Cysteine variants of interleukin-11
Disclosed are cysteine variants of interleukin-11 (IL-11) and methods of making and using such proteins in therapeutic applications.
1. A mutein of IL-11 of SEQ ID NO:17, wherein a cysteine residue is substituted for an amino acid selected from the group consisting of P22, G23, P24, G27 and A162 wherein the mutein retains biological activity.
2. The mutein of claim 1 , wherein the mutein is modified with at least one polyethylene glycol.
3. The mutein of claim 1 , wherein the cysteine residue is modified with at least one polyethylene glycol.
4. A cysteine mutein of IL-11 of SEQ ID NO:17, wherein P22 is deleted and wherein the mutein comprises two cysteine substitutions, wherein cysteine residues are substituted for amino acids in SEQ ID NO:17 selected from the group consisting of P25 and T77, P25 and S117, P25 and S165, P24 and P25, D69 and T77, and A162C and S165C, wherein the mutein retains biological activity.
5. The mutein of claim 4 , wherein the mutein is modified with at least one polyethylene glycol.
6. The mutein of claim 4 , wherein the cysteine residue is modified with at least one polyethylene glycol.
7. A mutein of IL-11 of SEQ ID NO:17, wherein amino acid P22 is deleted and wherein a cysteine residue is substituted for at least one amino acid selected from the group consisting of P24, P25, E38, L39, D69, L72, S74, T77, A114, S117, E123, A148, and S165, wherein the mutein retains biological activity.
8. The mutein of claim 7 , wherein the mutein is modified with at least one polyethylene glycol.
9. The mutein of claim 7 , wherein the cysteine residue is modified with at least one polyethylene glycol.
10. The mutein of claim 1 , wherein a cysteine residue is substituted for A162.
11. The mutein of claim 4 , wherein cysteine residues are substituted for P25 and S117.
12. The mutein of claim 4 , wherein cysteine residues are substituted for P25 and S165.
13. The mutein of claim 7 , wherein a cysteine residue is substituted for A148.
14. The mutein of claim 7 , wherein a cysteine residue is substituted for S165.
15. The mutein of claim 4 , wherein cysteine residues are substituted for A162 and S165.
16. The mutein of claim 7 , wherein a cysteine residue is substituted for P24.
17. The mutein of claim 7 , wherein a cysteine residue is substituted for P25.
18. A mutein of IL-11 of SEQ ID NO:17, wherein amino acids 22-26 are deleted and wherein the mutein retains biological activity.
19. A mutein of IL-11 of SEQ ID NO:17, wherein amino acids 22-29 are deleted and wherein the mutein retains biological activity.
20. The mutein of claim 19 , further comprising a cysteine residue added following the last amino acid of the protein.
21. The mutein of claim 20 , wherein the mutein is modified with at least one polyethylene glycol.
22. The mutein of claim 20 , wherein the cysteine residue is modified with at least one polyethylene glycol.