Bi-Specific Fusion Proteins
AssigneeMerrimack Pharmaceuticals, Inc.
InventorsUlrik Nielsen, Thomas Wickham Groton, Birgit Schoeberl, Brian Harms, Bryan Linggi, Matthew Onsum, Byron DeLaBarre
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Abstract
Bi-specific fusion proteins with therapeutic uses are provided, as well as pharmaceutical compositions comprising such fusion proteins, and methods for using such fusion proteins to repair damaged tissue. The bi-specific fusion proteins generally comprise: (a) a targeting polypeptide domain that binds to an ischemia-associated molecule; and (b) an activator domain that that detectably modulates the activity of a cellular network.
Claims35
A bi-specific fusion protein comprising:
- (a) a targeting domain having a binding specificity to an ischemia-associated molecule;
- (b) an activator domain that detectably modulates activation of a receptor;
- and
- (c) a polypeptide linker, wherein the polypeptide linker extends the half life of the bi-specific fusion protein.
A bi-specific fusion protein comprising:
- (a) a targeting domain having a binding specificity to an ischemia-associated molecule;
- and
- (b) an activator domain having a binding specificity to a growth factor receptor or cytokine receptor, wherein upon exposure of the activator domain to the growth factor receptor or cytokine receptor, the activator domain binds the growth factor receptor or cytokine receptor so as to modulate regeneration of a cardiac tissue.
A bi-specific fusion protein comprising:
- (a) a targeting domain having a binding specificity to a target molecule;
- (b) an activator domain having a binding specificity to a receptor, wherein upon exposure of the activator domain to the receptor, the activator domain binds the receptor so as to modulate activation of the receptor;
- and
- (c) a polypeptide linker, wherein the polypeptide linker extends the half life of the bi-specific fusion protein.
A bi-specific fusion protein comprising:
- (a) a targeting domain having a binding specificity to a target molecule;
- (b) an activator domain having a binding specificity to a receptor, wherein upon exposure of the activator domain to the receptor, the activator domain binds the receptor so as to modulate tissue regeneration;
- and
- (c) a polypeptide linker, wherein the polypeptide linker extends the half life of the bi-specific fusion protein.
A bi-specific fusion protein comprising:
- (a) a targeting domain having a binding specificity to a tissue-associated molecule;
- and
- (b) an activator domain having a binding specificity to a molecule associated with the surface of a cell in the tissue, wherein upon exposure of the activator domain to surface-associated molecule, the activator domain binds the membrane-associated molecule so as to modulate regeneration of the tissue,
- wherein the targeting domain and the activator domain are linked via a linker, and wherein the linker extends the half life of the bi-specific fusion protein.
A method of promoting tissue regeneration in a patient, the method comprising:
- (a) providing a bi-specific fusion protein comprising (i) a targeting domain having a binding specificity to a ischemia-associated molecule;
- and (ii) an activator domain having a binding specificity to growth factor receptor or cytokine receptor;
- and
- (b) administering in a patient in need thereof a therapeutically effective amount of the bi-specific fusion protein whereby the targeting domain specifically binds to the ischemia-associated molecule thereby targeting the bi-specific fusion protein to a tissue and whereby upon exposure of the activator domain to the growth factor receptor or cytokine receptor, the activator domain specifically activates the growth factor receptor or cytokine receptor so as to promote tissue regeneration.
A method of promoting tissue regeneration in a patient, the method comprising
- (a) providing a bi-specific fusion protein comprising (i) a targeting domain having a binding specificity to a target molecule;
- (ii) an activator domain having a binding specificity to a receptor;
- (iii) a polypeptide linker, wherein the polypeptide linker extends the half life of the bi-specific fusion protein;
- and
- (b) administering in a patient in need thereof a therapeutically effective amount of the bi-specific fusion protein whereby the targeting domain specifically binds to the target molecule thereby targeting the bi-specific fusion protein to a first cell and whereby upon exposure of the activator domain to the growth factor receptor, the activator domain specifically activates the receptor of a second cell of a tissue so as to promote tissue regeneration.
The method of claim 39 further comprising the administration of stem cells to the patient.
Dependencies are inferred from the claim text.