VGF fusion polypeptides

Abstract

The present invention provides novel VGF polypeptides and selective binding agents. The invention also provides host cells and methods for producing VGF polypeptides. The invention further provides VGF pharmaceutical compositions and methods for the diagnosis, treatment, amelioration, and/or prevention of diseases, conditions, and disorders associated with VGF polypeptides.

1 . An isolated polypeptide comprising the amino acid sequence as set forth in any of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, or SEQ ID NO: 10.  
     
     
         2 . (canceled)  
     
     
         3 . An isolated polypeptide comprising a fragment of the amino acid sequence as set forth in any of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, or SEQ ID NO: 10 wherein the fragment has an activity of the polypeptide as set forth in any of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO:9, or SEQ ID NO: 10.  
     
     
         4 . (canceled)  
     
     
         5 . An isolated polypeptide comprising the amino acid sequence selected from the group consisting of: 
 (a) the amino acid sequence as set forth in any of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, or SEQ ID NO: 10 with at least one conservative amino acid substitution and wherein the polypeptide has an activity of the polypeptide as set forth in any of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, or SEQ ID NO: 10;    (b) the amino acid sequence as set forth in any of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4,SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, or SEQ ID NO: 10 with at least one amino acid insertion and wherein the polypeptide has an activity of the polypeptide as set forth in any of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, or SEQ ID NO: 10;    (c) the amino acid sequence as set forth in any of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, or SEQ ID NO: 10 with at least one amino acid deletion and wherein the polypeptide has an activity of the polypeptide as set forth in any of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, or SEQ ID NO: 10;    (d) the amino acid sequence as set forth in any of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, or SEQ ID NO: 10 which has a C- and/or N-terminal truncation and wherein the polypeptide has an activity of the polypeptide as set forth in wherein the polypeptide has an activity of the polypeptide as set forth in any of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, or SEQ ID NO: 10; and    (e) the amino acid sequence as set forth in any of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, or SEQ ID NO: 10 with at least one modification selected from the group consisting of amino acid substitutions, amino acid insertions, amino acid deletions, carboxyl-terminal truncation, and amino-terminal truncation and wherein the polypeptide has an activity of the polypeptide as set forth in any of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, or SEQ ID NO: 10.    
     
     
         6 . A fusion polypeptide comprising the polypeptide of any of claims  1 ,  3 , or  5  fused to a heterologous amino acid sequence.  
     
     
         7 . The fusion polypeptide of  claim 7  wherein the heterologous amino acid sequence is an IgG constant domain or fragment thereof.  
     
     
         8 . A composition comprising the polypeptide of any of claims  1 ,  3 , or  5  and a pharmaceutically acceptable formulation agent.  
     
     
         9 . The composition of  claim 8  wherein the pharmaceutically acceptable formulation agent is a carrier, adjuvant, solubilizer,-stabilizer, or anti-oxidant.  
     
     
         10 . A polypeptide comprising a derivative of the polypeptide of any of claims  1 ,  3 , or  5 .  
     
     
         11 . The polypeptide of  claim 10  which is covalently modified with a water-soluble polymer.  
     
     
         12 . The polypeptide of  claim 11  wherein the water-soluble polymer is selected from the group consisting of polyethylene glycol, monomethoxy-polyethylene glycol, dextran, cellulose, poly-(N-vinyl pyrrolidone) polyethylene glycol, propylene glycol homopolymers, polypropylene oxide/ethylene oxide co-polymers, polyoxyethylated polyols, and polyvinyl alcohol.  
     
     
         13 . The polypeptide of  claim 11  wherein the water-soluble polymer is selected from the group consisting of polyethylene glycol and dextran.  
     
     
         14 . A method for treating, preventing or ameliorating a VGF polypeptide-related disease, disorder, or condition comprising administering to a patient the polypeptide of any of claims  1 ,  3 , or  5 .  
     
     
         15 . The method of  claim 14  wherein the VGF polypeptide-related disease, disorder, or condition is obesity.  
     
     
         16 . The method of  claim 14  wherein the VGF polypeptide-related disease, disorder, or condition is selected from the group consisting of sterility, cachexia, eating disorders, AIDS-related complex, hypermetabolic conditions, hyperactivity, hypoactivity, and hyperinsulin production.  
     
     
         17 . The method of  claim 16  wherein the eating disorder is bulimia and anorexia nervosa.  
     
     
         18 . A method of diagnosing a VGF polypeptide-related condition or a susceptibility to a VGF polypeptide-related condition in a subject comprising: 
 (a) determining the presence or amount of expression of the polypeptide of any of claims  1 ,  3 , or  5  and    (b) diagnosing a VGF polypeptide-related condition or a susceptibility to a VGF polypeptide-related condition based on the presence or amount of expression of the polypeptide.    
     
     
         19 . A method of identifying a compound which binds to a polypeptide comprising: 
 (a) contacting the polypeptide of any of claims  1 ,  3 , or  5  with a compound; and    (b) determining the extent of binding of the polypeptide to the compound.    
     
     
         20 . The method of  claim 19  further comprising determining the activity of the polypeptide when bound to the compound.  
     
     
         21 . A device, comprising: 
 (a) a membrane suitable for implantation; and    (b) cells encapsulated within said membrane, wherein said cells secrete a protein of any of claims  1 ,  3 , or  5 ; and said membrane is permeable to said protein and impermeable to materials detrimental to said cells.