Methods for treating asthma in human and non human primates using IL-4 mutant compositions
The present invention relates generally to methods and compounds for treating pulmonary disorders, and more specifically to the inhalation administration and use of hIL-4 mutant proteins to treat asthma.
1. A method of treating asthma comprising administering to a subject in need thereof, a pharmaceutical composition containing a therapeutically effective amount of a mutant human IL-4 (hIL-4) protein comprising the amino acid sequence of wild-type hIL-4 with two modifications, wherein the first modification is replacement of the amino acids occurring in the wild-type hIL-4 protein at positions 121 and 124 with aspartic acid, and the second modification is at least one modification selected from the group consisting of:
a) N-terminal methionine;
b) deletion of up to five amino acids from the C-terminus;
c) deletion of potential glycosylation sites therein; and
d) coupling of the protein to a non-protein polymer,
wherein the mutant hIL-4 protein is an antagonist of wild-type hIL-4, and wherein the composition is administered for a period of at least about 28 days via inhalation, thereby ameliorating the symptoms associated with asthma.
2. The method of claim 1 , wherein the second modification consists of coupling of the protein to a non-protein polymer selected from the group consisting of polyethylene glycol, polypropylene glycol, and polyoxyalkylenes, wherein the mutant hIL-4 protein is an antagonist of wild-type hIL-4.
3. The method of claim 1 , wherein the composition is aerosolized prior to administration.
4. The method of claim 1 , wherein the composition is nebulized as a liquid or aerosolized as a dry powder prior to administration.
5. The method of claim 1 , wherein the administering occurs twice per day.
6. The method of claim 1 , wherein the amount of IL-4 is about 0.3 mg.
7. The method of claim 1 , wherein the amount of IL-4 is about 3.0 mg.
8. The method of claim 1 , wherein the amount of IL-4 is about 30 mg.
9. The method of claim 1 , wherein the amount of IL-4 is about 60 mg.
10. The method of claim 1 , wherein the composition further contains a pharmaceutically acceptable carrier.
11. The method of claim 10 , wherein the carrier is selected from the group consisting of lactate, citrate and sucrose buffer.
12. The method of claim 1 , wherein the amount of IL-4 is about 0.1 to 1 mg/kg.
13. A method of treating asthma comprising administering to a subject in need thereof, a pharmaceutical composition containing a therapeutically effective amount of a mutant human IL-4 (hIL-4) protein comprising the amino acid sequence of wild-type hIL-4 with two modifications, wherein the first modification is replacement of the amino acids occurring in the wild-type hIL-4 protein at positions 121 and 124 with aspartic acid, and the second modification is at least one modification selected from the group consisting of:
a) N-terminal methionine;
b) deletion of up to five amino acids from the C-terminus;
c) deletion of potential glycosylation sites therein; and
d) coupling of the protein to a non-protein polymer,
wherein the mutant hIL-4 protein is an antagonist of wild-type hIL-4, and wherein the composition is administered for a period of at least about 28 days via subcutaneous injection, thereby ameliorating the symptoms associated with asthma.
14. The method of claim 13 , wherein the second modification consists of coupling of the protein to a non-protein polymer selected from the group consisting of polyethylene glycol, polypropylene glycol, and polyoxyalkylenes, wherein the mutant hIL-4 protein is an antagonist of wild-type hIL-4.
15. The method of claim 13 , wherein the amount of IL-4 is about 0.7 mg.
16. The method of claim 13 , wherein the amount of IL-4 is about 7.0 mg.
17. The method of claim 13 , wherein the amount of IL-4 is about 20 mg.
18. The method of claim 13 , wherein the amount of IL-4 is about 30 mg.
19. The method of claim 13 , wherein the amount of IL-4 is about 0.1 to 1 mg/kg.
20. The method of claim 13 , wherein the administering occurs twice per day.
21. The method of claim 13 , wherein the composition further contains a pharmaceutically acceptable carrier.
22. The method of claim 21 , wherein the carrier is selected from the group consisting of lactate, citrate and sucrose buffer.
23. The method of claim 1 , wherein the administering occurs once per day.
24. The method of claim 13 , wherein the administering occurs once per day.