Novel Polypeptides That Bound to IL-23 Receptor and Inhibit Binding of IL-23 and Cell Signaling Thereof

• US 20130029907A1
• Filed: 06/14/2012
• Published: 01/31/2013
• Est. Priority Date: 06/14/2011
• Status: Active Grant

• Current Assignee: Medical Diagnostic Laboratories LLC
• Original Assignee: Medical Diagnostic Laboratories LLC
• Inventors: Gallagher, Grant, Yu, Raymond, Brazaitis, Jonathan
• Granted Patent: US 8,946,150 B2
• Time in Patent Office: Days
• US Class Current: 514/7.6
• CPC Class Codes: A61K 38/20 Interleukins [IL]
• CPC Class Codes: A61P 1/00 Drugs for disorders of the alimentary tract or the digestive system
• CPC Class Codes: A61P 17/06 Antipsoriatics
• CPC Class Codes: C07K 14/54 Interleukins [IL]

Abstract

The present invention relates to novel polypeptides that bind to IL-23 receptor and inhibit the binding of IL-23 to its corresponding receptor and cell signaling thereof. The novel polypeptides of the present invention has a core structure of WX₁X₂X₃W, where W is tryptophan, and X₁, X₂ and X₃ are amino acids, with the proviso that when one of X₁, X₂ or X₃ is W, the remaining two of X₁, X₂ or X₃ cannot be W. The present invention relates a composition containing the novel polypeptides, and use of same in treating IL-23 associated human diseases including, for example, inflammatory bowel diseases, psoriasis and Crohn'"'"'s disease.

Claims

1. An isolated polypeptide of 9-18 amino acids in length, said isolated polypeptide comprises a core structure having an amino acid sequence of WX₁X₂X₃W,

wherein X₁, X₂ and X₃ are amino acids, with the proviso that when one of X₁, X₂ or X₃ is W, the remaining X₁, X₂ or X₃ cannot be W, and

wherein said isolated polypeptide is capable of inhibiting the binding of IL-23 to IL-23 receptor and the IL-23-mediated signaling.

2. The isolated polypeptide of claim 1, wherein X₃ is Y.

3. The isolated polypeptide of claim 2, wherein WX₁X₂YW is selected from the group consisting of SEQ NO:

2, SEQ ID NO;

4, SEQ ID NO;

7, SEQ ID NO;

10, SEQ ID NO;

13, SEQ ID NO;

14, SEQ ID NO;

15, SEQ ID NO;

17, SEQ ID NO;

21, SEQ ID NO;

22, SEQ ID NO;

24, SEQ ID NO;

26, SEQ ID NO;

27 and SEQ ID NO;

28, SEQ NO;

54, SEQ ID NO;

55, SEQ ID NO;

72, SEQ ID NO;

73, SEQ ID NO;

76, SEQ ID NO;

79, SEQ ID NO;

80, SEQ ID NO;

81, SEQ ID NO;

82, SEQ ID NO;

91, and SEQ ID NO;

126.

4. The isolated polypeptide of claim 2, wherein said WX₁X₂YW is selected from the group consisting of WVQYW (SEQ ID NO:

94), WYNYW (SEQ ID NO;

     95), WMTYW (SEQ ID NO;

     96), WATYW (SEQ ID NO;

     97), WEMYW (SEQ ID NO;

     98), WKDYW (SEQ ID NO;

     99), WEHYW (SEQ ID NO;

     100), WQNYW (SEQ ID NO;

     101), WMQYW (SEQ ID NO;

     103), WHAYW (SEQ ID NO;

     104), WQTYW (SEQ ID NO;

     105), WYAYW (SEQ ID NO;

     107), WEDYW (SEQ ID NO;

     108), WLQYW (SEQ ID NO;

     111), and WLNYW (SEQ ID NO;

     112).

5. The isolated polypeptide of claim 1, wherein X₃ is W.

6. The isolated polypeptide of claim 5, wherein WX₁X₂WW is selected from the group consisting of SEQ ID NO:

1, SEQ ID NO;

20, SEQ NO;

57, SEQ ID NO;

58, SEQ ID NO;

83, SEQ ID NO;

84, SEQ ID NO;

85, SEQ ID NO;

86, SEQ ID NO;

87, SEQ ID NO;

88, SEQ ID NO;

89, and SEQ ID NO;

90.

7. The isolated polypeptide of claim 5, wherein WX₁X₂WW is selected from the group consisting of WEDWW (SEQ ID NO:

116), WIDWW (SEQ ID NO;

     117), WDDWW (SEQ ID NO;

     118), WEEWW (SEQ ID NO;

     119), WQDWW (SEQ ID NO;

     120), WENWW (SEQ ID NO;

     121), WQNWW (SEQ ID NO;

     122), WEKWW (SEQ ID NO;

     123), WKDWW (SEQ ID NO;

     124), and WKKWW (SEQ ID NO;

     125).

8. The isolated polypeptide of claim 1, wherein X₃ is F.

9. The isolated polypeptide of claim 8, wherein WX₁X₂FW is selected from the group consisting of SEQ NO:

18, SEQ ID NO;

29, SEQ ID NO;

71, SEQ ID NO;

74, SEQ ID NO;

92, SEQ ID NO;

106, SEQ ID NO;

109, SEQ ID NO;

114, and SEQ ID NO;

115.

10. The isolated polypeptide of claim 1, wherein X₁ is W.

11. The isolated polypeptide of claim 1, wherein said isolated polypeptide is selected from the group consisting of SEQ ID NO:

102, SEQ ID NO;

110, and SEQ ID NO;

113.

12. The isolated polypeptide of claim 1, wherein said isolated polypeptide is a cyclic peptide through a disulfide bridge between two cysteine residues.

13. The isolated polypeptide of claim 12, wherein said cyclic polypeptide is selected from the group consisting of SEQ ID NO:

130 and SEQ ID NO;

131.

15. A pharmaceutical composition comprising said isolated polypeptide of claim 1, 3, 6, 9, 11, 13 or 14 and a pharmaceutically acceptable carrier.

16. The isolated polypeptide of claim 1, wherein said isolated polypeptide is 12 amino acids in length.

18. A method of inhibiting the binding of IL-23 to IL-23 receptor on a cell and IL-23 mediated signaling thereof, comprising the steps of:

a) providing a cell in need of treatment; and

b) exposing said cell to said isolated polypeptide of claim 1, 3, 6, 9, 11, 13 or 14.

14. An isolated polypeptide consisting of an amino acid sequence selected from the group consisting of SEQ ID NO:

3, SEQ ID NO;

5, SEQ ID NO;

19, SEQ ID NO;

25, SEQ ID NO;

70, and SEQ ID NO;

93, wherein said isolated polypeptide is capable of inhibiting the binding of IL-23 to IL-23 receptor and the IL-23-mediated signaling.

17. An isolated polypeptide of 9-18 amino acids in length, said isolated polypeptide comprises a core structure having an amino acid sequence of WX₁X₂X₃W,

wherein W is tryptophan, X₁, X₂ and X₃ are amino acids, with the proviso that when one of X₁, X₂ or X₃ is W, the remaining X₁, X₂ or X₃ cannot be W, and

wherein said isolated polypeptide binds to soluble recombinant human IL-23R and inhibits binding between IL-23 and its corresponding receptor thereof.