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: Herein described are antibodies to epidermal growth factor receptor (EGFR) having an EGFR binding affinity that is sufficient to kill disease cells presenting EGFR at high density, but is insufficient for binding to normal cells. A therapeutic effect is thus achieved while avoiding adverse events that result from unintended binding to normal cells.

Abstract: Herein described are antibodies to epidermal growth factor receptor (EGFR) having an EGFR binding affinity that is sufficient to kill disease cells presenting EGFR at high density, but is insufficient for binding to normal cells. A therapeutic effect is thus achieved while avoiding adverse events that result from unintended binding to normal cells.

Abstract: An erbB2 antibody is provided that binds preferentially to disease cells having an erbB2 density greater than a normal erbB2 density. The erbB2 antibody comprises a heavy chain and a light chain. Each chain has a constant region and a variable region. Each variable region comprises framework regions and complementarity determining regions (CDRs), wherein the CDRs have an amino acid sequence set forth below: For the heavy chain: CDR1 GFNIKDTYIH (SEQ ID No. 1) CDR2 RIYPTNGY57TR59YADSVKG (SEQ ID No. 2) CDR3 WGGDGFYAMDY (SEQ ID No. 3). For the light chain: CDR1 RASQDVN30TAVA (SEQ ID No. 4) CDR2 SASF53LYS (SEQ ID No. 5) CDR3 QQHY92TTPPT (SEQ ID NO. 6). At least one of Y57, R59, N30, F53, and Y92 is substituted by an amino acid that confers on said antibody a reduced erbB2 binding affinity (Kd) that is in the range from 0.1 nM to 100 nM. The substitution is other than N30A, F53N, Y92A and Y92F when there is a single substitution in the antibody light chain.

Abstract: An erbB2 antibody is provided that binds preferentially to disease cells having an erbB2 density greater than a normal erbB2 density. The erbB2 antibody comprises a heavy chain and a light chain. Each chain has a constant region and a variable region. Each variable region comprises framework regions and complementarity determining regions (CDRs), wherein the CDRs have an amino acid sequence set forth below: For the heavy chain: CDR1 GFNIKDTYIH (SEQ ID No. 1) CDR2 RIYPTNGY57TR59 YADSVKG (SEQ ID No. 2) CDR3 WGGDGFYAMDY (SEQ ID No. 3) For the light chain: CDR1 RASQDVN30TAVA (SEQ ID No. 4) CDR2 SASF53LYS (SEQ ID No. 5) CDR3 QQHY92TTPPT (SEQ ID No. 6). At least one of Y57, R59, N30, F53, and Y92 is substituted by an amino acid that confers on said antibody a reduced erbB2 binding affinity (Kd) that is in the range from 0.1 nM to 100 nM. The substitution is other than N30A, F53N, Y92A and Y92F when there is a single substitution in the antibody light chain.

Abstract: Provided is a method of quantitatively determining the ability of individual IgG heavy chains to selectively pair with a particular IgG light chain when the heavy chains and two unique light chains are co-expressed. The method provides results with reasonable throughput and is robust and accurate. The co-expressed heavy and light chains do not need to be isolated and purified which enables more efficient screening.

Abstract: Provided is a method of quantitatively determining the ability of individual IgG heavy chains to selectively pair with a particular IgG light chain when the heavy chains and two unique light chains are co-expressed. The method provides results with reasonable throughput and is robust and accurate. The co-expressed heavy and light chains do not need to be isolated and purified which enables more efficient screening.

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: Herein described are antibodies to epidermal growth factor receptor (EGFR) having an EGFR binding affinity that is sufficient to kill disease cells presenting EGFR at high density, but is insufficient for binding to normal cells. A therapeutic effect is thus achieved while avoiding adverse events that result from unintended binding to normal cells.

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: An erbB2 antibody is provided that binds preferentially to disease cells having an erbB2 density greater than a normal erbB2 density. The erbB2 antibody comprises a heavy chain and a light chain. Each chain has a constant region and a variable region. Each variable region comprises framework regions and complementarity determining regions (CDRs), wherein the CDRs have an amino acid sequence set forth below: For the heavy chain: CDR1 GFNIKDTYIH (SEQ ID No. 1) CDR2 RIYPTNGY57TR59 YADSVKG (SEQ ID No. 2) CDR3 WGGDGFYAMDY (SEQ ID No. 3) For the light chain: CDR1 RASQDVN30TAVA (SEQ ID No. 4) CDR2 SASF53LYS (SEQ ID No. 5) CDR3 QQHY92TTPPT (SEQ ID No. 6). At least one of Y57, R59, N30, F53, and Y92 is substituted by an amino acid that confers on said antibody a reduced erbB2 binding affinity (Kd) that is in the range from 0.1 nM to 100 nM. The substitution is other than N30A, F53N, Y92A and Y92F when there is a single substitution in the antibody light chain.

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.