IL-7 fusion proteins
View Patent ↗The invention is directed to a fusion protein which includes a first portion including an immunoglobulin (Ig) chain and a second portion including interleukin-7 (IL-7).
1. A fusion protein comprising:
a first portion comprising an immunoglobulin chain; and
a second portion comprising a polypeptide comprising an amino acid sequence at least 85% identical to mature human interleukin-7 (IL-7), wherein the mature human IL-7 comprises amino acid residues 26-177 of SEQ ID NO:1, and wherein the polypeptide comprises disulfide bonding between residues corresponding to positions Cys2 and Cys92, Cys34 and Cys 129, and Cys47 and Cys141 of mature human IL-7.
2. The fusion protein of claim 1 , wherein the second portion polypeptide further comprises a deletion comprising an eighteen amino acid deletion from amino acid 96 to amino acid 114 of mature human IL-7.
3. The fusion protein of claim 1 , wherein the amino acid residue at position 116 of mature human IL-7 is non-glycosylated.
4. The fusion protein of claim 1 , wherein the amino acid residue at position 116 of mature human IL-7 is asparagine.
5. The fusion protein of claim 1 , wherein the amino acid residue at position 116 of mature human IL-7 is altered such that it does not serve as a glycosylation site.
6. The fusion protein of claim 1 , wherein the amino acid residues at positions 70 and 91 of mature human IL-7 are glycosylated.
7. The fusion protein of claim 1 , wherein the immunoglobulin chain comprises at least a portion of one or more constant domains.
8. The fusion protein of claim 7 , wherein the constant domain is selected from the group consisting of CH1, CH2, and CH3.
9. The fusion protein of claim 1 , further comprising a linker between the first portion and the second portion.
10. The fusion protein of claim 7 , wherein the constant domain is an IgG1 constant domain.
11. The fusion protein of claim 10 , wherein Asn297 of the constant domain is modified.
12. The fusion protein of claim 11 , wherein the Asn297 modification is Asn297G1n.
13. The fusion protein of claim 11 , further comprising a modification at Tyr296.
14. The fusion protein of claim 13 , wherein the Tyr296 modification is Tyr296Ala.
15. The fusion protein of claim 7 , wherein the constant domain is an IgG2 constant domain.
16. The fusion protein of claim 7 , wherein the immunoglobulin chain further comprises an IgG1 hinge.
17. The fusion protein of claim 16 , wherein Asn297 is modified.
18. The fusion protein of claim 17 , wherein the Asn297 modification is Asn297G1n.
19. The fusion protein of claim 16 , further comprising a modification at Phe296.
20. The fusion protein of claim 19 , wherein the Phe296 modification is Phe296Ala.