METHODS OF INHIBITING THE ALTERNATIVE PATHWAY OF COMPLEMENT IMMUNE SYSTEM ACTIVATION AND COMPOSITIONS USED THEREIN
Methods and compositions are provided for treating diseases implicating alternative pathway complement immune system activation.
1 . A method of treating or delaying the progression of a disorder alleviated by inhibiting alternative pathway complement immune system activation in a patient in need of such treatment, the method comprising administering a therapeutically effective amount of C1-esterase inhibitor (C1-INH).
2 . A method of treating or delaying the progression of a disorder alleviated by inhibiting the accumulation of protein degradation products of a protein on red blood cells in a patient in need of such treatment, the method comprising administering a therapeutically effective amount of C1-esterase inhibitor (C1-INH).
3 . The method according to claim 2 , wherein the protein is C3.
4 . The method according to claim 2 , wherein the C1esterase inhibitor (C1INH) comprises a human plasma-derived C1-INH (hC1-INH) or a recombinant C1-INH (rC1-INH).
5 . The method according to claim 2 , wherein the disorder is selected from the group consisting of paroxysmal nocturnal hemoglobinuria (PNH), dense deposit disease (DDD), factor H deficiency, age-related macular degeneration (AMD), atypical hemolytic uremic syndrome (aHUS), and sepsis.
6 . The method according to claim 2 , comprising administering an additional biologically active agent effective for treating or delaying the progression of a disorder selected from the group consisting of paroxysmal nocturnal hemoglobinuria (PNH), dense deposit disease (DDD), factor H deficiency, age-related macular degeneration (AMD), atypical hemolytic uremic syndrome (aHUS), and sepsis.
7 . The method according to claim 6 , comprising administering eculizumab, TT30, or a combination thereof, as the additional biologically active agent.
8 . The method according to claim 6 , wherein the C1-INH and the biologically active agent are administered concurrently.
9 . The method according to claim 6 , wherein the C1-INH and the biologically active agent are administered sequentially.
10 . A method of treating or delaying the progression of paroxysmal nocturnal hemoglobinuria (PNH) in a patient in need of such treatment, the method comprising administering therapeutically effective amounts of at least a C1-esterase inhibitor (C1-INH) and eculizumab.
11 . The method according to claim 10 , wherein the C1-esterase inhibitor (C1-INH) comprises a human plasma derived C1-INH (hC1INH) or a recombinant C1-INH (rC1INH).
12 . The method according to claim 10 , wherein the C1-INH and eculizumab are administered concurrently.
13 . The method according to claim 10 , wherein the C1-INH and eculizumab are administered sequentially.
14 . A method of treating the opsonization of blood cells in an organ in a patient in need of such treatment, the method comprising administering a therapeutically effective amount of a C1-esterase inhibitor (C1-INH).
15 . The method of claim 14 , wherein the C1-esterase inhibitor (C1-INH) comprises a human plasma derived C1-INH (hC1-INH) or a recombinant C1-INH (rC1-INH).
16 . The method of claim 14 , wherein the organ is selected from the group consisting of spleen, liver, and a combination thereof.
17 . The method according to claim 14 , wherein the opsonization of blood cells is due to eculizumab treatment.
18 . A pharmaceutical composition for treating or delaying the progression of a disorder alleviated by inhibiting alternative pathway complement immune system activation in a patient in need of such treatment, the composition comprising
a C1-esterase inhibitor (C1-INH);
a biologically active agent selected from the group consisting of eculizumab, TT30, or a combination thereof; and
a pharmaceutically acceptable carrier medium.
19 . The method according to claim 1 , wherein the C1-esterase inhibitor (C1-INH) comprises a human plasma-derived C1-INH (hC1-INH) or a recombinant C1-INH (rC1-INH).
20 . The method according to claim 1 , wherein the disorder is selected from the group consisting of paroxysmal nocturnal hemoglobinuria (PNH), dense deposit disease (DDD), factor H deficiency, age-related macular degeneration (AMD), atypical hemolytic uremic syndrome (aHUS), and sepsis.
21 . The method according to claim 1 , comprising administering an additional biologically active agent effective for treating or delaying the progression of a disorder selected from the group consisting of paroxysmal nocturnal hemoglobinuria (PNH), dense deposit disease (DDD), factor H deficiency, age-related macular degeneration (AMD), atypical hemolytic uremic syndrome (aHUS), and sepsis.