Abstract: The present invention relates, in general, to polypeptides capable of transmigrating the blood-brain barrier, and uses thereof. More specifically, the present invention relates to polypeptides derived by site-directed mutagenesis of an existing antibody fragment and uses thereof, and methods of making such molecules. The polypeptides of the present invention show enhanced blood-brain barrier crossing and brain exposure levels in vitro and in vivo.

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 present invention relates to antibodies and fragments thereof derived by humanization of an existing antibody, and methods of making them. The humanized antibodies of the present invention show enhanced binding to the brain endothelial antigen, improved transmigration across the blood-brain barrier, and increased thermal stability relative to the parent non-humanized antibody.

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 relates, in general, to polypeptides capable of transmigrating the blood-brain barrier, and uses thereof. More specifically, the present invention relates to polypeptides derived by site-directed mutagenesis of an existing antibody fragment and uses thereof, and methods of making such molecules. The polypeptides of the present invention show enhanced blood-brain barrier crossing and brain exposure levels in vitro and in vivo.

Abstract: Novel antibodies and antigen binding fragments that specifically bind to KAAG1 and which may be used in the treatment, detection and diagnosis of cancer comprising KAAG1-expressing cells are disclosed herein. Cells expressing the antibodies and antigen binding fragments as well as methods of detecting and treating cancer using the antibodies and fragments are also disclosed. Cancer indications which may benefit from such treatment or detection include ovarian cancer, renal cancer, lung cancer, colorectal cancer, breast cancer, brain cancer, and prostate cancer, as well as melanomas.

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: There are described herein novel soluble IGF receptor Fc fusion proteins and compositions and methods of use thereof for treating angiogenesis associated disorders and malignant disease, such as cancer and metastasis, wherein the fusion proteins bind specifically to IGF-1 or IGF-2.

Abstract: Recombinant transforming growth factor (TGF)-? monomers modified to inhibit dimerization and block TGF-? signaling are described. The recombinant TGF-? monomers lack the ability to bind and recruit TGF-? type I receptor (T?R1), but retain the capacity to bind the high affinity TGF-? type II receptor (T?RII), and in some instances, include mutations that increase their affinity for T?RII. Nucleic acid molecules and vectors encoding the recombinant TGF-? monomers are also described. Isolated cells, such as T cells, can be re-programmed with a TGF-? monomer-encoding nucleic acid or vector to secrete the monomer. Use of the recombinant TGF-? monomers and/or cells producing the recombinant TGF-? monomers, to inhibit TGF-? signaling, such as to treat disorders associated with aberrant TGF-? signaling, are also described.

Abstract: The present invention relates to antibodies and fragments thereof derived by humanization of an existing antibody, and methods of making them. The humanized antibodies of the present invention show enhanced binding to the brain endothelial antigen, improved transmigration across the blood-brain barrier, and increased thermal stability relative to the parent non-humanized antibody.

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: Novel monoclonal antibodies that specifically bind to KAAG1 are described. In some embodiments, the antibodies block the biological activity of KAAG1 and are useful in composition in certain cancers, more particularly in cancers that have increased cell surface expression of KAAG1, such as ovarian, renal, lung, colorectal, breast, brain, and prostate cancer, as well as melanoma. The invention also relates to cells expressing the monoclonal antibodies and antigen binding fragments such as humanized and chimeric antibodies. Additionally, methods of detecting and treating cancer using the antibodies and fragments are also disclosed.

Abstract: The blood-brain barrier (BBB) prevents transport of molecules larger than 500 Dal tons from blood to brain. Receptor-mediated transcytosis (RMT) facilitates transport across the BBB of specific molecules that bind receptors on brain endothelial cells that form the BBB. An insulin-like growth factor 1 receptor (IGF 1R)-binding antibody or fragment thereof is identified that transmigrates the BBB by RMT. The antibody or fragment is used to deliver a cargo molecule across the BBB, wherein the cargo molecule may be a therapeutic or detectable agent. The antibody is a camelid VHH, prepared by immunizing a llama with a 933-amino acid IGF 1R polypeptide. Humanized forms of the camelid VHH are also generated.

Abstract: The blood-brain barrier (BBB) prevents transport of molecules larger than 500 Daltons from blood to brain. Receptor-mediated transcytosis (RMT) facilitates transport across the BBB of specific molecules that bind receptors on brain endothelial cells that form the BBB. An insulin-like growth factor 1 receptor (IGF1R)-binding antibody or fragment thereof is identified that transmigrates the BBB by RMT. The antibody or fragment is used to deliver a cargo molecule across the BBB, wherein the cargo molecule may be a therapeutic or detectable agent. The antibody is a camelid VHH, prepared by immunizing a llama with a 933-amino acid IGF1R polypeptide. Humanized forms of the camelid VHH are also generated.

Abstract: The blood-brain barrier (BBB) prevents transport of molecules larger than 500 Dal tons from blood to brain. Receptor-mediated transcytosis (RMT) facilitates transport across the BBB of specific molecules that bind receptors on brain endothelial cells that form the BBB. An insulin-like growth factor 1 receptor (IGF 1R)-binding antibody or fragment thereof is identified that transmigrates the BBB by RMT. The antibody or fragment is used to deliver a cargo molecule across the BBB, wherein the cargo molecule may be a therapeutic or detectable agent. The antibody is a camelid VHH, prepared by immunizing a llama with a 933-amino acid IGF 1R polypeptide. Humanized forms of the camelid VHH are also generated.

Abstract: Novel antibodies and antigen binding fragments that specifically bind to KAAG1 and which may be used in the treatment, detection and diagnosis of cancer comprising KAAG1-expressing cells are disclosed herein. Cells expressing the antibodies and antigen binding fragments as well as methods of detecting and treating cancer using the antibodies and fragments are also disclosed. Cancer indications which may benefit from such treatment or detection include ovarian cancer, renal cancer, lung cancer, colorectal cancer, breast cancer, brain cancer, and prostate cancer, as well as melanomas.

Abstract: Novel monoclonal antibodies that specifically bind to KAAG1 are described. In some embodiments, the antibodies block the biological activity of KAAG1 and are useful in composition in certain cancers, more particularly in cancers that have increased cell surface expression of KAAG1, such as ovarian, renal, lung, colorectal, breast, brain, and prostate cancer, as well as melanoma. The invention also relates to cells expressing the monoclonal antibodies and antigen binding fragments such as humanized and chimeric antibodies. Additionally, methods of detecting and treating cancer using the antibodies and fragments are also disclosed.

Abstract: Novel antibodies and antigen binding fragments that specifically bind to KAAG1 and which may be used in the treatment, detection and diagnosis of cancer comprising KAAG1-expressing cells are disclosed herein. Cells expressing the antibodies and antigen binding fragments as well as methods of detecting and treating cancer using the antibodies and fragments are also disclosed. Cancer indications which may benefit from such treatment or detection include ovarian cancer, renal cancer, lung cancer, colorectal cancer, breast cancer, brain cancer, and prostate cancer, as well as melanomas.

Abstract: Novel antibodies and antigen binding fragments that specifically bind to clusterin are described. In some embodiments, the antibodies block the biological activity of clusterin and are useful in composition in certain cancers, more particularly in cancers, such as endometrial carcinoma, breast carcinoma, hepatocellular carcinoma, prostate carcinoma, a renal cell carcinoma, ovarian carcinoma, pancreatic carcinoma, and colorectal carcinoma. The invention also relates to cells expressing the humanized or hybrid antibodies. Additionally, methods of detecting and treating cancer using the antibodies and fragments are also disclosed.