NOVEL ACTIVIN RECEPTOR AND USES THEREOF

摘要

The present invention provides novel activin IIB5 receptor polypeptides capable of binding and inhibiting the activities of activin A, myostatin, or GDF-11. The present invention also provides polynucleotides, vectors and host cells capable of producing the receptor polypeptides. Compositions and methods for treating muscle-wasting, metabolic and other disorders are also provided.

主权项

1. An isolated protein comprising a human IgG Fc polypeptide linked to an activin receptor IIB (ActRIIB) polypeptide comprising a sequence that is at least 95% identical to the amino acid sequence set forth in SEQ ID NO:2 or an antigen-binding fragment thereof, wherein the ActRIIB polypeptide or antigen-binding fragment thereof is capable of binding myostatin, activin A, or GDF-11, and wherein the protein comprises at least one of: (1) the protein has activin A neutralizing activity IC50 (nM) vs. 20 nM activin that is less than the activin A neutralizing activity IC50 (nM) vs. 20 nM activin of a control protein comprising amino acids 1-124 of the sequence set forth in SEQ ID NO:5 linked to human IgG1 Fc; and (2) the protein has myostatin-neutralizing activity IC50 (nM) vs. 4 nM myostatin that is less than the myostatin-neutralizing activity IC50 (nM) vs. 4 nM myostatin of the control protein.