Methods and compositions for CNS delivery of heparan n-sulfatase

Patent metadata

Field	Value
Publication number	US-11065308-B2
Application number	US-201816036584-A
Country	US
Kind code	B2
Filing date	Jul 16, 2018
Priority date	Jun 25, 2010
Publication date	Jul 20, 2021
Grant date	Jul 20, 2021

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 a heparan N-sulfatase (HNS) protein, salt, and a polysorbate surfactant for the treatment of Sanfilippo Syndrome Type A.

First claim

The invention claimed is:

1. A method of treating Sanfilippo A Syndrome comprising a step of
administering intrathecally to a subject in need of treatment a formulation comprising a heparan N-sulfatase (HNS) protein at a concentration at or greater than 5 mg/ml, and no greater than 50 mM phosphate.

2. The method of claim 1 , wherein the intrathecal administration of the formulation results in reduction of lysosomal storage in the brain target tissues, spinal cord neurons and peripheral target tissues.

3. The method of claim 1 , wherein the intrathecal administration of the formulation results in reduced intensity, severity, or frequency, or delayed onset of at least one symptom or feature of the Sanfilippo A Syndrome.

4. The method of claim 1 , wherein the intrathecal administration is used in conjunction with intravenous administration.

5. The method of claim 1 , wherein the intrathecal administration is used in absence of concurrent immunosuppressive therapy.

Assignees

• Shire Human Genetic Therapies

Inventors

• Natoli Farah
• Zhu Gaozhong
• Terew Jennifer
• Jiang Yuan
• Tsung Jamie
• Shahrokh Zahra
• Vernaglia Brian
• Pan Jing
• Pfeifer Richard
• Calias Pericles

Classifications

• A61P25/00

  Drugs for disorders of the nervous system · CPC title

• A61P25/02

  for peripheral neuropathies · CPC title

• C12Y302/01045

  Glucosylceramidase (3.2.1.45), i.e. beta-glucocerebrosidase · CPC title

• A61P3/02

  Nutrients, e.g. vitamins, minerals · CPC title

• A61K9/19

  lyophilised {, i.e. freeze-dried, solutions or dispersions (lyophilised products with subsequent particle size reduction A61K9/14; granules or pellets made by lyphilisation A61K9/1682; solid oral dosage forms made by lyophilisation A61K9/2095; lyophilisation additives A61K47/00)} · CPC title