Receptor based antagonists and methods of making and using
The present invention provides a fusion polypeptide capable of binding a cytokine to form a nonfunctional complex. It also provides a nucleic acid sequence encoding the fusion polypeptide and methods of making and uses for the fusion polypeptide.
1. A method of inhibiting IL-4-mediated inflammation comprising administering an IL-4 inhibitor, wherein the IL-4 inhibitor comprises a fusion polypeptide comprising an IL-2Rγ component encoded by nucleotides 1-762 of SEQ ID NO:17, an IL-4Rα component encoded by nucleotides 772-1395 of SEQ ID NO:17, and a multimerizing component.
2. The method of claim 1 , wherein the multimerizing component is an immunoglobulin domain.
3. The method of claim 2 , wherein the immunoglobulin domain is selected from the group consisting of an Fc domain of IgG and a heavy chain of IgG.
4. The method of claim 3 , wherein the immunoglobulin domain is an Fc domain of IgG.
5. The method of claim 4 , wherein the Fc domain is encoded by nucleotides 1396-2082 of SEQ ID NO:17.
6. The method of claim 5 , wherein the IL-4 inhibitor further comprises a linker region between the IL-2Rγ component and the IL- 4 Rα component, wherein the linker region is encoded by nucleotides 763-771 of SEQ ID NO:17.
7. The method of claim 6 , wherein the IL-4 inhibitor is encoded by a polynucleotide sequence having SEQ ID NO:17.
8. A method of inhibiting IL-4-mediated inflammation comprising administering an IL-4 inhibitor, wherein the IL-4 inhibitor has the amino acid sequence of SEQ ID NO:18.