Abstract: The disclosure relates to a protein composed of a first polypeptide or polypeptide domain having a first specific binding activity for Cytotoxic T-lymphocyte Antigen 4 (CTLA-4) expressed on a T-cell cell surface and a second specific binding activity for Glucose Transporter 2 (GLUT2) or an extracellular ectodomain thereof expressed on a pancreatic ?-cell surface, wherein binding of the first polypeptide or polypeptide domain to CTLA-4 induces a CTLA-4 specific agonist response in the T-cell, and binding of the second polypeptide or polypeptide domain to GLUT2 or an ectodomain thereof does not inhibit GLUT2 glucose transporter function, wherein said agonist response in the T-cell induces a response that reduces immunoreactivity against pancreatic ?-cells.

Abstract: Provided are multispecific binding proteins and methods for using these multispecific binding proteins to modulate the activation state of immune cells, such as T-cells (e.g., cytotoxic T-cells). Also provided are methods of modulating an immune response (e.g., cell killing by cytotoxic T-cells) in a subject (e.g., a human subject). Also provided are nucleic acids, expression vectors and host cells encoding the multispecific binding proteins.

Abstract: The present invention generally relates to novel bispecific antigen binding molecules for T cell activation and re-direction to specific target cells. In addition, the present invention relates to polynucleotides encoding such bispecific antigen binding molecules, and vectors and host cells comprising such polynucleotides. The invention further relates to methods for producing the bispecific antigen binding molecules of the invention, and to methods of using these bispecific antigen binding molecules in the treatment of disease.

Abstract: The present invention generally relates to novel bispecific antigen binding molecules for T cell activation and re-direction to specific target cells. In addition, the present invention relates to polynucleotides encoding such bispecific antigen binding molecules, and vectors and host cells comprising such polynucleotides. The invention further relates to methods for producing the bispecific antigen binding molecules of the invention, and to methods of using these bispecific antigen binding molecules in the treatment of disease.

Abstract: The invention relates to multispecific antibody constructs comprising Fab fragments having mutations at the interface of the CH1 and CL domains, said mutations preventing heavy/light chain mispairing.

Abstract: The present disclosure provides compositions and methods for treating CEA-expressing cancers. Methods for dosing a patient with an antibody that binds to CEA and human CD3 are also provided.

Abstract: Methods for treating diseases such as cancer comprising administering a Wnt pathway inhibitor, either alone or in combination with other anti-cancer agents, and monitoring for skeletal-related side effects and/or toxicity.

Abstract: Described herein are polypeptides and related antibodies comprising a variant Fc domain. The variant Fc domain provide for stabilized Fc:Fc interactions when the polypeptide(s), antibody or antibodies are bound to its target, antigen or antigens on the surface of a cell, thus providing for improved effector functions, such as CDC-response.

Abstract: The subject invention provides methods for recruitment of bone marrow-derived cells, including bone marrow-derived endothelial cells (BMDEC), and increasing their function by administration of relaxin. The methods of the invention can be used in, for example, treating 5 conditions amenable to treatment by recruitment of bone marrow-derived cells, such as BMDEC and bone marrow-derived angio-osteogcnic progenitor cell.

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 invention provides Nrp2 antagonists, such as anti-Nrp2 antibodies, and their use in the prevention and treatment of tumor metastasis.

Abstract: The present invention concerns chimeric or humanized antibodies or antigen-binding fragments thereof that comprise specific CDR sequences, disclosed herein. Preferably, the antibodies or fragments comprise specific heavy and light chain variable region sequences disclosed herein. More preferably, the antibodies or fragments also comprise specific constant region sequences, such as those associated with the nG1m1,2 or Km3 allotypes. The antibodies or fragments may bind to a human histone protein, such as H2B, H3 or H4. The antibodies or fragments are of use to treat a variety of diseases that may be associated with histones, such as autoimmune disease (e.g.

Abstract: Anti-EGFR antibodies, therapeutic compositions comprising combinations of anti-EGFR antibodies, as well as methods for using such antibodies and compositions to treat EGFR-related disorders (e.g., cancers), are disclosed.

Abstract: The invention describes methods of treating erosive polyarthritis comprising administering a TNF? antibody, or antigen-binding portion thereof. The invention also describes a method for testing the efficacy of a TNF? antibody, or antigen-binding portion thereof, for the treatment of erosive polyarthritis.

Abstract: Methods are disclosed for preventing toxic drug-drug interactions during combination cancer therapy with a drug that is an anti-ErbB3 agent, such as an anti-ErbB3 antibody, together with a drug that is a tyrosine kinase inhibitor and/or a drug that binds to alpha-1 acid glycoprotein (e.g., erlotinib). Health care practitioners obtaining any one of the drugs are warned that when co-administering the drug that is an anti-ErbB3 agent with either or both of a drug that is a tyrosine kinase inhibitor and a drug that binds to alpha-1 acid glycoprotein, at least one of the co-administered drugs should be administered using a reduced dosage to prevent toxicity. In a reduced dosage, the amount of drug administered per unit time is reduced as compared to a dose that would be administered if the drug was administered as monotherapy. The reduced dosage can be, for example, a reduced drug dose or a reduced drug dosing frequency, or both. Compositions useful in practicing the disclosed methods are also provided.

Abstract: The present invention provides progastrin-binding molecules that are useful therapeutically for passive immunization against progastrin in gastrin-promoted diseases or conditions. The progastrin-binding molecules are specific for progastrin but do not bind gastrin-17(G17), gastrin-34(G34), glycine-extended gastrin-17(G17-Gly) or glycine-extended gastrin-34(G34-Gly). The progastrin-binding molecules include monoclonal antibodies (MAbs) selective for sequences at the N-terminus and the C-terminus of the gastrin precursor molecule, progastrin.

Abstract: The present invention relates in essence to a compound which decreases or inhibits the binding of mammalian T-cells to mammalian endothelial cells for use in a method of prophylaxis and/or amelioration and/or treatment of clinical adverse events caused by therapy which comprises re-directing of T-cells against target cells in a patient. Methods of treatment of patients having or being at risk of clinical adverse events caused by therapy which comprises re-directing of T-cells against target cells are also contemplated.

Abstract: Engineered multispecific binding proteins that bind at least one ligand for a receptor are provided, along with methods of making and uses in the prevention, diagnosis, and/or treatment of disease.

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: Provided is a prophylactic, symptom progress-suppressive, and/or therapeutic agent for an autoimmune disease. The agent lowers the risk of infections and reduces the burden of administration to patients. The prophylactic, symptom progress-suppressive, and/or therapeutic agent includes a PD-1 agonist as an active ingredient and is administered (a) 1 to 10 times within one month from the first administration, (b) in a total PD-1 agonist dose of 20 to 1250 ?g/kg, and (c) without requiring administration for at least 3 months after the last administration.

Abstract: Proteins that bind IL-1? and IL-1? are described along with their use in compositions and methods for treating, preventing, and diagnosing IL-1-related disorders and for detecting IL-1? and IL-1? in cells, tissues, samples, and compositions.

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: Novel anti-NRP1 antibodies and variants thereof having unique structural and functional characteristics are disclosed. Also provided are uses of the antibodies in research, diagnostic and therapeutic applications.

Abstract: The present invention relates to tri- or tetraspecific antibodies, their manufacture and use.

Abstract: The invention relates to binding molecules capable of specifically recognizing soluble oligomers of N-terminal truncated A? starting with pyroglutamate (A??E), pharmaceutical compositions comprising same, and their respective therapeutic uses. Particularly, the invention relates to an antibody molecule capable of specifically recognizing A? oligomers, wherein said antibody binds and/or detects an epitope as bound and/or detected by antibody PG3-38 9D5H6 as deposited under DSM AC-C3056.

Abstract: The present disclosure relates to antibodies directed to the tumor necrosis factor alpha (“TNF-?”) and uses of such antibodies, for example, to treat diseases associated with the activity and/or overproduction of TNF-?.

Abstract: Disclosed are methods and compositions of anti-B cell antibodies, preferably anti-CD22 antibodies, for diagnosis, prognosis and therapy of B-cell associated diseases, such as B-cell malignancies, autoimmune disease and immune dysfunction disease. Preferably, the antibodies induce trogocytosis of B-cell antigens, such as CD19, CD20, CD21, CD22, CD79b, CD44, CD62L, or ?7-integrin. Trogocytosis may play a significant role in determining antibody efficacy, disease responsiveness and prognosis of therapeutic intervention and trogocytosis-dependent responses may be monitored by measuring the levels of trogocytosis of one or more B-cell surface antigens induced by the bispecific antibody.

Abstract: Engineered multivalent and multispecific binding proteins capable of penetrating the blood-brain barrier (BBB) are provided, along with methods of making and uses in the prevention, diagnosis, and/or treatment of disease.

Abstract: Provided herein are methods for inhibiting tumor angiogenesis in a cancer patient, the method comprising administering to the subject an effective amount of a first isolated binding molecule which specifically binds to semaphorin-4D (SEMA4D) and an effective amount of a second isolated binding molecule which specifically binds to VEGF.

Abstract: The present invention provides a pharmaceutical composition comprising a bispecific single chain antibody construct. Said bispecific single chain antibody construct is characterized to comprise or consist of at least two domains, whereby one of said at least two domains specifically binds to human EpCAM and comprises at least one CDR-H3 region comprising the amino acid sequence NXID antigen and a second domain binds to human CD3 antigen. The invention further provides a process for the production of the pharmaceutical composition of the invention, a method for the prevention, treatment or amelioration of a tumorous disease and the use of the disclosed bispecific single chain antibody construct and corresponding means in the prevention, treatment or amelioration of a tumorous disease.

Abstract: The present invention relates to antibodies or fragments thereof that specifically bind Fc?RIIB, particularly human Fc?RIIB, with greater affinity than the antibodies or fragments thereof bind Fc?RIIA, particularly human Fc?RIIA. The present invention also provides the use of an anti-Fc?RIIB antibody or an antigen-binding fragment thereof, as a single agent therapy for the treatment, prevention, management, or amelioration of a cancer, preferably a B-cell malignancy, particularly, B-cell chronic lymphocytic leukemia or non-Hodgkin's lymphoma, an autoimmune disorder, an inflammatory disorder, an IgE-mediated allergic disorder, or one or more symptoms thereof. The invention provides methods of enhancing the therapeutic effect of therapeutic antibodies by administering the antibodies of the invention to enhance the effector function of the therapeutic antibodies. The invention also provides methods of enhancing efficacy of a vaccine composition by administering the antibodies of the invention.

Abstract: The present invention provides a method for the preparation of a human binding molecule, fragment or derivative thereof which specifically binds to the human CD3 complex. Furthermore, the invention provides a human binding molecules specifically binding to the human CD3 complex and means comprising said human binding molecules.

Abstract: The present invention relates to a method for assessing (analyzing) the risk of potential adverse effects for a human patient mediated by the administration of a CD19xCD3 bispecific antibody to said patient comprising determining the ratio of B cells to T cells of said patient, wherein a ratio of about 1:5 or lower is indicative for a risk of potential adverse effects for said patient or determining the total B cell count of said patient, wherein a total B cell count of less than about 50 B cells per microliter of peripheral blood is indicative for a risk of potential adverse effects for said patient.

Abstract: The present invention relates to DDR1 binding agents and methods of using the agents for treating diseases such as cancer. The present invention provides antibodies that specifically bind to an extracellular domain of DDR1 and modulate DDR1 activity. The present invention further provides methods of using agents that modulate the activity of DDR1, such as antibodies that specifically bind DDR1, to reduce the tumorigenicity of tumors comprising cancer stem cells by reducing the frequency or number of cancer stem cells in the tumor. Also described are methods of treating cancer comprising administering a therapeutically effect amount of an agent or antibody of the present invention to a patient having a tumor or cancer.

Abstract: This invention provides an antibody targeting a cancer antigenic protein specifically expressed on the surface of cancer cells and use thereof as a therapeutic and/or preventive agent for cancer. More specifically, the present invention provides an antibody, or a fragment thereof which has immunological reactivity with a CAPRIN-1 protein, the antibody comprising a heavy chain variable region comprising complementarity determining regions of SEQ ID NOs: 5, 6, and 7 and a light chain variable region comprising complementarity determining regions of SEQ ID NOs: 9, 10, and 11, and a pharmaceutical composition for treatment and/or prevention of cancer, comprising the same as an active ingredient.

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: Disclosed are methods, compositions and uses of high concentration antibody or immunoglobulin formulations for subcutaneous, intramuscular, transdermal or other local (regional) administration, in a volume of than 3, less than 2 or less than 1 ml. Preferably, the formulation contains a high concentration formulation (HCF) buffer comprising phosphate, citrate, polysorbate 80 and mannitol at a pH of about 5.2. The formulation more preferably comprises at least 100, 150, 200, 250 mg/ml or 300 mg/ml of antibody. The methods for preparing the high concentration formulation include ultrafiltration and diafiltration to concentrate the antibody and exchange the medium for HCF buffer. Other embodiments concern use of non-G1m1 (nG1m1) allotype antibodies, such as G1m3 and/or a nG1m1,2 antibodies. The nG1m1 antibodies show decreased immunogenicity compared to G1m1 antibodies.

Abstract: The present invention provides methods and compositions for treatment, screening, diagnosis and prognosis of acute myeloid leukemia (AML), B-cell chronic lymphocytic leukemia, breast cancer, colorectal cancer, kidney cancer, head and neck cancer, lung cancer, ovarian cancer or pancreatic cancer, for monitoring the effectiveness of acute myeloid leukemia (AML), B-cell chronic lymphocytic leukemia, breast cancer, colorectal cancer, kidney cancer, head and neck cancer, lung cancer, ovarian cancer or pancreatic cancer treatment, and for drug development. The present invention also provides methods and compositions for depletion of immune cells to treat inflammatory diseases.

Abstract: The present invention relates to bispecific anti-EGFR/anti IGF-1R antibodies, methods for their production, pharmaceutical compositions containing said antibodies, and uses thereof.

Abstract: The present invention relates to binding proteins that bind to HER-3 and polynucleotides encoding the same. Expression vectors and host cells comprising the same for the production of the binding protein of the invention are also provided. In addition, the invention provides compositions and methods for diagnosing and treating diseases associated with HER-3 mediated signal transduction and/or its ligand heregulin.

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 invention relates to anti-HER3/HER4 antigen binding proteins, e.g. anti-HER3/HER4 antibodies, that bind to the beta-hairpin of HER3 and the beta-hairpin of HER4, methods for selecting these antigen binding proteins, their preparation and use as medicament.

Abstract: The invention relates to antibody molecules having specificity for antigenic determinants of both IL-17A and IL-17F, therapeutic uses of the antibody molecules and methods for producing said antibody molecules.

Abstract: The present invention relates to a method for producing multivalent Fab fragments. In particular, the invention relates to a method for the generation of trimeric Fab fragments by co-expression of a gene construct comprising a heavy chain portion of a Fab fragment and an in-frame fused collagen-like peptide, and a gene construct consisting of a light chain portion of an IgG in mammalian cells. Uses of molecules generated using the method of the invention are also described.

Abstract: The disclosure provides binding proteins that specifically bind to IL-1? and IL-1?. These binding proteins can be organized into DVD-Igs. These proteins can be used to modulate the activity of IL-1? and/or IL-1? and can be used for the treatment immunological diseases such as rheumatoid arthritis, osteoarthritis, psoriasis, multiple sclerosis, and other autoimmune diseases. In addition, their uses in the amelioration and/or treatment of pain in an individual suffering from a disease or disorder associated with IL-1 accumulation.

Abstract: Disclosed are methods, compositions and uses of high concentration antibody or immunoglobulin formulations for subcutaneous, intramuscular, transdermal or other local (regional) administration, in a volume of than 3, less than 2 or less than 1 ml. Preferably, the formulation contains a high concentration formulation (HCF) buffer comprising phosphate, citrate, polysorbate 80 and mannitol at a pH of about 5.2. The formulation more preferably comprises at least 100, 150, 200, 250 mg/ml or 300 mg/ml of antibody. The methods for preparing the high concentration formulation include ultrafiltration and diafiltration to concentrate the antibody and exchange the medium for HCF buffer. Other embodiments concern use of non-G1m1 (nG1m1) allotype antibodies, such as G1m3 and/or a nG1m1,2 antibodies. The nG1m1 antibodies show decreased immunogenicity compared to G1m1 antibodies.

Abstract: Methods are provided for treatment of hematologic cancers, particularly lymphomas and leukemias, including without limitation myelogenous and lymphocytic leukemias. A combination of antibodies specific for CD47; and specific for a cancer associated cell surface marker are administered to the patient, and provide for a synergistic decrease in cancer cell burden. The combination of antibodies may comprise a plurality of monospecific antibodies, or a bispecific or multispecific antibody. Markers of interest include without limitation, CD20, CD22, CD52, CD33; CD96; CD44; CD123; CD97; CD99; PTHR2; and HAVCR2.

Abstract: Provided herein are compositions for increasing transport of agents across the blood-brain barrier, in some embodiments in both directions, while allowing their activity once across the barrier to remain substantially intact. The agents are transported across the blood-brain barrier via one or more endogenous receptor-mediated transport systems. In some embodiments the agents are therapeutic, diagnostic, or research agent. Also provided herein are nucleic acids encoding proteins contained in the compositions.

Abstract: Bispecific antibodies which comprise antigen-binding regions binding to two different epitopes of human epidermal growth factor receptor 2 (HER2), and related antibody-based compositions and molecules, are disclosed. Pharmaceutical compositions comprising the antibodies and methods of preparing and using the antibodies are also disclosed.

Abstract: Bispecific antibodies which comprise one antigen-binding region binding to an epitope of human epidermal growth factor receptor 2 (HER2) and one antigen-binding region binding to human CD3, and related antibody-based compositions and molecules, are disclosed. Pharmaceutical compositions comprising the antibodies and methods for preparing and using the antibodies are also disclosed.