# US 11,439,685 B2 · Formulations for treating a fibrotic disease

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- Number: US 11,439,685 B2
- Document ID: US11439685B2
- Status: Granted
- Kind: B2
- Application number: 17/327,011
- Filed: 2021-05-21
- Published: 2021-11-25
- Granted: 2022-09-13
- Earliest claimed: 2020-05-22
- Assignees: Trustees of Boston University; Beth Israel Deaconess Medical Center, Inc.
- Applicants: Trustees of Boston University; Beth Israel Deaconess Medical Center
- Inventors: Mark W. Grinstaff; William Blessing; Amanda Williamson; Jack Kirsch; Katherine Cook; Ara Nazarian; Edward K. Rodriguez
- Web page: https://patentgrep.com/patent/US11439685B2

## CPC

- A61K 38/2221: {Relaxins}
- 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)}
- A61K 9/0024: {Solid, semi-solid or solidifying implants, which are implanted or injected in body tissue (compositions for intravenous administration, normal injectable solutions or dispersions for, e.g. subcutaneous administration A61K9/0019; brain implants A61K9/0085; (coated) prostheses, catheters or stents A61L)}
- A61K 9/008: {comprising drug dissolved or suspended in liquid propellant for inhalation via a pressurized metered dose inhaler [MDI]}
- A61K 9/1635: {obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates}
- A61K 9/1647: {Polyesters, e.g. poly(lactide-co-glycolide)}
- 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 47/02: Inorganic compounds
- A61K 47/36: Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
- A61K 47/38: Cellulose; Derivatives thereof
- A61P 11/00: Drugs for disorders of the respiratory system
- A61P 19/02: for joint disorders, e.g. arthritis, arthrosis
- A61P 19/04: for non-specific disorders of the connective tissue
- 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

The present invention provides formulations for the treatment of fibrotic diseases and disorders. In some embodiments, the formulation comprises a microparticle that includes an antifibrotic.

## Claims

### Claim 1

A formulation comprising microparticles comprising an aliphatic polyester and an antifibrotic agent, wherein (i) said microparticles have a diameter of 1-100 μm; (ii) the antifibrotic agent is relaxin and is present in an amount that is 0.01-33% of total mass; (iii) said aliphatic polyester is of molecular weight 10,000-200,000 Daltons; or (iv) the microparticles further comprise a vinyl polymer.

### Claim 2 (depends on 1)

The formulation of claim 1, wherein said antifibrotic agent is an agonist of the receptor RXFP1.

### Claim 3 (depends on 1)

The formulation of claim 1, wherein said antifibrotic agent is human relaxin-2 or an analog or variant.

### Claim 4 (depends on 1)

The formulation of claim 1, wherein the aliphatic polyester is poly-lactide-co-glycolide or polycaprolactone.

### Claim 5 (depends on 1)

The formulation of claim 1, wherein said aliphatic polyester is terminated by an ester functional group, an alkyl-ester functional group or a carboxylic acid functional group.

### Claim 6 (depends on 1)

The formulation of claim 1, wherein said formulation comprises a vinyl polymer that is poly(vinyl alcohol) or poly(pyrrolidone).

### Claim 7 (depends on 1)

The formulation of claim 1, wherein said formulation comprises a vinyl polymer that is of molecular weight 10,000-200,000 Daltons.

### Claim 8 (depends on 1)

The formulation of claim 1, wherein the diameter of said microparticles is 1-75 μm; or 1-50 μm; or 5-50 μm; or 25-50 μm; or 30-50 μm; or 40-50 μm.

### Claim 9 (depends on 1)

The formulation of claim 1, wherein said aliphatic polyester is poly-lactide-co-glycolide with a molar ratio of 15:85-25:75, lactide:glycolide.

### Claim 10 (depends on 1)

The formulation of claim 1, wherein the formulation comprises the vinyl polymer in an amount of 0.01-0.1% of total mass.

### Claim 11 (depends on 1)

The formulation of claim 1, wherein said antifibrotic agent is 0.005-5% of the total formulation mass.

### Claim 12 (depends on 1)

The formulation of claim 1, wherein said formulation comprises microparticles suspended in a sodium chloride liquid solution or a sodium carboxymethylcellulose solution.

### Claim 13 (depends on 1)

The formulation of claim 1, wherein said formulation is a sustained release formulation.

### Claim 14 (depends on 1)

The formulation of claim 1, wherein the formulation is formulated for administration via inhalation as an aerosol, administration via intra-articular injection or administration via intramuscular injection.

### Claim 15 (depends on 1)

The formulation of claim 1, wherein the formulation is administered to the subject such that the antifibrotic agent is administered to a subject at a dose between 1-2000 μg/kg body weight.

### Claim 16 (depends on 1)

The formulation of claim 1, wherein said formulation is a sustained release formulation wherein the antifibrotic agent is released over an extended period time selected from the group consisting of between 1-5 days; between 2-5 days; between 1-2 days; between 2-3 days; between 3-4 days; between 4-5 days; between 3-10 days; between 1-15 weeks; between 2-10 weeks; between 4-8 weeks; and between 8-15 weeks.