Lactam-modified adeno-associated virus vectors
AssigneeCoave Therapeutics
InventorsWillem Broekaert, Melanie Glossop, Karl Gibson, Nicolas Ferry, Gaëlle Lefèvre
Life of this patent
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Abstract
Adeno-associated virus (AAV) vectors are provided. The vectors are modified by the covalent coupling of at least one compound comprising a lactam moiety (e.g., β-lactam) to at least one amino group of an amino acid residue of the capsid of the AAV vectors. The AAV vectors are useful in transducing a cell, especially for gene therapy.
Claims20
A compound of formula (Ia):
- or a salt thereof, wherein
- Z is a functional moiety comprising a cell-type specific ligand, a labelling agent, a steric shielding agent, a drug moiety or combinations thereof;
- L1 is an optionally substituted aryl or heteroaryl group;
- L2 is an optionally substituted heteroaryl group;
- and
- L3 is a linker;
- and
- R1, R1′, R2 and R2′ are each independently hydrogen, halogen, or an optionally substituted C1-6 alkyl;
- or
- R1 and R1′ or R2 and R2′, together with their intervening atoms, may come together to form an optionally substituted spiro-fused ring;
- or
- R1 and R2, together with their intervening atoms, may form an optionally substituted 3- to 7-membered saturated, partially unsaturated, or aryl or heteroaryl ring having 0-2 heteroatoms independently selected from nitrogen, oxygen, or sulfur.
A method of manufacturing an AAV vector comprising a moiety according to formula (II):
- or a pharmaceutically acceptable salt thereof, the method comprising a step of incubating an AAV with a compound of formula (I):
- or a salt thereof, under conditions suitable to obtain the AAV vector of formula (II);
- wherein
- N* is a nitrogen atom of an amino group of an amino acid residue of the AAV vector's capsid;
- - - - represents the point of attachment to the AAV vector's capsid;
- Z is a functional moiety comprising a cell-type specific ligand, a labelling agent, a steric shielding agent, a drug moiety or combinations thereof;
- L is a linker;
- R1, R1′, R2 and R2′ are each independently hydrogen, halogen, or an optionally substituted C1-6 alkyl;
- or
- R1 and R1′ or R2 and R2′, together with their intervening atoms, may come together of form an optionally substituted spiro-fused ring;
- or
- R1 and R2, together with their intervening atoms, may form an optionally substituted 3- to 7-membered saturated, partially unsaturated, or aryl or heteroaryl ring having 0-2 heteroatoms independently selected from nitrogen, oxygen, or sulfur.
A method for transducing a cell of a subject, comprising administering to said subject an AAV vector comprising a moiety according to formula (II):
- or a pharmaceutically acceptable salt thereof, wherein
- N* is a nitrogen atom of an amino group of an amino acid residue of the AAV vector's capsid;
- - - - represents the point of attachment to the AAV vector's capsid;
- Z is a functional moiety comprising a cell-type specific ligand, a labelling agent, a steric shielding agent, a drug moiety or combinations thereof;
- L is a linker;
- R1, R1′, R2 and R2′ are each independently hydrogen, halogen, or an optionally substituted C1-6 alkyl;
- or
- R1 and R1′ or R2 and R2′, together with their intervening atoms, may come together of form an optionally substituted spiro-fused ring;
- or
- R1 and R2, together with their intervening atoms, may form an optionally substituted 3- to 7-membered saturated, partially unsaturated, or aryl or heteroaryl ring having 0-2 heteroatoms independently selected from nitrogen, oxygen, or sulfur.
Dependencies are inferred from the claim text.