Abstract: Methods of using anti-FceRI or anti-IgE antibodies for treating an autoimmune disease are disclosed. Also disclosed is a composition comprising an anti-FceRI antibody or anti-IgE antibody for use in treating an autoimmune disease. Also disclosed are non-antibody compounds that specifically activate basophils and/or mast cells, either by cross-linking IgE or FceRI, or by activating the cells through an FceRI-independent pathway and methods of using the same to treat autoimmune diseases.

Abstract: The present invention provides peptides, and fragments thereof, and antibodies, or fragments thereof comprising the same, wherein the peptide comprises at least one amino acid substitution compared to wild type 5c8 antibody. The present invention also provides compositions and methods of treating CD154-related diseases or disorders in a subject.

Abstract: The present invention comprises a humanized monoclonal antibody that binds to the chemokine receptor CCR4. This antibody is derived from Mab 1567 and recognizes the same epitope. Binding of the invented antibody to CCR4 inhibits ligand-mediated activities and is used to treat symptoms of cancer. Moreover, the antibody is used in combination with vaccines to suppress the activity of regulatory T cells.

Abstract: The present invention provides for the treatment of multiple sclerosis through the use of chimeric and humanized versions of anti-CD19 antibodies that may mediate ADCC, CDC, and/or apoptosis.

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: Provided is a porcine CD28 receptor molecule, which is: 1) a protein consisting of an amino acid sequence represented by SEQ ID NO:2, or 2) a protein derived from 1) by substitution, deletion or addition of one or several amino acids in the amino acid sequence represented by SEQ ID NO:2 and having equivalent activity with 1). Further provided is a gene for coding the porcine CD28 receptor, the nucleotide sequence of which is shown as SEQ ID NO:1. When the provided co-stimulating receptor CD28 is expressed specifically and highly in a T cell, the activation, proliferation and cell factor secretion activity of the T cell when stimulated by an antigen can be enhanced, thereby enhancing the acquired immune response of a host and enhancing the immune effect of a vaccine. FIG. 8 is selected as the drawing attached to the Abstract.

Abstract: The present invention relates to use of an antagonist of BIR1 (B cell immunoglobulin receptor 1) related to the present invention, a method for screening the antagonist, in addition to subtype polypeptides of BIR1, the polynucleotide encoding them and antibodies for the polypeptides. BIR1 functions as an immunosuppressive receptor, and the antagonist of BIR1 has immunopotentive activity, which is able to use for preventing and/or treating a cancer, an immunodeficiency disease or an infectious disease.

Abstract: Stable liquid pharmaceutical compositions comprising an antagonist anti-CD40 antibody as a therapeutically or prophylactically active component and methods useful in their preparation are provided. These compositions comprise the antagonist anti-CD40 antibody, a buffering agent to maintain the pH of the composition between about pH 5.0 and about pH 7.0, and an amount of arginine-HCl sufficient to render the liquid composition near isotonic. The stable liquid antagonist anti-CD40 antibody-containing pharmaceutical compositions of the invention find use in methods for treating proliferative diseases and diseases having an autoimmune and/or inflammatory component.

Abstract: Method of identifying a modulator of CD28 comprising comparing a structural model of a candidate modulator with a structural model of CD28 to thereby determine whether the modulator will bind to CD28, wherein the structural model is derived from, or comprises, structural coordinates of a crystal of: (i) CD28, (ii) a fragment of CD28, or (iii) a homolog of (i) or (ii). The crystal of CD28 in a soluble form complexed with the Fab fragment of a mitogenic (superagonistic) antibody has been obtained and used for the determination of the 3D-structure of the receptor. The application also relates to modulators of superagonistic signalling for any receptor of the CD28 family, i.e. to superagonistic antibodies and chimeric proteins thereof, and to the screening of the superagonistic modulators. In the methods of screening, the binding of the candidate modulators to a portion of the receptor proximal to the cell membrane is investigated.

Abstract: The present invention relates to antibodies or fragments thereof that specifically bind Fc?RIIB, particularly human Fc?RIIB, more particularly the extracellular domain of Fc?RIIB with greater affinity than said antibodies or fragments thereof bind Fc?RIIA, particularly human Fc?RIIA, and block the Fc binding site of Fc?RIIB. The present invention also encompasses 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 present invention also encompasses the use of an anti-Fc?RIIB antibody or an antigen-binding fragment thereof, in combination with other cancer therapies.

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: Methods for treating a human patient for a cancer or pre-malignant condition that is associated with CD40-expressing cells are provided, where the human patient is heterozygous or homozygous for Fc?RIIIa-158F (genotype V/F or F/F). Also provided are methods of inhibiting antibody production by B cells in a human patient who is heterozygous or homozygous for Fc?RIIIa-158F (genotype V/F or F/F). The methods comprise administering to the human patient a therapeutically or prophylactically effective amount of an anti-CD40 antibody. Methods and kits for identifying a human patient with a cancer or pre-malignant condition that is treatable with an anti-CD40 antibody and which is refractory to treatment with rituximab (Rituxan®), as well as methods and kits for selecting an antibody therapy for treatment of a human patient having a cancer or pre-malignant condition that is refractory to treatment with rituximab (Rituxan®), are also provided.

Abstract: Disclosed are methods and compositions for the detection, diagnosis, prognosis, and therapy of hematological malignancies, and in particular, B cell leukemias, lymphomas and multiple myelomas. Disclosed are compositions, methods and kits for eliciting immune and T cell responses to specific malignancy-related antigenic polypeptides and antigenic polypeptide fragments thereof in an animal. Also disclosed are compositions and methods for use in the identification of cells and biological samples containing one or more hematological malignancy-related compositions, and methods for the detection and diagnosis of such diseases and affected cell types. Also disclosed are diagnostic and therapeutic kits, as well as methods for the diagnosis, therapy and/or prevention of variety of leukemias and lymphomas.

Abstract: This method provides a method for reducing HIV-1 viral load in an HIV-1-infected human subject which comprises administering to the subject at a predefined interval effective HIV-1 viral load-reducing doses of (a) a humanized antibody designated PRO 140, or of (b) an anti-CCR5 receptor monoclonal antibody. This invention also provides a method for inhibiting in a human subject the onset or progression of an HIV-1-associated disorder, the inhibition of which is effected by inhibiting fusion of HIV-1 to CCR5+CD4+ target cells in the subject. This invention also provides a method for treating a subject infected with HIV-1 comprising administering to the subject (a) a monoclonal antibody which (i) binds to a CCR5 receptor on the surface of the subject's CD4+ cells and (ii) inhibits fusion of HIV-1 to the subject's CCR5+CD4+ cells, and (b) a non-antibody CCR5 receptor antagonist, in amounts effective to treat the subject.

Abstract: The present invention relates generally to binding agents useful in the selective depletion of T cells in vivo. More specifically, the invention relates to ICOS-binding agents which once bound to ICOS expressed on the surface of cells, in particular ICOS-bearing activated T cells, result in the in vivo depletion of cells to which they are bound. Methods of treating T cell related diseases using said ICOS-binding agents, and pharmaceutical compositions comprising said ICOS-binding agents, a method of identifying an ICOS-binding agent, and monoclonal anti-ICOS antibodies capable of eliminating cells in vivo which express ICOS on their surface are also provided.

Abstract: A highly stable mutant of human IgG4 antibody is provided. Such antibody is an antibody in which the CH3 domain of human IgG4 is substituted with the CH3 domain of human IgG1 and which exhibits inhibited aggregate formation, an antibody in which the CH3 and CH2 domains of human IgG4 are substituted with the CH3 and CH2 domains of human IgG1, respectively, or an antibody in which arginine at position 409 indicated in the EU index proposed by Kabat et al. of human IgG4 is substituted with lysine and which exhibits inhibited aggregate formation.

Abstract: A method is provided for preventing rejection by an immune system of a recipient subject of a tissue transplanted from a donor subject into the recipient subject without the need for long-term administration of non-specific immunosuppressive drugs.

Abstract: The invention provides methods for treating a malignant neoplastic cell proliferative disorder or disease, comprising administering to a subject in need thereof an effective amount of an mTOR inhibitor and an effective amount of a CD4 lymphocyte depleting agent. Such methods find utility in the treatment of certain subsets of malignant neoplastic cell proliferative disorders or diseases, e.g. renal cell carcinoma and melanoma. The invention also provides for pharmaceutical compositions comprising a therapeutically effective amount of an mTOR inhibitor and an effective amount of a CD4 lymphocyte depleting agent in a pharmaceutically acceptable carrier.

Abstract: Antibodies which block binding of hPD-1 to hPD-L1 or hPD-L2 and their variable region sequences are disclosed. A method of increasing the activity (or reducing downmodulation) of an immune cell through the PD-1 pathway is also disclosed.

Abstract: Antibody polypeptides that specifically bind human CD40L are provided. The antibody polypeptides do not activate platelets. The antibody polypeptides are useful in the treatment of diseases involving CD40L activation, such as graft-related diseases and autoimmune diseases. The antibody polypeptides may be domain antibodies (dAbs) comprising a single VH or VK domain. The half-life of the antibody polypeptides may be increased by modifying the antibody polypeptides to be dual specific reagents that can also bind human serum albumin (HSA) or another antigen.

Abstract: In accordance with the present invention, there are provided fully human monoclonal antibodies against human cytotoxic T-lymphocyte antigen 4 (CTLA-4). Nucleotide sequences encoding and amino acid sequences comprising heavy and light chain immunoglobulin molecules, particularly contiguous heavy and light chain sequences spanning the complementarity determining regions (CDRs), specifically from within FR1 and/or CDR1 through CDR3 and/or within FR4, are provided. Further provided are antibodies having similar binding properties and antibodies (or other antagonists) having similar functionality as antibodies disclosed herein.

Abstract: An Fc variant of a parent Fc polypeptide, wherein said Fc variant exhibits altered binding to one or more Fc?Rs, wherein said Fc variant comprises at least one amino acid insertion in the Fc region of said parent Fc polypeptide.

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 disclosure relates to antibodies or antigen binding fragments that specifically bind to CXCR4 and inhibit the biological activity of CXCR4 and uses of such agents. More specifically the disclosure relates to fully human antibodies or antigen binding fragments directed to CXCR4 that specifically bind to CXCR4 and uses of these antibodies. Aspects of the disclosure also relate to hybridomas or other cell lines expressing such antibodies. The disclosed antibodies (including antigen binding fragments) are useful as diagnostics and for the treatment of diseases associated with the activity and/or expression of CXCR4.

Abstract: The invention encompasses compounds having formula I-V and the compositions and methods using these compounds in the treatment of conditions in which modulation of the JAK pathway or inhibition of JAK kinases, particularly JAK3, may be therapeutically useful.

Abstract: The present disclosure relates to combinations comprising (a) methotrexate, and (b) a DHODH inhibitor and their uses.

Abstract: The present invention relates to optimized Fc variants, methods for their generation, and antibodies and Fc fusions comprising optimized Fc variants.

Abstract: Improved anti-CD154 antibodies are provided herein which have ablated FcR binding. The use of these antibodies for inducing tolerance and treating immune diseases including autoimmunity, inflammation and allergic disorders is disclosed herein.

Abstract: The present invention relates to treatment of inflammatory diseases. In particular, the present invention relates to antagonistic DR3 ligands useful for treating inflammatory diseases.

Abstract: The present invention contemplates induction of immunological tolerance thereby providing permanent allograft acceptance. This method obviates the need for a lifelong regimen of immunosuppressive agents which can increase the risk of infection, autoimmunity, and cancer. Immunological tolerance is thought to be mediated by regulatory T lymphocytes (Treg cells) with immunosuppressive capabilities. A therapeutically relevant platform comprising artificial constructs are contemplated comprising numerous soluble and surface bound Treg cell stimulating factors that may induce tolerance following allograft transplantation. Such artificial constructs, being the size of a cell, have surface bound monoclonal antibodies specific to regulatory T-cell surface moieties and encapsulated soluble regulatory T-cell modulating factors.

Abstract: The present invention concerns human antibodies recognizing the human C5a receptor. By binding to C5aR the antibodies inhibit C5a signalling, whereby the pro-inflammatory signal is inhibited. Based on the role of C5a and its receptor in stimulation of inflammation the invention further relates to therapeutic use of said human anti-C5aR antibodies and in particular in relation to treatment of immunological disorders.

Abstract: The invention refers to an in vitro method of functionally determining at physiological conditions deficiencies in the lectin pathway of the complement system, the method comprising the steps of (a) providing a sample of mammalian blood, serum, plasma or another body fluid; (b) preventing in the sample the activation of the classical pathway by contacting the sample with an inhibitor of a molecule of the C1 complex of the complement system; (e) preventing in the sample the activation of the alternative pathway; (d) activating the lectin pathway in the sample; and (e) determining in the sample any activation of the autologous C5b-9 complex.

Abstract: Immunoglobulin chains or antibodies having light or heavy chain complementarity determining regions of antibodies that bind to P-Selectin Glycoprotein Ligand-1. Also disclosed are methods of inducing death of an activated T-cell and of modulating a T cell-mediated immune response in a subject.

Abstract: The present invention relates generally to methods for treating cancer. In one respect, the present invention relates to a method of treating a hematological cancer (e.g., multiple myeloma, leukemia, lymphoma) comprising administering to a patient in need thereof a therapeutically effective amount of a histone deacetylase inhibitor, for example, a histone deacetylase (HDAC) inhibitor as described herein, for example, PXD-101. In another respect, the present invention relates to a method of treating cancer (e.g., solid tumor cancer, e.g., rectal cancer, colon cancer, ovarian cancer; hematological cancer, e.g.

Abstract: Compositions and methods for the therapy of Inflammatory Bowel Disease (IBD), including Celiac Disease, Crohn's Disease, and Ulcerative Colitis, are disclosed. Illustrative compositions comprise one or more anti-type 1 interferon antagonists, such as anti-type 1 interferon receptor antibody antagonists and fragments thereof, as well as polypeptides and small molecules that inhibit the interaction of type 1 interferon with its receptor (IFNAR).

Abstract: This invention relates to methods of treating IgE mediated disorders such as allergy and asthma based on activating surface-bound IgD molecules on basophils. The invention also relates to methods of making IgD, as well as methods of screening for antimicrobial agents from IgD-activated basophils.

Abstract: This invention provides methods for preventing, reducing, delaying or inhibiting the proliferation and/or growth and/or metastasis of lung cancers and prostate cancer that express or overexpress CD22 by contacting the lung cancer cell or prostate cancer cell with an antigen binding molecule that binds to CD22 expressed on the surface of the cancer cell.

Abstract: Disclosed are monoclonal antibodies that specifically bind to the B7 family member B7H6, including antibodies capable of inhibiting the interaction of B7H6 with NKp30. Also disclosed are anti-B7H6 antibody-drug conjugates comprising an anti-B7H6 monoclonal antibody conjugated to a therapeutic agent. The anti-B7H6 antibodies and antibody-drug conjugates are useful in methods for exerting therapeutic effects against B7H6-expressing cells, as well as in diagnostic methods for the detection of B7H6 or B7H6-expressing cells.

Abstract: The present invention concerns methods for the treatment of diffuse large cell lymphoma by administration of an anti-CD20 antibody and chemotherapy. Particular embodiments include the administration of anti-CD20 antibody in combination with chemotherapy comprising CHOP (cyclophosphamide, hydroxydaunorubicin/doxorubicin, vincristine, and prednisone/prednisolone) and/or in combination with a transplantation regimen.

Abstract: The invention is drawn to a composition comprising an isolated mixture of cytotoxic anti-CD20 antibody molecules produced in a transgenic avian. The antibody molecules have a heavy chain and a light chain whose amino acid sequences set forth in SEQ ID NOs: 4 and 5 and exhibit an increased level of cytotoxicity as compared to anti-CD20 antibody molecules produced in CHO cells.

Abstract: An object of the present invention is to provide a radioactive metal anti-cadherin antibody which is highly accumulated specifically in cancer tissue. Another object is to provide a cancer therapeutic agent having high anti-cancer effect and safety and a cancer diagnostic agent. The radioactive metal-labeled anti-cadherin antibody is obtained by binding a radioactive metallic element to an anti-cadherin antibody via a metal-chelating reagent.

Abstract: The present invention provides novel human sequence antibodies against human CTLA-4 and methods of treating human diseases, infections and other conditions using these antibodies.

Abstract: A method of preferentially delivering an active agent to an immune cell, such as a myeloid progenitor cell, a dendritic cell, a monocyte, a macrophage or a T-lymphocyte, or other cell type restricted to a functional organ system or an anatomic entity, of a mammalian subject by administering a lipid-drug complex to the subject. The lipid-drug complex is comprised of an active agent, such as a drug, and an outer surface with a targeting ligand that binds a marker on the surface of the immune cell or other cell type that is infected with or susceptible to infection with an infectious agent. The other cell type that is infected with or susceptible to infection with an infectious agent may belong to a malignant tumor or a part of the immune system contributing to the development, maintenance, or exacerbation of an autoimmune disease or chronic inflammatory disease.

Abstract: The present invention is directed to humanized antibodies which bind the human C5a receptor and their use as therapeutic and diagnostic agents. The present invention is further directed toward nucleic acid sequences which encode said humanized antibodies, and their expression in recombinant host cells. In particular, the present invention is directed towards humanized antibodies derived from murine antibody 7F3 which specifically binds to the human C5a receptor.

Abstract: The present invention relates to new aminopyrimidine inhibitors of tyrosine kinase activity, pharmaceutical compositions thereof, and methods of use thereof.

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: 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: Methods and uses for the prevention and intervention of Type 1 diabetes comprising administration of a modulator of CD3 and a GLP-1 compound.

Abstract: The present invention provides isolated monoclonal antibodies, particularly human monoclonal antibodies, that specifically bind to PD-1 with high affinity. 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 detecting PD-1, as well as methods for treating various diseases, including cancer and infectious diseases, using anti-PD-1 antibodies. The present invention further provides methods for using a combination immunotherapy, such as the combination of anti-CTLA-4 and anti-PD-1 antibodies, to treat hyperproliferative disease, such as cancer. The invention also provides methods for altering adverse events related to treatment with such antibodies individually.

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.