Constructs for delivery of threrapeutic agents to neuronal cells
AssigneeSyntaxin Limited
InventorsClifford Charles Shone, John Mark Sutton, Nigel Silman
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Abstract
A non-toxic polypeptide, for delivery of a therapeutic agent to a neuronal cell, comprises a binding domain that binds to the neuronal cell, and a translocation domain that translocates the therapeutic agent into the neuronal cell, wherein the translocation domain is not a HN domain of a clostridial toxin and is not a fragment or derivative of a HN domain of a clostridial toxin.
Claims29
A composition comprising a therapeutic agent linked to a polypeptide, wherein the polypeptide is a non-toxic polypeptide, for delivery of a therapeutic agent to a neuronal cell, comprising:—
- a binding domain that binds to the neuronal cell and is comprised of or derived from clostridial heavy chain fragments or modified clostridial heavy chain fragments, and
- a translocation domain that translocates the therapeutic agent into the neuronal cell,
- wherein the translocation domain is not a HN domain of a clostridial toxin and is not a fragment or derivative of a HN domain of a clostridial toxin and wherein the therapeutic agent is for reduction of neuronal damage after ischemia/reperfusion or is for promotion of neuronal growth after damage.
A composition comprising a therapeutic agent linked to a polypeptide, wherein the polypeptide is for delivery of a therapeutic agent to a neuronal cell, comprising:—
- a binding domain that binds to the neuronal cell and is comprised of or derived from clostridial heavy chain fragments or modified clostridial heavy chain fragments, and
- a translocation domain that translocates the therapeutic agent into the neuronal cell,
- wherein the translocation domain is a non-aggregating translocation domain as measured by its size in physiological buffer and wherein the therapeutic agent is for reduction of neuronal damage after ischemia/reperfusion or is for promotion of neuronal growth after damage.
A composition comprising a therapeutic agent linked to a polypeptide, wherein the polypeptide is for delivery of a therapeutic agent to a neuronal cell, comprising:—
- a binding domain that binds to the neuronal cell and is comprised of or derived from clostridial heavy chain fragments or modified clostridial heavy chain fragments, and
- a translocation domain that translocates the therapeutic agent into the neuronal cell,
- wherein the translocation domain is selected from (1) a HN domain of a diphtheria toxin, (2) a fragment or derivative of (1) that substantially retains the translocating activity of the HN domain of a diphtheria toxin, (3) a fusogenic peptide, (4) a membrane disrupting peptide, and (5) translocating fragments and derivatives of (3) and (4) and wherein the therapeutic agent is for reduction of neuronal damage after ischemia/reperfusion or is for promotion of neuronal growth after damage.
A composition comprising a therapeutic agent linked to a polypeptide, wherein the polypeptide is for delivery of a therapeutic agent to a neuronal cell, comprising:—
- a binding domain that binds to the neuronal cell and is comprised of or derived from clostridial heavy chain fragments or modified clostridial heavy chain fragments, and
- a translocation domain that translocates the therapeutic agent into the neuronal cell,
- wherein the polypeptide has reduced affinity to neutralising antibodies to tetanus toxin compared with the affinity to such antibodies of native tetanus toxin and wherein the therapeutic agent is for reduction of neuronal damage after ischemia/reperfusion or is for promotion of neuronal growth after damage.
A composition according to any previous claim wherein the binding domain comprises a botulinum HC domain.
Dependencies are inferred from the claim text.