# US 11,439,613 B2 · Levodopa fractionated dose composition and use

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- Number: US 11,439,613 B2
- Document ID: US11439613B2
- Status: Granted
- Kind: B2
- Application number: 17/219,253
- Filed: 2021-03-31
- Published: 2021-07-22
- Granted: 2022-09-13
- Earliest claimed: 2018-03-29
- Assignees: Avion Pharmaceuticals, LLC
- Applicants: Avion Pharmaceuticals, LLC
- Inventors: Thomas N Chase; Kathleen E. Clarence-Smith
- Web page: https://patentgrep.com/patent/US11439613B2

## CPC

- A61K 9/2086: {Layered tablets, e.g. bilayer tablets; Tablets of the type inert core-active coat (active cores with a complete drug-free outer coat A61K9/28)}
- A61K 31/197: the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid [GABA], beta-alanine, epsilon-aminocaproic acid or pantothenic acid (carnitine A61K31/205)
- A61K 9/0053: {Mouth and digestive tract, i.e. intraoral and peroral administration}
- A61K 9/2013: {Organic compounds, e.g. phospholipids, fats}
- A61K 9/2054: {Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose}
- A61K 9/2059: {Starch, including chemically or physically modified derivatives; Amylose; Amylopectin; Dextrin}
- A61K 9/209: {containing drug in at least two layers or in the core and in at least one outer layer}
- A61K 31/198: Alpha-amino acids, e.g. alanine or edetic acid [EDTA] (betaine A61K31/205; proline A61K31/401; tryptophan A61K31/405; histidine A61K31/4172; peptides not degraded to individual amino acids A61K38/00)
- A61P 25/16: Anti-Parkinson drugs
- A61K 9/2072: {characterised by shape, structure or size; Tablets with holes, special break lines or identification marks; Partially coated tablets; Disintegrating flat shaped forms (A61K9/0004, A61K9/0056, A61K9/0065 take precedence)}
- 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

There is provided a convenient new treatment of Parkinson disease by a frequent administration of optimal levodopa doses mimicking a continuous intravenous or infusion treatment, thus mitigating motor complications; and a new carbidopa/levodopa pharmaceutical unit form providing said new treatment.

## Claims

### Claim 1

A method for the treatment of Parkinson's disease or related levodopa (LD)-responsive disorders, comprising orally administering to a patient in need thereof, carbidopa/levodopa (CD/LD) at an effective dose to simulate continuous intravenous administration of LD, up to 9 times per day,
wherein the effective dose comprises CD within a range of 6.25 mg to 18.75 mg and LD within a range of 25 mg to 75 mg, and
wherein entacapone is not concurrently administered.

### Claim 2 (depends on 1)

The method of claim 1, wherein the effective dose comprises CD within a range of 6.25 mg to 8.3 mg and LD within a range of 25 mg to 33.3 mg.

### Claim 3 (depends on 1)

The method of claim 1, wherein the patient is administered from one to six unit doses as the effective dose, each unit dose comprising a carbidopa/levodopa amount selected from the group consisting of carbidopa-6.25 mg/levodopa-25 mg and carbidopa-8.3 mg/levodopa-33.3 mg.

### Claim 4 (depends on 1)

The method of claim 1, wherein said patient is a newly diagnosed patient at the initial stage of Parkinson's disease.

### Claim 5 (depends on 1)

The method of claim 1, wherein said patient is a parkinsonian patient previously administered a standard treatment with carbidopa/levodopa (CD/LD).

### Claim 6 (depends on 5)

The method of claim 5, wherein said patient suffers from motor response complications.

### Claim 7 (depends on 1)

The method of claim 1, wherein the effective dose is administered from 5 to 9 times per day.

### Claim 8 (depends on 7)

The method of claim 7, wherein the effective dose is administered from 5 to 6 times per day.

### Claim 9 (depends on 1)

The method of claim 1, wherein the effective dose to simulate continuous intravenous administration of LD provides a constant plasma concentration range of the LD for full efficacy with no motor response complications.

### Claim 10 (depends on 1)

The method of claim 1, wherein the blood plasma concentration range of LD in the patient is within a physiologic range in comparison to when the patient is not treated with the effective dose of CD/LD.

### Claim 11

A method for the treatment of Parkinson's disease or levodopa (LD)-responsive disorders in a patient who is hypersensitive to LD, comprising orally administering to the patient, carbidopa/levodopa (CD/LD) at an effective dose to simulate continuous intravenous administration of LD, up to 9 times per day,
wherein the effective dose comprises CD within a range of 6.25 mg to 18.75 mg and LD within a range of 25 mg to 75 mg, and
wherein entacapone is not concurrently administered.

### Claim 12 (depends on 11)

The method of claim 11 wherein the effective dose comprises CD within a range of 6.25 mg to 8.3 mg and LD within a range of 25 mg to 33 mg.

### Claim 13 (depends on 11)

The method of claim 11, wherein the patient is administered from one to six unit doses as the effective dose, each unit dose comprising a carbidopa/levodopa amount selected from the group consisting of carbidopa-6.25 mg/levodopa-25 mg and carbidopa-8.3 mg/levodopa-33.3 mg.

### Claim 14 (depends on 11)

The method of claim 11, wherein the patient is a minor child.

### Claim 15 (depends on 11)

The method of claim 11, wherein the LD-responsive disorder is generalized dystonia.

### Claim 16 (depends on 11)

The method of claim 11, wherein the effective dose is administered two times a day (b.i.d.) or three times a day (t.i.d.).

### Claim 17 (depends on 11)

The method of claim 11, wherein the effective dose comprises a carbidopa/levodopa amount of carbidopa-12.5 mg/levodopa-50 mg, and the effective dose is administered two times a day (b.i.d.).

### Claim 18

A method of treating, alleviating, or delaying the onset of, motor response complications related to Parkinson's disease or related levodopa (LD)-responsive disorder, comprising orally administering to a patient in need thereof, carbidopa/levodopa (CD/LD) at an effective dose to simulate continuous intravenous administration of LD, up to 9 times per day,
wherein the effective dose comprises CD within a range of 6.25 mg to 18.75 mg and LD within a range of 25 mg to 75 mg, and
wherein entacapone is not concurrently administered.

### Claim 19 (depends on 18)

The method of claim 18, wherein the effective dose comprises CD within a range of 6.25 mg to 8.3 mg and LD within a range of 25 mg to 33. mg.

### Claim 20 (depends on 18)

The method of claim 18, wherein the patient is administered from one to six unit doses as the effective dose, each unit dose comprising a carbidopa/levodopa amount selected from the group consisting of carbidopa-6.25 mg/levodopa-25 mg and carbidopa-8.3 mg/levodopa-33.3 mg.

### Claim 21 (depends on 18)

The method of claim 18, wherein the effective dose is administered from 5 to 9 times per day.

### Claim 22 (depends on 21)

The method of claim 21, wherein the effective dose is administered from 5 to 6 times per day.

### Claim 23 (depends on 18)

The method of claim 18, wherein the effective dose to simulate continuous intravenous administration of LD provides a constant plasma concentration range of the LD for full efficacy with no motor response complications.

### Claim 24 (depends on 1)

The method of claim 1, wherein the effective dose to simulate continuous intravenous administration of LD provides a constant plasma concentration range of the LD for full efficacy with reduced motor response complications in comparison to when the patient is not treated with the effective dose of CD/LD.

### Claim 25 (depends on 11)

The method of claim 11, wherein the effective dose to simulate continuous intravenous administration of LD provides a constant plasma concentration range of the LD for full efficacy with reduced motor response complications in comparison to when the patient is not treated with the effective dose of CD/LD.

### Claim 26 (depends on 6)

The method of claim 6, wherein said method relieves said motor response complications.

### Claim 27 (depends on 1)

The method of claim 1, wherein said method delays the onset of motor response complications.

### Claim 28 (depends on 1)

The method of claim 1, wherein the effective dose comprises CD 6.25 mg and LD 75 mg.

### Claim 29 (depends on 1)

The method of claim 1, wherein the effective dose comprises CD 8.3 mg and LD 33.3 mg.