# US 8,999,937 B2 · Glucocorticoid induced leucine zipper mimetics as therapeutic agents in multiple sclerosis

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- Number: US 8,999,937 B2
- Document ID: US8999937B2
- Status: Granted
- Kind: B2
- Application number: 14/001,716
- Filed: 2012-02-28
- Published: 2013-12-19
- Granted: 2015-04-07
- Earliest claimed: 2011-02-28
- Assignees: Indiana University Research and Technology Corporation
- Applicants: Mythily Srinivasan
- Inventors: Mythily Srinivasan
- Web page: https://patentgrep.com/patent/US8999937B2

## CPC

- C07K 14/4713: {Autoimmune diseases, e.g. Insulin-dependent diabetes mellitus, multiple sclerosis, rheumathoid arthritis, systemic lupus erythematosus; Autoantigens}
- A61K 38/07: Tetrapeptides
- A61K 38/08: Peptides having 5 to 11 amino acids {(A61K38/043 - A61K38/046 take precedence)}
- A61K 38/10: Peptides having 12 to 20 amino acids {(A61K38/043 - A61K38/046 take precedence)}
- A61K 38/16: Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof {(enzyme inhibitors A61K38/005)}
- C07K: PEPTIDES (peptides in foodstuffs A23; obtaining protein compositions for foodstuffs, working-up proteins for foodstuffs A23J; preparations for medicinal purposes A61K; peptides containing beta-lactam rings C07D; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, C07D; ergot alkaloids of the cyclic peptide type C07D519/02; macromolecular compounds having statistically distributed amino acid units in their molecules, i.e. when the preparation does not provide for a specific; but for a random sequence of the amino acid units, homopolyamides and block copolyamides derived from amino acids C08G69/00; macromolecular products derived from proteins C08H1/00; preparation of glue or gelatine C09H; single cell proteins, enzymes C12N; genetic engineering processes for obtaining peptides C12N15/00; compositions for measuring or testing processes involving enzymes C12Q; investigation or analysis of biological material G01N33/00)
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)

## Abstract

Polypeptide compositions that mimic the activity of glucocorticoid induced leucine zipper (GILZ) on the immune system are described. Also described is a method of treating multiple sclerosis using compositions comprising GILZ or lower molecular weight polypeptides with structural relationships to GILZ.

## Claims

### Claim 1

A pharmaceutical composition comprising a polypeptide from 6 to 35 amino acid residues, the polypeptide comprising 1 to 3 tetrapeptides having the sequence of PXXP, wherein
P is proline; and
X is any amino acid, and
wherein the polypeptide comprises the amino acid sequence of CLSPEEPAPESPQVPEAPGGSAV (SEQ ID NO: 6),
and wherein the pharmaceutical composition further comprises a cell penetrating peptide, wherein the polypeptide and the cell penetrating peptide form a complex.

### Claim 2 (depends on 1)

The pharmaceutical composition of claim 1, wherein at least one tetrapeptide comprises the amino acid sequence of SEQ ID NO: 3.

### Claim 3 (depends on 1)

The pharmaceutical composition of claim 1, wherein at least one tetrapeptide comprises the amino acid sequence of SEQ ID NO: 4.

### Claim 4 (depends on 1)

The pharmaceutical composition of claim 1, wherein at least one tetrapeptide comprises the amino acid sequence of SEQ ID NO: 5.

### Claim 5 (depends on 1)

The pharmaceutical composition of claim 1, wherein the polypeptide comprises a polyproline helical conformation.

### Claim 6 (depends on 1)

The pharmaceutical composition of claim 1, wherein the cell penetrating peptide is Pep-1.

### Claim 7 (depends on 1)

The pharmaceutical composition of claim 1, wherein the composition provides a Th-2 bias in the Th-1/Th-2 balance.

### Claim 8 (depends on 1)

A pharmaceutical formulation comprising the pharmaceutical composition of claim 1.

### Claim 9 (depends on 8)

The pharmaceutical formulation of claim 8 further comprising a pharmaceutically acceptable carrier.

### Claim 10 (depends on 8)

A lyophilisate or powder of the pharmaceutical formulation of claim 8.