonal antibody. 21. The method of claim 1, wherein the anti-C5 monoclonal antibody is eculizumab or ALXN1210. 22. The method of claim 6, wherein the anti-C5 monoclonal antibody is eculizumab or ALXN1210. 23. The method of claim 10, wherein the anti-C5 monoclonal antibody is eculizumab or ALXN1210. 24. The method of claim 15, wherein the anti-C5 monoclonal antibody is eculizumab or ALXN1210.