# US 10,441,528 B2 · Devices, formulations, and methods for delivery of multiple beneficial agents

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- Number: US 10,441,528 B2
- Document ID: US10441528B2
- Status: Granted
- Kind: B2
- Application number: 15/923,720
- Filed: 2018-03-16
- Published: 2018-09-13
- Granted: 2019-10-15
- Earliest claimed: 2008-02-13
- Assignees: Intarcia Therapeutics, Inc.
- Applicants: Intarcia Therapeutics Inc.
- Inventors: Thomas R. Alessi; Karling Alice Leung; Ryan D. Mercer; Cristina G. Negulescu; Catherine Manya Rohloff; Bing Yang
- Web page: https://patentgrep.com/patent/US10441528B2

## CPC

- A61K 9/0004: {Osmotic delivery systems; Sustained release driven by osmosis, thermal energy or gas}
- 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 9/5084: {Mixtures of one or more drugs in different galenical forms, at least one of which being granules, microcapsules or (coated) microparticles according to A61K9/16 or A61K9/50, e.g. for obtaining a specific release pattern or for combining different drugs (tablets containing such a mixture A61K9/2077)}
- A61K 38/22: Hormones (derived from pro-opiomelanocortin, pro-enkephalin or pro-dynorphin A61K38/33, e.g. corticotropin A61K38/35)
- A61K 38/2264: {Obesity-gene products, e.g. leptin}
- A61K 38/2278: {Vasoactive intestinal peptide [VIP]; Related peptides (e.g. Exendin)}
- A61K 38/26: Glucagons
- A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- A61K 47/14: Esters of carboxylic acids, e.g. fatty acid monoglycerides, medium-chain triglycerides, parabens or PEG fatty acid esters
- A61K 47/32: Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers {, poly(meth)acrylates, or polyvinyl pyrrolidone}
- A61P 3/04: Anorexiants; Antiobesity agents
- A61P 3/10: for hyperglycaemia, e.g. antidiabetics
- A61K 9/1617: {Organic compounds, e.g. phospholipids, fats}
- A61K 9/1623: {Sugars or sugar alcohols, e.g. lactose; Derivatives thereof; Homeopathic globules}
- 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 relates to osmotic delivery devices, formulations, and methods for delivery of two or more beneficial agents. In one aspect, the present invention provides osmotic delivery devices useful for substantially concurrent administration of two or more beneficial agents. In another aspect, the present invention provides beneficial agent formulations for use in the osmotic delivery devices. The formulations include formulations wherein beneficial agents are soluble in the vehicle, suspension formulations comprising particle formulations of one or more beneficial agent, and combinations thereof. Further, methods for treatment of a variety of diseases or conditions using two or more beneficial agents are disclosed, wherein the methods are preferably practiced using the osmotic delivery devices and/or formulations of the invention.

## Claims

### Claim 1

An osmotic delivery device comprising: a beneficial agent formulation comprising (i) a non-aqueous vehicle comprising a solvent and a polymer, the vehicle having a viscosity of about 5,000 to about 50,000 poise at 33° C., and (ii) two or more polypeptides, wherein a first polypeptide is a glucagon-like peptide-1 (GLP-1) receptor agonist, and a second polypeptide is a PYY derivative or analogue; wherein the two or more polypeptides are suspended in the vehicle.

### Claim 2 (depends on 1)

The device of claim 1, wherein the two or more polypeptides are formulated into one particle formulation that is suspended in the vehicle.

### Claim 3 (depends on 1)

The device of claim 1, wherein the first polypeptide is formulated into a first particle formulation and the second polypeptide is formulated into a second particle formulation, and the first and second particle formulations are suspended in the vehicle.

### Claim 4 (depends on 1)

The device of claim 1, wherein the first polypeptide is exenatide.

### Claim 5 (depends on 1)

The device of claim 1, wherein the solvent is selected from the group consisting of lauryl lactate, lauryl alcohol and benzyl benzoate.

### Claim 6 (depends on 1)

The device of claim 1, wherein the polymer is polyvinylpyrrolidone.

### Claim 7 (depends on 4)

The device of claim 4, wherein the polymer is polyvinylpyrrolidone.

### Claim 8 (depends on 1)

The device of claim 1, wherein the solvent is benzyl benzoate and the polymer is polyvinylpyrrolidone.

### Claim 9 (depends on 4)

The device of claim 4, wherein the solvent is benzyl benzoate and the polymer is polyvinylpyrrolidone.

### Claim 10 (depends on 1)

The device of claim 1, wherein the vehicle comprises about 25 wt % to about 80 wt % polymer and about 75 wt % to about 20 wt % solvent.

### Claim 11 (depends on 4)

The device of claim 4, wherein the vehicle comprises about 25 wt % to about 80 wt % polymer and about 75 wt % to about 20 wt % solvent.

### Claim 12 (depends on 3)

The device of claim 3, wherein the first particle formulation and the second particle formulation comprise a carbohydrate, an antioxidant, and a buffer.

### Claim 13 (depends on 2)

The device of claim 2, wherein the particle formulation comprises a carbohydrate, an antioxidant, and a buffer.

### Claim 14 (depends on 13)

The device of claim 13, wherein the carbohydrate is a non-reducing sugar, the antioxidant is an amino acid, and the buffer is an organic buffer.

### Claim 15 (depends on 14)

The device of claim 14, wherein the non-reducing sugar is selected from the group consisting of sucrose, trehalose, and raffinose.

### Claim 16 (depends on 14)

The device of claim 14, wherein the amino acid is selected from the group consisting of cysteine, methionine, and tryptophan.

### Claim 17 (depends on 14)

The device of claim 14, wherein the organic buffer is selected from the group consisting of citrate, histidine, succinate, and tris.

### Claim 18 (depends on 2)

The device of claim 2, wherein the solvent is benzyl benzoate and the polymer is polyvinylpyrrolidone, and the vehicle comprises about 25 wt % to about 80 wt % polyvinylpyrrolidone and about 75 wt % to about 20 wt % benzyl benzoate, and the particle formulation further comprises sucrose, methionine, and citrate buffer.

### Claim 19 (depends on 1)

The device of claim 1, wherein the vehicle has a viscosity of between about 12,000 to about 18,000 poise at 33° C.

### Claim 20 (depends on 1)

A method of treating a disease or condition in a subject in need of treatment, comprising: providing the osmotic delivery device of claim 1 to the subject, wherein (i) the osmotic delivery device delivers a therapeutically effective amount of the two or more polypeptides to treat the disease or condition, and (ii) the disease or condition is selected from the group consisting of type ii diabetes, being overweight, and obesity.

### Claim 21 (depends on 20)

The method of claim 20, wherein (i) the first polypeptide is exenatide, and (ii) the two polypeptides are formulated into one particle formulation that is suspended in the vehicle or the first polypeptide is formulated into a first particle formulation and the second polypeptide is formulated into a second particle formulation and the first and second particle formulations are suspended in the vehicle.