Claims
- 1. A composition for oral administration of an interferon, comprising
an interferon and a species effective to stabilize the interferon in an active form by interaction between the interferon and the species.
- 2. The composition of claim 1, wherein said species is a buffer.
- 3. The composition of claim 2, wherein said buffer is histidine.
- 4. The composition of claim 1, wherein the interferon is a type I interferon.
- 5. The composition of claim 4, wherein said interferon is selected from interferon-α, interferon-β, interferon-ω, and interferon-τ.
- 6. The composition of claim 1, wherein said protein is interferon-τ.
- 7. The composition of claim 1, wherein said protein is a hybrid protein comprising selected N-terminal residues of interferon-τ.
- 8. The composition of claim 7, wherein said hybrid protein is comprised of an N-terminal segment corresponding to amino acid residues 1 to about amino acid residue 28 of interferon-τ, and a C-terminal segment corresponding to about residue 29 to the C-terminal residue of interferon-α.
- 9. The composition of claim 7, wherein said hybrid protein is comprised of an N-terminal segment corresponding to amino acid residues 1 to about amino acid residue 37 of interferon-τ, and a C-terminal segment corresponding to about residue 38 to the C-terminal residue of interferon-α.
- 10. The composition of claim 7, wherein said hybrid protein is comprised of an N-terminal segment of amino acid residues 1-27 of interferon-α having modifications at one or more of positions 19, 20, 22, 24, and 27 and a C-terminal segment corresponding to residue 28 to the C-terminal residue of interferon-α.
- 11. The composition of claim 1, wherein said species is effective to bind with said interferon to stabilize its α-helical tertiary structure.
- 12. The composition of claim 1, wherein said composition has a pH value of between about 6-8.
- 13. The composition of claim 1, wherein said interferon is interferon-τ, said species is histidine at a concentration of between about 10 mM to about 80 mM.
- 14. The composition of claim 1, wherein said interferon is interferon-τ, said species is histidine at a concentration of about 20 mM.
- 15. A method of preparing a protein for oral administration, comprising
formulating said protein with a species effective to stabilize the protein in an active form by binding interaction between said protein and said species, whereby said formulating results in a composition suitable for oral administration.
- 16. The method of claim 15, wherein said formulating includes formulating said protein with a buffer species.
- 17. The method of claim 15, wherein said formulating includes formulating said protein with a buffer species comprised of histidine.
- 18. The method of claim 15, wherein said formulating includes formulating a cytokine.
- 19. The method of claim 18, wherein said formulating includes a type I interferon.
- 20. The method of claim 19, wherein said formulating includes formulating a type-I interferon selected from interferon-αa, interferon-β, interferon-ω, and interferon-τ.
- 21. The method of claim 15, wherein said formulating is comprised of formulating interferon-τ.
- 22. The method of claim 21, wherein said formulating is comprised of formulating interferon-τ with histidine.
- 23. The method of claim 15, wherein said formulating comprises formulating with a species effective to bind with said protein to stabilize the protein's tertiary structure.
- 24. The method of claim 15, wherein said formulating includes formulating said protein and said buffer at a pH value of between about 6-8.
- 25. A method for selecting a dosage form composition for a protein that achieves protein stabilization for biological activity upon in vivo administration, comprising
selecting a protein for formulation; preparing solutions of the selected protein or polypeptide in different buffers at different pH values; and measuring the effect of the buffer on the protein's tertiary structure, whereby said measuring identifies buffers that result retention of the protein's tertiary structure.
- 26. The method of claim 25, wherein said selecting comprises selecting a type I interferon.
- 27. The method of claim 25, wherein said measuring is by spectroscopy.
Parent Case Info
[0001] This application claims priority to U.S. provisional patent application No. 60/417,292 filed on Oct. 9, 2002, which is incorporated herein in its entirety by reference.
Provisional Applications (1)
|
Number |
Date |
Country |
|
60417292 |
Oct 2002 |
US |