Methods for dosing an actriib antagonist and monitoring of treated patients

Abstract

In certain aspects, the present invention provides methods for dosing a patient with an ActRIIb antagonist and methods for managing patients treated with an ActRIIb anatagonist. In certain aspects, the methods involve measuring one or more hematologic parameters in a patient.

1 . A method for managing a patient that has been treated with, or is a candidate to be treated with, a follistatin fusion protein, the method comprising monitoring in the patient one or more hematologic parameters that correlate with increased red blood cell levels. 
     
     
         2 . The method of  claim 1 , wherein the hematologic parameters are one or more of the following: red blood cell levels, blood pressure, or iron stores. 
     
     
         3 . The method of  claim 1 , the method further comprising administering to the patient the follistatin fusion protein in an amount that is appropriate to the observed level of said hematologic parameter in the patient. 
     
     
         4 . The method of  claim 1 , wherein, if the patient has blood pressure elevated above baseline or is hypertensive, dosing with the follistatin fusion protein is reduced, delayed or terminated. 
     
     
         5 . The method of  claim 1 , wherein, if the patient has blood pressure elevated above baseline or is hypertensive, the patient is treated with a blood pressure lowering agent prior to administration of the follistatin fusion protein. 
     
     
         6 . The method of  claim 1 , wherein if the patient has uncontrolled hypertension, dosing with the follistatin fusion protein is reduced, delayed or terminated. 
     
     
         7 . The method of  claim 1 , wherein if the patient has a red blood cell level greater than the normal range for patients of similar age and sex, dosing with the follistatin fusion protein is reduced, delayed or terminated. 
     
     
         8 . The method of  claim 1 , wherein if the patient has a hemoglobin level of greater than 15 g/dl, dosing with the follistatin fusion protein is reduced, delayed or terminated. 
     
     
         9 . The method of  claim 1 , wherein if the patient has a hemoglobin level greater than 10, 11 or 12 g/dl, dosing with the activin-follistatin fusion protein is reduced, delayed or terminated. 
     
     
         10 . The method of  claim 1 , wherein if the patient has iron stores that are lower than the normal range for patients of similar age and sex, dosing with the follistatin fusion protein is reduced, delayed or terminated. 
     
     
         11 . The method of  claim 1 , wherein if the patient has a transferrin saturation of less than 20%, dosing with the follistatin fusion protein is reduced, delayed or terminated. 
     
     
         12 . The method of  claim 1 , wherein if the patient has a ferritin level of less than 100 ng/ml, dosing with the follistatin fusion protein is reduced, delayed or terminated. 
     
     
         13 . The method of  claim 1 , wherein if the patient has iron stores that are lower than the normal range for patients of similar age and sex, the patient is treated with an iron supplement prior to dosing with the follistatin fusion protein. 
     
     
         14 . The method of  claim 1 , wherein if the patient has a transferrin saturation of less than 20%, the patient is treated with an iron supplement prior to dosing with the activin-follistatin fusion protein. 
     
     
         15 . The method of  claim 1 , wherein if the patient has a ferritin level of less than 100 ng/ml, the patient is treated with an iron supplement prior to dosing with the follistatin fusion protein. 
     
     
         16 - 18 . (canceled) 
     
     
         19 . A method for dosing a patient with follistatin fusion protein, the method comprising dosing the patient in amounts and at intervals selected so as to reduce the risk of causing a rise in hemoglobin levels greater than 1 g/dl in two weeks. 
     
     
         20 . The method of  claim 1  or  claim 19 , wherein the patient is suffering from anemia, a bone-related disorder, cancer, or a disorder associated with muscle loss or insufficient muscle growth. 
     
     
         21 . The method of  claim 1  or  claim 19 , wherein the patient is in need of bone growth, increased bone density or increased bone strength. 
     
     
         22 - 23 . (canceled) 
     
     
         24 . The method of  claim 20 , wherein the patient has breast cancer. 
     
     
         25 - 45 . (canceled) 
     
     
         46 . The method of  claim 1 , wherein the follistatin fusion protein comprises a first amino acid sequence and a second amino acid sequence, wherein the first amino acid sequence comprises a sequence that is at least 90% identical to SEQ ID NO: 17 or that is at least 90% identical to a mature form of SEQ ID NO: 17, and wherein the second amino acid sequence comprises an immunoglobulin Fc domain; wherein the fusion protein comprises a linker between the first amino acid sequence and the second amino acid sequence; and wherein the linker comprises three glycines.