Immunoglobulin chimeric monomer-dimer hybrids
The invention relates to a chimeric monomer-dimer hybrid protein wherein the protein comprises a first and a second polypeptide chain, the first polypeptide chain comprising at least a portion of an immunoglobulin constant region and a biologically active molecule, and the second polypeptide chain comprising at least a portion of an immunoglobulin constant region without the biologically active molecule of the first chain. The invention also relates to methods of using and methods of making the chimeric monomer-dimer hybrid protein of the invention.
1. A pharmaceutical composition comprising (a) a chimeric protein and (b) a pharmaceutically acceptable carrier, wherein the chimeric protein comprises a first and second polypeptide chain, wherein the first polypeptide chain comprises (i) a biologically active molecule selected from a hormone, a cytokine, or a cell surface receptor, and (ii) an immunoglobulin constant region or a portion thereof that is an FcRn binding partner; and wherein the second polypeptide chain comprises an immunoglobulin constant region or a portion thereof that is an FcRn binding partner without any biologically active molecule or variable region of an immunoglobulin.
2. The pharmaceutical composition of claim 1 , wherein both of the immunoglobulin constant regions or portions thereof are an Fc fragment.
3. The pharmaceutical composition of claim 1 , wherein the biologically active molecule comprises a hormone.
4. The pharmaceutical composition of claim 1 , wherein the biologically active molecule is human growth hormone (hGH), gonadotropin releasing hormone (GnRH), leuprolide, follicle stimulating hormone, progesterone, estrogen, or testosterone.
5. The pharmaceutical composition of claim 4 , wherein the biologically active molecule is hGH.
6. The pharmaceutical composition of claim 3 , wherein the hormone and the immunoglobulin constant region or the portion thereof in the first polypeptide chain are connected by a linker.
7. The pharmaceutical composition of claim 6 , wherein the linker comprises polyethylene glycol (PEG).
8. The pharmaceutical composition of claim 1 , wherein the biologically active molecule comprises a cytokine.
9. The pharmaceutical composition of claim 1 , wherein the biologically active molecule is granulocyte macrophage colony stimulating factor (GM-CSF), RANTES, MIP1α, MIP1β, IL-2, IL-3, Interferon α, Interferon β, tumor necrosis factor α, or tumor necrosis factor β.
10. The pharmaceutical composition of claim 9 , wherein the biologically active molecule is GM-CSF.
11. The pharmaceutical composition of claim 8 , wherein the cytokine and the immunoglobulin constant region or the portion thereof in the first polypeptide chain are connected by a linker.
12. The pharmaceutical composition of claim 11 , wherein the linker comprises polyethylene glycol (PEG).
13. The pharmaceutical composition of claim 1 , wherein the biologically active molecule comprises a cell surface receptor.
14. The pharmaceutical composition of claim 1 , wherein the biologically active molecule is CD4, CCR5, CXCR4, CD21, CD46, TNFα receptor, the erythropoietin receptor, CD25, CD122, or CD132.
15. The pharmaceutical composition of claim 13 , wherein the cell surface receptor and the immunoglobulin constant region or the portion thereof in the first polypeptide chain are connected by a linker.
16. The pharmaceutical composition of claim 15 , wherein the linker comprises polyethylene glycol (PEG).
17. A chimeric protein comprising a first and second polypeptide chain, wherein the first polypeptide chain comprises (i) a biologically active molecule selected from a hormone, a cytokine, or a cell surface receptor, and (ii) an immunoglobulin constant region or a portion thereof that is an FcRn binding partner; and wherein the second polypeptide chain comprises an immunoglobulin constant region or a portion thereof that is an FcRn binding partner without any biologically active molecule or variable region of an immunoglobulin.
18. The chimeric protein of claim 17 , wherein the biologically active molecule comprises a hormone.
19. The chimeric protein of claim 17 , wherein the biologically active molecule is human growth hormone (hGH), gonadotropin releasing hormone (GnRH), leuprolide, follicle stimulating hormone, progesterone, estrogen, or testosterone.
20. The chimeric protein of claim 17 , wherein the biologically active molecule comprises a cytokine.
21. The chimeric protein of claim 17 , wherein the biologically active molecule is granulocyte macrophage colony stimulating factor (GM-CSF), RANTES, MIP1α, MIP1β, IL-2, IL-3, Interferon α, Interferon β, tumor necrosis factor α, or tumor necrosis factor β.
22. The chimeric protein of claim 17 , wherein the biologically active molecule comprises a cell surface receptor.
23. The chimeric protein of claim 17 , wherein the biologically active molecule is CD4, CCR5, CXCR4, CD21, CD46, TNFα receptor, the erythropoietin receptor, CD25, CD122, or CD132.
24. The chimeric protein of claim 17 , wherein the biologically active molecule and the immunoglobulin constant region or a portion thereof in the first polypeptide chain are connected by a linker.
25. The chimeric protein of claim 24 , wherein the linker comprises polyethylene glycol (PEG).
26. The chimeric protein of claim 24 , wherein the linker comprise an amino acid.
27. A chimeric protein comprising a first and second polypeptide chain, wherein the first polypeptide chain comprises a biologically active molecule selected from a hormone, a cytokine, a growth factor, or a cell surface receptor connected by a linker comprising polyethylene glycol (PEG) to an immunoglobulin constant region or a portion thereof that is an FcRn binding partner; and wherein the second polypeptide chain comprises an immunoglobulin constant region or a portion thereof that is an FcRn binding partner without any biologically active molecule or variable region of an immunoglobulin.