Methods for treating dermatitis using mutant human IL-4 compositions

1 . A method for suppressing or inhibiting a dermatitis response in a subject comprising:

administering to a subject in need thereof a therapeutic effective amount of a mutant human IL-4 protein, or functional fragment thereof, wherein the protein comprises at least a first modification of replacing one or more of the amino acids occurring in the wild-type human IL-4 protein at positions 121, 124 and/or 125 with another natural amino acid.

2 . The method of claim 1 , wherein the therapeutic effective amount is from about 0.3 mg/kg to about 0.6 mg/kg daily.

3 . The method of claim 1 , further comprising a second modification selected from a group consisting of a modification at the N-terminus, C-terminus, deletion of potential glycosylation sites therein, and/or coupling of the protein to a non-protein polymer.

4 . The method of claim 3 , wherein the modification of the N-terminus is deletion or insertion of one or more amino acids.

5 . The method of claim 3 , wherein the modification of the C-terminus is deletion or insertion of one or more amino acids.

6 . The method of claim 3 , wherein the non-protein polymer is selected from the group consisting of polyethylene glycol (PEG), polypropylene glycol and polyoxyalkylenes.

7 . The method of claim 6 , wherein the human IL-4 mutein is coupled to the non-protein polymer at amino acid residue position 38, 102 and/or 104.

8 . The method of claim 6 , wherein the human IL-4 mutein is coupled to the non-protein polymer at amino acid residue position 38 of IL-4.

9 . The method of claim 6 , wherein the human IL-4 mutein is coupled to the non-protein polymer at amino acid residue position 102.

10 . The method of claim 6 , wherein the human IL-4 mutein is coupled to the non-protein polymer at amino acid residue position 104.

11 . The method of claims 6 - 10 wherein the non-protein polymer is polyethylene glycol PEG.

12 . The method of claim 1 , wherein the human IL-4 mutein modification comprises substitutions R121D or R121E.

13 . The method of claim 12 , wherein the human IL-4 mutein modification comprises substitutions R121D.

14 . The method of claim 1 , wherein the human IL-4 mutein modification comprises substitutions Y124D or Y124E.

15 . The method of claim 14 , wherein the human IL-4 mutein modification comprises substitutions Y124D.

16 . The method of claim 1 , wherein the human IL-4 mutein modification comprises substitutions S125D or S125E.

17 . The method of claim 16 , wherein the human IL-4 mutein modification comprises substitutions S125D.

18 . The method of claim 1 , wherein the human IL-4 mutein modification comprises substitutions R121D and Y124D.

19 . The method of claim 1 , wherein the human IL-4 mutein modification comprises substitutions R121D, Y124D and S125D.

20 . The method of claim 3 , wherein the modification of the N-terminus is insertion of an amino acid residue at position +2.

21 . The method of claim 1 , wherein the dermatitis is an allergic or atopic reaction.

22 . The method of claim 1 , wherein the dermatitis is a hypersensitivity reaction.

23 . The method of claim 22 , wherein the hypersensitivity reaction is contact dermatitis.

24 . The method of claim 22 , wherein the hypersensitivity reaction is atopic dermatitis.

25 . The method of claim 1 , wherein the subject is human.

26 . A method for treating a subject having atopic dermatitis, comprising,

administering to the subject having atopic dermatitis a therapeutically effective amount of a composition comprising a mutant human IL-4 protein, wherein the protein comprises a first modification of replacing one or more of the amino acids occurring in the wild-type human IL-4 protein at positions 121, 124 and/or 125 with another natural amino acid, and a second modification selected from a group consisting of a modification at the N-terminus, C-terminus, deletion of potential glycosylation sites therein, and/or coupling of the protein to a non-protein polymer, and wherein the therapeutic effective amount is from about 0.3 mg/kg to about 0.6 mg/kg daily.

27 . The method of claim 26 , wherein the subject is human.

28 . The method of claim 26 , wherein the non-protein polymer is selected from the group consisting of polyethylene glycol (PEG), polypropylene glycol and polyoxyalkylenes.

29 . The method of claim 26 , wherein the human IL-4 mutein is coupled to the non-protein polymer at amino acid residue position 38, 102 and/or 104.

30 . The method of claim 29 , wherein the human IL-4 mutein is coupled to the non-protein polymer at amino acid residue position 38.

31 . The method of claim 29 , wherein the human IL-4 mutein is coupled to the non-protein polymer at amino acid residue position 102.

32 . The method of claim 29 , wherein the human IL-4 mutein is coupled to the non-protein polymer at amino acid residue position 104.

33 . The method of claim 30 - 32 , wherein the non-protein polymer is polyethylene glycol PEG.

34 . The method of claim 26 , wherein the human IL-4 mutein modification comprises substitutions R121D or R121E.

35 . The method of claim 34 , wherein the human IL-4 mutein modification comprises substitutions R121D.

36 . The method of claim 26 , wherein the human IL-4 mutein modification comprises substitutions Y124D or Y124E.

37 . The method of claim 36 , wherein the human IL-4 mutein modification comprises substitutions Y124D.

38 . The method of claim 26 , wherein the human IL-4 mutein modification comprises substitutions S125D or S125E.

39 . The method of claim 38 , wherein the human IL-4 mutein modification comprises substitutions S125D.

40 . The method of claim 26 , wherein the human IL-4 mutein modification comprises substitutions R121D and Y124D.

41 . The method of claim 26 , wherein the human IL-4 mutein modification comprises substitutions R121D, Y124D and S125D.

42 . The method of claim 26 , wherein the modification of the N-terminus is deletion or insertion of one or more amino acids.

43 . The method of claim 42 , wherein the modification of the N-terminus is insertion of an amino acid residue at position +2.

44 . The method of claim 26 , wherein the modification of the C-terminus is deletion or insertion of one or more amino acids.