Methods of treatment and novel constructs

Inventors

Green, Colin Richard • COUTINHO, Frazer Paul • Rupenthal, Ilva Dana

Assignees

Auckland Uniservices Ltd • Inflammx Therapeutics Inc

Abstract

The present invention provides novels method of targeting delivery of a compound to hypoxic cells, for example treatment of diseases and disorders associated with hypoxia, comprising administration of a construct comprising a targeting carrier peptide and a compound for delivery to a hypoxic cell. The invention also provides novel methods for the treatment of diseases or disorders of the eye by administration of a novel construct, a nucleic acid encoding a novel construct, and/or a nucleic acid vector comprising a nucleic acid encoding a novel construct. The invention further provides novel constructs, nucleic acids encoding such constructs, and/or nucleic acid vectors comprising nucleic acids encoding such constructs.

Core Innovation

The invention relates to a polypeptide construct comprising a targeting carrier peptide derived from the X-protein of the Hepatitis B virus and a peptide capable of interacting with an intracellular domain of connexin43 (Cx43). The construct uses the HBV X-derived targeting carrier peptide together with a Cx43 intracellular-domain-interacting peptide to enable a specific interaction with Cx43.

The Cx43-interacting peptide is defined as a peptide capable of interacting with an intracellular domain of Cx43, including interactions involving the intracellular C-terminal tail of Cx43 and/or the intracellular loop of Cx43. The construct is further characterized by inhibiting intracellular C-terminal tail/loop interaction and/or inhibiting Cx43 hemichannel opening, thereby linking Cx43 intracellular interaction to functional inhibition.

Architecturally, the construct can connect the HBV X-derived targeting carrier peptide to the Cx43 intracellular-domain-interacting peptide via an optional linker, including a glycine linker or a polyglutamine linker. In addition, the invention specifies particular targeting carrier peptide amino acid sequences selected from defined groups and provides a construct having the amino acid sequence of SEQ ID NO: 1 with either all L-amino acids or a mixture of L- and D-amino acids.

Claims Coverage

The partial independent-claim set includes multiple independent claims directed to polypeptide or protein constructs. Across the independent claims, the inventive coverage centers on an HBV X-derived targeting carrier peptide linked to a Cx43 intracellular-domain-interacting peptide, with additional scope defined by sequence options, linker options, and stereochemistry options.

Overall, the claim coverage centers on constructs that pair HBV X-derived targeting carrier peptides with peptides that interact with the intracellular domain of connexin43 (Cx43). The inventive scope is further refined by specific targeting sequence patterns, a defined LCL targeting carrier sequence, and stereochemistry constraints for SEQ ID NO:1.

Stated Advantages

Documented Applications