# US 2014/0194461 A1 · Rapamycin formulations and methods of their use

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- Number: US 2014/0194461 A1
- Document ID: US20140194461A1
- Status: Published application
- Kind: A1
- Application number: 14/151,647
- Filed: 2014-01-09
- Published: 2014-07-10
- Earliest claimed: 2005-02-09
- Assignees: Santen Pharmaceutical Co., Ltd.
- Applicants: Santen Pharmaceutical Co., Ltd.
- Inventors: Sreenivasu MUDUMBA; Philippe JM DOR; Thierry NIVAGGIOLI; David A. WEBER; Sidiq FAROOQ
- Web page: https://patentgrep.com/patent/US20140194461A1

## CPC

- A61K 9/0046: {Ear}
- 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 9/0048: {Eye, e.g. artificial tears}
- A61K 31/045: Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates
- A61K 31/436: the heterocyclic ring system containing a six-membered ring having oxygen as a ring hetero atom, e.g. rapamycin
- A61K 31/44: Non condensed pyridines; Hydrogenated derivatives thereof
- A61K 31/4745: condensed with ring systems having nitrogen as a ring hetero atom, e.g. phenantrolines (yohimbine derivatives, vinblastine A61K31/475; ergoline derivatives A61K31/48)
- A61K 47/10: Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
- A61K 47/12: Carboxylic acids; Salts or anhydrides thereof
- A61K 47/44: Oils, fats or waxes according to two or more groups of A61K47/02-A61K47/42; Natural or modified natural oils, fats or waxes, e.g. castor oil, polyethoxylated castor oil, montan wax, lignite, shellac, rosin, beeswax or lanolin (synthetic glycerides, e.g. medium-chain triglycerides, A61K47/14)
- A61P 9/10: for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
- A61P 27/02: Ophthalmic agents
- A61P 27/08: Mydriatics or cycloplegics
- A61P 37/06: Immunosuppressants, e.g. drugs for graft rejection
- 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

Described herein are liquid rapamycin formulations. Described herein are methods of treating or preventing diseases or conditions, such as choroidal neovascularization, wet AMD and dry AMD, and preventing transition of dry AMD to wet AMD, using the liquid rapamycin formulations described herein.

## Claims

### Claim 1

A method for treating dry age-related macular degeneration in a human subject, the method comprising administering to the human subject by intraocular or periocular injection of a liquid formulation containing an amount of rapamycin effective to treat dry-age macular degeneration in the human subject, wherein the liquid formulation is a liquid solution that forms a non-dispersed mass when injected into the vitreous, and the liquid formulation comprises about 2% (w/w) rapamycin, about 94% (w/w) PEG 400, and about 4% (w/w) ethanol.

### Claim 2 (depends on 1)

The method of claim 1, wherein the volume of liquid formulation contains between 20 μg and 2.5 mg of rapamycin.

### Claim 3 (depends on 1)

The method of claim 1, wherein the volume of liquid formulation contains between 20 μg and 4 mg of rapamycin.

### Claim 4 (depends on 1)

The method of claim 1, wherein the volume of the liquid formulation is administered to the human subject by injection into the vitreous.

### Claim 5 (depends on 1)

The method of claim 1, wherein the volume of the liquid formulation is administered to the human subject by injection between the sclera and conjunctiva.

### Claim 6 (depends on 1)

The method of claim 1, wherein the volume of the liquid formulation when injected into the vitreous delivers an amount of rapamycin sufficient to achieve one or both of:
an average concentration of rapamycin in the retina choroid of at least 0.01 ng/mg for a period of time of at least 30 days following administration of the liquid formulation, and
an average concentration of rapamycin in the vitreous of at least 1000 ng/ml for a period of time of at least 30 days following administration of the liquid formulation.

### Claim 7 (depends on 1)

The method of claim 1, wherein the volume of the liquid formulation when injected between the sclera and conjunctiva delivers an amount of rapamycin sufficient to achieve one or both of:
an average concentration of rapamycin in the vitreous of at least 0.01 ng/ml for a period of time of at least 30 days following administration of the liquid formulation; and
an average concentration of rapamycin in the retina choroid of at least 0.001 ng/mg for a period of time of at least 30 days following administration of the liquid formulation.

### Claim 8 (depends on 1)

The method of claim 1, wherein the non-dispersed mass is a solid depot of rapamycin.