US2023331801A1PendingUtilityA1

Il-2r-beta-gamma binding compounds

73
Assignee: MEDIKINE INCPriority: Nov 5, 2019Filed: May 22, 2023Published: Oct 19, 2023
Est. expiryNov 5, 2039(~13.3 yrs left)· nominal 20-yr term from priority
Inventors:William J. DowerMichael C. NeedelsRonald W. BarrettAlice V. BakkerSteven E. Cwirla
C07K 14/55C07K 16/30C07K 2319/01C07K 2319/30C07K 2319/75C07K 2317/92A61K 38/00A61K 2039/505C07K 14/7155A61P 37/04C07K 16/2866
73
PatentIndex Score
0
Cited by
0
References
0
Claims

Abstract

IL-2Rβγc binding compounds, and pharmaceutical compositions comprising the IL-2Rβγc binding compounds are disclosed. IL-2Rβγc binding compounds can act as IL-2R agonists and are useful in treating cancer, autoimmune diseases and inflammatory diseases.

Claims

exact text as granted — not AI-modified
1 . An IL-2Rβγc binding compound, wherein the IL-2Rβγc binding compound comprises an IL-2Rβγc ligand, wherein the IL-2Rβγc ligand comprises:
 a ligand linker; 
 an IL-2Rγc ligand bound to the ligand linker, wherein the IL-2Rγc ligand comprises any one of SEQ ID NO: 944-1028, 1032, 1034, 1042, 1044, 1051-1060, and 1601-1613; and 
 an IL-2Rβ ligand bound to the ligand linker, wherein the IL-2Rβ ligand comprises any one of Formula (1) (SEQ ID NO: 805), Formula (1a) (SEQ ID NO: 806), Formula (1b) (SEQ ID NO: 807), Formula (1c) (SEQ ID NO: 808), and Formula (1d) (SEQ ID NO: 809):
   -X 211 -X 212 -X 213 -X 214 -C-X 215 -X 216 -X 217 -X 218 -X 219 -X 220 -X 221 -X 222 -C-X 223 -X 224 -X 225   (1)
 
   -X 212 -X 213 -X 214 -C-X 215 -X 216 -X 217 -X 218 -X 219 -X 220 -X 221 -X 222 -C-X 223 -X 224 -  (1a)
 
   -X 213 -X 214 -C-X 215 -X 216 -X 217 -X 218 -X 219 -X 220 -X 221 -X 222 -C-X 223 -X 224 -  (1b)
 
   -X 24 -C-X 215 -X 216 -X 127 -X 218 -X 219 -X 220 -X 221 -X 222 -C-X 223 -  (1c)
 
   -C-X 215 -X 216 -X 217 -X 218 -X 219 -X 220 -X 221 -X 222 -C-  (1d)
 
 
 wherein,
 X 211  is selected from an amino acid; 
 X 212  is selected from F, H, W, and Y; 
 X 213  is selected from F, H, I, L, M, V, W, and Y; 
 X 214  is P; 
 X 215  is selected from F, H, W, and Y; 
 X 216  is selected from F, I, L, M, V, W, and Y; 
 X 217  is A; 
 X 218  is selected from H, K, N, Q, R, S, T, and Y; 
 X 219  is selected from F, I, L, M, V, W, and Y; 
 X 220  is G; 
 X 221  is selected from D, E, H, N, Q, S, T, and Y; 
 X 222  is L; 
 X 223  is D; 
 X 224  is selected from F, I, L, M, V, W, and Y; and 
 X 225  is selected from D and E. 
 
 
     
     
         2 . The IL-2Rβγc binding compound of  claim 1 , wherein the Rγc ligand comprises SEQ ID NO: 965. 
     
     
         3 . The IL-2Rβγc binding compound of  claim 1 , wherein X 211  is selected from H, K, and R. 
     
     
         4 . The IL-2Rβγc binding compound of  claim 1 , wherein X 212  is W. 
     
     
         5 . The IL-2Rβγc binding compound of  claim 1 , wherein X 213  is selected from L and Y. 
     
     
         6 . The IL-2Rβγc binding compound of  claim 1 , wherein X 215  is W. 
     
     
         7 . The IL-2Rβγc binding compound of  claim 1 , wherein X 216  is M. 
     
     
         8 . The IL-2Rβγc binding compound of  claim 1 , wherein X 218  is selected from K, Q, and R. 
     
     
         9 . The IL-2Rβγc binding compound of  claim 1 , wherein X 219  is L. 
     
     
         10 . The IL-2Rβγc binding compound of  claim 1 , wherein X 221  is E. 
     
     
         11 . The IL-2Rβγc binding compound of  claim 1 , wherein X 224  is L. 
     
     
         12 . The IL-2Rβγc binding compound of  claim 1 , wherein,
 X 211  is selected from H, K, and R; 
 X 212  is W; 
 X 213  is Y; 
 X 214  is P; 
 X 215  is W; 
 X 216  is M; 
 X 217  is A; 
 X 218  is selected N and Q; 
 X 219  is selected from L and V; 
 X 220  is G; 
 X 221  is selected from E, D, and Q; 
 X 222  is L; 
 X 223  is D; 
 X 224  is selected from L and M; and 
 X 225  is selected from D and E. 
 
     
     
         13 . The IL-2Rβγc binding compound of  claim 1 , wherein,
 X 211  is selected from H and R; 
 X 212  is selected from F and W; 
 X 213  is selected from F, L, W, and Y; 
 X 214  is P; 
 X 215  is selected from W and Y; 
 X 216  is selected from F, I, L, M, and V; 
 X 217  is A; 
 X 218  is selected H, K, N, Q, and R; 
 X 219  is selected from L and V; 
 X 220  is G; 
 X 221  is selected from D, E, and Q; 
 X 222  is L; 
 X 223  is D; 
 X 224  is selected L, M, and V; and 
 X 225  is selected from D and E. 
 
     
     
         14 . The IL-2Rβγc binding compound of  claim 1 , wherein,
 X 211  is selected from H and R; 
 X 22  is W; 
 X 213  is selected from P and Y; 
 X 214  is P; 
 X 215  is W; 
 X 216  is M; 
 X 217  is A; 
 X 218  is selected from K, Q and R; 
 X 219  is L; 
 X 220  is G; 
 X 221  is Q; 
 X 222  is L; 
 X 223  is D; 
 X 224  is L; and 
 X 225  is selected from D and E. 
 
     
     
         15 . The IL-2Rβγc binding compound of  claim 1 , wherein, the IL-2Rβ ligand comprises any one of SEQ ID NO: 810-903. 
     
     
         16 . The IL-2Rβγc binding compound of  claim 1 , wherein the ligand linker comprises (G) n  (SEQ ID NO: 9380), (GS) n (SEQ ID NO: 9381), (GGS) n  (SEQ ID NO: 9382), (GGGS) n  (SEQ ID NO: 9383), (GGGGS) n  (SEQ ID NO: 9384), or a combination of any of the foregoing, wherein n is an integer from 1 to 20. 
     
     
         17 . The IL-2Rβγc binding compound of  claim 1 , wherein the ligand linker comprises (GGGGS) (SEQ ID NO: 9395), (GGGGS)2 (SEQ ID NO: 9396), (GGGGS)3 (SEQ ID NO: 9397), (GGGGS)4 (SEQ ID NO: 9398), (GG) (SEQ ID NO: 9399), (GGG) (SEQ ID NO: 9400), (GGGGG) (SEQ ID NO: 9401), (GGS) (SEQ ID NO: 9402), (GGGS) (SEQ ID NO: 9403), (GGGGSGG) (SEQ ID NO: 9404), (GGS)2 (SEQ ID NO: 9405), (G)5 (SEQ ID NO: 9406), or (GS)10 (SEQ ID NO: 9407). 
     
     
         18 . The IL-2Rβγc binding compound of  claim 1 , wherein the ligand linker comprises (PA)n, wherein n is an integer from 1 to 20. 
     
     
         19 . The IL-2Rβγc binding compound of  claim 1 , wherein the IL-2Rβγc binding compound comprises a construct partner, wherein the IL-2Rβγc ligand is bound to the construct partner. 
     
     
         20 . The IL-2Rβγc binding compound of  claim 19 , wherein in the IL-2Rβγc ligand is bound to the construct partner through a construct linker. 
     
     
         21 . The IL-2Rβγc binding compound of  claim 20 , wherein the construct linker comprises a peptidyl construct linker. 
     
     
         22 . The IL-2Rβγc binding compound of  claim 21 , wherein the peptidyl construct linker is selected from any one of SEQ ID NO: 9380-9401 and 9420-9425, wherein n is an integer from 1 to 30. 
     
     
         23 . The IL-2Rβγc binding compound of  claim 22 , wherein the construct partner is selected from a polymer, a polypeptide, an Fc-fragment, an immunoglobulin fragment, an antibody, a viral surface antigen or a virus-like particle, a cytokine, and a recombinant fusion protein. 
     
     
         24 . The IL-2Rβγc binding compound of  claim 23 , wherein the construct partner is selected from a polyethylene glycol, a hIgG-Fc recombinant fusion protein, and a hIgG1-Fc recombinant fusion protein. 
     
     
         25 . The IL-2Rβγc binding compound of  claim 19 , wherein the construct partner comprises an antibody and the antibody is directed to a tumor antigen. 
     
     
         26 . The IL-2Rβγc binding compound of  claim 19 , wherein the construct partner comprises a cell-targeting moiety. 
     
     
         27 . The IL-2Rβγc binding compound of  claim 26 , wherein cell-targeting moiety comprises a tumor-targeting moiety, an immune cell-targeting moiety, or a combination thereof. 
     
     
         28 . A pharmaceutical composition comprising the IL-2Rβγc binding compound of  claim 1 .

Cited by (0)

No later patents cite this yet.

References (0)

No backward citations on record.