Abstract: The present invention relates to a bispecific (monoclonal) antibody molecule with a first binding domain binding an antigen on CD8+ T-cells that does not naturally occur in and/or on CD8+ T-cells and a second binding domain binding to a tumor specific antigen naturally occurring on the surface of a tumor cell. The bispecific (monoclonal) antibody molecules are particularly useful in combination with transduced CD8+ T-cells comprising an antigen which does not naturally occur in and/or on CD8+ T-cells and/or a T-cell receptor.

Abstract: The invention relates to isolated, synthetic or recombinant antibodies and functional parts thereof specific for multiple influenza A virus subtypes. The invention further relates to the use of such antibodies for diagnosis of an influenza A virus infection and as a medicament and/or prophylactic agent for at least in part treating or alleviating symptoms of an influenza A virus infection.

Abstract: The present invention relates to RSPO-binding agents and methods of using the agents for treating diseases such as cancer. The present invention provides antibodies that specifically bind human RSPO proteins and modulate ?-catenin activity. The present invention further provides methods of using agents that modulate the activity of RSPO proteins, such as antibodies that specifically bind RSPO1, RSPO2, and/or RSPO3 and 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: 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: An anti-E1 ion channel antibody or binding fragment thereof, pharmaceutical compositions comprising said antibodies, use of the antibodies and compositions comprising the same, in treatment, for example in the treatment/modulation of pain and processes for generating and preparing said antibodies.

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 present invention relates to engineered multivalent and multispecific binding proteins, methods of making, and specifically to their uses in the prevention and/or treatment of acute and chronic inflammatory and other diseases.

Abstract: Adjuvant combinations comprising at least one NKT activator, such as alpha-galactosylceramide (?-Gal-Cer) or iGb3, a CD40 agonist and optionally an antigen are disclosed. The use of these immune adjuvants for treatment of various chronic diseases such as cancers is also provided.

Abstract: Disclosed herein are methods to inhibit cleavage of a type I receptor of transforming growth factor beta (T?RI) and reduce cancer cell invasiveness/metastasis, and agents and pharmaceutical compositions for use in these methods. Also disclosed herein are methods for identifying agents that inhibit cleavage of T?RI and methods for diagnosing and/or prognosing cancer based on nuclear localization of a intracellular domain of T?RI, which is a product of T?RI cleavage.

Abstract: The present invention is directed to optimized anti-CD3 variable sequences for use in a variety of bispecific formats, including those that utilize scFv components. The invention further relates to nucleic acids encoding for the polypeptide, to vectors comprising the same and to host cells comprising the vector. In another aspect, the invention provides for a pharmaceutical composition comprising the mentioned polypeptide and medical uses of the polypeptide.

Abstract: Multivalent antibody analogs that co-engage at least two different antigens or epitopes (also referred to “targets”, used interchangeably throughout), are provided, as well as methods for their production and use.

Abstract: It was found that association between CH1 and CL can be suppressed by substituting amino acids that exist on the interface between CH 1 and CL with electrically-charged amino acids, and that formation of heterogeneous molecules is enabled more efficiently than by introducing knobs into holes mutations into CH3 domain.

Abstract: The present invention relates to bispecific antibodies comprising at least one antigen binding site specific for DR5 and at least one antigen binding site specific for FAP, antibodies specific for DR5, methods for their production, pharmaceutical compositions containing said antibodies, and uses thereof.

Abstract: The present invention provides antibodies which bind to CXC chemokine receptor 4 (CXCR4) and which do not induce significant apoptosis of CXCR4 expressing cells. Also provided are inter alia immunoconjugates and compositions comprising such antibodies and methods and uses involving such antibodies, particularly in the medical and diagnostic fields.

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 invention concerns uses of anti-KL? agents, and detection of KL? and/or FGF19 and/or FGFR4.

Abstract: Disclosed are compositions and methods comprising combinations of anti-CD74 antibodies with a therapeutic agent that is attached to the anti-CD74 antibody or separately administered. Preferably, the therapeutic agent is an antibody that binds to an antigen different from CD74, such as CD19, CD20, CD21, CD22, CD23, CD37, CD40, CD40L, CD52, CD80, IL-6, CXCR4 or HLA-DR. However, the therapeutic agent may be an immunomodulator, a cytokine, a toxin or other known therapeutic agent. Preferably, the anti-CD74 antibody is part of a DNL complex. More preferably, combination therapy with the anti-CD74 antibody and therapeutic agent is more effective than antibody alone, therapeutic agent alone, or the combination of unconjugated anti-CD74 antibody and therapeutic agent. Administration of combination induces apoptosis of target cells in diseases in which CD74 is overexpressed, such as solid tumors, B-cell lymphomas or leukemias, autoimmune disease, immune dysfunction disease or diabetes.

Abstract: The present invention concerns methods and compositions for stably tethered structures of defined compositions with multiple functionalities and/or binding specificities. Particular embodiments concern stably tethered structures comprising a homodimer of a first monomer, comprising a dimerization and docking domain attached to a first precursor, and a second monomer comprising an anchoring domain attached to a second precursor. The first and second precursors may be virtually any molecule or structure, such as antibodies, antibody fragments, antibody analogs or mimetics, aptamers, binding peptides, fragments of binding proteins, known ligands for proteins or other molecules, enzymes, detectable labels or tags, therapeutic agents, toxins, pharmaceuticals, cytokines, interleukins, interferons, radioisotopes, proteins, peptides, peptide mimetics, polynucleotides, RNAi, oligosaccharides, natural or synthetic polymeric substances, nanoparticles, quantum dots, organic or inorganic compounds, etc.

Abstract: Methods and agents are disclosed based on the finding that 5T4 interacts with CXCR4 in the cell membrane to form a complex, and that the 5T4 transmembrane region is involved in the promotion of CXCR4 membrane expression and chemotactic response.

Abstract: Engineered multivalent and multispecific binding proteins that bind IL-1? and/or IL-17 are provided, along with methods of making and uses in the prevention, diagnosis, and/or treatment of disease.

Abstract: A method of target membrane protein depletion comprising treating a cell with a dual binding molecule comprising a first binding domain which binds to a driver membrane protein and a second binding domain which binds to a target membrane protein, wherein the cell comprises a cell membrane, and the driver membrane protein and target membrane protein are associated with the cell membrane where the target membrane protein positions, and are internalized into a cell and degraded when the first binding domain of the dual binding molecule binds the driver membrane protein; as well as related methods and compositions.

Abstract: The present invention relates to antibodies (including anti-B7-H4 antibodies) and their antigen-binding fragments and to other molecules (including fusion proteins that bind to the cognate antigen/receptor, etc.) that are capable of immunospecifically binding to B7-H4 and the uses of such molecules in the diagnosis and the treatment of cancer and other diseases. The invention particularly concerns the use of such molecules to retard or prevent tumor growth, inhibit tumor-mediated suppression, eliminate tumors and/or deplete or block the activity of tumor associated macrophages (“TAMs”) so as to alter their activity and/or decrease TAM—mediated immune suppression.

Abstract: The invention relates to novel methods for the treatment of tumors, comprising administration of a bispecific antibody or a combination of two or more non-cross-blocking antibodies that recognize the same target antigen or antigenic complex. In particular, the invention relates to a method for inducing complement-mediated cell killing in the treatment of a tumor, said method comprising combined administration, to a human being in need thereof, of a first antibody and a second antibody, wherein said first antibody binds EGFR, said second antibody binds EGFR, said first and second antibody are non-cross-blocking, and the dosage regimen is such that CDC is obtained at the tumor site.

Abstract: The present invention relates to antibodies (and fragments, variants, fusions and derivatives thereof) with multivalent binding specificity for CD40, which have a potency for dendritic cell activation which is higher than, or is equal to, the potency for B cell activation and wherein the antibody, antigen-binding fragment, or fusion, variant or derivative thereof has an affinity (KD) for CD40 of less than 1×10?10 M, which have utility in the treatment of diseases such as cancer. The invention also relates to pharmaceutical compositions, uses, methods and kits comprising such antibodies.

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: The invention relates to amino acid sequences that are directed against and/or that can specifically bind to IL-6 receptor, compounds or constructs that comprise said amino acid sequence, nucleic acids that encode said amino acid sequences, compounds or constructs, pharmaceutical compositions comprising said amino acid sequences, compounds or constructs as well as methods for the prevention and/or treatment of diseases and disorders associated with IL-6 receptor.

Abstract: The present invention provides a bispecific biologic comprising a ligand specific for CTLA-4 and a ligand specific for a pMHC complex.

Abstract: Disclosed herein are multivalent and multispecific binding proteins, methods of making the binding proteins, and their uses in the diagnosis, monitoring, inhibition, prevention and/or treatment of cancers, tumors, and/or other angiogenesis-dependent diseases diseases characterized by aberrant DLL4 and/or VEGF expression or activity.

Abstract: Proteins that bind IL-17 and/or IL-17F are described along with their 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: 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: The technology relates in part to engineered antibodies. In particular, multispecific engineered antibodies. Such antibodies can be utilized for diagnostic and therapeutic applications in some aspects.

Abstract: The present invention relates to therapeutic agents comprising bispecific recombinant antibody fragments to selectively clear a protein associated with a neurological disease and methods of use of these therapeutic agents to treat neurological diseases.

Abstract: The present invention features inter alia polypeptides comprising heterodimeric Fc regions. In addition, the instant invention provides methods for treating or preventing a disease or disorder in subject by administering the polypeptides of the invention to said subject.

Abstract: The present invention relates to the treatment of osteoarthritis and pain using IL-1? and IL-1? binding proteins, including anti-IL-1? and anti-IL-1? antibodies and engineered multivalent and multispecific IL-1? and IL-1? binding proteins.

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 inventors created antigen-binding molecules containing an antigen-binding domain and an Fc?-receptor-binding domain, wherein the molecules have human-FcRn-binding activity in an acidic pH range condition, the antigen-binding domain changes the antigen-binding activity of the antigen-binding molecules depending on the ion-concentration condition, and the Fc? receptor-binding domain has higher binding activity to the Fc? receptor in a neutral pH range condition than an Fc region of a native human IgG in which the sugar chain bound at position 297 (EU numbering) is a fucose-containing sugar chain.

Abstract: Methods of treating or delaying onset of a neurodegenerative disorder with ?-synuclein pathology in an individual comprise administering an antibody which is produced from a stabilized soluble ?-synuclein oligomer and capable of binding a stabilized soluble ?-synuclein oligomer, the stabilized soluble ?-synuclein oligomer having a lower formation rate to a non-soluble aggregated form than a non-stabilized soluble oligomer of the ?-synuclein. The antibody has been collected from a non-human animal to which stabilized soluble ?-synuclein oligomer had been administered or has been produced by hybridoma technology, phage display, ribosome display, mammalian cell display or bacterial display, and the disorder with ?-synuclein pathology is characterized by deposition of Lewy bodies and Lewy neurites or is selected from the group consisting of Parkinson's disease (PD), dementia with Lewy bodies (DLB), the Lewy body variant of Alzheimer's disease, and multiple system atrophy (MSA).

Abstract: Methods for treating cancer comprising administering a DLL4 antagonist and one or more anti-hypertensive agents are described. Also described are pharmaceutical compositions comprising a DLL4 antagonist and one or more anti-hypertensive agents, and kits comprising the same.

Abstract: The present invention relates to LRP6 constructs that bind to LRP6 receptor. The LRP6 constructs comprise at least one LRP6 binding moiety and a half-life extender molecule such that the LRP6 construct inhibit the Wnt signaling pathway without potentiation of the Wnt signal. The LRP6 constructs also have an increased half-life to provide more time for the therapeutic benefit.

Abstract: The present invention relates to methods of treatment, prevention, management or amelioration of one or more symptoms of diseases or disorders associated with CD20 expression that encompass administration of a combination of: (A) one or more antibodies that specifically bind Fc?RIIB, particularly human Fc?RIIB, with greater affinity than said antibodies bind Fc?RIIA, and (B) one or more antibodies that specifically bind to CD20. Such methods include methods of treating, preventing, managing or ameliorating one or more symptoms of a B cell related disease or disorder or an inflammatory disorder. The invention also provides pharmaceutical compositions comprising an anti-Fc?RIIB antibody and an anti-CD20 antibody.

Abstract: The present invention relates to antibodies 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 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: In certain aspects, the present invention provides compositions and methods for increasing thermogenic adipocytes (e.g., brown adipocytes or other UCP-1 expressing adipocytes) by administering an antagonist of an ActRIIB signaling pathway. Examples of such antagonists include ActRIIB polypeptides, anti-ActRIIB antibodies, anti-myostatin antibodies, anti-GDF3 antibodies, anti-Noda1, anti-activin, and anti-GDF11 antibodies. A variety of metabolic and other disorders may be treated by causing an increase in thermogenic adipocytes.

Abstract: This invention relates to methods that provide immunosuppressants and therapeutic macromolecules that are administered within a pharmacodynamically effective window of the immunosuppressants to induce immune tolerance to the therapeutic macromolecules. The methods allow shifting the immune response in favor of tolerogenic immune response development specific to the therapeutic macromolecule.

Abstract: The invention relates to antibodies that are reactive to the cell surface of CD19+ B cells, including B-cell chronic lymphocytic leukemia (B-CLL) cells, and compositions and methods for using such antibodies, including in the diagnosis and treatment of disorders associated with CD19+ B cells, such as B-CLL.

Abstract: The present application describes engineered antibodies, with three or more functional antigen binding sites, and uses, such as therapeutic applications, for such engineered antibodies.

Abstract: The present invention provides to a antibody construct comprising a first human binding domain capable of binding to human CDH19 on the surface of a target cell and a second domain capable of binding to human CD3 on the surface of a T cell. Moreover, the invention relates to a nucleic acid sequence encoding the antibody construct, a vector comprising said nucleic acid sequence and a host cell transformed or transfected with said vector. Furthermore, the invention relates a process for the production of the antibody construct of the invention, a medical use of said antibody construct and a kit comprising said antibody construct.

Abstract: Disclosed are the surprising discoveries that aminophospholipids, such as phosphatidylserine and phosphatidylethanolamine, are stable and specific markers accessible on the luminal surface of tumor blood vessels, and that the administration of an anti-aminophospholipid antibody alone is sufficient to induce thrombosis, tumor necrosis and tumor regression in vivo. This invention therefore provides anti-aminophospholipid antibody-based methods and compositions for use in the specific destruction of tumor blood vessels and in the treatment of solid tumors. Although various antibody conjugates and combinations are thus provided, the use of naked, or unconjugated, anti-phosphatidylserine antibodies is a particularly important aspect of the invention, due to simplicity and effectiveness of the approach.

Abstract: Disclosed herein are compositions and methods of use comprising hexavalent DNL complexes. Preferably, the complexes comprise anti-CD20 and/or anti-CD22 antibodies or fragments thereof. More preferably, the anti-CD20 antibody is veltuzumab and the anti-CD22 antibody is epratuzumab. Administration of the subject hexavalent DNL complexes induces apoptosis and cell death of target cells in diseases such as B-cell lymphomas or leukemias, autoimmune disease or immune dysfunction disease. In most preferred embodiments, the DNL complexes increase levels of phosphorylated p38 and PTEN, decrease levels of phosphorylated Lyn, Akt, ERK, IKK?/? and I?B?, increase expression of RKIP and Bax and decrease expression of Mcl-1, Bcl-xL, Bcl-2, and phospho-BAD in target cells. The subject DNL complexes show EC50 values for inhibiting tumor cell growth in the low nanomolar or even sub-nanomolar concentration range.

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: The present invention relates generally to antibodies cross-reactive with IL-17A and IL-17F, and bispecific anti-IL-17A/F and their uses.