Il-2rbeta binding compounds

Abstract

IL-2Rβ ligands and IL-2Rγc ligands and compounds comprising the ligands are disclosed. The ligands and compounds such as heterodimers and fusion proteins comprising the IL-2Rβ ligands and/or the IL-2Rγc ligands can be IL-2 receptor agonists.

What is claimed is: 
     
         1 . An IL-2Rβ ligand comprising the amino acid sequence of Formula (10) (SEQ ID NO: 578):
   -X 191 -X 192 -X 193 -X 194 -X 195 -C-X 196 -X 197 -X 198 -X 199 -X 200 -X 201 -X 202 -X 203 -C-X 204 -X 205 -X 206 -X 207 -X 208 -   (10)
 
 wherein,
 X 191  is selected from A, D, E, F, G, H, I, K, L, N, M, P, Q, R, S, T, V, W, and Y; 
 X 192  is selected from A, D, E, F, G, H, I, K, L, M, N, P, Q, R, S, T, V, W, and Y; 
 X 193  is selected from A, C, D, F, G, H, I, L, M, N P, R, S, T, V, W, and Y; 
 X 194  is selected from F, H, I, K, L, N, P, Q, R, S, T, V, W, and Y; 
 X 195  is selected from A, D, E, F, G, H, K, L, M, N, P, Q, S, W, and Y; 
 X 196  is selected from A, E, F, G, H, Q, R, S, W, and Y; 
 X 197  is selected from A, D, E, F, I, K, L, M, N, Q, R, S, T, V, W, and Y; 
 X 198  is A; 
 X 199  is selected from A, D, H, K, L, N, P, Q, R, S, and Y; 
 X 200  is selected from I, L, M, P, and V; 
 X 201  is selected from G, H, and W; 
 X 202  is selected from D, E, and Q; 
 X 203  is L; 
 X 204  is selected from A, D, E, H, I, L, T, V, and Y; 
 X 205  is selected from F, I, L, M, V, W, and Y; 
 X 206  is selected from A, D, E, F, G, H, I, K, L, M, N, P, Q, R, S, T, V, W, and Y; 
 X 207  is selected from A, C, D, E, F, G, H, I, L, M, N, P, Q, R, S, T, V, W, and Y; and 
 X 208  is selected from A, D, E, F, G, H, K, L, M, N, P, Q, R, S, T, V, W, and Y. 
 
 
     
     
         2 . The IL-2Rβ ligand of  claim 1 , wherein,
 X 193  is selected from F, H, W, and Y; and 
 X 194  is selected from F, H, L, W, and Y. 
 
     
     
         3 . The IL-2Rβ ligand of  claim 1 , wherein,
 X 195  is selected from D, E, and P; and 
 X 196  is selected from F, H, R, S, W, and Y. 
 
     
     
         4 . The IL-2Rβ ligand of  claim 1 , wherein,
 X 197  is selected from F, I, L, M, and V; and 
 X 199  is selected from H, K, Q, N, and R. 
 
     
     
         5 . The IL-2Rβ ligand of  claim 1 , wherein,
 X 200  is selected from I, L, and V; and 
 X 202  is selected from D, E, and Q. 
 
     
     
         6 . The IL-2Rβ ligand of  claim 1 , wherein,
 X 204  is selected from D and E; and 
 X 205  is selected from F, I, L, M, V, and W. 
 
     
     
         7 . The IL-2Rβ ligand of  claim 1 , wherein,
 X 193  is selected from F, H, W, and Y; 
 X 194  is selected from F, H, L, W, and Y; 
 X 195  is selected from D, E, and P; 
 X 196  is selected from F, H, R, S, W, and Y; 
 X 197  is selected from F, I, L, M, and V; 
 X 198  is A; 
 X 199  is selected from H, K, Q, N, and R; 
 X 200  is selected from I, L, and V; 
 X 201  is G; 
 X 202  is selected from D, E, and Q; 
 X 203  is L; 
 X 204  is selected from D and E; and 
 X 205  is selected from F, I, L, M, V, and W. 
 
     
     
         8 . The IL-2Rβ ligand of  claim 1 , wherein,
 X 193  is selected from F, H, W, and Y; 
 X 194  is selected from F, H, L, W, and Y; 
 X 195  is selected from D, E, and P; 
 X 196  is selected from F, H, R, S, W, and Y; 
 X 197  is selected from F, I, L, M, and V; and 
 X 198  is A. 
 
     
     
         9 . The IL-2Rβ ligand of  claim 1 , wherein,
 X 199  is selected from H, K, Q, N, and R; and 
 X 200  is selected from I, L, and V. 
 
     
     
         10 . The IL-2Rβ ligand of  claim 1 , wherein,
 X 201  is G; 
 X 202  is selected from D, E, and Q; 
 X 203  is L; 
 X 204  is selected from D and E; and 
 X 205  is selected from F, I, L, M, V, and W. 
 
     
     
         11 . The IL-2Rβ ligand of  claim 10 , wherein,
 X 202  is E; 
 X 204  is D; and 
 X 205  is L. 
 
     
     
         12 . The IL-2Rβ ligand of  claim 1 , wherein the amino acid sequence of Formula (10) comprises from 1 to 5 of the following conservative substitutions: amino acids having a small hydrophobic side chain comprising alanine (A), glycine (G), proline (P), serine (S), or threonine (T); amino acids having a hydroxyl-containing side chain comprising serine (S), threonine (T), or tyrosine (Y); amino acids having an acidic side chain comprising aspartate (D) or glutamate (E); amino acids having a polar-neutral side chain comprising histidine (H), asparagine (N), glutamine (Q), serine (S), threonine (T), or tyrosine (Y); amino acids having a basic side chain comprising arginine (R), lysine (K), or histidine (H); amino acids having a large hydrophobic side chain comprising isoleucine (I), leucine (L), methionine (M), valine (V), phenylalanine (F), tyrosine (Y), or tryptophan (W); and amino acids having an aromatic side chain comprising phenylalanine (F), histidine (H), tryptophan (W), or tyrosine (Y). 
     
     
         13 . The IL-2β ligand of  claim 1 , wherein the IL-2Rβ ligand exhibits a binding affinity (IC 50 ) to the human IL-21213 subunit of less than 100 μM. 
     
     
         14 . The IL-2Rβ ligand of  claim 1 , wherein the amino acid sequence is terminated with amino acids -G-G- on the N-terminus, on the C-terminus, or on both the N- and C-termini. 
     
     
         15 . A pharmaceutical composition comprising the IL-2Rβ ligand of  claim 1 . 
     
     
         16 . A compound comprising at least one IL-2Rβ ligand of  claim 1 . 
     
     
         17 . The compound of  claim 16 , wherein the compound is selected from a peptide comprising the IL-2Rβ ligand, a conjugate, and a fusion protein. 
     
     
         18 . The compound of  claim 16 , wherein the compound comprises an IL-2Rα ligand, an IL-2Rγc ligand, or both an IL-2Rα ligand and an IL-2Rγc ligand. 
     
     
         19 . A pharmaceutical composition comprising the compound of  claim 16 .