Activin-actrii antagonists and uses for treating anemia
AssigneeCelgene Corporation
InventorsKenneth M. Attie, Christopher Rovaldi, Abderrahmane Laadem
Life of this patent
Estimating the term…
Abstract
Provided herein are methods for the treatment in a subject of anemia, anemia requiring RBC transfusion, low or intermediate- 1 -risk myelodysplastic syndromes (MDS), and/or non-proliferative chronic myelomonocytic leukemia (CMML) in any mammals wherein the methods comprise administration of Activin-ActRII signaling inhibitors to a subject in need of the treatment.
Claims34
1-6. (canceled)
A method of treating anemia in a subject, comprising administering to the subject an activin receptor type II (ActRII) signaling inhibitor at a pharmaceutically effective dose and for a period of time to achieve (i) a long-term reduction in a percentage of erythroblasts in the subject that are ring sideroblasts as compared to an initial percentage of erythroblasts in the subject that are ring sideroblasts;
- and/or (ii) a long-term increase in hemoglobin level in the subject as compared to the hemoglobin level in the subject a period of time prior to administering to the subject an initial dose of the ActRII signaling inhibitor;
- wherein the pharmaceutically effective dose is between 0.1 mg/kg and 2.0 mg/kg, and wherein the initial percentage of erythroblasts in the subject that are ring sideroblasts is at least 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, or at least 20%.
8-9. (canceled)
A method for treating non-proliferative CMML in a subject, comprising administering to the subject an ActRII signaling inhibitor at a pharmaceutically effective dose and for a period of time to achieve (i) a long-term reduction in a percentage of erythroblasts in the subject that are ring sideroblasts as compared to an initial percentage of erythroblasts in the subject that are ring sideroblasts;
- and/or (ii) a long-term increase in hemoglobin level in the subject as compared to the hemoglobin level in the subject a period of time prior to administering to the subject an initial dose of the ActRII signaling inhibitor;
- wherein the pharmaceutically effective dose is between 0.1 mg/kg and 2.0 mg/kg, and wherein the initial percentage of erythroblasts in the subject that are ring sideroblasts is at least 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, or at least 20%.
11-28. (canceled)
A method for treating anemia in a subject, wherein the method comprises:
- (a) determining a first percentage of erythroblasts in the subject that are ring sideroblasts;
- and
- (b) (i) administering an ActRII signaling inhibitor to the subject at a pharmaceutically effective dose of between 0.1 mg/kg and 2.0 mg/kg for a short period of time if the first percentage of erythroblasts in the subject that are ring sideroblasts is at least 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, or at least 20%, or (ii) administering an ActRII signaling inhibitor to the subject at a pharmaceutically effective dose of between 0.1 mg/kg and 2.0 mg/kg for a long period of time if the percentage of erythroblasts in the subject that are ring sideroblasts is less than 10%.
30-31. (canceled)
A method for treating non-proliferative CMML in a subject, wherein the method comprises:
- (a) determining a first percentage of erythroblasts in the subject that are ring sideroblasts;
- and
- (b) (i) administering an ActRII signaling inhibitor to the subject at a pharmaceutically effective dose of between 0.1 mg/kg and 2.0 mg/kg for a short period of time if the first percentage of erythroblasts in the subject that are ring sideroblasts is at least 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, or at least 20%, or (ii) administering an ActRII signaling inhibitor to the subject at a pharmaceutically effective dose of between 0.1 mg/kg and 2.0 mg/kg for a long period of time if the percentage of erythroblasts in the subject that are ring sideroblasts is less than 10%.
33-39. (canceled)
43-47. (canceled)
49-50. (canceled)
52-72. (canceled)
74-75. (canceled)
77-81. (canceled)
A method of promoting erythropoiesis in a subject having a blood-related disorder, the method comprising:
- (a) determining a percentage of erythroblasts in the subject that are ring sideroblasts;
- (b) administering a pharmaceutically effective dose of an ActRII signaling inhibitor to the subject for a first period of time;
- (c) after the first period of time, if the percentage of erythroblasts in the subject that are ring sideroblasts in step (a) had been above 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, or 20%, reducing the dose of the ActRII signaling inhibitor administered to the subject, reducing the frequency of administration of the ActRII signaling inhibitor to the subject, or discontinuing administering of the ActRII signaling inhibitor.
84-102. (canceled)
A method for increasing the level of neutrophils in a subject, comprising administering to the subject a pharmaceutically effective dose of an activin receptor type II (ActRII) signaling inhibitor.
(canceled)
A method for increasing the level of platelets in a subject, comprising administering to the subject a pharmaceutically effective dose of an activin receptor type II (ActRII) signaling inhibitor.
106-112. (canceled)
114-117. (canceled)
Dependencies are inferred from the claim text.