US 8,697,665 B2 · Porphobilinogen deaminase gene therapy

Porphobilinogen deaminase gene therapy

AssigneesProyecto De Biomedicina Cima, S.L., uniQure biopharma B.V.

InventorsAntonio Fontanellas Romá, Gloria González Aseguinolaza, Maria Sol Rodriguez Pena, Maria Astrid Pañeda Rodriguez, Jaap Twisk, Jesús Maria Prieto Valtueña, Harald Petry, Sander Jan Hendrik Van Deventer

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Abstract

The present invention relates to nucleotide sequences coding for human porphobilinogen deaminase that are optimised for higher expression in mammalian cells. The invention further relates to DNA constructs comprising such optimised synthetic coding sequences for use in gene therapy of conditions caused by a deficiency in porphobilinogen deaminase, such as acute intermittent porphyria. Accordingly, the present invention relates to a nucleic acid or a nucleic acid construct comprising a nucleotide sequence coding for a human porphobilinogen deaminase, wherein at least 320 of the codons coding for the human porphobilinogen deaminase are identical to the codons in SEQ ID NO: 1 or wherein at least 305 of the codons coding for the human porphobilinogen deaminase are identical to the codons in SEQ ID NO: 3.

Claims5

Dependent claims

A method for treating a mammalian subject with acute intermittent porphyria, said method comprising intravenously administering to a mammalian subject in need thereof an effective amount of adeno-associated virus (AAV) virions that comprise:

(a) a nucleic acid construct comprising the nucleotide sequence as set forth in SEQ ID NO:1 that encodes human porphobilinogen deaminase (PBGD) protein, operably linked to an α1-anti-trypsin (AAT) promoter combined with a mouse albumin gene enhancer (Ealb) element, and AAV serotype 2 inverted terminal repeats (ITRs);
and
(b) capsid proteins from AAV serotypes 1, 2, 5 or 8;
wherein said administration results in expression of the human PBGD protein in the liver of said mammal.

1 more element

Dependencies are inferred from the claim text.

Facts

Application

13/121,532Filed 29 Sep 2009 · us provisional application

Priority

EP 0816539329 Sep 2008

Published

US 2011/0262399 A127 Oct 2011

Granted

15 Apr 2014

Term ends

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Classification11 codes

C12N 9/88
Enzymes; Proenzymes; Compositions thereof ; Processes for preparing, activating, inhibiting, separating or purifying enzymes: lyases
A61K 48/0058
Characterised by an aspect of the 'active' part of the composition delivered, i.e. the nucleic acid delivered: nucleic acids adapted for tissue…
A61P 25/00
Drugs for disorders of the nervous system
A61P 43/00
Drugs for specific purposes, not provided for in groups a61p1/00-a61p41/00