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US 2015/0030593 A1Published application
Compositions of penetration-enhanced targeting proteins and methods of use
AssigneePermeon Biologics, Inc.
InventorsKatherine S. Bowdish, James S. Huston, Erik M. Vogan
Life of this patent
Estimating the term…
Abstract
The disclosure relates to penetration-enhanced targeted proteins and their uses for therapeutics delivery.
Claims54
A protein entity comprising:
- a target binding region that binds a cell surface target with a dissociation constant (KD) of greater than 0.01 nM or with an avidity of greater than 0.001 nM, or with a KD of less than 1 μM or with an avidity of less than 1 μM, and
- a charged protein moiety (CPM) that enhances penetration into cells;
- wherein the CPM a) has tertiary structure and a molecular weight of at least 4 kDa and has surface positive charge and a net theoretical charge of less than +20;
- or b) has tertiary structure and a molecular weight of at least 4 kDa and has surface positive charge, a net positive charge of at least +5, and a charge per molecular weight ration of less than 0.75;
- wherein the cell surface target is distinct from that bound by the CPM;
- and wherein the protein entity binds the cell surface target with sufficient affinity or avidity to effect penetration of the protein entity into cells that express the cell surface target, wherein penetration of the protein entity into the cells is increased relative to that of at least one of the target binding region alone or the CPM alone.
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A fusion protein comprising:
- a target binding portion that binds a cell surface target with a dissociation constant (KD) of greater than 0.01 nM or with an avidity of greater than 0.001 nM, or with a KD of less than 1 μM or with an avidity of less than 1 μM, and
- a CPM that enhances penetration into cells;
- wherein the CPM a) is a polypeptide having tertiary structure and a molecular weight of at least 4 kDa and has surface positive charge and a net theoretical charge of less than +20;
- or b) is a polypeptide having tertiary structure, a molecular weight of at least 4 kDa and a theoretical net charge of at least +5 and has surface positive charge and a charge per molecular weight ratio of less than 0.75;
- wherein the cell surface target is distinct from that bound by the CPM;
- and wherein the protein entity binds the cell surface target with sufficient affinity or avidity to effect penetration of the protein entity into cells that express the cell surface target, wherein penetration of the protein entity into the cells is increased relative to that of at least one of the target binding region alone or the CPM alone.
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A fusion protein comprising:
- a first polypeptide portion comprising a target binding region that binds a cell surface target with a dissociation constant (KD) of less than 1 μM or with an avidity of less than 1 μM, and
- a second polypeptide portion comprising a CPM that enhances penetration into cells;
- wherein the CPM a) is a polypeptide having tertiary structure and a molecular weight of at least 4 kDa and has surface positive charge and a net theoretical charge of less than +20;
- or b) is a polypeptide having tertiary structure and a molecular weight of at least 4 kDa and a theoretical net charge of at least +5, wherein the CPM has surface positive charge and a charge per molecular weight ratio of less than 0.75;
- wherein the cell surface target is distinct from that bound by the CPM;
- and wherein the protein entity binds the cell surface target with sufficient affinity or avidity to effect penetration of the protein entity into cells that express the cell surface target, wherein penetration of the protein entity into the cells is increased relative to that of at least one of the target binding region alone or the CPM alone.
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Dependencies are inferred from the claim text.