Abstract: Provided herein are novel monospecific and bispecific antibodies that are useful as anti-neoplastic agents and that bind specifically to human IGF-1R and human ErbB3. Exemplary antibodies inhibit signal transduction through either or both of IGF-1R and ErbB3. Exemplary polyvalent proteins comprise at least one anti-IGF-1R binding site and at least one anti-ErbB3 binding site. In certain embodiments the binding sites may be linked through an immunoglobulin constant region. Novel antiErbB3 and anti-IGF-1R antibodies (e.g., monoclonal antibodies) are also provided.

Abstract: Engineered multivalent and multispecific binding proteins, methods of making, and their uses in the prevention, diagnosis, and/or treatment of disease are provided.

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 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: Engineered multivalent and multispecific binding proteins, methods of making, and their uses in the prevention, diagnosis, and/or treatment of disease are provided.

Abstract: The present invention relates to the anti-L1 monoclonal antibody 9.3 as well as to related antibodies or binding molecules and well as to the uses thereof, especially in tumor treatment.

Abstract: The present invention relates to methods for identifying and using modulators of FDF03 biological activity in vitro and in vivo that are useful in the treatment of cancer.

Abstract: Specific binding members that bind the ED-A isoform of fibronectin for use in methods of diagnosis, detection, imaging and/or treatment of inflammatory bowel disease such as ulcerative colitis and/or for use in delivery to the neovasculature of intestinal tissue of a molecule conjugated to the specific binding member. Specific binding members that bind tenascin-C, especially the A1, A2, A3, A4 and/or D domain tenascin-C large isoform, for use in methods of diagnosis, detection, imaging and/or treatment of ulcerative colitis and/or for use in delivery to the neovasculature of inflammatory bowel disease tissue of a molecule conjugated to the specific binding member.

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 invention describes the use of a pharmaceutical preparation containing a trifunctional bispecific and/or trispecific having the following properties: a) binding to a T cell; b) binding to at least an antigen on a tumor cell associated with malignant ascites and/or pleural effusion; c) binding, by its Fc portion (in the case of bispecific antibodies) or by a third specificity (in the case of trispecific antibodies), to Fc receptor-positive cells for the destruction of the tumor cells in the treatment of malignant ascites and/or pleural effusion.

Abstract: Disclosed are bispecific binding agents that specifically target both of the IGF-1 and the ErbB intracellular signaling pathways. For example, bispecific binding agents that comprise an anti-IGF-1R antibody and an anti-ErbB3 antibody connected by a linker are described herein. These bispecific agents are capable of antagonizing signal transduction by both of the IGF-1 and the ErbB signaling pathways and are useful in inhibiting the proliferation of tumor cells whose growth involves the signaling activity of both pathways.

Abstract: Isolated human monoclonal antibodies which bind to and inhibit human CD25, and related antibody-based compositions and molecules, are disclosed. The human antibodies can be produced by a hybridoma, a transfectoma or in a nonhuman transgenic animal, e.g., a transgenic mouse, capable of producing multiple isotypes of human monoclonal antibodies by undergoing V-D-J recombination and isotype switching. Also disclosed are pharmaceutical compositions comprising the human antibodies, nonhuman transgenic animals, hybridomas and transfectomas which produce the human antibodies, and therapeutic and diagnostic methods for using the human antibodies.

Abstract: Compounds of Formula I are useful inhibitors of CDK 4, CDK6, and FLT3. Such compounds are useful in treating cancer and various other disease conditions. Compounds of Formula I have the following structure: where R1 is a group of Formula IA, Formula IB, Formula IC, or Formula ID and the definitions of the other variables are provided herein.

Abstract: The present invention relates to a polypeptide comprising a first human binding domain capbable of binding to an epitope of human and non-chimpanzee CD3? (epsilon) chain and a second binding domain capable of binding to EGFR, Her2/neu or IgE of a human and/or a non-chimpanzee primate as well as to a process for the production of the mentioned polypeptide. The invention further relates to nucleic acid sequences encoding the polypeptide, to vectors comprising the nucleic acid sequences and to host cells comprising the nucleic acid sequences or vectors containing the nucleic acid sequences. In another aspect, the invention provides for a pharmaceutical composition comprising the polypeptide and methods of medical treatment or use of the polypeptide.

Abstract: The present invention relates to a method (dosage regimen) for administering an EpCAMxCD3 bispecific antibody to a human patient, comprising (a) administering continually a first dose of said antibody for a first period of time; and consecutively (b) administering continually a second dose of said antibody for a second period of time, wherein said second dose exceeds said first dose. The methods of the invention (and likewise the dosage regimen of the invention) are also suitable for treating EpCAM positive epithelial cancer cells in a human patient, or for ameliorating and/or preventing a medical condition mediated by the continued administration of an EpCAMxCD3 bispecific antibody to a human patient. The present invention also relates to the use of an EpCAMxCD3 bispecific antibody for the preparation of a pharmaceutical composition to be used in a method as defined in any one of the preceding claims.

Abstract: The invention relates to anti-Factor D antibodies, their nucleic acid and amino acid sequences, the cells and vectors that harbor these antibodies and their production and their use in the preparation of compositions and medicaments for treatment of diseases and disorders associated with excessive or uncontrolled complement activation. These antibodies are useful for diagnostics, prophylaxis and treatment of disease.

Abstract: The present invention concerns compositions and use of multivalent and/or multispecific antibodies or immunoconjugates, preferably made by the dock-and-lock technique. The antibodies or immunoconjugates may comprise a first and second polypeptide, each comprising VH and VL domains in series, wherein the first and second polypeptides bind to each other, wherein a VH domain on one polypeptide binds to a complementary VL domain on the other polypeptide to form an antigen binding site, wherein VH and VL domains on the same polypeptide do not bind to each other and wherein one polypeptide is attached to the amino terminal end of a CH1 domain and the other polypeptide is attached to the amino terminal end of a CL domain. The carboxyl terminal end of the CH1 domain may be attached to a CH2-CH3 domain. The antibodies or immunoconjugates are of use to treat a wide variety of diseases.

Abstract: The present inventors produced a variety of bispecific antibodies that specifically bind to both F. IX/F. IXa and F. X, and functionally substitute for F. VIIIa, i.e., have a cofactor function to promote F. X activation via F. IXa. Among these antibodies, the antibody A44/B26 reduced coagulation time by 50 seconds or more as compared to that observed when the antibody was not added. The present inventors produced a commonly shared L chain antibody from this antibody using L chains of A44, and showed that A44L can be used as commonly shared L chains, although the activity of the resulting antibody is reduced compared to the original antibody (A44HL-B26HL). Further, with appropriate CDR shuffling, the present inventors successfully produced highly active multispecific antibodies that functionally substitute for coagulation factor VIII.

Abstract: The present invention relates to bispecific antibodies against human VEGF and against human ANG-2, methods for their production, pharmaceutical compositions containing said antibodies, and uses thereof.

Abstract: The invention concerns the prevention and treatment of complement-associated eye conditions, such as choroidal neovascularization (CNV) and age-related macular degeneration (AMD), by administration of Factor D antagonists.

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: Methods and compositions for immunotherapy of inflammatory and immune-dysregulatory diseases are disclosed, using multispecific antagonists that target at least two different markers. The different targets are proinflammatory effectors of the innate immune system. The multispecific antagonists can be used to treat sepsis or septic shock.

Abstract: The invention concerns the prevention and treatment of complement-associated eye conditions, such as choroidal neovascularization (CNV) and age-related macular degeneration (AMD), by administration of factor B antagonists.

Abstract: This invention provides antibodies that specifically bind to and neutralize botulinum neurotoxin type A (BoNT/A) and the epitopes bound by those antibodies. The antibodies and derivatives thereof and/or other antibodies that specifically bind to the neutralizing epitopes provided herein can be used to neutralize botulinum neurotoxin and are therefore also useful in the treatment of botulism.

Abstract: A set of markers for melanoma cancer stem cells are provided. The cells can be prospectively isolated or identified from primary tumor samples, and possess the unique properties of cancer stem cells in functional assays for tumor initiation, cancer stem cell self-renewal and differentiation. In addition, cancer stem cells can be used as a predictor for disease progression. The CSC have the phenotype of being positive for expression CD271.

Abstract: Use of a compound comprising at least a structural entity which binds or is an antagonist for interleukin-6 (IL-6) and/or the IL-6 receptor or parts of it, preferably human IL-6 which compound depletes IL-6 from a solution or blocks at least one or more IL-6 functions on cell surfaces or in a solution for manufacturing of a medicament for the treatment or prevention of diseases selected from the group consisting of endothelial injury, destruction, increased risk for endothelial injury or destruction or immune disorders other than rheumatoid arthritis and combinations thereof.

Abstract: The present invention relates to nucleic acids which encode the heavy chains and light chains of a novel domain exchanged, bivalent, bispecific antibody, and vectors comprising the same.

Abstract: The present invention relates to stable formulations of polypeptides, e.g. immunoglobulin single variable domains.

Abstract: The present invention provides isolated monoclonal antibodies, particularly human antibodies, that bind to IP-10 with high affinity, inhibit the binding of IP-10 to its receptor, inhibit IP-10-induced calcium flux and inhibit IP-10-induced cell migration. Nucleic acid molecules encoding the antibodies of the invention, expression vectors, host cells and methods for expressing the antibodies of the invention are also provided. Immunoconjugates, bispecific molecules and pharmaceutical compositions comprising the antibodies of the invention are also provided. The invention also provides methods for inhibiting IP-10 activity using the antibodies of the invention, including methods for treating various inflammatory and autoimmune diseases.

Abstract: The present invention relates to Notch1 binding agents and methods of using the agents for treating diseases, such as hematologic cancers. The present invention provides antibodies that specifically bind to a non-ligand binding membrane proximal region of the extracellular domain of human Notch1. The present invention further provides methods of using agents that inhibit Notch1 activity for treating cancer. Also described are methods of treating hematologic cancers comprising administering a therapeutically effective amount of a binding agent or antibody of the present invention to a subject having a hematologic cancer such as T-cell lymphoblastic leukemia.

Abstract: The invention relates to storage-stable anti-TNFR1 antibody single variable domains (dAbs), antagonists and multispecific ligands, as well as methods and uses of these. The anti-TNFR1 polypeptides, antibody single variable domains (dAbs), antagonists and multispecific ligands are useful for treating and/or preventing inflammatory disease, such as arthritis or COPD, as well as for pulmonary administration, oral administration, delivery to the lung and delivery to the GI tract of a patient.

Abstract: The present invention relates to a substance specific to human PD-1 comprising a part that recognizes human PD-1, a part that recognizes a membrane protein in cell membrane of human PD-1-expressing cells, and linkers. Since the substance specific to human PD-1 selectively can recognize human PD-1 and a membrane protein on cell membrane of human PD-1-expressing cells and can transmit inhibitory signal of human PD-1, it is useful for therapy and/or prevention of diseases caused by immunopathy.

Abstract: The present invention relates to novel domain exchanged, bivalent, bispecific antibodies, their manufacture and use.

Abstract: The present invention provides methods and means to reduce gastrointestinal inflammation. In particular, the invention provides methods and means to treat inflammatory bowel disease (IBD) and related conditions. The invention further provides methods and means to treat psoriasis. The invention further provides methods and means to treat asthma.

Abstract: The invention concerns an improved method for treating tumor, including cancer, which combines the administration of a chemotherapeutic agent and an antagonist of a gene product the expression of which is upregulated by the chemotherapeutic agent. The invention further concerns methods and means for the diagnosis and classification of tumors, and for the prognosis of the outcome of tumor treatment, and patient response to a particular treatment modality.

Abstract: The present invention provides antagonists of APRIL. In particular, the APRIL antagonists block unique receptor binding sited on APRIL, BCMA. TACI, and/or HSPG. Also provided are methods of use.

Abstract: The present invention relates to uses of bispecific antibodies exhibiting cross-species specificity for evaluating the in vivo safety and/or activity and/or pharmacokinetic profile of the same in non-human species and humans. The present invention moreover relates to methods for evaluating the in vivo safety and/or activity and/or pharmacokinetic profile of said bispecific anti-bodies exhibiting cross-species specificity. The present invention also relates to methods of measuring the biological activity and/or efficacy of such bispecific antibodies exhibiting cross-species specificity. In addition, the present invention relates to pharmaceutical compositions comprising bispecific single chain antibodies exhibiting cross-species specificity and to methods for the preparation of pharmaceutical compositions comprising said bispecific single chain antibodies exhibiting cross-species specificity for the treatment of diseases.

Abstract: The invention relates generally to the field of immunology, in particular, to bispecific antibodies. Methods for designing a bispecific antibody for use in treating diseases relating to the immune system are disclosed. Specific examples relate to bispecific antibodies which recognize an activating receptor and an inhibiting receptor.

Abstract: The present invention provides engineered multivalent and multispecific binding proteins, as well as methods of making them. Methods for using the multivalent and multispecific binding proteins of the invention in the prevention, diagnosis, and/or treatment of disease are also provided.

Abstract: Compositions and methods for making and using anti-LPA agents, for example, monoclonal antibodies, are described.

Abstract: Methods useful for effecting prophylaxis or treatment of amyloidosis, including AA Amyloidosis and AL amyloidosis, by administering peptides comprising neoepitopes, such as AA fragments from a C-terminal region of AA, and antibodies specific for neoepitopes of aggregated amyloid proteins, for example, antibodies specific for the C-terminal region of AA fibrils. Antibodies for inhibition of formation and/or increasing clearance of amyloid deposits in a patient thus effecting prophylaxis or treating amyloid disease.

Abstract: We have constructed bispecific antibody engaging molecules which have one arm that specifically engages a tumor cell which expresses the human EGFRvIII mutant protein on its surface, and a second arm that specifically engages T cell activation ligand CD3. The engaging molecules are highly cytotoxic and antigen-specific. These are promising therapeutic agents.

Abstract: Methods and pharmaceutical compositions for treating severe ischemic events including cerebral infarction, cardiac infarction, or pulmonary embolism, comprising a thrombolytic intervention including thrombolytic agents and an inhibitor of vascular endothelial growth factor (VEGF) receptor-mediated signal transduction are disclosed.

Abstract: The present invention relates to engineered multivalent and multispecific binding proteins, methods of making, and specifically to their uses in the prevention, diagnosis, and/or treatment of disease.

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: The present invention relates to novel domain exchanged, bivalent, bispecific antibodies, their manufacture and use.

Abstract: The present invention disclosed recombinant anti-VLA-4 antibody molecules, including humanized recombinant anti-VLA-4 antibody molecules. These antibodies are useful in the treatment of specific and non-specific inflammation, including asthma and inflammatory bowel disease. In addition, the humanized recombinant anti-VLA-4 antibodies disclosed can be useful in methods of diagnosing and localizing sites of inflammation.

Abstract: The present invention provides novel methods of inhibiting fibrosis, as well as methods of treating or inhibiting fibrotic disorders, using BMP9 and/or BMP10 antagonists. The present invention also provides methods of assessing whether a subject has or is at risk of developing a fibrotic disorder by detecting levels of BMP9 and/or BMP10. Further provided are methods of assessing the efficacy of a treatment regimen for treating a fibrotic disorder by detecting and comparing pre-treatment levels of BMP9 and BMP10 with post-treatment levels of BMP9 and BMP10.

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: Multivalent, multispecific molecules having at least one specificity for a pathogen and at least one specificity for the HLA class II invariant chain (Ii) are administered to induce clearance of the pathogen. In addition to pathogens, clearance of therapeutic or diagnostic agents, autoantibodies, anti-graft antibodies, and other undesirable compounds may be induced using the multivalent, multispecific molecules.