# US 8,785,388 B2 · TAT-BH3 methods for treating arthritis

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- Number: US 8,785,388 B2
- Document ID: US8785388B2
- Status: Granted
- Kind: B2
- Application number: 12/031,118
- Filed: 2008-02-14
- Published: 2008-09-25
- Granted: 2014-07-22
- Earliest claimed: 2007-02-14
- Assignees: Saint Louis University
- Applicants: Harris R. Perlman
- Inventors: Harris R. Perlman
- Web page: https://patentgrep.com/patent/US8785388B2

## CPC

- A61K 38/1709: {from mammals}
- A61K 9/0019: {Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner (non-active ingredients are additionally classified in A61K47/00)}
- A61P 37/02: Immunomodulators
- Y02A 50/30: Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
- 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)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- Y02A: TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE

## Abstract

The present invention is directed to compositions and methods for treating immune system mediated disease. In particular, certain embodiments of the present invention use BH3 mimetic therapy as an efficacious treatment of the effector phase of RA wherein the compositions and methods of the present invention markedly reduce the level of the Bcl-2 antagonist protein Bim present in RA synovial tissue as compared to control patients. Therefore, the present invention involves restoring the function of Bim in order to ameliorate inflammatory arthritis. In connection therewith, systemic delivery of a peptide to the BH3 domain of Bim effectively inhibits the development of K/B×N serum transfer-induced arthritis which closely resembles the effector phase of RA.

## Claims

### Claim 1

A method of treating an immune-mediated disease in a patient comprising the step of:
administering a pharmaceutical composition to said patient in need thereof, said composition including a cell delivery agent that is a cell-penetrating peptide selected from the group consisting of TAT, penetratin, VP22, transportan, synthetic oligoarginines, and combinations thereof that is conjugated to a cell death agent that is the BH3 domain of Bim, in an amount sufficient to provide a clinically observable improvement in the disease symptoms of said patient;
wherein said immune-mediated disease is selected from the group consisting of rheumatoid arthritis and juvenile polyarticular rheumatoid arthritis.

### Claim 2 (depends on 1)

The method of claim 1 wherein said patient is a human.

### Claim 3 (depends on 1)

The method of claim 1 wherein said patient is an animal.

### Claim 4 (depends on 1)

The method of claim 1 wherein said administering step is selected from the group consisting of intraperitoneal, intrarteriole, intramuscular, interdermal, subcutaneous, perenteral and intraventricular.

### Claim 5 (depends on 1)

The method of claim 1 wherein said amount is about 0.1-10 mg/kg per day.

### Claim 6 (depends on 1)

The method of claim 1 wherein said composition is dispersed in a pharmaceutically acceptable carrier.

### Claim 7 (depends on 1)

The method of claim 1 composition suppresses the number of neutrophils in said patient.

### Claim 8 (depends on 1)

The method of claim 1 where the immune-mediated disease is rheumatoid arthritis.

### Claim 9 (depends on 1)

The method of claim 1 where the cell delivery agent conjugated to the BH3 domain of Bim is the polypeptide of SEQ ID:1 and the immune-mediated disease is rheumatoid arthritis.