Abstract: The invention describes the use of trifunctional bispecific and trispecific antibodies for destroying tumor cells which e.g. are disseminated intraperitoneally due to a surgical intervention, wherein the antibody is administered intraoperatively, preferably directly locally into the abdominal cavity.

Abstract: The invention provides antibody-like binding proteins comprising four polypeptide chains that form four antigen binding sites, wherein each pair of polypeptides forming an antibody-like binding protein possesses dual variable domains having a cross-over orientation. The invention also provides methods for making such antigen-like binding proteins.

Abstract: The present invention relates to novel bispecific three-chain antigen-binding polypeptides and their preparation and use in the treatment and/or diagnosis of various diseases, and also relates to bispecific three-chain antibody-like molecules (TCAs) capable of activating immune effector cells and their use in diagnosis and/or treatment of various diseases.

Abstract: Disclosed are methods and compositions for inhibiting the growth of a tumor (e.g., a malignant tumor) in a subject. In particular, combination therapies for treating a tumor in a subject by co-administering either i) an effective amount of an anti-estrogen agent or ii) an effective amount of a receptor tyrosine kinase inhibitor and an effective amount of a bispecific anti-ErbB2/anti-ErbB3 antibody, and optionally an effective amount trastuzumab. Also disclosed is a bispecific anti-ErbB2/anti-ErbB3 antibody for use in the therapy of a tumor in combination with either i) an anti-estrogen agent or ii) a receptor tyrosine kinase inhibitor, and optionally in use with trastuzumab.

Abstract: The present invention provides substituted azaindole prodrugs, methods of making said prodrugs, pharmaceutical compositions of said prodrugs and methods of using said prodrugs and pharmaceutical compositions thereof to treat or prevent diseases or disorders such as cancer.

Abstract: The invention provides anti-HER antibodies, including multispecific anti-HER antibodies, compositions comprising and methods of using these antibodies. Also provided herein are EGFR/HER3 multispecific antibodies that are less toxic than traditional EGFR antagonists.

Abstract: The invention relates to immunotherapeutic compositions and methods for the treatment of B cell diseases and disorders in human subjects, such as, but not limited to, B cell malignancies and autoimmune diseases and disorders, using therapeutic antibodies that bind to the human CD19 antigen and that preferably mediate human ADCC. The present invention relates to pharmaceutical compositions comprising human or humanized anti-CD19 antibodies of the IgG1 or IgG3 human isotype. The present invention relates to pharmaceutical compositions comprising human or humanized anti-CD19 antibodies of the IgG2 or IgG4 human isotype that preferably mediate human ADCC. The present invention also relates to pharmaceutical compositions comprising chimerized anti-CD19 antibodies of the IgG1, IgG2, IgG3, or IgG4 isotype that mediate human ADCC. In preferred embodiments, the present invention relates to pharmaceutical compositions comprising monoclonal human, humanized, or chimeric anti-CD19 antibodies.

Abstract: The present invention relates to antibodies directed to EGFR and uses of such antibodies, for example, to treat diseases associated with the activity and/or overproduction of EGFR.

Abstract: This invention discloses monoclonal antibodies (MAbs) which have little or no signaling activity as monomers become potent anti-tumor agents when they are converted into homoconjugates. The homoconjugates exert anti-growth activity by signaling G0/G1 arrest or apoptosis, depending upon which cell surface molecule they bind. This activity is specific and does not require an Fc portion. These conjugates are potent, anti-tumor agents.

Abstract: The present invention relates to a method for diagnosing neuroendocrine cancers via detecting the presence of N-methyl D-asparate-associated (NMDA) glutamate receptors type 1 and/or type 2. Methods for preventing and treating neuroendocrine cancers are also disclosed.

Abstract: The present invention relates to method for treating medical disorders mediated by mutations in the APC gene by administering an IGF1R inhibitor. Such disorders include, for example, familial adenomatous polyposis (FAP).

Abstract: Methods of diagnosing and treating disorders related to TH2 inhibition, including but not limited to asthma, are provided. Also provided are methods of selecting or identifying patients for treatment with certain therapeutic agents that are TH2 pathway inhibitors.

Abstract: Provided herein are antibodies or antigen-binding fragments thereof that immunospecifically bind to the fusion (F) protein of Respiratory Syncytial Virus (RSV). Also provided are methods for of prevention, treatment and diagnosis of viral infection and/or the treatment of one more symptoms of RSV-mediated disease. Methods of generating antibodies that immunospecifically bind RSV F protein also are provided.

Abstract: Disclosed herein are human monoclonal antibodies that specifically bind both IGF-I and IGF-II with picomolar affinity and potently inhibit the IGF-IR signal transduction function. These antibodies are active in both an IgG and a scFv format. Bispecific forms of these antibodies are also disclosed. Nucleic acids encoding these antibodies, vectors including these nucleic acids, and host cells transformed with these vectors are also disclosed herein. Also disclosed are pharmaceutical compositions including these antibodies. Methods are provided for treating a subject with cancer and for inhibiting phosphorylation of the insulin-like growth factor-I receptor. Methods are also provided for diagnosing cancer.

Abstract: Methods of diagnosing and treating disorders related to TH2 inhibition, including but not limited to asthma, are provided. Also provided are methods of selecting or identifying patients for treatment with certain therapeutic agents that are TH2 pathway inhibitors.

Abstract: The invention is directed to a method for producing a polypeptide composition comprising: combining a polypeptide with a volatile additive to form a liquid mixture and lyophilizing the liquid mixture to obtain a lyophilized polypeptide composition.

Abstract: Various bispecific antibodies that specifically bind to both blood coagulation factor IX/activated blood coagulation factor IX and blood coagulation factor X and functionally substitute for the cofactor function of blood coagulation factor VIII, that is, the function to promote activation of blood coagulation factor X by activated blood coagulation factor IX, were produced. From these antibodies, multispecific antigen-binding molecules having a high activity of functionally substituting for blood coagulation factor VIII were successfully discovered.

Abstract: The present invention relates to antigen binding formats for use in therapeutic treatments or diagnostic assays. The present invention relates to an antigen-binding format consisting of: a first fusion protein wherein the CH1 constant domain of an antibody is fused i) by its N-terminal end to the C-terminal end of a variable domain of an antibody and ii) by its C-terminal end to the N-terminal end of a variable domain of an antibody and, a second fusion protein wherein the CL constant domain of an antibody is fused by its N-terminal end to the C-terminal end of a variable domain of an antibody.

Abstract: The present invention concerns the treatment of disorders characterized by the overexpression of ErbB2. More specifically, the invention concerns the treatment of human patients susceptible to or diagnosed with cancer overexpressing ErbB2 with a combination of an anti-ErbB2 antibody and a chemotherapeutic agent other than an anthracycline, e.g. doxorubicin or epirubicin. The invention further provides a method of treating cancer in a human patient comprising administering effective amounts of an anti-ErbB2 antibody and a cardioprotectant to the patient.

Abstract: Disclosed herein are fusion antibodies created to provide both an antigen-binding site that targets the CD4 receptor and an antigen-binding site that targets the HIV envelope. The fusion antibodies disclosed herein provide improved potency and breadth against HIV as compared to monospecific antibodies, and additionally provide high barrier against viral resistance. Also disclosed are pharmaceutical formulations and therapeutic methods utilizing such fusion proteins.

Abstract: An antagonist of FERM domain-containing protein 4A (FRMD4A) and/or of the Hippo pathway for use in a method of treating a cancer in a mammalian subject, wherein the cancer is selected from: squamous cell carcinoma (SCC), an epithelial cancer, an adenocarcinoma and a carcinoma is disclosed, as well as related methods of treatment of cancer, methods of screening and generating such antagonists, including anti-FRMD4A antibodies.

Abstract: The present invention relates to novel humanized anti-IL-4 and IL-13 antibodies and fragments thereof and novel bispecific antibodies and fragments thereof that specifically bind to IL-4 and IL-13. The invention also includes uses of the antibodies to treat or prevent IL-4 and/or IL-13 mediated diseases or disorders, including allergic asthma and dermatitis.

Abstract: Isolated monoclonal antibodies or an antigen binding portion thereof which bind to prostate specific membrane antigen in its native form occurring on the surface of tumor cells characterized in that it is linked to a label or a cytotoxic agent or constructed as a part of a bispecific antibody or a recombinant diabody.

Abstract: Proteins that bind IL-17 and/or IL-17F are described along with there use in composition and methods for treating, preventing, and diagnosing IL-17 related diseases and for detecting IL-17 in cells, tissues, samples, and compositions.

Abstract: The present invention provides humanized, chimeric and human anti-CD19 antibodies, anti-CD19 antibody fusion proteins, and fragments thereof that bind to a human B cell marker. Such antibodies, fusion proteins and fragments thereof are useful for the treatment and diagnosis of various B-cell disorders, including B-cell malignancies and autoimmune diseases. In more particular embodiments, the humanized anti-CD19 antibodies may comprise one or more framework region amino acid substitutions designed to improve protein stability, antibody binding and/or expression levels. In a particularly preferred embodiment, the substitutions comprise a Ser91Phe substitution in the hA19 VH sequence.

Abstract: Disclosed herein is a method of treating dry eye with a KLK-13 antibody.

Abstract: The present invention relates to bispecific antibody against human vascular endothelial growth factor (VEGF/VEGF-A) and against human angiopoietin-2 (ANG-2) of human IgG1 or IgG4 subclass with mutations I253A, H310A, and H435A, methods for their production, pharmaceutical compositions containing said antibodies, and uses thereof.

Abstract: Described herein are materials and methods for treating subjects having a HER-3 associated disease, by administering a first agent that binds to HER-3, in combination with a second agent that binds and/or inhibits another member of the HER family. The first and the second agent may be a biologic, such as an antigen-binding protein, or a small molecular tyrosine kinase inhibitor, for example.

Abstract: The invention concerns the use of human or humanized chimeric monoclonal antibodies which are produced in selected cell lines, said antibodies bringing about a high ADCC activity as well as a high secretion of cytokines and interleukins, for treating underpopulations of so-called weak-response patients exhibiting CD16 FCGR3A-158F homozygote or FCGR3A-158V/F heterozygote polymorphism.

Abstract: The present invention is directed toward a humanized neutralizing monoclonal antibody to hepatocyte growth factor, a pharmaceutical composition comprising same, and methods of treatment comprising administering such a pharmaceutical composition to a patient.

Abstract: An antibody is provided. The antibody comprises an Fc region and a Fab region, wherein: (i) the Fc region comprises two non-identical heavy chains, wherein at least one of the two non-identical heavy chains comprises an amino acid modification so as to form complementation between the two non-identical heavy chains thereby increasing the probability of forming heterodimers of the non-identical heavy chains and decreasing the probability of forming homodimers of identical heavy chains; and (ii) the Fab region comprises a first covalent link between a first heavy chain and a first light chain of the Fab region and a second covalent link between a second heavy chain and a second light chain of said Fab region, wherein a position of the first covalent link relative to the first heavy chain is different to a position of the second covalent link relative to the second heavy chain.

Abstract: The present invention is directed to a cross-reactive antibody that specifically inhibits or blocks mammalian Toll-like receptor 2 (TLR2)-mediated immune cell activation. The invention is further directed to an isolated nucleic acid or vector coding for the variable regions of the heavy and/or light chain of such an antibody. Also provided is a pharmaceutical composition comprising such an antibody, or a nucleic acid or vector encoding it. Further provided are methods of use of such compositions in the prevention and/or treatment of inflammatory processes or any other process induced by bacterial infection, trauma, or chronic inflammation, or for the prevention and/or treatment of bacteriaemia or sepsis.

Abstract: The present invention relates to amino acid sequences that are directed against RANK-L, as well as to compounds or constructs, and in particular proteins and polypeptides, that comprise or essentially consist of one or more such amino acid sequences. The invention also relates to nucleic acids encoding such amino acid sequences and polypeptides; to methods for preparing such amino acid sequences and polypeptides; to host cells expressing or capable of expressing such amino acid sequences or polypeptides; to compositions, and in particular to pharmaceutical compositions, that comprise such amino acid sequences, polypeptides, nucleic acids and/or host cells; and to uses of such amino acid sequences or polypeptides, nucleic acids, host cells and/or compositions, in particular for prophylactic, therapeutic or diagnostic purposes.

Abstract: The present invention relates to the use of VEGF antagonists and alpha5beta1 antagonists for treating cancer and inhibiting angiogenesis and/or vascular permeability, including inhibiting abnormal angiogenesis in diseases. The present invention also relates to use of a VEGFR agonists and alpha5beta1 agonists to promote angiogenesis and vascular permeability. The present invention also relates to new anti-alpha5beta1 antibodies, compositions and kits comprising them and methods of making and using them.

Abstract: The present invention provides for the treatment of Alzheimer's disease. More specifically, a recombinant bispecific antibody fragment that simultaneously blocks beta-secretase activity while also promoting alpha-secretase activity, comprising a first portion and a second portion, wherein the first portion blocks beta secretase activity and the second portion promotes alpha-secretase activity.

Abstract: Uses of a dual V region antibody-like protein or a fragment of a dual V region antibody-like region.

Abstract: The invention provides VEGF-C antagonists, such as anti-VEGF-C antibodies, and their use in the prevention and treatment of tumor progression.

Abstract: The present invention provides compositions and methods of use of humanized, chimeric or human Class I anti-CEA antibodies or fragments thereof, preferably comprising the light chain variable region CDR sequences SASSRVSYIH (SEQ ID NO:1); GTSTLAS (SEQ ID NO:2); and QQWSYNPPT (SEQ ID NO:3); and the heavy chain variable region CDR sequences DYYMS (SEQ ID NO:4); FIANKANGHTTDYSPSVKG (SEQ ID NO:5); and DMGIRWNFDV (SEQ ID NO:6). The Class I anti-CEA antibodies or fragments are useful for treating diseases, such as cancer, wherein the diseased cells express CEACAM5 and/or CEACAM6 antigens. The Class I anti-CEA antibodies or fragments are also of use for interfering with specific processes, such as metastasis, invasiveness and/or adhesion of cancer cells, or for enhancing sensitivity of cancer cells to cytotoxic agents and have favorable effects on the survival of subjects with cancer.

Abstract: In one aspect, the invention provides methods and compositions for inhibiting MASP-3-dependent complement activation in a subject suffering from or at risk for developing, a disease or disorder selected from the group consisting of paroxysmal nocturnal hemoglobinuria, age-related macular degeneration, arthritis, disseminated intravascular coagulation, thrombotic microangiopathy, asthma, dense deposit disease, pauci-immune necrotizing crescentic glomerulonephritis, traumatic brain injury, aspiration pneumonia, endophthalmitis, neuromyelitis optica and Behcet's disease by administering to the subject a composition comprising an amount of a MASP-3 inhibitory agent in an amount effective to inhibit MASP-3-dependent complement activation.

Abstract: The present invention provides antibodies that bind human TGF-alpha and human Epiregulin and are characterized as having high affinity, selective, and strong neutralizing properties. The antibodies are useful in the treatment of diabetic nephropathy.

Abstract: Disclosed is a novel photosensitizer based on polymer derivatives-photosensitizer conjugates for photodynamic therapy capable of being selectively accumulated in cancerous tissues and producing singlet oxygen or free radical by laser irradiation. The polymer derivatives-photosensitizer conjugates for photodynamic therapy are prepared as nano-sized particles, and have excellent selection and accumulation ratio for cancerous tissues. The photosensitizer conjugates can produce singlet oxygen or free radical by a specific laser wavelength. Owing to the excellent selection and accumulation ratio for cancerous tissues, the conjugates minimizes photo-cytotoxicity of the conventional photosensitizer having a low molecular amount. Accordingly, the conjugates are very useful as a photosensitizes for photodynamic therapy with reduced side effects and excellent therapeutic effectiveness.

Abstract: The invention provides means and methods for producing one or more Ig-like molecules in a single host cell. Novel CH3 mutations enabling the production of monospecific and/or bispecific Ig-like molecules of interest are also provided.

Abstract: The present invention relates to ST2L antagonists, polynucleotides encoding the antagonists or fragments thereof, and methods of making and using the foregoing.

Abstract: Methods of inducing T cell proliferation and expansion in vivo for treating conditions wherein antigen-specific T cell immune response are therapeutically desirable such as cancer, infection, inflammation, allergy and autoimmunity and for enhancing the efficacy of vaccines are provided. These methods comprise the administration of at least one CD27 agonist, preferably an agonistic CD27 antibody, alone or in association with another moiety such as immune stimulant or immune modulator such as an anti-CD40, OX-40, 4-1BB, or CTLA-4 antibody or an agent that depletes regulatory cells, or a cytokine. These mono and combination therapies may also optionally include the administration of a desired antigen such as a tumor antigen, an allergen, an autoantigen, or an antigen specific to an infectious agent or pathogen against which a T cell response (often CD8+) is desirably elicited.

Abstract: The present invention relates to polypeptides directed against or specifically binding to chemokine receptor CXCR2 and in particular to polypeptides capable of modulating signal transduction from CXCR2. The invention also relates to nucleic acids, vectors and host cells capable of expressing the polypeptides of the invention, pharmaceutical compositions comprising the polypeptides and uses of said polypeptides and compositions for treatment of diseases involving aberrant functioning of CXCR2.

Abstract: Various bispecific antibodies that specifically bind to both blood coagulation factor IX/activated blood coagulation factor IX and blood coagulation factor X and functionally substitute for the cofactor function of blood coagulation factor VIII, that is, the function to promote activation of blood coagulation factor X by activated blood coagulation factor IX, were produced. From these antibodies, multispecific antigen-binding molecules having a high activity of functionally substituting for blood coagulation factor VIII were successfully discovered.

Abstract: Provided herein are methods of using the antibodies that bind to RGMc to treat and diagnose iron-related disorders.

Abstract: The present invention provides compositions and methods of use of humanized, chimeric or human Class I anti-CEA antibodies or fragments thereof, preferably comprising the light chain variable region CDR sequences SASSRVSYIH (SEQ ID NO:1); GTSTLAS (SEQ ID NO:2); and QQWSYNPPT (SEQ ID NO:3); and the heavy chain variable region CDR sequences DYYMS (SEQ ID NO:4); FIANKANGHTTDYSPSVKG (SEQ ID NO:5); and DMGIRWNFDV (SEQ ID NO:6). The Class I anti-CEA antibodies or fragments are useful for treating diseases, such as cancer, wherein the diseased cells express CEACAM5 and/or CEACAM6 antigens. The Class I anti-CEA antibodies or fragments are also of use for interfering with specific processes, such as metastasis, invasiveness and/or adhesion of cancer cells, or for enhancing sensitivity of cancer cells to cytotoxic agents and have favorable effects on the survival of subjects with cancer.

Abstract: The instant invention describes methods of separating or preferentially synthesizing dimers which are linked via at least one interchain disulfide linkage from dimers which are not linked via at least one interchain disulfide linkage from a mixture comprising the two types of polypeptide dimers. These forms can be separated from each other using hydrophobic interaction chromatography. In addition, the invention pertains to connecting peptides that result in the preferential biosynthesis of dimers that are linked via at least one interchain disulfide linkage or that are not linked via at least one interchain disulfide linkage. The invention also pertains to compositions in which a majority of the dimers are linked via at least one interchain disulfide linkage or are not linked via at least one interchain disulfide linkage. The invention still further pertains to novel binding molecules, e.g., comprising connecting peptides of the invention.

Abstract: Novel methods and drug products for treating autoimmune ocular inflammatory disease are disclosed, which involve administration of agents that antagonize one or both of IL-17 and IL-23 activity.