Immunoglobulin chimeric monomer-dimer hybrids

Patent metadata

Field	Value
Publication number	US-9636416-B2
Application number	US-201414530256-A
Country	US
Kind code	B2
Filing date	Oct 31, 2014
Priority date	May 6, 2003
Publication date	May 2, 2017
Grant date	May 2, 2017

Abstract

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.

First claim

The invention claimed is:

1. A pharmaceutical composition comprising (a) a chimeric protein and (b) a pharmaceutically acceptable carrier, wherein the chimeric protein comprises (i) a biologically active molecule selected from a hormone, a cytokine, a growth factor, and a cell surface receptor and (ii) two immunoglobulin constant regions or portions thereof, each of which comprising a neonatal Fc Receptor binding site, wherein the immunoglobulin constant regions or portions thereof in (ii) are linked to the biologically active molecule of (i) by a linker.

2. The pharmaceutical composition of claim 1 , wherein one of the immunoglobulin constant regions or portions thereof is an Fc fragment.

3. The pharmaceutical composition of claim 1 , wherein the immunoglobulin constant regions or portions thereof are identical.

4. The pharmaceutical composition of claim 1 , wherein the biological active molecule comprises a hormone.

5. The pharmaceutical composition of claim 4 , wherein the hormone is selected from human growth hormone (hGH), gonadotropin releasing hormone (GnRH), leuprolide, follicle stimulating hormone, progesterone, estrogen, and testosterone.

6. The pharmaceutical composition of claim 4 , wherein the hormone is hGH.

7. The pharmaceutical composition of claim 4 , wherein the linker comprises polyethylene glycol (PEG).

8. The pharmaceutical composition of claim 1 , wherein the biologically active molecule comprises a cytokine or growth factor.

9. The pharmaceutical composition of claim 8 , wherein the cytokine or growth factor is selected from granulocyte macrophage colony stimulating factor (GM-CSF), RANTES, MIP1α, MIP1β, IL-2, 1 L-3, Interferon α, Interferon β, tumor necrosis factor α, and tumor necrosis factor β.

10. The pharmaceutical composition of claim 8 , wherein the growth factor is GM-CSF.

11. The pharmaceutical composition of claim 8 , wherein the linker comprises polyethylene glycol (PEG).

12. The pharmaceutical composition of claim 1 , wherein the biologically active molecule comprises the cell surface receptor.

13. The pharmaceutical composition of claim 12 , wherein the cell surface receptor is selected from CD4, CCR5, CXCR4, CD21, CD46, TNFα receptor, the erythropoietin receptor, CD25, CD122, and CD132.

14. The pharmaceutical composition of claim 1 , wherein the linker comprises polyethylene glycol (PEG).

15. The pharmaceutical composition of claim 1 , wherein the linker comprises an amino acid.

16. A chimeric protein comprising (i) a biologically active molecule selected from a hormone, a cytokine, a growth factor, and a cell surface receptor and (ii) two immunoglobulin constant regions or portions thereof, each of which comprising a neonatal Fe Receptor binding site, wherein the immunoglobulin constant regions or portions thereof in (ii) are linked to the biologically active molecule of (i) by a linker.

17. The chimeric protein of claim 16 , wherein the biologically active molecule is a hormone.

18. The chimeric protein of claim 16 , wherein the linker comprises polyethylene glycol (PEG).

19. The chimeric protein of claim 17 , wherein the linker comprises polyethylene glycol (PEG).

20. The pharmaceutical composition of claim 1 , wherein the biologically active molecule or the two immunoglobulin constant regions or portions thereof are glycosylated.

21. The chimeric protein of claim 16 , wherein the biologically active molecule or the two immunoglobulin constant regions or portions thereof are glycosylated.

22. The chimeric protein of claim 17 , wherein the hormone or the two immunoglobulin constant regions or portions thereof are glycosylated.

Assignees

• Bioverativ Therapeutics Inc

Inventors

• Peters Robert T
• Mezo Adam R
• Rivera Daniel S
• Bitoni Alan J
• Low Susan C

Classifications

• A61P31/18

  for HIV · CPC title

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A61P7/00

  Drugs for disorders of the blood or the extracellular fluid · CPC title

• A61P9/00

  Drugs for disorders of the cardiovascular system · CPC title

• A61P7/06

  Antianaemics · CPC title