Abstract: The present invention provides to methods of preventing, treating or ameliorating an autoimmune or inflammatory disorder or one or more symptoms thereof utilizing combinatorial therapy. In particular, the present invention provides methods of preventing, treating, or ameliorating an autoimmune or inflammatory disorder or one or more symptoms thereof comprising administering to a subject in need thereof one or more CD2 antagonists and at least one other prophylactic or therapeutic agent. The present invention also provides compositions and articles of manufacture for use in preventing, treating or ameliorating one or more symptoms associated with an autoimmune or inflammatory disorder.

Abstract: The present invention provides a combination which comprises (a) methotrexate and (b) a non-hepatotoxic DHODH inhibitor of formula (I): wherein: R1 is selected from the group consisting of hydrogen atoms, halogen atoms, C1-4 alkyl, C3-4 cycloalkyl, —CF3 and —OCF3, R2 is selected from the group consisting of hydrogen atoms, halogen atoms and C1-4 alkyl groups, R3 is selected from the group consisting of —COOR5, —CONHR5, tetrazolyl, —SO2NHR5 and —CONHSO2R5 groups, wherein R5 is selected from the group consisting of a hydrogen atom and linear or branched C1-4 alkyl groups, R4 is selected from the group consisting of a hydrogen atom and a C1-4 alkyl group, R9 is selected from the group consisting of a hydrogen atom and a phenyl group, G1 represents a group selected from N and CR6 wherein R6 is selected from the group consisting of hydrogen atoms, halogen atoms, C1-4 alkyl, C3-4 cycloalkyl, C1-4 alkoxy, —CF3, —OCF3, monocyclic N-containing C5-7 heteroaryl, monocyclic N— containing C3-7 heterocyclyl groups and C6-1

Abstract: We previously reported that NKG2A, a key inhibitory ligand for HLA-E, is expressed on activated TH2, but not TH1, cells. Here we measured cytokine expression in ex vivo TH2 cells and in a mouse model of asthma upon activation with antiCD3/28 and challenge with an NKG2A-specific agonist. We show that signaling through NKG2A modulates Th2 cell effector function. This new molecular pathway data provides a novel explanation and treatment for respiratory virus-associated asthma. RSV and hMPV suppress IFN-? and HLA-E expression and therefore decrease NKG2A signaling in activated TH2 cells. This results in a relatively robust Th2 response and an unfavorable shift in Th1/Th2 balance. The data presented here suggest that increasing signaling via the NKG2A receptor suppresses Th2 effector function and could positively impact Th1/Th2 balance in asthma.

Abstract: The present invention provides humanized, chimeric and human anti-CD20 antibodies and CD20 antibody fusion proteins that bind to a human B cell marker, referred to as CD20, which is useful for the treatment and diagnosis of B-cell disorders, such as B-cell malignancies and autoimmune diseases, and methods of treatment and diagnosis.

Abstract: This invention relates to the diagnosis and treatment of cancerous diseases, particularly to the mediation of cytotoxicity of primary and metastatic human tumor cells; and most particularly to the use of an isolated monoclonal antibody or cancerous disease modifying antibodies (CDMAB) thereof, optionally in combination with one or more chemotherapeutic agents, as a means for initiating the cytotoxic response in human tumors, e.g. any primary or metastatic tumor sites which arise from hepatocytes and to binding assays which utilize the CDMAB of the instant invention.

Abstract: This invention provides an agonist antibody to a human thrombopoietin receptor (alias: human c-Mpl).

Abstract: The present invention relates to antibodies or fragments thereof that specifically bind Fc?RIIB, particularly human Fc?RIIB, with greater affinity than said antibodies or fragments thereof bind Fc?RIIA, particularly human Fc?RIIA. 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 are provided for decreasing demyelinating inflammatory disease in a subject by inhibiting the activity of chemokine-like receptor 1 (CMKLR1). Methods are also provided for screening for agents that find use in treating demyelinating inflammatory disease in a subject.

Abstract: This invention relates to compositions and methods comprising “lymphotoxin-?-receptor blocking agents”, which block lymphotoxin-? receptor signalling. Lymphotoxin-? receptor blocking agents are useful for treating lymphocyte-mediated immunological diseases, and more particularly, for inhibiting Th1 cell-mediated immune responses. This invention relates to soluble forms of the lymphotoxin-? receptor extracellular domain that act as lymphotoxin-? receptor blocking agents. This invention also relates to the use of antibodies directed against either the lymphotoxin-? receptor or its ligand, surface lymphotoxin, that act as lymphotoxin-? receptor blocking agents. A novel screening method for selecting soluble receptors, antibodies and other agents that block LT-? receptor signalling is provided.

Abstract: 2F1 polypeptides are provided, along with DNA sequences, expression vectors and transformed host cells useful in producing the polypeptides. Soluble 2F1 polypeptides find use in inhibiting prostaglandin synthesis and treating inflammation.

Abstract: The present invention relates to methods of treating immune disorders, particularly autoimmune or inflammatory disorders, and methods of producing antibodies and other compounds for use in therapeutic strategies for treating such disorders. Generally, the present methods involve the use of antibodies or other compounds that prevent the stimulation of NKG2A receptors on NK cells, leading to the lysis of dendritic cells that contribute to the pathology of the disorders.

Abstract: The present invention provides compositions and methods for inhibiting the growth of a GITR-expressing cancer cell which cells may include, but are not limited to cells of epithelial origin such as NSCLC, prostate cancer, breast cancer, colon cancer and ovarian cancer and to treat or ameliorate the symptoms associated with the presence of these cells in a subject. Suitable compositions for use in these methods are antibodies that selectively recognize and bind to GITR (Glucocorticoid-induced TNFR-related protein) present on these cancer cells. The antibodies can be either polyclonal or monoclonal antibodies.

Abstract: The invention includes antibodies that provide superior anti-coagulant activity by binding native human TF with high affinity and specificity. Antibodies of the invention can effectively inhibit blood coagulation in vivo. Antibodies of the invention can bind native human TF, either alone or present in a TF:FVIIa complex, effectively preventing factor X or FIX binding to TF or that complex, and thereby reducing blood coagulation. Preferred antibodies of the invention specifically bind a conformational epitope predominant to native human TF, which epitope provides an unexpectedly strong antibody binding site. Also provided are humanized antibodies and fragments thereof that bind to the TF.

Abstract: A therapeutic agent for chronic arthritides diseases of childhood-related diseases, for example chronic arthritides diseases of childhood, Still's disease and the like, comprising an interleukin-6 (IL-6) antagonist as an active ingredient.

Abstract: The present invention provides immunostimulatory combinations. Generally, the immunostimulatory combinations include a TLR agonist and a TNF/R agonist. Certain immunostimulatory combinations also may include an antigen.

Abstract: A synergistic adjuvant is provided comprising synergistically effective amounts of at least one type 1 interferon and at least one CD40 agonist, wherein these moieties may be in the same or separate compositions. In addition, fusion proteins and DNA conjugates which contain a type 1 interferon/CD40 agonist/antigen combination are provided. The use of these compositions, protein and DNA conjugates as immune adjuvants for treatment of various chronic diseases such as HIV infection and for enhancing the efficacy of vaccines (prophylactic and therapeutic) is also provided.

Abstract: Compositions and methods for treating or preventing unwanted immune responses are provided. The compositions relate to novel soluble CD83 (sCD83) polypeptides and nucleic acids encoding such polypeptides, improved (sCD83) formulations, and the use of such polypeptides and formulations in the treatment or prevention of allergy, autoimmune disease and transplant rejection. A sCD83 polypeptide is provided, comprising SEQ ID NO:7 or an amino acid sequence having at least 70% identity to SEQ ID NO:7; wherein one or more of amino acid residues 12, 20, 85 and 92 of SEQ ID NO:7 is an amino acid other than cysteine; and optionally, one or more of amino acid residues 1, 2, 3, 4 and 130 are absent.

Abstract: The invention relates to methods for treating and diagnosing hematologic malignancies, Chronic lymphocytic leukemia and Small Lymphocytic Lymphoma in particular, using PD-1 ligands (PD-L1, PD-L2 or anti-PD-1 antibodies).

Abstract: The present application describes therapy with antagonists which bind to B cell surface markers, such as CD20. In particular, the application describes the use of such antagonists to treat autoimmune disease in a mammal who experiences an inadequate response to a TNF?-inhibitor.

Abstract: The present invention provides methods for diagnosing a patient with emphysema or COPD by detecting the levels of EMAP II in a sample. Alternatively, methods are provided for determining the susceptibility of a patient to develop emphysema or COPD by detecting the levels of EMAP II in a sample. The levels of EMAP II may be determined by immunoassay techniques. The present invention also provides methods for treating patients with emphysema or COPD by administering a therapeutically effective amount of an EMAP II neutralizing compound. The compound may be an antibody, siRNA, antisense RNA or an antagonist of CXCR3.

Abstract: Compositions and methods included herein describe the treatment of atherosclerosis and other vascular diseases such as thrombosis, restenosis after angioplasty and/or stenting, and vein-graft disease after bypass surgery, by inhibition of the expression or biologic activity of the toll-like receptor 4 (TLR4) and/or myeloid differentiation factor 88 (MyD88). TLR4 cell signal transduction is at least partially responsible for the manifestation, continuation, and/or worsening of atherosclerosis and other forms of vascular disease. The present invention provides several means with which to inhibit this signal transduction pathway by affecting the biological activity of the TLR4 receptor and/or MyD88.

Abstract: This invention relates to binding members, especially antibody molecules, for IgE. The binding members are useful for, inter alia, treatment of disorders mediated by IgE including allergies and asthma.

Abstract: A therapeutic agent for chronic arthritides diseases of childhood-related diseases, for example chronic arthritides diseases of childhood, Still's disease and the like, comprising an interleukin-6 (IL-6) antagonist as an active ingredient.

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

Abstract: Antibodies directed to the antigen CD20 and uses of such antibodies are disclosed herein. In particular, fully human monoclonal antibodies directed to the antigen CD20. Nucleotide sequences encoding, and amino acid sequences comprising, heavy and light chain immunoglobulin molecules, particularly sequences corresponding to contiguous heavy and light chain sequences spanning the framework regions and/or complementarity determining regions (CDR's), specifically from FR1 through FR4 or CDR1 through CDR3 are disclosed. Hybridomas or other cell lines expressing such immunoglobulin molecules and monoclonal antibodies are also disclosed.

Abstract: Methods and compositions comprising GnRH-I and GnRH-II, GnRH-I and GnRH-II antibodies, anti-receptor antibodies, polynucleotide constructs and GnRH-I and GnRH-II analogs for immune enhancement and suppression, prevention and treatment of diseases and conditions characterized by abnormal T-cell activity, treatment of viral and prion-related diseases, and treatment of T-cell related neoplastic diseases are disclosed.

Abstract: The invention provides for the treatment of diseases or disorders characterized by cells expressing the CD40 membrane glycoprotein. The invention provides methods for the treatment of various diseases or disorders characterized by cells expressing CD40 with a combination of an agent causes the depletion of cells expressing CD40 and a second agent which causes the depletion of cells expressing the CD20 membrane antigen. Pharmaceutical compositions and articles of manufacture such as kits comprising the agents and combinations thereof are also provided.

Abstract: Inducing tolerance in a primate by use of a compound, or a combination of at least two compounds, that has certain characteristics when tested in vitro. The compound, alone or in combination, is preferably TRX1 antibody and the compound or combination is preferably used in accordance with a specified dosing regimen.

Abstract: This invention relates to the diagnosis and treatment of cancerous diseases, particularly to the mediation of cytotoxicity of tumor cells; and most particularly to the use of cancerous disease modifying antibodies (CDMAB), optionally in combination with one or more chemotherapeutic agents, as a means for initiating the cytotoxic response. The invention further relates to binding assays which utilize the CDMAB of the instant invention.

Abstract: B-cell malignancies, such as the B-cell subtype of non-Hodgkin's lymphoma and chronic lymphocytic leukemia, are significant contributors to cancer mortality. The response of B-cell malignancies to various forms of treatment is mixed. Traditional methods of treating B-cell malignancies, including chemotherapy and radiotherapy, have limited utility due to toxic side effects. Immunotherapy with anti-CD20 antibodies have also provided limited success. The use of antibodies that bind with the CD22 or CD19 antigen, however, provides an effective means to treat B-cell malignancies such as indolent and aggressive forms of B-cell lymphomas, and acute and chronic forms of lymphatic leukemias. Moreover, immunotherapy with anti-CD22 and/or anti-CD19 antibodies requires comparatively low doses of antibody protein, and can be used effectively in multimodal therapies.

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: The present invention relates to methods for the treatment and diagnosis of immune related diseases, including those mediated by cytokines released primarily either Th1 or Th2 cells in response to antigenic stimulation. The present invention further relates to methods for biasing the differentiation of T-cells in either the Th1 subtype or the Th2 subtype, based on the relative expression levels of the gene TCCR, and its agonists or antagonists. The present invention further relates to a method of diagnosing Th1- and Th2-mediated diseases.

Abstract: Described are generally a T cell immune response cDNA 7 (TIRC7) encoding a novel T-cell transmembrane protein as well as peptides und polypeptides derived therefrom and antibodies recognizing said (poly)peptides. More particularly, peptide and polypeptide as well as antibodies being capable of inhibiting T-cell stimulation through the T-cell membrane protein (TIRC7) are provided. Furthermore, vectors comprising the aforementioned polynucleotides and host cells transformed therewith as well as their use in the production of the above-defined proteins, peptides or polypeptides are described. Additionally, pharmaceutical and diagnostic compositions are provided comprising any one of the afore described polynucleotide, vector, protein, peptide, polypeptide, or antibody. Furthermore, methods and uses for modulating immune responses through the novel TIRC7 membrane protein as well as pharmaceutical compositions comprising agents which act on the TIRC7 membrane protein or its ligand are described.

Abstract: CD40 antagonists are used to prepare compositions, including pharmaceutical compositions, for treating autoimmune and neoplastic diseases in a mammal. The CD40 antagonist compositions are useful for reversing or substantially diminishing such autoimmune diseases as systemic lupus erythematosus, rheumatoid arthritis, multiple sclerosis and psoriasis.

Abstract: The invention relates to antibody polypeptides that monovalently bind CD40L. Antibody polypeptides that are monovalent for binding of CD40L can inhibit CD40L activity while avoiding potential undesirable effects that can occur with antibodies capable of divalent or multivalent binding of DC40L. in one aspect, a monovalent anti-CD40L antibody polypeptide consists of or comprises a single immunoglobulin variable domain that specifically binds and antagonizes the activity of DC40L, preferably without substantially agonizing CD40 activity. In another aspect, the monovalent anti-CD40L antibody polypeptide is a human antibody polypeptide. The invention further encompasses methods of antagonizing CD40/CD40L interactions in an individual and methods of treating diseases or disorders involving CD40/DC40L interactions, the methods involving administering a monovalent anti-CD40L antibody polypeptide to the individual.

Abstract: The invention relates to C2a inhibitors, which bind to C2a and block the functional activity of C2a in complement activation. The inhibitors include antibody molecules, as well as homologues, analogues and modified or derived forms thereof, including immunoglobulin fragments like Fab, F(ab?)2 and Fv,b small molecules, including peptides, oligonucleotides, peptidomimetics and organic compounds. A monoclonal antibody, which bound to C2a and blocked its ability to activate complement was generated and designated 175-62. The hybridoma producing this antibody was deposited at the American Type Culture Collection, 10801 University Blvd., Manassas, Va. 20110-2209, under Accession Number PTA-1553.

Abstract: Methods for modulating HIV-1 fusion cofactor expression by manipulating an accessory molecule on the surface of T cells, such as CD28, are described. The invention encompasses methods for modulating HIV-1 fusion cofactor expression by stimulating or inhibiting one or more intracellular signals which result from ligation of a surface receptor on a T cell which binds a costimulatory molecule. In one embodiment, expression of an HIV-1 fusion cofactor, such as CCR5, is downregulated by stimulating a CD28-associated signal in the T cell.

Abstract: The invention provides various antibodies that bind to lymphotoxin-?, methods for making such antibodies, compositions and articles incorporating such antibodies, and their uses in treating, for example, an autoimmune disorder. The antibodies include murine, chimeric, and humanized antibodies.

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: A mammalian C-type lectin receptor type is identified which is shown to bind IgG antibodies or Fc fragments, thus inducing IVIG-related reversal of inflammation associated with various immune disorders. The identification of a DC-SIGN receptor type which interacts with IgG to promote a biological response reducing inflammation associated with immune disorders provides for methods of screening and selecting compounds which may be useful in treating various immune disorders by acting to modulate a DC-SIGN(+) cell to signal a second effector macrophage, causing an increase in expression of the Fc?RIIB receptor and in turn inhibiting a cellular-mediated inflammatory response.

Abstract: The present invention relates to novel human secreted proteins and isolated nucleic acids containing the coding regions of the genes encoding such proteins. Also provided are vectors, host cells, antibodies, and recombinant methods for producing human secreted proteins. The invention further relates to diagnostic and therapeutic methods useful for diagnosing and treating disorders related to these novel human secreted proteins.

Abstract: The present invention relates to novel antibodies capable of binding specifically to the human insulin-like growth factor I receptor IGF-IR and/or capable of specifically inhibiting the tyrosine kinase activity of said IGF-IR receptor, especially monoclonal antibodies of murine, chimeric and humanized origin, as well as the amino acid and nucleic acid sequences coding for these antibodies. The invention likewise comprises the use of these antibodies as a medicament for the prophylactic and/or therapeutic treatment of cancers overexpressing IGF-IR or any pathology connected with the overexpression of said receptor as well as in processes or kits for diagnosis of illnesses connected with the overexpression of the IGF-IR receptor. The invention finally comprises products and/or compositions comprising such antibodies in combination with anti-EGFR antibodies and/or compounds and/or anti-cancer agents or agents conjugated with toxins and their use for the prevention and/or the treatment of certain cancers.

Abstract: This invention relates to anti-OX40L antibodies and, in particular, to anti-OX40L antibodies and variants thereof that contain a Fc part derived from human origin and do not bind complement factor C1q. These antibodies have new and inventive properties causing a benefit for a patient suffering from inflammatory diseases.

Abstract: Antibodies that specifically bind to VLA-1 integrin and methods of using these antibodies to treat immunological disorders in a subject. Also included are crystal structures of complexes formed by VLA-1 antibodies and their ligands, and VLA-1 antagonists and agonists identified by using the structure coordinates of these structures.

Abstract: B-cell malignancies, such as the B-cell subtype of non-Hodgkin's lymphoma and chronic lymphocytic leukemia, are significant contributors to cancer mortality. The response of B-cell malignancies to various forms of treatment is mixed. Traditional methods of treating B-cell malignancies, including chemotherapy and radiotherapy, have limited utility due to toxic side effects. Immunotherapy with anti-CD20 antibodies have also provided limited success. The use of antibodies that bind with the CD22 or CD19 antigen, however, provides an effective means to treat B-cell malignancies such as indolent and aggressive forms of B-cell lymphomas, and acute and chronic forms of lymphatic leukemias. Moreover, immunotherapy with anti-CD22 and/or anti-CD19 antibodies requires comparatively low doses of antibody protein, and can be used effectively in multimodal therapies.

Abstract: The present invention provides for modified forms of anti-CD52 antibodies with reduced numbers of potential T-cell epitopes that are expected to display decreased immunogenicity.

Abstract: A novel protein Common Lymphatic Endothelial and Vascular Endothelial Receptor-1 (CLEVER-1) is described. CLEVER-1 mediates leukocyte and malignant cell binding to vascular and lymphoid endothelial cells. CLEVER-1 is the first protein that has been reported to mediate both influx into and efflux from the lymph nodes. Also provided are methods of treating inflammation and preventing metastasis of malignant cells by providing an inhibitor of CLEVER-1 binding.

Abstract: The present invention relates to human anti-IL-13 binding molecules, particularly antibodies, and to methods for using anti-IL-13 antibody molecules in diagnosis or treatment of IL-13 related disorders, such as asthma, atopic dermatitis, allergic rhinitis, fibrosis, inflammatory bowel disease and Hodgkin's lymphoma.

Abstract: The invention relates to the use of monoclonal antibodies which are specific for CD28 and activate the T lymphocytes of several up to all subgroups without the occupation of an antigen receptor of the T lymphocytes and which therefor activate said lymphocytes in an antigen unspecific manner or the invention relates to the use of an analogue thereof for producing a pharmaceutical composition in the form of a preparation or a preparation packet for treating virus infections in humans or lower warm-blooded animals having infected T lymphocytes. The pharmaceutical composition additionally contains a virus inhibitor. The invention also relates to a corresponding pharmaceutical composition and a treatment plan including the pharmaceutical composition.

Abstract: The present invention concerns methods and compositions for forming anti-cancer vaccine DNL complexes using dock-and-lock technology. In preferred embodiments, the anti-cancer vaccine DNL complex comprises an antibody moiety that binds to dendritic cells, such as an anti-CD74 antibody or antigen-binding fragment thereof, attached to an AD (anchoring domain) moiety and a xenoantigen, such as CD20, attached to a DDD (dimerization and docking domain) moiety, wherein two copies of the DDD moiety form a dimer that binds to the AD moiety, resulting in the formation of the DNL complex. The anti-cancer vaccine DNL complex is capable of inducing an immune response against xenoantigen expressing cancer cells, such as CD138negCD20+ MM stem cells, and inducing apoptosis of and inhibiting the growth of or eliminating the cancer cells.