TACI-immunoglobulin fusion proteins
Molecules that interfere with the binding of a tumor necrosis factor receptor with its ligand, such as a soluble receptor, have proven usefulness in both basic research and as therapeutics. The present invention provides improved soluble transmembrane activator and calcium modulator and cyclophilin ligand-interactor (TACI) receptors.
1. A fusion protein comprising:
(a) a transmembrane activator and calcium modulator and cyclophilin ligand-interactor (TACI) receptor moiety, wherein the TACI receptor moiety is a polypeptide consisting of amino acid residues 30 to 154 of SEQ ID NO:2 and wherein the TACI receptor moiety binds at least one of ZTNF2 or ZTNF4, and
(b) an immunoglobulin moiety that comprises a heavy chain constant region of an immunoglobulin.
2. The fusion protein of claim 1 , wherein the immunoglobulin moiety comprises a heavy chain constant region.
3. The fusion protein of claim 1 , wherein the heavy chain constant region is an IgG1 heavy chain constant region.
4. The fusion protein of claim 1 , wherein the immunoglobulin moiety is an IgG1 Fc fragment that comprises C H2 , and C H3 domains.
5. The fusion protein of claim 1 , wherein the immunoglobulin moiety is an IgG1 Fc fragment comprising the amino acid sequence of SEQ ID NO:33.
6. The fusion protein of claim 1 , wherein the TACI-immunoglobulin fusion protein is a dimer.
7. A fusion protein comprising:
(a) a transmembrane activator and calcium modulator and cyclophilin ligand-interactor (TACI) receptor moiety, wherein the TACI receptor moiety is a polypeptide consisting of amino acid residues 30 to 110 of SEQ ID NO:2 and wherein the TACI receptor moiety binds at least one of ZTNF2 or ZTNF4, and
(b) an immunoglobulin moiety that comprises a heavy chain constant region of an immunoglobulin.
8. The fusion protein of claim 7 , wherein the immunoglobulin moiety comprises a human heavy chain constant region.
9. The fusion protein of claim 7 , wherein the heavy chain constant region is an IgG1 heavy chain constant region.
10. The fusion protein of claim 7 , wherein the immunoglobulin moiety is an IgG1 Fc fragment that comprises C H2 , and C H3 domains.
11. The fusion protein of claim 7 , wherein the immunoglobulin moiety is an IgG1 Fc fragment comprising the amino acid sequence of SEQ ID NO:33.
12. The fusion protein of claim 7 , wherein TACI-immunoglobulin fusion protein has the amino acid sequence of SEQ ID NO:54.
13. The fusion protein of claim 7 , wherein the TACI-immunoglobulin fusion protein is a dimer.