Methods and compositions for the treatment of metabolic disorders

Patent metadata

Field	Value
Publication number	US-9433624-B2
Application number	US-201113297644-A
Country	US
Kind code	B2
Filing date	Nov 16, 2011
Priority date	Nov 17, 2003
Publication date	Sep 6, 2016
Grant date	Sep 6, 2016

Abstract

The present invention is directed to a novel methods and compositions for the therapeutic intervention in hyperphenylalaninemia. More specifically, the specification describes methods and compositions for treating various types of phenylketonurias using compositions comprising BH4. Combination therapies of BH4 and other therapeutic regimens are contemplated.

First claim

What is claimed is:

1. A method for treating a subject suffering from hyperphenylalaninemia (HPA) due to BH4-responsive phenylketonuria (PKU) comprising administering to said subject tetrahydrobiopterin (BH4) or pharmaceutically acceptable salt thereof at a daily dose of 10 mg/kg to 20 mg/kg, wherein the administering is multiday, oral, and only once per day.

2. The method of claim 1 , wherein said subject is administered BH4 for at least 7 days.

3. The method of claim 1 , wherein the subject is administered BH4 for at least 2 weeks.

4. The method of claim 1 , wherein said subject is administered BH4 for at least 6 weeks.

5. The method of claim 1 , wherein said BH4 is administered as a crystallized form stable for at least 3 months at 40° C. and 75% relative humidity.

6. The method of claim 5 , wherein said crystallized form of BH4 comprises at least 99.5% pure (6R)-5,6,7,8-tetrahydrobiopterin.

7. The method of claim 1 , further comprising administering to said subject a protein-restricted diet.

8. The method of claim 1 , wherein said subject is pregnant, is an infant of 0 to 3 years, or has a plasma phenylalanine concentration of greater than 600 μM prior to treatment with BH4.

9. The method of claim 1 , wherein said BH4 is in the form of a tablet.

10. The method of claim 1 , wherein said BH4 is dissolved in a liquid.

11. The method of claim 1 , wherein the BH4 is administered at a dose of about 10 mg/kg.

12. The method of claim 1 , wherein the BH4 is administered at a dose of about 20 mg/kg.

Assignees

• Oppenheimer Daniel I
• Kakkis Emil D
• Price Fredric D
• Dorenbaum Alejandro
• Moser Rudolf
• Groehn Viola
• Egger Thomas
• Blatter Fritz
• Biomarin Pharm Inc

Inventors

• Oppenheimer Daniel I
• Kakkis Emil D
• Price Fredric D
• Dorenbaum Alejandro
• Moser Rudolf
• Groehn Viola
• Egger Thomas
• Blatter Fritz

Classifications

• A61K31/00

  Medicinal preparations containing organic active ingredients · CPC title

• A61K31/519 Primary

  ortho- or peri-condensed with heterocyclic rings · CPC title

• A61K31/198

  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) · CPC title

• A23L33/175

  Amino acids · CPC title

• A61K9/0053

  Mouth and digestive tract, i.e. intraoral and peroral administration · CPC title