Cortistatin: neuropeptides, compositions and methods

Abstract

The present invention relates generally to nucleic acids encoding a novel neuropeptide designated cortistatin, anti-cortistatin antibodies and pharmaceutical compositions thereof. The cortistatin nucleic acids, proteins and polypeptides along with anti-cortistatin antibodies are useful in both screening methods, diagnostic methods and therapeutic methods related to modulation of sleep and disorders thereof.

1 - 20 . (canceled)  
     
     
         21 . An antibody to a protein having cortistatin-like activity wherein said protein is selected from the group consisting of SEQ ID NOs 2, 6, 7, 8 and 9 and sequences having at least about 95% amino acid residue similarity to SEQ ID NOs 2, 6, 7, 8 or 9.  
     
     
         22 . The antibody of  claim 21 , wherein the antibody is substantially free from immunoreaction with neuropeptides other than cortistatin.  
     
     
         23 . The antibody of  claim 21 , wherein the antibody is a monoclonal antibody.  
     
     
         24 . An immunologically active fragment of an antibody of  claim 21  selected from the group consisting of the Fab, Fab′, F(ab′) 2  and F(v) fragments.  
     
     
         25 . A method of making an antibody of  claim 21 , comprising the steps of: 
 (i) immunizing a mammal with an inoculum containing an immunologically effective amount of a cortistatin polypeptide to induce in the mammal antibody molecules having immunospecificity to the cortistatin polypeptide;    (ii) collecting the antibody molecules; and    (iii) isolating the antibody molecules that have immunospecificity to the cortistatin polypeptide.    
     
     
         26 . A method of making an antibody of  claim 23 , comprising the steps of: 
 (i) initiating a monoclonal hybridoma culture with a nutrient medium containing a hybridoma that produces and secretes antibody molecules with cortistatin specificity;    (ii) maintaining the culture under conditions and for a time period sufficient for the hybridoma to secrete the antibody molecules into the medium;    (iii) collecting the antibody-containing medium; and    (iv) isolating the antibody molecules that have cortistatin specificity.    
     
     
         27 . A hybridoma cell that produces a monoclonal antibody of  claim 23 .  
     
     
         28 . A pharmaceutical composition comprising an antibody of  claim 21  and a pharmaceutically acceptable adjuvant.  
     
     
         29 . An antibody to a protein having cortistatin-like activity wherein said protein is selected from the group consisting of SEQ ID NOs 5, 10, 11 and 12 and sequences having at least about 95% amino acid residue similarity to SEQ ID NOs 5, 10, 11 or 12.  
     
     
         30 . The antibody of  claim 29 , wherein the antibody is substantially free from immunoreaction with neuropeptides other than cortistatin.  
     
     
         31 . The antibody of  claim 29 , wherein the antibody is a monoclonal antibody.  
     
     
         32 . An immunologically active fragment of an antibody of  claim 29  selected from the group consisting of the Fab, Fab′, F(ab′) 2  and F(v) fragments.  
     
     
         33 . A method of making an antibody of  claim 29 , comprising the steps of: 
 (i) immunizing a mammal with an inoculum containing an immunologically effective amount of a cortistatin polypeptide to induce in the mammal antibody molecules having immunospecificity to the cortistatin polypeptide;    (ii) collecting the antibody molecules; and    (iii) isolating the antibody molecules that have immunospecificity to the cortistatin polypeptide.    
     
     
         34 . A method of making an antibody of  claim 31 , comprising the steps of: 
 (i) initiating a monoclonal hybridoma culture with a nutrient medium containing a hybridoma that produces and secretes antibody molecules with cortistatin specificity;    (ii) maintaining the culture under conditions and for a time period sufficient for the hybridoma to secrete the antibody molecules into the medium;    (iii) collecting the antibody-containing medium; and    (iv) isolating the antibody molecules that have cortistatin specificity.    
     
     
         35 . A hybridoma cell that produces a monoclonal antibody of  claim 31 .  
     
     
         36 . A pharmaceutical composition comprising an antibody of  claim 29  and a pharmaceutically acceptable adjuvant.