Peptidyl calcineurin inhibitors

• US 10,456,443 B2
• Filed: 08/27/2015
• Issued: 10/29/2019
• Est. Priority Date: 08/27/2014
• Status: Active Grant

• Current Assignee: Ohio State Innovation Foundation (Ohio State University)
• Original Assignee: Ohio State Innovation Foundation (Ohio State University)
• Inventors: Pei, Dehua, Qian, Ziqing, Christman, John W, Karpurapu, Manjula
• Primary Examiner(s): Coffa, Sergio
• Application Number:
  US15/506,877
• Publication Number:
  US 20170281723A1
• Time in Patent Office: 1,524 Days
• Field of Search: None
• CPC Class Codes: A61K 38/13 Cyclosporins
• CPC Class Codes: A61K 38/1709 from mammals
• CPC Class Codes: A61K 47/645 Polycationic or polyanionic oligopeptides, polypeptides or polyamino acids, e.g. polylysine, polyarginine, polyglutamic acid or peptide TAT
• CPC Class Codes: A61P 11/00 Drugs for disorders of the respiratory system

Abstract

Improved calcineurin inhibitors and methods of using these improved calcineurin inhibitors to inhibit calcineurin-NFAT signaling in cells and in subjects are disclosed.

Claims

1. A composition, comprising a peptide 7 to 100 amino acids in length comprising the amino acid sequence SEQ ID NO:

1, and wherein the composition inhibits calcineurin (CN) —

nuclear factor of activated T cell (NFAT) signaling.

2. The composition of claim 1, wherein the peptide comprises the amino acid sequence SEQ ID NO:

2.

3. The composition of claim 1, wherein the peptide comprises the amino acid sequence SEQ ID NO:

3.

4. The composition of claim 1, wherein the peptide comprises the amino acid sequence SEQ ID NO:

4.

5. The composition of claim 1, wherein the peptide comprises an amino acid sequence selected from the group consisting of SEQ NOs:

33-46.

6. The composition of claim 1, wherein the composition binds to CN with at least about 10-fold higher affinity than SEQ ID NO:

47.

7. The composition of claim 1, having a K_D (nM) for CN of about 43±

12 or less.

8. The composition of claim 1, having a K_D (nM) for CN of about 2.6±

0.8.

9. A method for inhibiting CN-NFAT signaling in a cell, comprising contacting the cell with the composition of claim 1.