Interleukin-21 receptor binding proteins
View Patent ↗The present invention provides binding proteins and antigen-binding fragments thereof that specifically bind to the human interleukin-21 receptor (IL-21R). The binding proteins can act as, e.g., antagonists of IL-21R activity, thereby modulating immune responses in general, and those mediated by IL-21R in particular. The disclosed compositions and methods may be used, e.g., in diagnosing and/or treating IL-21R-associated disorders, e.g., inflammatory disorders, autoimmune diseases, allergies, transplant rejection, cancer, and other immune system disorders.
1. An isolated binding protein or antigen-binding fragment thereof that binds to interleukin-21 receptor (“IL-21R”), wherein the binding protein or antigen-binding fragment thereof comprises the CDR sequences set forth in SEQ ID NOs:163, 164, 169, 194, 195, and 176.
2. The isolated binding protein or antigen-binding fragment of claim 1 , wherein the binding protein or antigen-binding fragment is an antibody.
3. The isolated binding protein or antigen-binding fragment of claim 1 , wherein the binding protein or antigen-binding fragment is an scFv.
4. An isolated binding protein or antigen-binding fragment thereof that binds to IL-21R, wherein the binding protein or antigen-binding fragment thereof comprises the CDR sequences encoded by the nucleotide sequences of:
(a) nucleotide 148 to 165 of SEQ ID NO:239;
(b) nucleotide 208 to 255 of SEQ ID NO:239;
(c) nucleotide 352 to 378 of SEQ ID NO:239;
(d) nucleotide 124 to 156 of SEQ ID NO:97;
(e) nucleotide 202 to 222 of SEQ ID NO:97; and
(f) nucleotide 319 to 354 of SEQ ID NO:97.
5. The isolated binding protein or antigen-binding fragment of claim 4 , wherein the binding protein or antigen-binding fragment is an antibody.
6. The isolated binding protein or antigen-binding fragment of claim 4 , wherein the binding protein or antigen-binding fragment is an scFv.
7. An isolated binding protein or antigen-binding fragment thereof that binds to IL-21R, wherein the binding protein or antigen-binding fragment thereof comprises a V L , domain and a V H domain, and wherein the V L domain comprises
SEQ ID NO:221, and the V H domain comprises amino acid 1 to 118 of SEQ ID NO:219.
8. The binding protein or antigen-binding fragment of any one of claim 1 , 2 , 4 , or 5 , wherein the association constant of the binding protein or antigen-binding fragment for human IL-21R is at least about 10 5 M −1 s −1 .
9. The binding protein or antigen-binding fragment of any one of claim 1 , 2 , 4 , or 5 , wherein the binding protein or antigen-binding fragment inhibits interleukin-21 (“IL-21”)-mediated proliferation of BaF3 cells with an IC 50 of about 1.75 nM or less, and wherein the BaF3 cells comprise a human IL-21R.
10. The binding protein or antigen-binding fragment of any one of claim 1 , 2 , 4 , or 5 , wherein the binding protein or antigen-binding fragment inhibits IL-21-mediated proliferation of TF1 cells with an IC 50 of about 14.0 nM or less, and wherein the TF1 cells comprise a human IL-21R.
11. The binding protein or antigen-binding fragment of any one of claim 1 , 2 , 4 , or 5 , wherein the binding protein or antigen-binding fragment inhibits IL-21-mediated proliferation of primary human B cells with an IC 50 of about 1.9 nM or less, and wherein the B cells comprise a human IL-21R.
12. The binding protein or antigen-binding fragment of any one of claim 1 , 2 , 4 , or 5 , wherein the binding protein or antigen-binding fragment inhibits IL-21-mediated proliferation of primary human CD4 + cells with an IC 50 of about 1.5 nM or less, and wherein the CD4 + cells comprise a human IL-21R.
13. The binding protein or antigen-binding fragment of any one of claim 1 , 2 , 4 , or 5 , wherein the binding protein or antigen-binding fragment specifically binds to an amino acid sequence that is at least about 95% identical to any sequence of at least 100 contiguous amino acids of SEQ ID NO:2.
14. The binding protein or antigen-binding fragment of any one of claim 1 , 2 , 4 , or 5 , wherein the binding protein or antigen-binding fragment inhibits the binding of IL-21 to IL-21R.
15. The binding protein or antigen-binding fragment of any one of claim 1 , 2 , 4 , or 5 , wherein the binding protein or antigen-binding fragment is IgG1.
16. The binding protein or antigen-binding fragment of any one of claim 1 , 2 , 4 , or 5 , wherein the binding protein or antigen-binding fragment is human.
17. A pharmaceutical composition comprising the binding protein or antigen-binding fragment of any one of claim 1 , 2 , 4 , or 5 .
18. A diagnostic kit comprising the binding protein or antigen-binding fragment of any one of claim 1 , 2 , 4 , or 5 .
19. An isolated binding protein or antigen-binding fragment thereof that binds to IL-21R, wherein the binding protein or antigen-binding fragment thereof comprises a V L domain and a V H domain, and wherein the V L domain comprises the amino acid sequence encoded by nucleotide 58 to 384 of SEQ ID NO:97, and the V H domain comprises the amino acid sequence encoded by nucleotide 58 to 411 of SEQ ID NO:239.
20. The isolated binding protein or antigen-binding fragment of claim 7 or 19 , wherein the binding protein or antigen-binding fragment is an antibody.
21. The isolated binding protein or antigen-binding fragment of claim 7 or 19 , wherein the binding protein or antigen-binding fragment is an scFv.