# US 11,026,992 B2 · Compositions and methods for preventing and reducing inflammation and treating disorders associated with inflammation

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- Number: US 11,026,992 B2
- Document ID: US11026992B2
- Status: Granted
- Kind: B2
- Application number: 16/448,960
- Filed: 2019-06-21
- Published: 2020-02-13
- Granted: 2021-06-08
- Earliest claimed: 2015-02-27
- Assignees: Vanderbilt University
- Applicants: Vanderbilt University
- Inventors: Jack J. Hawiger; Ruth Ann Veach; Yan Liu; Huan Qiao; Lukasz S. Wylezinski
- Web page: https://patentgrep.com/patent/US11026992B2

## CPC

- A61K 38/10: Peptides having 12 to 20 amino acids {(A61K38/043 - A61K38/046 take precedence)}
- A61K 38/1825: {Fibroblast growth factor [FGF]}
- C07K 7/00: Peptides having 5 to 20 amino acids in a fully defined sequence; Derivatives thereof
- C07K 2319/00: Fusion polypeptide
- 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)
- 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)

## Abstract

The present invention relates to compositions and methods for preventing and reducing inflammation and preventing and treating diseases and disorders associated with inflammation. It has been shown that CRADD plays a pivotal role in maintaining the integrity of endothelial monolayers. The recombinant cell-penetrating CRADD protein (CP-CRADD)-based compositions and methods described herein provide for the development of a novel treatment for inflammatory vascular disorders including cardiovascular, cerebrovascular, respiratory, gastrointestinal, and renal systems.

## Claims

### Claim 1

A composition comprising a pharmaceutically acceptable carrier and a cell-penetrating caspase and receptor interacting protein adaptor with death domain (CP-CRADD) in an amount sufficient to reduce or block BCL10 expression or activity, reduce BCL-10-mediated inflammation, and/or treat BCL-10-mediated inflammation with a condition in a subject; wherein the death domain of CP-CRADD is deleted.

### Claim 2 (depends on 1)

The composition of claim 1, wherein the amount is sufficient to reduce production of IL-6, monocyte chemoattactant protein 1 or other cytokines and chemokines produced by endothelial cell, smooth muscle cells, and/or epithelial cells.

### Claim 3 (depends on 2)

The composition of claim 2, wherein the CP-CRADD comprises a membrane translocating motif (MTM) having the sequence AAVLLPVLLAAP (SEQ ID NO:1).

### Claim 4 (depends on 1)

A device impregnated with the composition of claim 1.

### Claim 5 (depends on 4)

The device of claim 4, wherein the device is a stent, scaffold, matrix, or inhaler.

### Claim 6 (depends on 1)

The composition of claim 1, wherein the condition comprises hypertension, atherosclerosis, aortic aneurysm formation, neurovascular lesions, epithelial injury in respiratory, gastrointestinal, hepatobiliary, and genitourinary systems.

### Claim 7 (depends on 1)

A method of treating BCL10-mediated inflammation in a mammalian subject comprising administering the composition of claim 1 to the mammalian subject in an amount effective for blocking or reducing BCL10 expression or activity thereby reducing or blocking BCL10-mediated inflammation and/or treating a condition associated pith BCL10-mediated inflammation with a condition in the mammalian subject.

### Claim 8 (depends on 7)

The method of claim 7, wherein administration of the composition inhibits proinflammatory signaling in at least one of: endothelial cells, vascular smooth muscle calls, epithelial cells, lymphocytes and leukocytes in the subject.

### Claim 9 (depends on 7)

The method of claim 7, wherein the subject is a human.

### Claim 10 (depends on 7)

The method of claim 7, wherein the CP-CRADD comprises an MTM having the sequence AAVLLPVLLAAP (SEQ ID NO:1).

### Claim 11 (depends on 7)

The method of claim 7, wherein the CP-CRADD lacks its CARD domain.

### Claim 12 (depends on 7)

The method of claim 7, wherein CP-CRADD comprises an MTM having the sequence AAVALLPAVLLALLAP (SEQ ID NO:2).

### Claim 13 (depends on 7)

The method of claim 7, wherein CP-CRADD comprises an MTM having the sequence VTVLALGALAGVGVG (SEQ ID NO:3).