Abstract: Disclosed herein are methods and compositions comprising anti-CD74 and/or anti-HLA-DR antibodies for treatment of GVHD and other immune dysfunction diseases. In preferred embodiments, the anti-CD74 and/or anti-HLA-DR antibodies are effective to deplete antigen-presenting cells, such as dendritic cells. Most preferably, administration of the therapeutic compositions depletes all subsets of APCs, including mDCs, pDCs, B cells and monocytes, without significant depletion of T cells. In alternative embodiments, administration of the therapeutic compositions suppresses proliferation of allo-reactive T cells, while preserving cytomegalovirus (CMV)-specific, CD8+ memory T cells. The compositions and methods provide a novel conditioning regimen for preventing aGVHD and/or treating chronic GVHD, without altering preexisting anti-viral immunity.

Abstract: The present invention relates to VEGF-binding agents, DLL4-binding agents, VEGF/DLL4 bispecific binding agents, and methods of using the agents for treating diseases such as cancer. The present invention provides antibodies that specifically bind human VEGF, antibodies that specifically bind human DLL4, and bispecific antibodies that specifically bind human VEGF and/or human DLL4. The present invention further provides methods of using the agents to inhibit tumor growth. 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: A method for treating or preventing an inflammatory bowel disease (IBD) in a subject, the method comprising administering to the subject a compound that inhibits granulocyte-macrophage colony stimulating factor (GM-CSF) signaling.

Abstract: A sterile pharmaceutically acceptable aqueous solution, which solution is provided in a sealed container and comprises: a pharmaceutically acceptable aqueous solvent; viral particles or a physiologically active polypeptide; an excipient selected from a polyethyleneimine; a compound of formula (I) or a physiologically acceptable salt or ester thereof; or a compound of formula (II) or a physiologically acceptable salt or ester thereof; and optionally, one or more sugars.

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 provides compositions and methods useful for diagnosing, treating, and preventing cancer, particularly ovarian cancer and uterine cancer, based on the discovery that the oocyte specific protein, SAS1R (Sperm Acrosomal SLL-P1 Receptor), which is a sperm protein receptor, is also expressed in various cancers, including ovarian cancer and uterine cancer. Six SAS1R variants have been previously identified, and they are encompassed by the invention. The present invention further provides antibodies useful for targeting SAS1R expressing cells and for killing such cells.

Abstract: The invention relates to bispecific anti-sclerostin/anti-DKK1 binding agents and combinations of anti-sclerostin and anti-DKK1 binding agents, and related methods of treatment.

Abstract: A fusion polypeptide comprising (A)x-M-(A?)y, wherein A and A? are each polypeptides capable of binding a target receptor. The fusion polypeptides of the invention form multimeric proteins which activate the target receptor. A and A? may be each be an antibody or fragment derived from an antibody specific for a target receptor, such as the same or different scFv fragments, and/or a ligand or ligand fragment or derivative capable of binding the target protein, M is a multimerizing component, and X and Y are independently a number between 1-10.

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: Described herein are novel approaches for regenerating injured or defective lung epithelium for the treatment of respiratory disorders using, in part, cord blood-derived hematopoietic stem cells. The methods and uses described herein relate to the administration of or use of hematopoietic stem cells, specifically those isolated or enriched from umbilical cord blood, to a subject in need thereof having a respiratory disorder, such as BPD, or any disorder characterized by insufficient or defective or injured lung epithelium or lung vasculature.

Abstract: The present invention relates to bispecific antibodies against human ErbB-1 and against human c-Met, methods for their production, pharmaceutical compositions containing the antibodies, and uses thereof.

Abstract: The present invention relates to a binding molecule which is at least bispecific comprising a first and a second binding domain, wherein the first binding domain is capable of binding to epitope cluster 3 of BCMA, and the second binding domain is capable of binding to the T cell CD3 receptor complex. Moreover, the invention provides a nucleic acid sequence encoding the binding molecule, a vector comprising said nucleic acid sequence and a host cell transformed or transfected with said vector. Furthermore, the invention provides a process for the production of the binding molecule of the invention, a medical use of said binding molecule and a kit comprising said binding molecule.

Abstract: The present invention relates to a binding molecule comprising a first and a second binding domain, wherein the first binding domain is capable of binding to epitope clusters of BCMA, and the second binding domain is capable of binding to the T cell CD3 receptor complex. Moreover, the invention provides a nucleic acid sequence encoding the binding molecule, a vector comprising said nucleic acid sequence and a host cell transformed or transfected with said vector. Furthermore, the invention provides a process for the production of the binding molecule of the invention, a medical use of said binding molecule and a kit comprising said binding molecule.

Abstract: Described herein are novel compositions comprising bispecific and multispecific polypeptide agents, and methods using these agents for targeting cells, such as functionally exhausted or unresponsive immune cells, that co-express the inhibitory receptors PD-1 and TIM-3. These compositions and methods are useful for the treatment of chronic immune conditions, such as persistent infections or cancer.

Abstract: The invention provides shuttle agents and methods of using the same to facilitate the translocation of therapeutic or diagnostic molecules into the CNS.

Abstract: The present invention concerns antibodies to EGFL7 and the uses of same.

Abstract: The present invention relates to compositions and methods for treatment of disease. More particularly, the present invention relates to anti-IL-1? and anti-IL-18 antibodies, including anti-IL-1? and anti-IL-18 bispecific antibodies, and methods of treating disease using such antibodies.

Abstract: The present invention relates to antibodies and their fragments that are immunoreactive to the mammalian, and more particularly, the human B7-H3 receptor and to uses thereof, particularly in the treatment of cancer and inflammation. The invention thus particularly concerns humanized B7-H3-reactive antibodies and their immunoreactive fragments that are capable of mediating, and more preferably enhancing the activation of the immune system against cancer cells that are associated with a variety of human cancers.

Abstract: The present invention relates to the identification of membrane proteins associated with B-cell non-Hodgkin's lymphoma, breast cancer, cervical cancer, colorectal cancer, gastric cancer, glioblastoma, hepatocellular carcinoma, lung cancer, lymphoid leukaemia (particularly acute T-cell leukaemia and chronic lymphocytic leukaemia), melanoma, neuroblastoma, osteosarcoma, ovarian cancer, pancreatic cancer, prostate cancer, renal cell cancer and retinoblastoma which have utility as markers and for treatment of said cancers and which also form biological targets against which antibodies such as therapeutic antibodies (or other affinity reagents) or other pharmaceutical agents can be made.

Abstract: In one aspect, the invention relates to a method suitable for administering protein therapeutic molecules orally, sublingually, topically, intravenously, subcutaneously, nasally, vaginally, rectally or by inhalation so as to avoid inactivation, by using VHH polypeptides derived from Camelidae antibodies. The invention further relates to the said therapeutic molecules. The invention further a method for delivering therapeutic molecules to the interior of cells. The invention further relates to anti-IgE therapeutic molecules. In one aspect, the present invention relates to a method wherein an immunoglobulin single variable domain (such as a Nanobody) and/or construct thereof are absorbed in pulmonary tissue. More particularly, the invention provides systemic delivery of an immunoglobulin single variable domain and/or construct thereof via the pulmonary route.

Abstract: The present disclosure relates generally to compositions and methods for the diagnosis, prognosis and treatment of leukemia, in particular leukemia in which leukemic cells, or neoplastic precursors thereof, express Fat1 or a homolog of Fat1 that is substantially not expressed on normal blood cells.

Abstract: The present invention concerns antibodies to EGFL7 and the uses of same.

Abstract: Method for producing microbially stabilized foods characterized in that a food containing a dialkyl dicarbonate is treated by means of electroporation.

Abstract: The invention provides anti-EGFL7 antibodies, and compositions comprising and methods of using these antibodies.

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 hA19VH sequence.

Abstract: The present invention provides compositions and methods which involve specifically antagonizing GDF8 and Activin A. In certain embodiments, compositions are provided which comprise a GDF8-specific binding protein and an Activin A-specific binding protein. For example, the invention includes compositions comprising an anti-GDF8 antibody and an anti-Activin A antibody. In other embodiments, antigen-binding molecules are provided which comprise a GDF8-specific binding domain and an Activin A-specific binding domain. For example, the invention includes bispecific antibodies that bind GDF8 and Activin A. The compositions of the present invention are useful for the treatment of diseases and conditions characterized by reduced muscle mass or strength, as well as other conditions which are treatable by antagonizing GDF8 and/or Activin A activity.

Abstract: Methods for improving the biological and pharmaceutical properties of bispecific binding agents are described herein where the bispecific binding agents are able to target cells by a high affinity binding domain to a first cell surface marker that does not induce a significant biological effect and a low affinity binding domain that binds specifically to a second cell surface marker, causing a significant and desired biological effect. Compositions of such bispecific binding agents, uses for them, and kits containing them are also provided.

Abstract: Described herein is an antibody format, which is amenable to bispecific antibody creation. This format is referred to herein as “Domain Insertion Immunoglobulin G” or “(Di-IgG)”. The Di-IgG molecules are capable of specifically binding two different antigens simultaneously, show high level recombinant expression, and are sufficiently aggregation-free to be amenable to commercial production. Further described herein are, Di-IgG-encoding nucleic acids and vectors, host cells for making Di-IgGs, Di-IgG pharmaceutical compositions, and methods of treatment.

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 invention relates to fusion proteins comprising a stress protein fused with an engineered antibody or fragment that binds to mesothelin, or a stress protein fused with a biotin-binding protein in combination with a biotinylated engineered antibody or fragment that binds to mesothelin. The invention also relates to fusion proteins comprising a stress protein fused with an antibody binding protein in combination with an engineered antibody or fragment that binds to mesothelin. The invention also relates to fusion proteins comprising an engineered antibody or fragment that binds specifically to mesothelin fused in frame with a biotin binding protein. The invention also provides fusion proteins comprising an engineered antibody or fragment, that binds to mesothelin, fused with an antibody binding protein. The invention also relates to methods of using fusion proteins of the invention to induce an immune response to mesothelin and to treat disease.

Abstract: The present invention relates to compositions and methods for characterizing, diagnosing, and treating cancer. In particular the invention provides the means and methods for the diagnosis, characterization, prognosis and treatment of cancer and specifically targeting cancer stem cells. The present invention provides an antibody that specifically binds to a non-ligand binding membrane proximal region of the extracellular domain of a human Notch receptor and inhibits tumor growth. The present invention further provides a method of treating cancer, the method comprising administering a therapeutically effective amount of an antibody that specifically binds to a non-ligand binding membrane proximal region of the extracellular domain of a human Notch receptor protein and inhibits tumor growth.

Abstract: An antikine antibody binds to two, three, four, five or more CC chemokines, such as RANTES/CCL5, MIP-1?/CCL3, MIP-1?/CCL4, or MCP-1/CCL2. Methods for affinity maturation and humanization of antikine antibodies as well as the production of hybridoma cell lines producing antikine antibodies by sequential immunization are also disclosed.

Abstract: The invention provides a fusion protein comprising (a) a first protein comprising a polypeptide which specifically binds to Annexin A1 and (b) a second protein comprising a polypeptide which induces a cytotoxic activity of a cytotoxic lymphocyte, pharmaceutical compositions comprising the fusion protein, and methods of treating or preventing cancer by administering the pharmaceutical compositions.

Abstract: The invention provides antibodies that bind to multiple antigens, said antibodies having at least two antibody light chain variable domains and two antibody heavy chain variable domains, wherein each light chain variable domain is linked to a heavy chain variable domain to form a VH/VL construct, and wherein at least one of the VH domains comprises a particular amino acid at AHo position 12, 103 and/or 144, and at least one of the VL domains comprises a particular amino acid at AHo position 47 and/or 50. Nucleic acid molecules, vectors and host cells for expression of the recombinant antibodies of the invention, methods for isolating them, and the use of said antibodies in medicine are also disclosed.

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: 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: The invention relates to use of the natural cytotoxicity receptor NKp46 for preventing and treating diabetes, including type I diabetes (TID) and type 2 diabetes. In particular, the invention provides compositions comprising a fragment of the extracellular region of NKp46 for preventing the onset and progression of diabetes.

Abstract: The present invention is directed to compositions of matter useful for the treatment of hematopoietic tumor in mammals and to methods of using those compositions of matter for the same.

Abstract: The present invention is directed to compositions of matter useful for the treatment of hematopoietic tumor in mammals and to methods of using those compositions of matter for the same.

Abstract: This disclosure provides immunoglobulin binding molecules that specifically bind to human macrophage stimulating receptor (MST1 R, also referred to herein as recepteur d'origine Nantaise or RON), including antibodies and monospecific and multispecific single chain binding proteins having one or more other domains, such as one or more antibody constant region domains. Also provided are therapeutic applications of such binding proteins, such as for the treatment of cancer and inflammatory disorders.

Abstract: The invention relates to a method of treatment of pulmonary edema, comprising the step of administering to a subject in need thereof a therapeutically effective amount of an agent capable of inhibiting signaling mediated by VEGFR-3, inhibiting lymphangiogenesis or inhibiting VEGF-D activity in the subject. The method may comprise the step of identifying a subject at risk of developing pulmonary edema. The invention also relates to an agent capable of inhibiting signaling mediated by VEGFR-3, inhibiting lymphangiogenesis, or inhibiting VEGF-D activity for treating pulmonary edema in a subject. Further, the invention relates to use of an agent capable of inhibiting signaling mediated by VEGFR-3, inhibiting lymphangiogenesis, or inhibiting VEGF-D activity in the manufacture of a medicament for treating pulmonary edema in a subject.

Abstract: The invention relates to a method of preparing heteromultimeric polypeptides such as bispecific antibodies, bispecific immunoadhesins, heteromultimers and antibody-immunoadhesin chimeras. Generally, the method involves introducing a protuberance at the interface of a first polypeptide and a corresponding cavity in the interface of a second polypeptide, such that the protuberance can be positioned in the cavity so as to promote heteromultimer formation and hinder homomultimer formation. The protuberance and cavity can be made by synthetic means such as altering the nucleic acid encoding the polypeptides or by peptide synthesis.

Abstract: The invention relates to the field of recombinant antibodies for use in human cancer therapy. More specifically the invention provides compositions or mixtures of antibodies capable of binding human EGFR. Antibody compositions with 3 or more antibodies showed synergy in reduction of proliferation of representative cancer cell lines. Advantageous results have also been obtained with a composition comprising two different chimeric anti-hEGFR antibodies which show a new mechanism of action based on rapid and efficient receptor internalisation, induction of terminal differentiation and subsequent tumour eradication in an animal model. The antibodies of the invention can be manufactured in one bioreactor as a polyclonal antibody.

Abstract: Methods of treating a food allergy, allergic reactions, hypersensitivity, inflammatory responses, inflammation are provided. In one method, histamine releasing factor (HRF)/translationally controlled tumor protein (TCTP) is contacted with a compound that inhibits or reduces binding of HRF/TCTP to an immunoglobulin in order to treat the food allergy, allergic reaction, hypersensitivity, inflammatory response, or inflammation. Methods of reducing or decreasing the probability, severity, frequency, duration or preventing a subject from having an acute or chronic food allergy, allergic reaction, hypersensitivity, an inflammatory response or inflammation, are also provided.

Abstract: The present invention relates generally to the generation and characterization of neutralizing anti-IFN-? monoclonal antibodies with broad reactivity against various IFN-? subtypes. The invention further relates to the use of such anti-IFN-? antibodies in the diagnosis and treatment of disorders associated with increased expression of IFN-?, in particular, autoimmune disorders such as insulin-dependent diabetes mellitus (IDDM) and systemic lupus erythematosus (SLE).

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: Bispecific binding molecules binding to both VEGF and Ang2, preferably in the form of immunoglobulin single variable domains like VHHs and domain antibodies, pharmaceutical compositions containing the same and their use in the treatment of diseases that are associated with VEGF- and/or Ang2-mediated effects on angiogenesis are disclosed. Further, nucleic acids encoding bispecific binding molecules, host cells and methods for preparing same are also described.

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: Bispecific binding molecules binding to both DII4 and Ang2, preferably in the form of immunoglobulin single variable domains like VHHs and domain antibodies, pharmaceutical compositions containing the same and their use in the treatment of diseases that are associated with DII4- and/or Ang2-mediated effects on angiogenesis are disclosed. Further, nucleic acids encoding bispecific binding molecules, host cells and methods for preparing same are also described.