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

• US 20160039878A1
• Filed: 10/26/2015
• Published: 02/11/2016
• 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 9,605,027 B2
• Time in Patent Office: Days
• US Class Current: 1/1
• CPC Class Codes: A61K 38/00 Medicinal preparations containing peptides peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00
• CPC Class Codes: A61K 38/12 Cyclic peptides , e.g. bacitracins; Polymyxins; Gramicidins S, C; Tyrocidins A, B or C A61K38/043 - A61K38/046 take precedence
• CPC Class Codes: C07K 14/435 from animals; from humans
• CPC Class Codes: C07K 7/06 having 5 to 11 amino acids
• CPC Class Codes: C07K 7/64 Cyclic peptides containing only normal peptide links
• CPC Class Codes: H04N 1/1013 with sub-scanning by translatory movement of at least a part of the main-scanning components H04N1/107 takes precedence
• CPC Class Codes: H04N 1/193 using electrically scanned linear arrays , e.g. linear CCD arrays
• CPC Class Codes: H04N 2201/0081 Image reader H04N2201/0091 - H04N2201/0094 take precedence
• CPC Class Codes: H04N 2201/0446 Constructional details not otherwise provided for, e.g. mounting of scanning components H04N2201/0448 takes precedence

Abstract

The present invention relates to novel linear and cyclic 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. Preferred core structures include WVDYW or WQDYW. The present invention relates a composition containing the novel polypeptides (linear or cyclic), and use of same in inhibiting cell functions including production of IL-22 and IL-17F from immune cells as well as in treating IL-23 associated human diseases including, for example, inflammatory bowel diseases, psoriasis and Crohn'"'"'s disease, ulcerative colitis and multiple sclerosis.

Claims

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

177, SEQ ID NO;

178 and SEQ ID NO;

179, wherein said isolated cyclic polypeptide inhibits binding of IL-23 to IL-23 receptor and inhibits IL-23-mediated cell signaling.

2. The isolated cyclic polypeptide of claim 1, wherein said isolated cyclic polypeptide consisting of SEQ ID NO:

177.

3. The isolated cyclic polypeptide of claim 1, wherein said isolated cyclic polypeptide consisting of SEQ ID NO:

178.

4. The isolated cyclic polypeptide of claim 1, wherein said isolated cyclic polypeptide consisting of SEQ ID NO:

179.

5. A method of inhibiting production of IL-17F in a Th17 cell in a human, comprising the steps of:

a) providing a human Th17 cell in need of inhibiting production of IL-17F; and

b) exposing said Th17 cell to said isolated cyclic polypeptide of claim 1.

6. The method of claim 5, wherein said IL-17F is IL-17F protein.

7. The method of claim 5, wherein said production of IL-17F is assayed by an ELISA.

8. A method of inhibiting production of IL-17F in a splenocyte in a human, comprising the steps of:

a) providing a human splenocyte in need of inhibiting production of IL-17F from said splenocyte; and

b) exposing said splenocyte to said isolated cyclic polypeptide of claim 1.

9. The method of claim 8, wherein said IL-17F is IL-17F mRNA.

10. The method of claim 8, wherein said production of IL-17F is assayed by RT-PCR.

11. A method of inhibiting production of IL-22 from a mononuclear cell in a human, comprising the steps of:

a) providing a human mononuclear cell in need of inhibiting production of IL-22 from said mononuclear cell; and

b) exposing said mononuclear cell to said isolated cyclic polypeptide of claim 1.

12. The method of claim 11, wherein said IL-22 is IL-22 protein.

13. The method of claim 11, wherein said production of IL-22 is assayed by an ELISA.