IP Library › Patent Application 10526164
Patent Application
App. No. 10/526,164

Protein tyrosine phosphatase inhibitors

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Patent No.
US None
App. No.
10/526,164
Abstract

The invention relates to phosphopeptides inhibiting protein tyrosine phosphatases, and their uses.

Claims (110)

1 .- 25 . (canceled)

26 . A phosphopeptide comprising an amino acid consensus sequence;

wherein said amino acid consensus sequence comprises amino acid positions −2, −1, 0, +1, +2, +3 and +4;

wherein said amino acid positions are defined by reference to amino acid position 0 which is a phosphorylated tyrosine (Y) residue;

wherein the amino acid at position −2 is selected from the group consisting of E, L and V;

wherein the amino acid at position −1 is a hydrophobic amino acid;

wherein the amino acid at position +1 is G;

wherein the amino acid at position +2 is selected from the group consisting of A, T and S;

wherein the amino acid at position +3 is selected from the group consisting of a hydrophobic amino acid and a phenolic amino acid; and

wherein the amino acid at position +4 is selected from the group consisting of A and G.

27 . The phosphopeptide of claim 26 , wherein the hydrophobic amino acid at position −1 is selected from the group consisting of I and L.

28 . The phosphopeptide of claim 26 , wherein the amino acid at position +3 is selected from the group consisting of F and Y.

29 . The phosphopeptide of claim 26 , wherein said phosphopeptide comprises an amino acid sequence selected from the group consisting of ELYGSYYA (SEQ ID NO: 1), EFYGAFA (SEQ ID NO: 2), EFYGAFG (SEQ ID NO: 3), and AEGELYGSLYA (SEQ ID NO: 4).

30 . A phosphopeptide comprising an amino acid consensus sequence;

wherein said amino acid consensus sequence comprises amino acid positions −2, −1, 0, +1, +2, +3 and +4;

wherein said amino acid positions are defined by reference to amino acid position 0 which is a phosphorylated tyrosine (Y) residue;

wherein the amino acid at position −2 is selected from the group consisting of E and P;

wherein the amino acid at position −1 is a hydrophobic amino acid;

wherein the amino acid at position +1 is selected from the group consisting of G and A;

wherein the amino acid at position +2 is T;

wherein the amino acid at position +3 is a hydrophobic amino acid; and

wherein the amino acid at position +4 is selected from the group consisting of G and A.

31 . The phosphopeptide of claim 30 , wherein the hydrophobic amino acid at position −1 is F.

32 . The phosphopeptide of claim 30 , wherein the hydrophogic amino acid at position +3 is selected from the group consisting of Y, F, I and L.

33 . The phosphopeptide of claim 30 , wherein said phosphopeptide comprises an amino acid sequence selected from the group consisting of EFYATYG (SEQ ID NO: 5), EFYGTYG (SEQ ID NO: 6), EFYATYA (SEQ ID NO: 7) and EFYGTYA (SEQ ID NO: 8).

34 . A phosphopeptide comprising an amino acid consensus sequence;

wherein said amino acid consensus sequence comprises amino acid positions −3, −2, −1, 0, +1, +2, +3 and +4;

wherein said amino acid positions are defined by reference to amino acid position 0 which is a phosphorylated tyrosine (Y) residue;

wherein the amino acid at position −3 is an acidic amino acid;

wherein the amino acid at position −2 is selected from the group consisting of L and E;

wherein the amino acid at position −1 is a hydrophobic amino acid;

wherein the amino acid at position +1 is selected from the group consisting of G and A;

wherein the amino acid at position +2 is S;

wherein the amino acid at position +3 is a selected from the group consisting of Y, L and acidic amino acids; and

wherein the amino acid at position +4 is a phenolic amino acid.

35 . The phosphopeptide of claim 34 , wherein the acidic amino acid at position −3 is selected from the group consisting of E and D.

36 . The phosphopeptide of claim 34 , wherein the hydrophobic amino acid at position −1 is L.

37 . The phosphopeptide of claim 34 , wherein the phenolic amino acid at position −4 is selected from the group consisting of Y and F.

38 . The phosphopeptide of claim 34 , wherein said phosphopeptide comprises the amino acid sequence ELLYGSYY (SEQ ID NO: 9).

39 . A phosphopeptide comprising an amino acid consensus sequence;

wherein said amino acid consensus sequence comprises amino acid positions −3, −2, −1, 0, +1, +2, +3 and +4;

wherein said amino acid positions are defined by reference to amino acid position 0 which is a phosphorylated tyrosine (Y) residue;

wherein the amino acid at position −2 is selected from the group consisting of E and P;

wherein the amino acid at position −1 is a hydrophobic amino acid;

wherein the amino acid at position +1 is A;

wherein the amino acid at position +2 is selected from the group consisting of E, Q and H;

wherein the amino acid at position +3 is a hydrophobic amino acid; and

wherein the amino acid at position +4 is G.

40 . The phosphopeptide of claim 39 , wherein the hydrophobic amino acid at position −1 is selected from the group consisting of F, Y and L.

41 . The phosphopeptide of claim 39 , wherein the hydrophobic amino acid at position +3 is selected from the group consisting of V and I.

42 . The phosphopeptide of claim 39 , wherein said phosphopeptide comprises the amino acid sequence EFYAEVG (SEQ ID NO: 10).

43 . A phosphopeptide comprising an amino acid consensus sequence;

wherein said amino acid consensus sequence comprises amino acid positions −3, −2, −1, 0, +1, +2, +3, +4 and +5;

wherein said amino acid positions are defined by reference to amino acid position 0 which is a phosphorylated tyrosine (Y) residue;

wherein the amino acid at position −2 is selected from the group consisting of E and F;

wherein the amino acid at position −1 is a hydrophobic amino acid;

wherein the amino acid at position +1 is A;

wherein the amino acid at position +2 is E;

wherein the amino acid at position +3 is a selected from the group consisting of V and I;

wherein the amino acid at position +4 is G; and

wherein the amino acid at position +5 is R.

44 . The phosphopeptide of claim 43 , wherein the hydrophobic amino acid at position −1 is a phenolic amino acid.

45 . The phosphopeptide of claim 43 , wherein the hydrophobic amino acid at position −1 is F.

46 . The phosphopeptide of claim 43 , wherein said phosphopeptide comprises the amino acid sequence EFYAEVGR (SEQ ID NO: 11).

47 . (canceled)

48 . A peptidomimetic or non-peptide mimetic designed on the basis of the sequence and/or the structure selected from the group consisting of:

(a) a phosphopeptide comprising an amino acid consensus sequence; wherein said amino acid consensus sequence comprises amino acid positions −2, −1, 0, +1, +2, +3 and +4; wherein said amino acid positions are defined by reference to amino acid position 0 which is a phosphorylated tyrosine (Y) residue; wherein the amino acid at position −2 is selected from the group consisting of E, L and V; wherein the amino acid at position −1 is a hydrophobic amino acid; wherein the amino acid at position +1 is G; wherein the amino acid at position +2 is selected from the group consisting of A, T and S; wherein the amino acid at position +3 is selected from the group consisting of a hydrophobic amino acid and a phenolic amino acid; and wherein the amino acid at position +4 is selected from the group consisting of A and G;

(b) a phosphopeptide comprising an amino acid consensus sequence; wherein said amino acid consensus sequence comprises amino acid positions −2, −1, 0, +1, +2, +3 and +4; wherein said amino acid positions are defined by reference to amino acid position 0 which is a phosphorylated tyrosine (Y) residue; wherein the amino acid at position −2 is selected from the group consisting of E and P; wherein the amino acid at position −1 is a hydrophobic amino acid; wherein the amino acid at position +1 is selected from the group consisting of G and A; wherein the amino acid at position +2 is T; wherein the amino acid at position +3 is a hydrophobic amino acid; and wherein the amino acid at position +4 is selected from the group consisting of G and A;

(c) a phosphopeptide comprising an amino acid consensus sequence; wherein said amino acid consensus sequence comprises amino acid positions −3, −2, −1, 0, +1, +2, +3 and +4; wherein said amino acid positions are defined by reference to amino acid position 0 which is a phosphorylated tyrosine (Y) residue; wherein the amino acid at position −3 is an acidic amino acid; wherein the amino acid at position −2 is selected from the group consisting of L and E; wherein the amino acid at position −1 is a hydrophobic amino acid; wherein the amino acid at position +1 is selected from the group consisting of G and A; wherein the amino acid at position +2 is S; wherein the amino acid at position +3 is a selected from the group consisting of Y, L and acidic amino acids; and wherein the amino acid at position +4 is a phenolic amino acid;

(d) a phosphopeptide comprising an amino acid consensus sequence; wherein said amino acid consensus sequence comprises amino acid positions −3, −2, −1, 0, +1, +2, +3 and +4; wherein said amino acid positions are defined by reference to amino acid position 0 which is a phosphorylated tyrosine (Y) residue; wherein the amino acid at position −2 is selected from the group consisting of E and P; wherein the amino acid at position −1 is a hydrophobic amino acid; wherein the amino acid at position +1 is A; wherein the amino acid at position +2 is selected from the group consisting of E, Q and H: wherein the amino acid at position +3 is a hydrophobic amino acid; and wherein the amino acid at position +4 is G; and

(e) a phosphopeptide comprising an amino acid consensus sequence; wherein said amino acid consensus sequence comprises amino acid positions −3, −2, −1, 0, +1, +2, +3, +4 and +5; wherein said amino acid positions are defined by reference to amino acid position 0 which is a phosphorylated tyrosine (Y) residue; wherein the amino acid at position −2 is selected from the group consisting of E and F; wherein the amino acid at position −1 is a hydrophobic amino acid; wherein the amino acid at position +1 is A; wherein the amino acid at position +2 is E; wherein the amino acid at position +3 is a selected from the group consisting of V and I; wherein the amino acid at position +4 is G: and wherein the amino acid at position +5 is R;

wherein said peptidomimetic or non-peptide mimetic does not comprise the amino acid sequence RNNEFYA (SEQ ID NO:75), and wherein Y is a phosphorylated tyrosine residue.

49 . A functional derivative of a phosphopeptide selected from the group consisting of:

(a) a phosphopeptide comprising an amino acid consensus sequence; wherein said amino acid consensus sequence comprises amino acid positions −2, −1, 0, +1, +2, +3 and +4; wherein said amino acid positions are defined by reference to amino acid position 0 which is a phosphorylated tyrosine (Y) residue; wherein the amino acid at position −2 is selected from the group consisting of E, L and V; wherein the amino acid at position −1 is a hydrophobic amino acid; wherein the amino acid at position +1 is G; wherein the amino acid at position +2 is selected from the group consisting of A, T and S; wherein the amino acid at position +3 is selected from the group consisting of a hydrophobic amino acid and a phenolic amino acid; and wherein the amino acid at position +4 is selected from the group consisting of A and G;

(b) a phosphopeptide comprising an amino acid consensus sequence; wherein said amino acid consensus sequence comprises amino acid positions −2, −1, 0, +1, +2, +3 and +4; wherein said amino acid positions are defined by reference to amino acid position 0 which is a phosphorylated tyrosine (Y) residue; wherein the amino acid at position −2 is selected from the group consisting of E and P; wherein the amino acid at position −1 is a hydrophobic amino acid; wherein the amino acid at position +1 is selected from the group consisting of G and A; wherein the amino acid at position +2 is T; wherein the amino acid at position +3 is a hydrophobic amino acid; and wherein the amino acid at position +4 is selected from the group consisting of G and A;

(c) a phosphopeptide comprising an amino acid consensus sequence; wherein said amino acid consensus sequence comprises amino acid positions −3, −2, −1, 0, +1, +2, +3 and +4; wherein said amino acid positions are defined by reference to amino acid position 0 which is a phosphorylated tyrosine (Y) residue; wherein the amino acid at position −3 is an acidic amino acid; wherein the amino acid at position −2 is selected from the group consisting of L and E; wherein the amino acid at position −1 is a hydrophobic amino acid; wherein the amino acid at position +1 is selected from the group consisting of G and A; wherein the amino acid at position +2 is S; wherein the amino acid at position +3 is a selected from the group consisting of Y, L and acidic amino acids; and wherein the amino acid at position +4 is a phenolic amino acid;

(d) a phosphopeptide comprising an amino acid consensus sequence; wherein said amino acid consensus sequence comprises amino acid positions −3, −2, −1, 0, +1, +2, +3 and +4; wherein said amino acid positions are defined by reference to amino acid position 0 which is a phosphorylated tyrosine (Y) residue; wherein the amino acid at position −2 is selected from the group consisting of E and P; wherein the amino acid at position −1 is a hydrophobic amino acid; wherein the amino acid at position +1 is A; wherein the amino acid at position +2 is selected from the group consisting of E, O and H; wherein the amino acid at position +3 is a hydrophobic amino acid; and wherein the amino acid at position +4 is G; and

(e) a phosphopeptide comprising an amino acid consensus sequence; wherein said amino acid consensus sequence comprises amino acid positions − 3 , − 2 , − 1 , 0 , + 1 , + 2 , + 3 , + 4 and +5; wherein said amino acid positions are defined by reference to amino acid position 0 which is a phosphorylated tyrosine (Y) residue; wherein the amino acid at position −2 is selected from the group consisting of E and F; wherein the amino acid at position −1 is a hydrophobic amino acid; wherein the amino acid at position +1 is A; wherein the amino acid at position +2 is E; wherein the amino acid at position +3 is a selected from the group consisting of V and I; wherein the amino acid at position +4 is G; and wherein the amino acid at position +5 is R;

comprising at least one moiety attached to said phosphopeptide, wherein the functional derivative does not comprise the amino acid sequence RNNEFYA (SEQ ID NO:75), and wherein Y is a phosphorylated tyrosine residue.

50 . (canceled)

51 . (canceled)

52 . A method of treating or preventing a PTP mediated disease comprising administering to a patient in need thereof a pharmaceutically effective amount of a phosphopeptide selected from the group consisting of:

(a) a phosphopeptide comprising an amino acid consensus sequence; wherein said amino acid consensus sequence comprises amino acid positions −2, −1, 0, +1, +2, +3 and +4; wherein said amino acid positions are defined by reference to amino acid position 0 which is a phoshorylated tyrosine (Y) residue; wherein the amino acid at position −2 is selected from the group consisting of E, L and V; wherein the amino acid at position −1 is a hydrophobic amino acid; wherein the amino acid at position +1 is G; wherein the amino acid at position +2 is selected from the group consisting of A, T and S; wherein the amino acid at position +3 is selected from the group consisting of a hydrophobic amino acid and a phenolic amino acid; and wherein the amino acid at position +4 is selected from the group consisting of A and G;

(b) a phosphopeptide comprising an amino acid consensus sequence; wherein said amino acid consensus sequence comprises amino acid positions −2, −1, 0, +1, +2, +3 and +4; wherein said amino acid positions are defined by reference to amino acid position 0 which is a phosphorylated tyrosine (Y) residue; wherein the amino acid at position −2 is selected from the group consisting of E and P; wherein the amino acid at position −1 is a hydrophobic amino acid; wherein the amino acid at position +1 is selected from the group consisting of G and A; wherein the amino acid at position +2 is T; wherein the amino acid at position +3 is a hydrophobic amino acid; and wherein the amino acid at position +4 is selected from the group consisting of G and A;

(c) a phosphopeptide comprising an amino acid consensus sequence; wherein said amino acid consensus sequence comprises amino acid positions −3, −2, −1, 0, +1, +2, +3 and +4; wherein said amino acid positions are defined by reference to amino acid position 0 which is a phosphorylated tyrosine (Y) residue; wherein the amino acid at position −3 is an acidic amino acid; wherein the amino acid at position −2 is selected from the group consisting of L and E; wherein the amino acid at position −1 is a hydrophobic amino acid; wherein the amino acid at position +1 is selected from the group consisting of G and A; wherein the amino acid at position +2 is S; wherein the amino acid at position +3 is a selected from the group consisting of Y, L and acidic amino acids; and wherein the amino acid at position +4 is a phenolic amino acid;

(d) a phosphopeptide comprising an amino acid consensus sequence; wherein said amino acid consensus sequence comprises amino acid positions −3, −2, −1, 0, +1, +2, +3 and +4; wherein said amino acid positions are defined by reference to amino acid position 0 which is a phosphorylated tyrosine (Y) residue; wherein the amino acid at position −2 is selected from the group consisting of E and P; wherein the amino acid at position −1 is a hydrophobic amino acid; wherein the amino acid at position +1 is A; wherein the amino acid at position +2 is selected from the group consisting of E, Q and H; wherein the amino acid at position +3 is a hydrophobic amino acid; and wherein the amino acid at position +4 is G; and

(e) a phosphopeptide comprising an amino acid consensus sequence; wherein said amino acid consensus sequence comprises amino acid positions −3, −2, −1, 0, +1, +2, +3, +4 and +5; wherein said amino acid positions are defined by reference to amino acid position 0 which is a phosphorylated tyrosine (Y) residue; wherein the amino acid at position −2 is selected from the group consisting of E and F; wherein the amino acid at position −1 is a hydrophobic amino acid; wherein the amino acid at position +1 is A; wherein the amino acid at position +2 is E; wherein the amino acid at position +3 is a selected from the group consisting of V and I; wherein the amino acid at position +4 is G; and wherein the amino acid at position +5 is R;

or a peptidomimetic, a non-peptide mimetic or a functional derivative of said phosphopeptide.

53 . The method of claim 52 , wherein said disease is cancer and wherein said phosphopeptide comprises an amino acid consensus sequence comprising amino acid positions −2, −1, 0, +1, +2, +3 and +4; wherein said amino acid positions are defined by reference to amino acid position 0 which is a phosphorylated tyrosine (Y) residue; wherein the amino acid at position −2 is selected from the group consisting of E, L and V; wherein the amino acid at position −1 is a hydrophobic amino acid; wherein the amino acid at position +1 is G; wherein the amino acid at position +2 is selected from the group consisting of A, T and S; wherein the amino acid at position +3 is selected from the group consisting of a hydrophobic amino acid and a phenolic amino acid; and wherein the amino acid at position +4 is selected from the group consisting of A and G; or a peptidomimetic, a non-peptide mimetic or a functional derivative of said phosphopeptide.

54 . (canceled)

55 . The method of claim 52 , wherein said disease is diabetes and wherein said phosphopeptide comprises an amino acid consensus sequence comprising amino acid positions −2, −1, 0, +1, +2, +3 and +4; wherein said amino acid positions are defined by reference to amino acid position 0 which is a phosphorylated tyrosine (Y) residue; wherein the amino acid at position −2 is selected from the group consisting of E and P; wherein the amino acid at position −1 is a hydrophobic amino acid; wherein the amino acid at position +1 is selected from the group consisting of G and A; wherein the amino acid at position +2 is T; wherein the amino acid at position +3 is a hydrophobic amino acid; and wherein the amino acid at position +4 is selected from the group consisting of G and A; or a peptidomimetic, a non-peptide mimetic or a functional derivative of said phosphopeptide.

56 . The method of claim 52 , wherein said disease is obesity and wherein said phosphopeptide comprises an amino acid consensus sequence comprising amino acid positions −2, −1, 0, +1, +2, +3 and +4; wherein said amino acid positions are defined by reference to amino acid position 0 which is a phosphorylated tyrosine (Y) residue; wherein the amino acid at position −2 is selected from the group consisting of E and P; wherein the amino acid at position −1 is a hydrophobic amino acid; wherein the amino acid at position +1 is selected from the group consisting of G and A; wherein the amino acid at position +2 is T; wherein the amino acid at position +3 is a hydrophobic amino acid; and wherein the amino acid at position +4 is selected from the group consisting of G and A; or a peptidomimetic, a non-peptide mimetic or a functional derivative of said phosphopeptide.

57 . A method of suppressing appetite, comprising administering to a subject in need thereof a therapeutically effective amount of a phosphopeptide comprising an amino acid consensus sequence; wherein said amino acid consensus sequence comprises amino acid positions −2, −1, 0, +1, +2, +3 and +4; wherein said amino acid positions are defined by reference to amino acid position 0 which is a phosphorylated tyrosine (Y) residue; wherein the amino acid at position −2 is selected from the group consisting of E and P; wherein the amino acid at position −1 is a hydrophobic amino acid; wherein the amino acid at position +1 is selected from the group consisting of G and A; wherein the amino acid at position +2 is T; wherein the amino acid at position +3 is a hydrophobic amino acid; and wherein the amino acid at position +4 is selected from the group consisting of G and A; or a peptidomimetic, non-peptide mimetic or functional derivative of such phosphopeptide.

58 . The method of claim 52 , wherein said disease is inflammation and wherein said phosphopeptide comprises an amino acid consensus sequence comprising amino acid positions −3, −2, −1, 0, +1, +2, +3 and +4; wherein said amino acid positions are defined by reference to amino acid position 0 which is a phosphorylated tyrosine (Y) residue; wherein the amino acid at position −3 is an acidic amino acid; wherein the amino acid at position −2 is selected from the group consisting of L and E; wherein the amino acid at position −1 is a hydrophobic amino acid; wherein the amino acid at position +1 is selected from the group consisting of G and A; wherein the amino acid at position +2 is S; wherein the amino acid at position +3 is a selected from the group consisting of Y, L and acidic amino acids; and wherein the amino acid at position +4 is a phenolic amino acid; or a peptidomimetic, a non-peptide mimetic or a functional derivative of said phosphopeptide.

59 . The method of claim 52 , wherein said disease is multiple sclerosis and wherein said phosphopeptide comprises an amino acid consensus sequence comprising amino acid positions −3, −2, −1, 0, +1, +2, +3 and +4; wherein said amino acid positions are defined by reference to amino acid position 0 which is a phosphorylated tyrosine (Y) residue; wherein the amino acid at position −3 is an acidic amino acid; wherein the amino acid at position −2 is selected from the group consisting of L and E; wherein the amino acid at position −1 is a hydrophobic amino acid; wherein the amino acid at position +1 is selected from the group consisting of G and A; wherein the amino acid at position +2 is S; wherein the amino acid at position +3 is a selected from the group consisting of Y, L and acidic amino acids; and wherein the amino acid at position +4 is a phenolic amino acid; or a peptidomimetic, a non-peptide mimetic or a functional derivative of said phosphopeptide.

60 . The method of claim 52 , wherein said disease is an angiogenesis-dependent disease and wherein said phosphopeptide comprises an amino acid consensus sequence comprising amino acid positions −3, −2, −1, 0, +1, +2, +3 and +4; wherein said amino acid positions are defined by reference to amino acid position 0 which is a phosphorylated tyrosine (Y) residue; wherein the amino acid at position −3 is an acidic amino acid; wherein the amino acid at position −2 is selected from the group consisting of L and E; wherein the amino acid at position −1 is a hydrophobic amino acid; wherein the amino acid at position +1 is selected from the group consisting of G and A; wherein the amino acid at position +2 is S; wherein the amino acid at position +3 is a selected from the group consisting of Y, L and acidic amino acids; and wherein the amino acid at position +4 is a phenolic amino acid; or a peptidomimetic, a non-peptide mimetic or a functional derivative of said phosphopeptide.

61 . (canceled)

62 . The method of claim 52 , wherein said disease is an infectious disease and wherein said phosphopeptide is selected from the group consisting of:

(a) a phosphopeptide comprising an amino acid consensus sequence; wherein said amino acid consensus sequence comprises amino acid positions −3, −2, −1, 0, +1, +2, +3 and +4; wherein said amino acid positions are defined by reference to amino acid position 0 which is a phosphorylated tyrosine (Y) residue; wherein the amino acid at position −2 is selected from the group consisting of E and P; wherein the amino acid at position −1 is a hydrophobic amino acid; wherein the amino acid at position +1 is A; wherein the amino acid at position +2 is selected from the group consisting of E, Q and H; wherein the amino acid at position +3 is a hydrophobic amino acid; and wherein the amino acid at position +4 is G; and

(b) a phosphopeptide comprising an amino acid consensus sequence; wherein said amino acid consensus sequence comprises amino acid positions −3, −2, −1, 0, +1, +2, +3, +4 and +5; wherein said amino acid positions are defined by reference to amino acid position 0 which is a phosphorylated tyrosine (Y) residue; wherein the amino acid at position −2 is selected from the group consisting of E and F; wherein the amino acid at position −1 is a hydrophobic amino acid; wherein the amino acid at position +1 is A; wherein the amino acid at position +2 is E; wherein the amino acid at position +3 is a selected from the group consisting of V and I; wherein the amino acid at position +4 is G; and wherein the amino acid at position +5 is R;

or a peptidomimetic, a non-peptide mimetic or a functional derivative of said phosphopeptide.

63 . (canceled)

64 . A pharmaceutical composition comprising a phosphopeptide selected from the group consisting of:

(a) a phosphopeptide comprising an amino acid consensus sequence; wherein said amino acid consensus sequence comprises amino acid positions −2, −1, 0, +1, +2, +3 and +4; wherein said amino acid positions are defined by reference to amino acid position 0 which is a phosphorylated tyrosine (Y) residue; wherein the amino acid at position −2 is selected from the group consisting of E, L and V; wherein the amino acid at position −1 is a hydrophobic amino acid; wherein the amino acid at position +1 is G; wherein the amino acid at position +2 is selected from the group consisting of A, T and S; wherein the amino acid at position +3 is selected from the group consisting of a hydrophobic amino acid and a phenolic amino acid; and wherein the amino acid at position +4 is selected from the group consisting of A and G;

(b) a phosphopeptide comprising an amino acid consensus sequence; wherein said amino acid consensus sequence comprises amino acid positions −2, −1, 0, +1, +2, +3 and +4; wherein said amino acid positions are defined by reference to amino acid position 0 which is a phosphorylated tyrosine (Y) residue; wherein the amino acid at position −2 is selected from the group consisting of E and P; wherein the amino acid at position −1 is a hydrophobic amino acid; wherein the amino acid at position +1 is selected from the group consisting of G and A; wherein the amino acid at position +2 is T; wherein the amino acid at position +3 is a hydrophobic amino acid; and wherein the amino acid at position +4 is selected from the group consisting of G and A;

(c) a phosphopeptide comprising an amino acid consensus sequence; wherein said amino acid consensus sequence comprises amino acid positions −3, −2, −1, 0, +1, +2, +3 and +4; wherein said amino acid positions are defined by reference to amino acid position 0 which is a phosphorylated tyrosine (Y) residue: wherein the amino acid at position −3 is an acidic amino acid; wherein the amino acid at position −2 is selected from the group consisting of L and E; wherein the amino acid at position −1 is a hydrophobic amino acid; wherein the amino acid at position +1 is selected from the group consisting of G and A; wherein the amino acid at position +2 is S; wherein the amino acid at position +3 is a selected from the group consisting of Y, L and acidic amino acids; and wherein the amino acid at position +4 is a phenolic amino acid;

(d) a phosphopeptide comprising an amino acid consensus sequence; wherein said amino acid consensus sequence comprises amino acid positions −3, −2, −1, 0, +1, +2, +3 and +4; wherein said amino acid positions are defined by reference to amino acid position 0 which is a phosphorylated tyrosine (Y) residue; wherein the amino acid at position −2 is selected from the group consisting of E and P; wherein the amino acid at position −1 is a hydrophobic amino acid; wherein the amino acid at position +1 is A; wherein the amino acid at position +2 is selected from the group consisting of E, Q and H; wherein the amino acid at position +3 is a hydrophobic amino acid; and wherein the amino acid at position +4 is G; and

(e) a phosphopeptide comprising an amino acid consensus sequence; wherein said amino acid consensus sequence comprises amino acid positions −3, −2, −1, 0, +1, +2, +3, +4 and +5; wherein said amino acid positions are defined by reference to amino acid position 0 which is a phosphorylated tyrosine (Y) residue; wherein the amino acid at position −2 is selected from the group consisting of E and F; wherein the amino acid at position −1 is a hydrophobic amino acid; wherein the amino acid at position +1 is A; wherein the amino acid at position +2 is E; wherein the amino acid at position +3 is a selected from the group consisting of V and I; wherein the amino acid at position +4 is G; and wherein the amino acid at position +5 is R;

or a peptidomimetic, non-peptide mimetic or functional derivative of said phosphopeptide.

65 . (canceled)

Assignments (2)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Sep 11, 2007
From: APPLIED RESEARCH SYSTEMS ARS HOLDING N.V.
To: LABORATOIRES SERONO SA
Reel/Frame 019966/0026 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Aug 24, 2005
From: VAN HUIJSDUIJNEN, ROB HOOFT; WALCHLI, SEBASTIEN; ARIGONI, FABRIZIO
To: APPLIED RESEARCH SYSTEMS ARS HOLDINGS N.V.
Reel/Frame 016663/0930 →