Vlp for the treatment of a lysosomal storage disease
AssigneeNEUWAY Pharma GmbH
InventorsVictoria DEMINA, Marcus Stapf, Sergey Sotnikov, Heiko Manninga
Life of this patent
Estimating the term…
Abstract
The invention relates to virus like particles (VLP) associated with a lysosomal enzyme or an expression vector encoding a lysosomal enzyme which are used in a method for the treatment of a lysosomal storage disease. The invention also relates to a pharmaceutical composition for use in a method for the treatment of a lysosomal storage disease, to an expression vector encoding a lysosomal enzyme and to a method of associating a VLP with an expression vector encoding a lysosomal enzyme.
Claims32
VLP incorporating a lysosomal enzyme or incorporating an expression vector encoding a lysosomal enzyme for use in a method for the treatment of Metachromatic Leukodystrophy Disease (MLD) in a subject, wherein the VLP is derived from JCV.
The VLP for use according to any of the preceding claims, wherein the subject has a neurologic deficit.
The VLP for use according to any of the preceding claims, wherein the lysosomal enzyme is a human enzyme.
The VLP for use according to any of the preceding claims, wherein the lysosomal enzyme is arylsulfatase A.
The VLP for use according to any of the preceding claims, wherein the lysosomal enzyme comprises an amino acid sequence which is at least 80%, more preferably at least 90% identical to the amino acid sequence according to SEQ ID NO:
- 1 over its entire length, most preferably has the amino acid sequence of SEQ ID NO:
- 1.
The VLP for use according to any of the preceding claims, wherein the expression vector has a size of less than 7 kb, preferably less than 6 kb.
The VLP for use according to any of the preceding claims, wherein the expression vector has a promoter selected from the group comprising CMV and CAG.
The VLP for use according to any of the preceding claims, wherein the lysosomal enzyme comprises a nucleotide sequence which is at least 70%, more preferably at least 80%, more preferably at least 90% identical to the nucleotide sequence of SEQ ID NO:
- 2 over its entire length, preferably is the nucleotide sequence of SEQ ID NO:
- 2.
The VLP for use according to any of the preceding claims, wherein the VLP crosses the blood-brain barrier, preferably the physiologically intact blood-brain barrier, to enter the CNS together with the lysosomal enzyme or the expression vector.
The VLP for use according to any of the preceding claims, wherein the VLP is administered orally or parenterally, preferably intravenously.
The VLP for use according to any of the preceding claims, wherein a target cell is contacted with an effective amount of the lysosomal enzyme.
The VLP for use according to any of the preceding claims, wherein the lysosomal enzyme has a therapeutically effective enzyme activity for at least 10 days, preferably for at least 20 days, more preferably for at least 30 days.
The VLP for use according to any of the preceding claims, wherein the VLP is composed of VP1 proteins of JC virus.
Expression vector having a coding region encoding a lysosomal enzyme, preferably human arylsulfatase A, a promoter selected from the group comprising CAG and CMV, preferably being CAG, and having a size of less than 7 kb, preferably less than 6 kb.
Method of incorporating a lysosomal enzyme, preferably human arylsulfatase A, or incorporating an expression vector encoding a lysosomal enzyme, preferably human arylsulfatase A, into a VLP, wherein the method comprises the following steps:
- a) providing a composition comprising VP1 proteins,
- b) exposing the VP1 proteins of the composition of a) to conditions Inducing the VP1 to assemble into VLP,
- c) exposing the VLP of the composition of b) to conditions disassembling the VLP into pentamers,
- d) exposing the pentamers of the composition of c) to conditions inducing the pentamers to reassemble into VLP
- e) exposing the VLP of the composition of d) to conditions disassembling the VLP into pentamers,
- f) exposing the pentamers of the composition of e) to the lysosomal enzyme or the expression vector to conditions inducing the pentamers to assemble into a VLP associated with the lysosomal enzyme or the expression vector.
Method of treating MLD with VLP incorporating a lysosomal enzyme or an expression vector encoding a lysosomal enzyme, wherein the VLP is derived from JCV.
VLP incorporating a lysosomal enzyme or an expression vector encoding a lysosomal enzyme for use in delivering the lysosomal enzyme or the expression vector encoding the lysosomal enzyme to a target, wherein the target is the CNS.
VLP incorporating a lysosomal enzyme or an expression vector encoding a lysosomal enzyme for use in enhancing the lysosomal enzyme activity.
Dependencies are inferred from the claim text.