# US 2021/0330741 A1 · Polypeptide therapeutics and uses thereof

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- Number: US 2021/0330741 A1
- Document ID: US20210330741A1
- Status: Published application
- Kind: A1
- Application number: 17/367,532
- Filed: 2021-07-05
- Published: 2021-10-28
- Earliest claimed: 2015-02-27
- Assignees: Board of Regents, The University of Texas System
- Applicants: Board of Regents, the University of Texas System
- Inventors: Robert O. WILLIAMS, III; Steven IDELL; Sreerama SHETTY
- Web page: https://patentgrep.com/patent/US20210330741A1

## CPC

- A61K 38/177: {Receptors; Cell surface antigens; Cell surface determinants}
- A61K 9/0078: {for inhalation via a nebulizer such as a jet nebulizer, ultrasonic nebulizer, e.g. in the form of aqueous drug solutions or dispersions}
- A61K 9/145: {with organic compounds}
- A61K 9/19: lyophilised {, i.e. freeze-dried, solutions or dispersions (lyophilised products with subsequent particle size reduction A61K9/14; granules or pellets made by lyphilisation A61K9/1682; solid oral dosage forms made by lyophilisation A61K9/2095; lyophilisation additives A61K47/00)}
- 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 38/49: Urokinase; Tissue plasminogen activator
- A61P 11/00: Drugs for disorders of the respiratory system
- A61P 11/06: Antiasthmatics
- A61P 11/16: Central respiratory analeptics
- A61P 31/04: Antibacterial agents
- A61K 47/26: Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
- 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

## Abstract

Methods and composition for delivery of enzymes to a subject's airway. In some aspects, nebulized composition of enzymes, such as plasminogen activators are provided. In further aspects perfluorocarbon compositions comprising enzymes, such as plasminogen activators are provided. Compositions may, in some aspects, be used for the treatment of lung infections or acute lung injury, such as inhalational smoke induced acute lung injury (ISALI).

## Claims

### Claim 1

A method of treating or preventing an injury, infection, or disease of the lungs in a subject comprising administering to the airway of the subject an effective amount of a nebulized solution of a caveolin-1 polypeptide comprising an amino acid sequence of FTTFTVT (SEQ ID NO: 1).

### Claim 2 (depends on 1)

The method of claim 1, wherein the caveolin-1 polypeptide is no more than 20 amino acids in length.

### Claim 3 (depends on 2)

The method of claim 2, wherein the caveolin-1 polypeptide consists of the amino acid sequence of DGIWKASFTTFTVTKYWFYR (SEQ ID NO:2).

### Claim 4 (depends on 2)

The method of claim 2, wherein the caveolin-1 polypeptide is no more than 10 amino acids in length.

### Claim 5 (depends on 4)

The method of claim 4, wherein the caveolin-1 polypeptide consists of the amino acid sequence of FTTFTVT (SEQ ID NO: 1).

### Claim 6 (depends on 1)

The method of claim 1, wherein the nebulized solution is produced using a vibrating mesh nebulizer.

### Claim 7 (depends on 6)

The method of claim 6, wherein the vibrating mesh nebulizer is an active vibrating mesh nebulizer or a passive vibrating mesh nebulizer.

### Claim 8 (depends on 1)

The method of claim 1, wherein the nebulized solution is produced using a jet nebulizer or an ultrasonic nebulizer.

### Claim 9 (depends on 1)

The method of claim 1, wherein the nebulized solution is an aqueous solution.

### Claim 10 (depends on 9)

The method of claim 9, wherein the nebulized solution comprises a pharmaceutically acceptable carrier.

### Claim 11 (depends on 9)

The method of claim 9, wherein the nebulized solution comprises a pH buffering agent.

### Claim 12 (depends on 9)

The method of claim 9, wherein the nebulized solution is phosphate buffered saline (PBS).

### Claim 13 (depends on 9)

The method of claim 9, wherein the nebulized solution is normal saline.

### Claim 14 (depends on 1)

The method of claim 1, wherein the nebulized solution comprises an enzyme.

### Claim 15 (depends on 14)

The method of claim 14, wherein the enzyme is a plasminogen activator enzyme.

### Claim 16 (depends on 15)

The method of claim 15, wherein the plasminogen activator enzyme is tissue plasminogen activator (tPA) or urokinase plasminogen activator (uPA).

### Claim 17 (depends on 1)

The method of claim 1, wherein the nebulized solution comprises a lyoprotectant.

### Claim 18 (depends on 17)

The method of claim 17, wherein the lyoprotectant is selected from the group consisting of dextrose, mannose, galactose, fructose, lactose, sucrose, maltose, sorbitol, and mannitol.

### Claim 19 (depends on 17)

The method of claim 17, wherein the lyoprotectant is present at a weight to weight (w/w) ratio of 100:1 to 5:1 relative to the caveolin-1 polypeptide.

### Claim 20 (depends on 1)

The method of claim 1, wherein the nebulized solution has a median particle size of between about 2.5 μm and 20 μm.

### Claim 21 (depends on 1)

The method of claim 1, wherein the nebulized solution has a median particle size of less than about 15 μm, less than about 10 μm, less than about 5 μm, or less than about 2 μm.

### Claim 22 (depends on 1)

The method of claim 1, wherein the nebulized solution has a median particle size of about 1 μm to about 5 μm.

### Claim 23 (depends on 1)

The method of claim 1, wherein the subject has acute lung injury.

### Claim 24 (depends on 23)

The method of claim 23, wherein the subject has inhalational smoke-induced acute lung injury (ISALI).

### Claim 25 (depends on 1)

The method of claim 1, wherein the subject has chemical-induced lung injury or infection-induced lung injury.

### Claim 26 (depends on 1)

The method of claim 1, wherein the subject has plastic bronchitis, asthma, acute respiratory distress syndrome, chronic obstructive pulmonary disease, bronchiectasis, bronchiolitis obliterans, interstitial lung disease, or bronchiolitis obliterans organizing pneumonia.

### Claim 27 (depends on 1)

The method of claim 1, wherein the subject has a fibrotic condition of the lungs.

### Claim 28 (depends on 26)

The method of claim 26, wherein the interstitial lung disease is idiopathic pulmonary fibrosis or sarcoidosis.

### Claim 29 (depends on 1)

The method of claim 1, wherein the caveolin-1 polypeptide is administered at a dose of about 5 μg/kg of body weight to about 500 mg/kg of body weight.

### Claim 30 (depends on 1)

The method of claim 1, wherein the nebulized solution is prepared by the steps comprising:
(i) obtaining a lyophilized caveolin-1 polypeptide comprising an amino acid sequence of FTTFTVT (SEQ ID NO: 1);
(ii) reconstituting the lyophilized caveolin-1 polypeptide in an aqueous solution; and nebulizing the aqueous solution comprising the caveolin-1 polypeptide using a nebulizer.