Abstract: The present invention relates, in general, to polypeptides capable of binding and neutralizing transforming growth factor beta (TGF-?) ligands, and uses of these polypeptides for treating disorders related to TGF-beta expression or activation (e.g. cancer and fibrotic diseases), and methods of making such molecules.

Abstract: The present invention relates, in general, to polypeptides capable of binding and neutralizing transforming growth factor beta (TGF-?) ligands, and uses of these polypeptides for treating disorders related to TGF-beta expression or activation (e.g. cancer and fibrotic diseases), and methods of making such molecules.

Abstract: The present invention relates, in general, to polypeptides capable of binding and neutralizing transforming growth factor beta (TGF-?) ligands, and uses of these polypeptides for treating disorders related to TGF-beta expression or activation (e.g. cancer and fibrotic diseases), and methods of making such molecules.

Abstract: The present invention relates, in general, to polypeptides capable of binding and neutralizing transforming growth factor beta (TGF-beta) ligands, and uses of these polypeptides for treating disorders related to TGF-beta expression or activation (e.g. cancer and fibrotic diseases), and methods of making such molecules.

Abstract: The present invention is directed to anti-Her2 antibodies and fragments thereof, compositions, and uses thereof. The antibodies and fragments thereof bind to Her2-expressing cells in a pH-dependent manner, with low affinity at the physiological pH typical of normal cells and tissues, and with high affinity at the slightly acidic pH characteristic to solid tumors. Furthermore, the antibodies inhibit the growth of tumor spheroids at a level comparable to that of the benchmark anti-Her2 antibody Herceptin at acidic pH, whereas these effects were significantly reduced at physiological pH. This pH selectivity of cellular growth inhibition is maintained upon antibody conjugation to cytotoxic drugs. The invention also includes methods of treating solid tumors, methods of detecting solid tumors, and methods of pH-dependent capturing of the Her-2 ectodomain.

Abstract: The present invention relates, in general, to polypeptides capable of binding and neutralizing transforming growth factor beta (TGF-beta) ligands, and uses of these polypeptides for treating disorders related to TGF-beta expression or activation (e.g. cancer and fibrotic diseases), and methods of making such molecules.

Abstract: The present invention addresses limitations of prior art receptor-based traps through a methodology called the clamp/click/cleave (CCC) approach. Two fusion proteins each comprising a binding domain fused to a coiled-coil are non-covalently dimerized through the coiled-coil (clamp), and the dimer so formed is stabilized by a covalent disulphide bond (click) between cysteine residues located on the fusion proteins between the binding domains and coiled-coils. Once the disulphide bond has formed, the coiled-coils are subsequently removed (cleave) by cleaving the fusions proteins at cleavage sites located between the cysteine residues and the coiled-coils to provide the covalently dimerized bivalent binding agent of the present invention. Such binding agents are useful in the treatment and diagnosis of disease states characterized by production and/or overexpression of a ligand to which the binding domains bind.

Abstract: The invention provides multivalent ligand binding agents (traps) for members of the TGF-? superfamily and polypeptide linkers and methods for making and using such constructs. The traps may be used as therapeutic or diagnostic (imaging or non-imaging) agents for diseases/disorders caused by over-production/activity of the target ligand. In an embodiment of the invention there is provided a multivalent binding agent with affinity for a member of the TGF-? superfamily, the agent having the general structure I: (<bd1>-linker1)k-[{<bd1>-linker2-<bd2>-linker3f-}n-(<bd3>)m-(linker4-<bd4>)d]h, where: n and h are independently greater than or equal to 1; d, f, m and k are independently equal to or greater than zero; bd's are polypeptide binding domains having an affinity for the same member of the TGF-? superfamily; and, linkers are unstructured polypeptide sequences.

Abstract: The invention provides hetero-multivalent ligand binging agents (traps) for members of the TGF-? superfamily, as well as methods for making and using such constructs. In an embodiment of the invention there is provided a hetero-multivalent binding agent with affinity for a member of the TGF-? superfamily. The agent comprises the general structure I: (<bd1>-linker1)k-[{<bd1>-linker2-<bd2>-linker3f-}n-(<bd3>)m-(linker4-<bd4>)d]h, where bd1, bd2, bd3 and bd4 are polypeptide binding domains having an affinity for different sites on the same member or for different members of the TGF-? superfamily; at least two of bd1, bd2, bd3, and bd4 are different from each other.

Abstract: The invention provides multivalent ligand binding agents (traps) for members of the TGF-? superfamily and polypeptide linkers and methods for making and using such constructs. The traps may be used as therapeutic or diagnostic (imaging or non-imaging) agents for diseases/disorders caused by over-production/activity of the target ligand. In an embodiment of the invention there is provided a multivalent binding agent with affinity for a member of the TGF-? superfamily, the agent having the general structure I: (<bd1>-linker1)k-[{<bd1>-linker2-<bd2>-linker3f-}n-(<bd3>)m-(linker4-<bd4>)d]h, where: n and h are independently greater than or equal to 1; d, f, m and k are independently equal to or greater than zero; bd's are polypeptide binding domains having an affinity for the same member of the TGF-? superfamily; and, linkers are unstructured polypeptide sequences.

Abstract: The present invention addresses limitations of prior art receptor-based traps through a methodology called the clamp/click/cleave (CCC) approach. Two fusion proteins each comprising a binding domain fused to a coiled-coil are non-covalently dimerized through the coiled-coil (clamp), and the dimer so formed is stabilized by a covalent disulphide bond (click) between cysteine residues located on the fusion proteins between the binding domains and coiled-coils. Once the disulphide bond has formed, the coiled-coils are subsequently removed (cleave) by cleaving the fusions proteins at cleavage sites located between the cysteine residues and the coiled-coils to provide the covalently dimerized bivalent binding agent of the present invention. Such binding agents are useful in the treatment and diagnosis of disease states characterized by production and/or overexpression of a ligand to which the binding domains bind.

Abstract: The invention provides multivalent ligand binding agents (traps) for members of the TGF-? superfamily and polypeptide linkers and methods for making and using such constructs. The traps may be used as therapeutic or diagnostic (imaging or non-imaging) agents for diseases/disorders caused by over-production/activity of the target ligand. In an embodiment of the invention there is provided a multivalent binding agent with affinity for a member of the TGF-? superfamily, the agent having the general structure I: (<bd1>-linker1)k-[{<bd1>-linker2-<bd2>-linker3f-}n-(<bd3>)m-(linker4-<bd4>)d]h, where: n and h are independently greater than or equal to 1; d, f, m and k are independently equal to or greater than zero; bd's are polypeptide binding domains having an affinity for the same member of the TGF-? superfamily; and, linkers are unstructured polypeptide sequences.

Abstract: The invention provides multivalent ligand binding agents (traps) for members of the TGF-? superfamily and polypeptide linkers and methods for making and using such constructs. The traps may be used as therapeutic or diagnostic (imaging or non-imaging) agents for diseases/disorders caused by over-production/activity of the target ligand. In an embodiment of the invention there is provided a multivalent binding agent with affinity for a member of the TGF-? superfamily, the agent having the general structure I: (<bd1>linker1)k-[{<bd1>-linker2-<bd2>linker3f-}n-(<bd3>)m-(linker4-<bd4>)d]h, where: n and h are independently greater than or equal to 1; d, f, m and k are independently equal to or greater than zero; bd's are polypeptide binding domains having an affinity for the same member of the TGF-? superfamily; and, linkers are unstructured polypeptide sequences.

Abstract: The invention provides multivalent ligand binding agents (traps) for members of the TGF-? superfamily and polypeptide linkers and methods for making and using such constructs. The traps may be used as therapeutic or diagnostic (imaging or non-imaging) agents for diseases/disorders caused by over-production/activity of the target ligand.

Abstract: The invention provides hetero-multivalent ligand binging agents (traps) for members of the TGF-? superfamily, as well as methods for making and using such constructs. In an embodiment of the invention there is provided a hetero-multivalent binding agent with affinity for a member of the TGF-? superfamily, said agent comprising the general structure (I): (<bd1>-linker1)k-[{<bd1>-linker2-<bd2>-linker3r-}n-(<bd3>)m-(linker4-<bd4>)d]h, where bd1, bd2, bd3 and bd4 are polypeptide binding domains having an affinity for different sites on the same member or for different members of the TGF-? superfamily, wherein at least two of bd1, bd2, bd3, and bd4 are different from each other.

Abstract: The invention provides multivalent ligand binging agents (traps) for members of the TGF-? superfamily and polypeptide linkers and methods for making and using such constructs. In an embodiment of the invention there is provided a multivalent binding agent with affinity for a member of the TGF-? superfamily, said agent comprising the general structure I: (<bd1>-linker1)k-[{bd1>-linker2-<bd2>-linker3f-}n-(<bd3>)m-(linker4-<bd4>)d]h, where: -n and h are independently greater than or equal to 1; -d, f, m and k arc independently equal to or greater than zero; -bd1, bd2, bd3 and bd4 are polypeptide binding domains having an affinity for the same member of the TGF-? superfamily, with bd1, bd2, bd3, and bd4 being independently the same or different from each other; and, -linkeri, linker2, linker3 and linker4 are unstructured polypeptide sequences; wherein the number of amino acids in each linker is determined independently and is greater than or equal to X/2.