Agonist antibodies

Abstract

Various forms of c-mpl agonist antibodies are shown to influence the replication, differentiation or maturation of blood cells, especially megakaryocytes and megakaryocyte progenitor cells. Accordingly, these compounds may be used for treatment of thrombocytopenia.

1 . An agonist antibody, fragment, or variant thereof which binds to a thrombopoietin receptor.  
     
     
         2 - 19 . (canceled)  
     
     
         20 . A library of different single chain antibodies, comprising a plurality of the antibody of  claim 1 .  
     
     
         21 . The library of  claim 20 , wherein the single chain antibodies are displayed on phage.  
     
     
         22 . The library of  claim 21 , wherein the phage is M13 and the antibodies are displayed as fusions of coat protein 3.  
     
     
         23 . The library of  claim 22 , wherein less than 20% of the phage display more than one fusion on the surface thereof.  
     
     
         24 . A phage displaying on the surface thereof, the antibody of  claim 1 .  
     
     
         25 . The phage of  claim 24 , wherein the phage is M13 and the antibodies are displayed as fusions of coat protein 3.  
     
     
         26 . The phage of  claim 25 , wherein the phage displays only one fusion on the surface thereof.  
     
     
         27 . A fusion protein, comprising at least a portion of a phage coat protein fused at the amino terminus thereof to the antibody of  claim 1 .  
     
     
         28 . The fusion protein of  claim 27 , wherein the phage coat protein is M13 coat protein 3.  
     
     
         29 . A method of stimulating proliferation, differentiation or growth of megakaryocytes, comprising contacting megakaryocytes with an effective amount of the antibody of  claim 1 .  
     
     
         30 . The method of  claim 29 , comprising administering the antibody of  claim 1  to a patient in need thereof.  
     
     
         31 . A method of increasing platelet production, comprising contacting megakaryocytes with an effective amount of the antibody of  claim 1 .  
     
     
         32 . The method of  claim 31 , comprising administering the antibody of  claim 1  to a patient in need thereof.  
     
     
         33 . Isolated nucleic acid encoding the antibody of  claim 1 .  
     
     
         34 . A vector comprising the nucleic acid of  claim 33 .  
     
     
         35 . A host cell comprising the vector of  claim 34 .  
     
     
         36 . A method of producing an agonist antibody comprising culturing the cell of  claim 35  under conditions wherein the nucleic acid is expressed.  
     
     
         37 . An agonist antibody, fragment or variant thereof which binds to a MuSK receptor.  
     
     
         38 . A method of activating a receptor protein having two sub-units, comprising contacting the receptor with a single chain antibody which binds to the receptor.  
     
     
         39 - 42 . (canceled)