# US 2021/0330601 A1 · Transdermal therapeutic system containing asenapine

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- Number: US 2021/0330601 A1
- Document ID: US20210330601A1
- Status: Published application
- Kind: A1
- Application number: 17/195,267
- Filed: 2021-03-08
- Published: 2021-10-28
- Earliest claimed: 2016-12-20
- Assignees: LTS Lohmann Therapie-Systeme AG
- Applicants: LTS LOHMANN Therapie-Systeme AG
- Inventors: Patrick MOHR; René RIETSCHER; René EIFLER; Olga BOURQUAIN
- Web page: https://patentgrep.com/patent/US20210330601A1

## CPC

- A61K 9/7061: {Polyacrylates}
- A61K 9/7038: {Transdermal patches of the drug-in-adhesive type, i.e. comprising drug in the skin-adhesive layer}
- A61K 9/7053: {obtained by reactions only involving carbon to carbon unsaturated bonds, e.g. polyvinyl, polyisobutylene, polystyrene}
- A61K 9/7069: {obtained otherwise than by reactions only involving carbon to carbon unsaturated bonds, e.g. polysiloxane, polyesters, polyurethane, polyethylene oxide}
- A61K 9/7084: {Transdermal patches having a drug layer or reservoir, and one or more separate drug-free skin-adhesive layers, e.g. between drug reservoir and skin, or surrounding the drug reservoir; Liquid-filled reservoir patches}
- A61K 31/407: condensed with other heterocyclic ring systems, e.g. ketorolac, physostigmine
- A61P 25/18: Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
- A61P 25/24: Antidepressants
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- 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)}
- A61K 9/7076: {the adhesive comprising ingredients of undetermined constitution or reaction products thereof, e.g. rosin or other plant resins}
- A61P 9/12: Antihypertensives
- 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 transdermal therapeutic systems (TTS) for the transdermal administration of asenapine comprising a self-adhesive layer structure containing a therapeutically effective amount of asenapine, such asenapine TTS for use in a method of treatment, processes of manufacture of such TTS as well as asenapine and transdermal therapeutic systems containing asenapine for use in a method of treatment and to a method of treating a human patient by transdermal administration of asenapine.

## Claims

### Claim at position 1

1-27. (canceled)

### Claim 28

A transdermal therapeutic system for the transdermal administration of asenapine comprising a self-adhesive layer structure containing asenapine, said self-adhesive layer structure comprising an asenapine-containing matrix layer comprising asenapine and a polymer,
wherein
the transdermal therapeutic system has an area of release of from 10 to 80 cm2;
the amount of asenapine in the asenapine-containing matrix layer ranges from 2% to 20% by weight;
the asenapine-containing matrix layer has an area weight ranging from 90 to 230 g/m2; and
further wherein, the transdermal therapeutic system provides:
a mean transdermal asenapine release rate of 0.5 to 20 mg/day; and
an asenapine Cmax value of from 0.5 to 10 ng/ml following administration of the transdermal system to the skin of a subject in need thereof.

### Claim 29 (depends on 28)

The transdermal therapeutic system according to claim 28, wherein the polymer is selected from the group consisting of acrylic polymers, polyisobutylenes, styrene-isoprene-styrene block copolymers, polysiloxanes, and mixtures thereof.

### Claim 30 (depends on 28)

The transdermal therapeutic system according to claim 28, wherein the transdermal therapeutic system provides an asenapine Cmax value of from 1 to 8 ng/ml or from 1.5 to 5 ng/ml following administration of the transdermal therapeutic system to the skin of the subject in need thereof.

### Claim 31 (depends on 28)

The transdermal therapeutic system according to claim 28, wherein the transdermal therapeutic system provides a mean transdermal asenapine release rate of 2.0 to 10 mg/day.

### Claim 32 (depends on 28)

The transdermal therapeutic system according to claim 28, wherein the transdermal therapeutic system contains from 0.70 mg/cm2 to 4.0 mg/cm2, from 0.80 mg/cm2 to 3.0 mg/cm2, from 0.82 mg/cm2 to 2.0 mg/cm2, or from 0.83 mg/cm2 to 1.7 mg/cm2 asenapine.

### Claim 33 (depends on 28)

The transdermal therapeutic system according to claim 28, wherein the polymer comprises an acrylic polymer.

### Claim 34 (depends on 28)

The transdermal therapeutic system according to claim 28, wherein the polymer comprises an acrylic polymer selected from the group consisting of acrylic polymers comprising functional groups; acrylic polymers comprising a functional group selected from the group consisting of hydroxyl groups, carboxylic acid groups, neutralized carboxylic acid groups, and mixtures thereof; acrylic polymers comprising hydroxyl groups and no carboxylic acid groups; a copolymer of vinyl acetate, 2-ethylhexyl-acrylate, 2-hydroxyethyl-acrylate and glycidyl-methacrylate; a copolymer of methyl acrylate, 2-ethylhexyl acrylate and t-octyl acrylamide; a copolymer of 2-ethylhexyl-acrylate and vinyl acetate; a copolymer of vinyl acetate, 2-ethylhexyl-acrylate, 2-hydroxyethyl-acrylate and glycidyl-methacrylate cross-linked by a cross-linking agent; and mixtures thereof.

### Claim 35 (depends on 28)

The transdermal therapeutic system according to claim 28, wherein the polymer is an acrylic polymer, and wherein the acrylic polymer is present in an amount ranging from 60 to 97%, from 70 to 96%, from 75 to 88%, or from 91 to 96% by weight of the asenapine-containing matrix layer.

### Claim 36 (depends on 28)

The transdermal therapeutic system according to claim 28, wherein the asenapine-containing matrix layer composition comprises a total amount of polymer content ranging from 75 to 97%, from 80 to 96%, or from 85 to 95% by weight of the asenapine-containing matrix layer.

### Claim 37 (depends on 28)

The transdermal therapeutic system according to claim 28, wherein the asenapine-containing matrix layer further comprises a tackifier selected from the group consisting of polyvinylpyrrolidone, soluble polyvinylpyrrolidone, triglycerides, dipropylene glycol, resins, resin esters, terpenes and derivatives thereof, ethylene vinyl acetate adhesives, dimethylpolysiloxanes, and polybutenes.

### Claim 38 (depends on 28)

The transdermal therapeutic system according to claim 28, wherein the asenapine-containing matrix layer further comprises a stabilizer selected from the group consisting of sodium metabisulfite, ascorbic acid and ester derivatives thereof, ascorbyl palmitate, butylated hydroxytoluene, tocopherol and ester derivatives thereof, α-tocopherol, and mixtures thereof.

### Claim 39 (depends on 28)

The transdermal therapeutic system according to claim 28, wherein the transdermal therapeutic system further provides an asenapine AUC0-24 ranging from about 20 [(ng/ml)h] to about 78 [(ng/ml)h] following administration of the system to the skin of the subject in need thereof.

### Claim 40 (depends on 28)

The transdermal therapeutic system according to claim 28, wherein the transdermal therapeutic system further provides a des-methyl-asenapine AUC0-24 ranging from about 0.4 [(ng/ml)h] to about 6 [(ng/ml)h] following administration of the system to the skin of the subject in need thereof.

### Claim 41 (depends on 28)

The transdermal therapeutic system according to claim 28, wherein the transdermal therapeutic system further provides an AUC0-24 within 10% to 1000% of the steady state AUC0-24 obtained upon administration of twice daily 5 mg sublingual asenapine following administration of the system to skin of the subject in need thereof.

### Claim 42 (depends on 28)

The transdermal therapeutic system according to claim 28, wherein the transdermal therapeutic system provides one or more pharmacokinetic parameter(s) selected from the group consisting of:
an asenapine AUC0-48 ranging from 20 to 300 [(ng/ml)h];
an asenapine AUC0-48 ranging from 300 to 450 [(ng/ml)h];
an asenapine AUC0-72 ranging from 30 to 400 [(ng/ml)h];
an asenapine AUC0-72 ranging from 400 to 600 [(ng/ml)h];
an asenapine AUC0-84 ranging from 35 to 450 [(ng/ml)h];
an asenapine AUC0-84 ranging from 450 to 700 [(ng/ml)h];
a Cmax to C48 ratio of less than 2.0;
a Cmax to C72 ratio of less than 3.0; and
a Cmax to C84 ratio of less than 3.5
following administration of the transdermal therapeutic system to the skin of the subject in need thereof.

### Claim 43 (depends on 28)

The transdermal therapeutic system according to claim 28, wherein the asenapine in the asenapine-containing matrix layer is included in the form of asenapine free base.

### Claim 44 (depends on 28)

The transdermal therapeutic system according to claim 28, wherein at least 90 mol %, at least 95 mol %, at least 98 mol %, or at least 99 mol % of the asenapine in the asenapine-containing matrix layer is present in the form of asenapine free base.

### Claim 45 (depends on 28)

The transdermal therapeutic system according to claim 28, wherein the asenapine-containing matrix layer comprises from 3 to 15%, or from 4 to 12% asenapine by weight of the asenapine-containing matrix layer.

### Claim 46 (depends on 28)

The transdermal therapeutic system according to claim 28, wherein the transdermal therapeutic system contains from about 5 to 100 mg asenapine.

### Claim 47 (depends on 28)

The transdermal therapeutic system according to claim 28, wherein the transdermal therapeutic system provides a skin permeation rate of asenapine as measured in a Franz diffusion cell with dermatomed human skin of
0 μg/(cm2h) to 10 μg/(cm2h) in the first 8 hours,
2 μg/(cm2h) to 20 μg/(cm2h) from hour 8 to hour 24,
3 μg/(cm2h) to 20 μg/(cm2h) from hour 24 to hour 32,
3 μg/(cm2h) to 20 μg/(cm2h) from hour 32 to hour 48, and
2 μg/(cm2h) to 15 μg/(cm2h) from hour 48 to hour 72.

### Claim 48 (depends on 28)

A method of treating schizophrenia, the method comprising administering the transdermal therapeutic system according to claim 28 to the skin of a human patient in need thereof.