Treating seizure with recombinant alkaline phosphatase

Patent metadata

Field	Value
Publication number	US-11224638-B2
Application number	US-201916657040-A
Country	US
Kind code	B2
Filing date	Oct 18, 2019
Priority date	Dec 5, 2014
Publication date	Jan 18, 2022
Grant date	Jan 18, 2022

Abstract

The present disclosure provides a method of treating seizure in a subject having aberrant alkaline phosphatase activities, comprising administering a therapeutically effective amount of at least one recombinant alkaline phosphatase to the subject.

First claim

What is claimed is:

1. A method of treating seizure in a human subject having aberrant levels of an alkaline phosphatase substrate selected from pyridoxal 5′-phosphate (PLP), inorganic pyrophosphate (PPi), and phosphoethanolamine (PEA), comprising administering a therapeutically effective amount of a recombinant alkaline phosphatase to the subject, wherein the human subject has non-detectable bone mineralization defects, wherein the subject is vitamin B6 responsive for the seizure, wherein the human subject has not been diagnosed with HPP, and wherein the recombinant alkaline phosphatase comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 4.

2. The method of claim 1 , wherein the human subject has:
a) increased serum pyridoxal 5′-phosphate (PLP); or
b) reduced intracellular pyridoxal 5′-phosphate (PLP).

3. The method of claim 1 , wherein the human subject has at least one of reduced brain Gamma-Aminobutyric Acid (GABA) and reduced brain serine.

4. The method of claim 1 , wherein the human subject has at least one of increased brain and urinary cystathionine.

5. The method of claim 1 , wherein the recombinant alkaline phosphatase is administered to the human subject:
a) daily for at least one week, one month, three months, six months, or one year;
b) in conjunction with the at least one additional therapeutic agent; or
c) in a dosage from about 0.1 mg/kg/day to about 20 mg/kg/day, or a comparable weekly dosage.

6. The method of claim 1 , wherein administration of the recombinant alkaline phosphatase elevates brain GABA.

7. The method of claim 5 , wherein the at least one additional therapeutic agent is an anti-seizure drug or at least one of vitamin B6 (pyridoxine) and a vitamin B6 vitamer.

8. The method of claim 5 , further comprising:
(i) maintaining co-administration of the at least one additional therapeutic agent with the recombinant alkaline phosphatase for a pre-determined time; and
(ii) withdrawing administration of the at least one additional therapeutic agent while maintaining administration of the recombinant alkaline phosphatase to the human subject.

9. The method of claim 7 , wherein the at least one additional anti-seizure drug and the recombinant alkaline phosphatase are co-administered to the human subject for at least one month, at least six months, or at least one year.

10. The method of claim 5 , wherein the recombinant alkaline phosphatase is administered in a dosage from about 0.5 mg/kg/day to about 5 mg/kg/day, or a comparable weekly dosage.

11. The method of claim 5 , wherein the recombinant alkaline phosphatase is administered in a dosage from about 0.1 mg/kg/day to about 1 mg/kg/day, or a comparable weekly dosage.

12. The method of claim 1 , wherein the recombinant alkaline phosphatase is administered by an intravenous, intramuscular, subcutaneous, sublingual, intrathecal, or intradermal route.

13. The method of claim 12 , wherein the recombinant alkaline phosphatase is administered intravenously.

14. The method of claim 13 , wherein the recombinant alkaline phosphatase is administered intravenously and then subcutaneously.

15. The method of claim 1 , wherein the recombinant alkaline phosphatase comprises the amino acid sequence of SEQ ID NO: 1.

16. The method of claim 1 , wherein the recombinant alkaline phosphatase comprises the amino acid sequence of SEQ ID NO: 4.

Assignees

• Alexion Pharma Inc

Inventors

• Marozsan Andre
• Devore Denise
• Liu-Chen Susan

Classifications

• A61K2300/00

  Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00 · CPC title

• A61P25/08

  Antiepileptics; Anticonvulsants · CPC title

• C12Y301/03001

  Alkaline phosphatase (3.1.3.1) · CPC title

• A61K31/4415

  Pyridoxine, i.e. Vitamin B6 (pyridoxal phosphate A61K31/675) · CPC title

• A61K38/46 Primary

  Hydrolases (3) · CPC title