Methods and compositions for CNS delivery of arylsulfatase A

Patent metadata

Field	Value
Publication number	US-12168041-B2
Application number	US-202016828731-A
Country	US
Kind code	B2
Filing date	Mar 24, 2020
Priority date	Jun 25, 2010
Publication date	Dec 17, 2024
Grant date	Dec 17, 2024

Abstract

The present invention provides, among other things, compositions and methods for CNS delivery of lysosomal enzymes for effective treatment of lysosomal storage diseases. In some embodiments, the present invention includes a stable formulation for direct CNS intrathecal administration comprising an arylsulfatase A (ASA) protein, salt, and a polysorbate surfactant for the treatment of Metachromatic Leukodystrophy Disease.

First claim

We claim:

1. A method of treating metachromatic leukodystrophy (MLD) comprising a step of administering directly into the cerebrospinal fluid of a subject in need of treatment a formulation comprising an arylsulfatase A (ASA) protein at a concentration at or greater than 10 mg/ml at a dose amount of at least 100 mg, salt, polysorbate, wherein the formulation comprises no greater than 10 mM phosphate, and wherein the formulation has a pH of between 5.5-6.5.

2. The method of claim 1 , wherein the formulation comprises phosphate at a concentration of no greater than 5 mM.

3. The method of claim 1 , wherein the ASA protein is present at a concentration of between about 10 mg/ml and 30 mg/ml.

4. The method of claim 1 , wherein the salt is NaCl and the polysorbate is polysorbate 20, and the formulation comprises NaCl at a concentration of approximately 154 mM, polysorbate 20 at a concentration of approximately 0.005%, and a pH of approximately 6.

5. The method of claim 1 , wherein the formulation is administered in a volume of about 1-5 ml.

6. The method of claim 1 , wherein direct administration into the cerebrospinal fluid is via intraparenchymal, intracerebral, intraventricular cerebral (ICV) or intrathecal (IT) administration.

Assignees

• Takeda Pharmaceuticals Co

Inventors

• Salamat-Miller Nazila
• Taylor Katherine
• Campolieto Paul
• Shahrokh Zahra
• Pan Jing
• Charnas Lawrence
• Wright Teresa Leah
• Calias Pericles

Classifications

• C12Y310/01001

  N-Sulfoglucosamine sulfohydrolase (3.10.1.1) · CPC title

• A61K47/26

  Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin · CPC title

• A61K47/02

  Inorganic compounds · CPC title

• A61K38/46 Primary

  Hydrolases (3) · CPC title

• C12Y302/01046

  Galactosylceramidase (3.2.1.46) · CPC title