# US 12,109,199 B2 · Topical mTOR inhibitors for cutaneous proliferative and vascular conditions

> Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt

- Number: US 12,109,199 B2
- Document ID: US12109199B2
- Status: Granted
- Kind: B2
- Application number: 16/967,457
- Filed: 2019-02-06
- Published: 2021-06-17
- Granted: 2024-10-08
- Earliest claimed: 2018-02-06
- Assignees: Georgetown University
- Applicants: Georgetown University
- Inventors: Cynthia Marie Carver Deklotz; Robert A. Silverman
- Web page: https://patentgrep.com/patent/US12109199B2

## CPC

- A61K 31/436: the heterocyclic ring system containing a six-membered ring having oxygen as a ring hetero atom, e.g. rapamycin
- A61P 35/00: Antineoplastic agents
- A61K 9/0014: {Skin, i.e. galenical aspects of topical compositions (non-active ingredients are additionally classified in A61K47/00; A61K9/0009, A61K9/0021, A61K9/7015, A61K9/7023 take precedence; cosmetic preparations A61K8/00, A61Q; preparations for wound dressings or bandages A61L26/00)}
- A61P 9/14: Vasoprotectives; Antihaemorrhoidals; Drugs for varicose therapy; Capillary stabilisers
- A61P 17/02: for treating wounds, ulcers, burns, scars, keloids, or the like
- 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 for the treatment of cutaneous vascular conditions and cutaneous proliferative conditions are provided. The methods employ topical administration of mammalian target of rapamycin (mTOR) inhibitors such as sirolimus (rapamycin) and everolimus. Conditions treatable by the disclosed methods include venolymphatic malformations, acne, acne rosacea, periorificial dermatitis, acne vulgaris, cutaneous capillary malformation-arteriovenous malformation (CM-AVM) syndrome, RASopathies, Langerhans cell histiocytosis, non-Langerhans cell histiocytosis, scars, hypertrophic or keloidal scars, Proteus syndrome, PIK3CA-related overgrowth spectrum (PROS), PTEN hamartoma tumor syndromes, cutaneous malignancies and tumors associated with PI3K/AKT/mTOR mutations, keratodermas, acanthosis nigricans, Birt-Hogg-Dube syndrome, Brooke-Speigler syndrome, cylindromas, and epidermal nevi. Also provided are formulations and pharmaceutical compositions having mTOR inhibitor as principal therapeutically active ingredient useful in practicing the methods.

## Claims

### Claim 1

A method of treating a cutaneous proliferative condition, comprising topically administering to an affected area of a subject in need thereof a therapeutically effective amount of a mammalian target of rapamycin (mTOR) inhibitor, thereby treating the condition, wherein the cutaneous proliferative condition is a cutaneous histiocytosis, wherein the mTOR inhibitor is selected from the group consisting of sirolimus and everolimus and is provided as a topical formulation comprising 0.01% to 10% (w/w) of the mTOR inhibitor in a pharmaceutically acceptable carrier.

### Claim 2 (depends on 1)

The method of claim 1, wherein the cutaneous proliferative condition is selected from the group consisting of Langerhans cell histiocytosis, non-Langerhans cell histiocytosis (non-LCH).

### Claim 3 (depends on 1)

The method of claim 1, wherein the affected area comprises at least a portion any one or more of the head, face, and neck.

### Claim 4 (depends on 1)

The method of claim 1, wherein the mTOR inhibitor is sirolimus.

### Claim 5 (depends on 1)

The method of claim 1, wherein the mTOR inhibitor is everolimus.

### Claim 6 (depends on 1)

The method of claim 1, wherein the subject is a human of less than 18 years of age.

### Claim 7 (depends on 1)

The method of claim 1, wherein the subject is a human at least 18 years of age.

### Claim 8 (depends on 2)

The method of claim 2, wherein the histiocytosis is selected from the group consisting of eosinophilic granuloma, Letterer-Siwe disease, Hand-Schuller-Christian syndrome, Hashimoto-Pritzker syndrome, benign cephalic histiocytosis (BCH), juvenile xanthogranuloma, xanthoma disseminatum, necrobiotic xanthogranuloma, generalized eruptive histiocytoma, progressive nodular histiocytoma, indeterminate cell histiocytosis, multicentric reticulohistiocytosis, and sinus histiocytosis with massive lymphadenopathy.

### Claim 9 (depends on 1)

The method of claim 1, wherein the topical formulation comprises 1% of the mTOR inhibitor in a pharmaceutically acceptable carrier.