Truncated activin type ii receptor and methods of use

Abstract

The present invention provides a substantially purified growth differentiation factor (GDF) receptor, including a GDF-8 (myostatin) receptor, as well as functional peptide portions thereof. In addition, the invention provides a virtual representation of a GDF receptor or a functional peptide portion thereof. The present invention also provides a method of modulating an effect of myostatin on a cell by contacting the cell with an agent that affects myostatin signal transduction in the cell. In addition, the invention provides a method of ameliorating the severity of a pathologic condition, which is characterized, at least in part, by an abnormal amount, development or metabolic activity of muscle or adipose tissue in a subject, by modulating myostatin signal transduction in a muscle cell or an adipose tissue cell in the subject. The invention also provides a method of modulating the growth of muscle tissue or adipose tissue in a eukaryotic organism by administering an agent that affects myostatin signal transduction to the organism.

1 . A pharmaceutical composition comprising a therapeutically effective amount of an Activin Receptor Type IIB (ActRIIB) polypeptide comprising the extracellular domain of ActRIIB. 
     
     
         2 . The pharmaceutical composition of  claim 1 , wherein the ActRIIB polypeptide is capable of modulating a GDF-8 activity. 
     
     
         3 . The pharmaceutical composition of  claim 1 , wherein the composition is formulated for oral or parenteral administration. 
     
     
         4 . The pharmaceutical composition of  claim 1 , wherein the ActRIIB polypeptide binds to GDF-8 with a dissociation constant (Kd) of at least 1×10-6M. 
     
     
         5 . The pharmaceutical composition of  claim 1 , wherein the ActRIIB polypeptide binds to GDF-8 with a dissociation constant (Kd) of at least 1×10-7M. 
     
     
         6 . The pharmaceutical composition of  claim 1 , wherein the ActRIIB polypeptide binds to GDF-8 with a dissociation constant (Kd) of at least 1×10-8M. 
     
     
         7 . The pharmaceutical composition of  claim 1 , wherein the ActRIIB polypeptide binds to GDF-8 with a dissociation constant (Kd) of at least 1×10-9M. 
     
     
         8 . The pharmaceutical composition of  claim 1 , wherein the ActRIIB polypeptide binds to GDF-8 with a dissociation constant (Kd) of at least 1×10-10M. 
     
     
         9 - 27 . (canceled)