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US 2015/0307576 A1Published application
Fgf-10 complexes
AssigneePermeon Biologics, Inc.
InventorsKatherine S. Bowdish, Erik M. Vogan, John F. Ross, Ann DeWitt
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Abstract
The present disclosure provides complexes comprising an FGF-10 portion and a heterologous protein or peptide, as well as methods of using such complexes.
Claims117
A complex comprising
- an FGF-10 portion comprising a domain of a full length, unprocessed, naturally occurring fibroblast growth factor receptor 10 (FGF-10) polypeptide having a net positive charge, surface positive charge, a molecular weight of at least 4 kDa, and a charge per molecular weight ratio greater than that of a corresponding full length, unprocessed, naturally occurring FGF-10 polypeptide, which domain is a variant having one, two, three, four, or five amino acid substitutions, deletions, or additions relative to the corresponding domain of the naturally occurring FGF-10 polypeptide and that retains cell penetrating activity and
- a cargo portion comprising a heterologous protein or peptide or a small organic molecule;
- wherein the complex does not include a full length, unprocessed, naturally occurring FGF-10 polypeptide.
A complex comprising
- an FGF-10 portion comprising the amino acid sequence set forth in SEQ ID NO:
- 2, in the presence of one, two, three, four, or five amino acid substitutions relative to the amino acid set forth in SEQ ID NO:
- 2, wherein the FGF-10 portion (i) has decreased binding affinity for FGFR2b relative to a naturally occurring, mature FGF-10 polypeptide and/or (ii) has decreased mitogenic activity relative to a naturally occurring, mature FGF-10 polypeptide and
- a cargo portion comprising a heterologous protein or peptide or a small organic molecule.
1 more element
A complex comprising
- an FGF-10 portion comprising SEQ ID NO:
- 10 and
- a cargo portion comprising a heterologous protein or peptide or a small organic molecule, wherein the heterologous protein or peptide is a therapeutic protein, and wherein the cargo portion does not comprise an antibody or antibody fragment.
A complex comprising
- an FGF-10 portion comprising a domain of a full length, unprocessed, naturally occurring fibroblast growth factor receptor 10 (FGF-10) polypeptide having a net positive charge, surface positive charge, a molecular weight of at least 4 kDa and a charge per molecular weight ratio greater than that of a corresponding full length, unprocessed, naturally occurring FGF-10 polypeptide and
- a cargo portion comprising a heterologous protein or peptide or a small organic molecule;
- wherein the complex does not include a full length, unprocessed, naturally occurring FGF-10 polypeptide.
A complex comprising
- an FGF-10 portion comprising a domain of a full length, unprocessed, naturally occurring fibroblast growth factor receptor 10 (FGF-10) polypeptide having a net positive charge, surface positive charge, and a charge per molecular weight ratio greater than that of a corresponding full length, unprocessed, naturally occurring FGF-10 polypeptide, which domain is a variant that retains cell penetrating activity and
- a cargo portion comprising a heterologous protein or peptide or a small organic molecule;
- wherein the complex does not include a full length, unprocessed, naturally occurring FGF-10 polypeptide.
A complex comprising
- an FGF-10 portion comprising a cell penetrating variant of a full length, unprocessed, naturally occurring fibroblast growth factor receptor 10 (FGF-10) polypeptide and
- a cargo portion comprising a heterologous protein or peptide or a small organic molecule.
A complex suitable for cell penetration comprising
- an FGF-10 portion comprising (i) a full length, unprocessed, naturally occurring fibroblast growth factor receptor 10 (FGF-10) polypeptide or (ii) a mature, naturally occurring fibroblast growth factor 10 (FGF-10) polypeptide and
- a cargo portion comprising a heterologous protein or peptide or a small organic molecule for delivery into a cell.
The complex of any of claims 1-49, wherein the cargo portion comprises a heterologous polypeptide or peptide.
A complex comprising the amino acid sequence set forth in SEQ ID NO:
- 4, in the presence or absence of the N-terminal tag.
Dependencies are inferred from the claim text.