Il-7r-alpha binding compounds

Abstract

IL-7Rα ligands and compounds comprising IL-7Rα ligands are disclosed. The IL-7Rα binding compounds include fusion proteins comprising the IL-7Rα ligands and can act as IL-7R agonists.

What is claimed is: 
     
         1 . An IL-7Rα ligand comprising:
 the amino acid sequence of any of any one of SEQ ID NOS: 393-410, 520-596, and 605-655; 
 an amino acid sequence having greater than 60% sequence similarity to any one of SEQ ID NOS: 393-410, 520-596, and 605-655; or 
 an amino acid sequence of any one of SEQ ID NOS: 393-410, 520-596, and 605-655 having from 1 to 5 amino acid substitutions. 
 
     
     
         2 . The IL-7Rα ligand of  claim 1 , wherein the IL-7Rα ligand has the amino acid sequence of any one of SEQ ID NOS: 393-410, 520-596, and 605-655. 
     
     
         3 . The IL-7Rα ligand of  claim 1 , wherein the IL-7Rα ligand has an amino acid sequence having greater than 80% sequence similarity to any one of SEQ ID NOS: 393-410, 520-596, and 605-655. 
     
     
         4 . The IL-7Rα ligand of  claim 1 , wherein the IL-7Rα ligand an amino acid sequence of any one of SEQ ID NOS: 393-410, 520-596, and 605-655 having from 1 to 3 amino acid substitutions. 
     
     
         5 . The IL-7Rα ligand of  claim 1 , wherein the IL-7Rα ligand binds to the hu-IL-7Rα subunit with an IC50 less than 100 μM. 
     
     
         6 . The IL-7Rα ligand of  claim 1 , wherein the IL-7Rα ligand comprises:
 the amino acid sequence of SEQ ID NO: 407; 
 an amino acid sequence having greater than 60% sequence similarity to SEQ ID NO: 407; or 
 an amino acid sequence of SEQ ID NO: 407 having from 1 to 5 amino acid substitutions. 
 
     
     
         7 . The IL-7Rα ligand of  claim 1 , wherein the IL-7Rα ligand comprises from 1 to 5 glycines on the carboxyl terminus, the amino terminus or on both the carboxyl terminus and the amino terminus. 
     
     
         8 . An IL-7Rα binding compound comprising the IL-7Rα ligand of  claim 1  bound to an Rγc ligand. 
     
     
         9 . The IL-7Rα binding compound of  claim 8 , wherein the IL-7Rα ligand is bound to the Rγc ligand through a peptidyl ligand linker. 
     
     
         10 . The IL-7Rα binding compound of  claim 8 , wherein the Rγc ligand comprises:
 an amino acid sequence of SEQ ID NO: 429; 
 an amino acid sequence having greater than 60% sequence similarity to SEQ ID NO: 429; or 
 an amino acid sequence of SEQ ID NO: 429 having from 1 to 5 amino acid substitutions. 
 
     
     
         11 . An IL-7Rα binding compound comprising the IL-7Rα ligand of  claim 1  bound to a construct partner. 
     
     
         12 . The IL-7Rα binding compound of  claim 11 , wherein the construct partner is selected from a polymer, a polypeptide, an Fc-fragment, an immunoglobulin fragment, antibody, a viral surface antigen or a virus-like particle, a cytokine and a recombinant fusion protein. 
     
     
         13 . The IL-7Rα binding compound of  claim 11 , wherein the construct partner is selected from a polyethylene glycol, a hIgG-Fc recombinant fusion protein. and a hIgG1-Fc recombinant fusion protein. 
     
     
         14 . The IL-7Rα binding compound of  claim 11 , wherein the construct partner comprises an antibody and the antibody is directed to a tumor antigen. 
     
     
         15 . The IL-7Rα binding compound of  claim 11 , wherein the construct partner comprises a cell-targeting moiety, wherein cell-targeting moiety comprises a tumor-targeting moiety, an immune cell-targeting moiety, or a combination thereof. 
     
     
         16 . The IL-7Rα binding compound of  claim 11 , wherein the IL-7Rα binding compound comprises a construct linker. 
     
     
         17 . The IL-7Rα binding compound of  claim 16 , wherein the construct linker comprises a peptidyl ligand linker. 
     
     
         18 . The IL-7Rα binding compound of  claim 11 , wherein the IL-7Rα binding compound comprises an amino acid sequence of any one of SEQ ID NOS: 411-419 and 420-428. 
     
     
         19 . The IL-7Rα binding compound of  claim 11 , wherein,
 the IL-7Rα binding compound binds to hu-IL-2R with an IC50 less than 100 μM and binds to hu-IL-7R with an IC50 less than 100 μM; and 
 the IL-7Rα binding compound exhibits an EC 50  for STAT5 phosphorylation in TF-1β cells and/or NK-92 cells of less than 100 μM. 
 
     
     
         20 . A pharmaceutical composition comprising the IL-7Rα ligand of  claim 1 . 
     
     
         21 . A pharmaceutical composition comprising the IL-7Rα binding compound of  claim 11 . 
     
     
         22 . A method of treating a disease in a patient comprising administering to a patient in need of such treatment a therapeutically effective amount of the IL-7Rα ligand of  claim 1 , wherein the disease is selected from cancer, an autoimmune disease, an inflammatory disease, an infectious disease, and a viral disease. 
     
     
         23 . A method of treating a disease in a patient comprising administering to a patient in need of such treatment a therapeutically effective amount of the IL-7Rα binding compound of  claim 11 , wherein the disease is selected from cancer, an autoimmune disease, an inflammatory disease, an infectious disease, and a viral disease.