Variants of C-Type Natriuretic Peptide

Abstract

The present disclosure provides variants of C-type natriuretic peptide (CNP), pharmaceutical compositions comprising CNP variants, and methods of making CNP variants. The CNP variants are useful as therapeutic agents for the treatment of diseases responsive to CNP, including but not limited to bone-related disorders, such as skeletal dysplasias (e.g., achondroplasia), and vascular smooth muscle disorders (e.g., restenosis and arteriosclerosis).

1 - 49 . (canceled) 
     
     
         50 . A pharmaceutical composition comprising a C-type natriuretic peptide and an antioxidant, wherein the C-type natriuretic peptide consists of the amino acid sequence PGQEHPNARKYKGANKKGLSKGCFGLKLDRIGSMSGLGC (SEQ ID NO:145). 
     
     
         51 . The pharmaceutical composition of  claim 50 , wherein the antioxidant is methionine. 
     
     
         52 . The pharmaceutical composition of  claim 50 , which is in liquid form. 
     
     
         53 . The pharmaceutical composition of  claim 50 , further comprising a detergent. 
     
     
         54 . The pharmaceutical composition of  claim 53 , wherein the detergent is polysorbate 80. 
     
     
         55 . The pharmaceutical composition of  claim 50 , further comprising a bulking agent. 
     
     
         56 . The pharmaceutical composition of  claim 55 , wherein the bulking agent is mannitol. 
     
     
         57 . The pharmaceutical composition of  claim 55 , wherein the bulking agent is trehalose. 
     
     
         58 . The pharmaceutical composition of  claim 50 , further comprising a detergent and a bulking agent. 
     
     
         59 . The pharmaceutical composition of  claim 50 , wherein said C-type natriuretic peptide is present at a concentration of from about 0.1 mg/ml to about 20 mg/ml.