Abstract: The present invention provides pharmaceutical compositions composing, as an active ingredient, a substance capable of activating the ? chain of Fc receptors (FcR?) (provided that the substance is not an immunoglobulin for intravenous injection), and agents for stimulating myelinogenesis. The invention also provides agents for stimulating the differentiation of oligodendroglial precursor cells, agents for activating Fyn tyrosine kinase, and agents for stimulating the expression of myelin basic protein, all comprising a substance capable of activating FcR? as an active ingredient. Further, the invention provides a method of detecting myelinogenetic oligodendroglias or precursor cells thereof which comprises using the expression of FcR? in oligodendroglias or precursor cells thereof as an indicator.

Abstract: The present invention provides compositions and methods for the use of antigenic peptides derived from the Fc portion of the epsilon heavy chain of an IgE molecule as vaccines for the treatment and prevention of IgE-mediated allergic disorders. In particular, the invention provides compositions, methods for the treatment and prevention of IgE-mediated allergic disorders comprising an immunogenic amount of one or more antigenic peptides derived from the CH3 domain or junction of Ch-3/CH4 domain of an IgE molecule and methods for the evaluation of IgE mediated allergies in dogs.

Abstract: Novel fully human anti-VAP-1 antibodies and fragments thereof are disclosed. Nucleic acids encoding anti-VAP-1 antibodies or fragments thereof, as well as expression vectors and host cells incorporating these nucleic acids for the recombinant expression of anti-VAP-1 antibodies are also given. Pharmaceutical compositions comprising said antibodies and therapeutic uses thereof are also disclosed.

Abstract: The invention relates to the use of a monovalent antibody fragment directed against the EC2 domain of the Fc?RI receptor for the treatment of inflammatory diseases.

Abstract: The invention provides a method of enumerating the number of cells of a cell type in a cell sample by (a) counting the white blood cells in the cell sample to obtain the white blood cell population of the sample; (b) determining the proportion or percentage of the cells of the cell type in the white blood cell population in the sample; and (c) calculating the number of cells of the cell type in the sample. The cell type may be a lymphocyte sub-set selected from the group comprising CD4+ lymphocytes, CD 45 cells, CD19 cells, CD16 and CD56 positive cells, CD8 cells, CD3 cells or any combination thereof. The method is particularly useful in monitoring the immune status of a patient infected with HIV or other immune deficiency state or disease or condition where CD4+ lymphocytes or CD4+ T cells are monitored or counted. The invention also provides a kit comprising antibodies necessary for carrying out said cell enumeration.

Abstract: The present invention provides antibodies that bind human CXCR4 and are characterized as having high affinity and strong neutralizing properties. The antibodies of the invention are useful in the treatment of tumorigenesis, including tumor growth, invasion, angiogenesis, or metastasis.

Abstract: Methods of modulating a T cell response are provided. Methods include, among other things, contacting a T cell that expresses TNF-related apoptosis-inducing ligand (TRAIL, Apo-2L) or TRAIL receptor (DR4 or DR5) with a molecule that binds to TRAIL (Apo-2L), a molecule that binds to TRAIL receptor (DR4 or DR5), or with a soluble TRAIL (Apo-2L) reagent.

Abstract: The invention provides novel methods of administering anti-CD3 antibodies, e.g., via oral or mucosal delivery. The invention also provides methods of treating, preventing, or delaying the onset of autoimmune disorders by oral or mucosal administration of anti-CD3 antibodies. Finally, the invention provides compositions including anti-CD3 antibodies, suitable for oral or mucosal administration.

Abstract: The invention teaches human-compatible monoclonal antibodies which are specific against human CD28 and human T-lymphocytes of several to all subgroups to activate without occupancy of an antigen receptor of the human T-lymphocytes and thus antigen-non-specifically.

Abstract: The present invention relates, generally, to methods and compositions for increasing the efficiency of therapeutic antibodies. Their efficiency is enhanced through the increase of the ADCC mechanism. More particularly, the invention relates to the use of a therapeutic antibody in combination with compounds that block an inhibitory receptor or stimulate an activating receptor of an NK cell in order to enhance the efficiency of the treatment with therapeutic antibodies in human subjects.

Abstract: Disclosed are methods of treating subjects having disorders or conditions characterized by an unwanted immune response including administering an effective amount of an early activation molecule agonist, antagonist or depletor, to the subject. Human monoclonal antibodies specific to the early activation molecules, and methods of use, are also disclosed.

Abstract: The present invention relates to a novel human protein called Human G-protein Chemokine Receptor (CCR5) HDGNR10, and isolated polynucleotides encoding this protein. The invention is also directed to human antibodies that bind Human G-protein Chemokine Receptor (CCR5) HDGNR10 and to polynucleotides encoding those antibodies. Also provided are vectors, host cells, antibodies, and recombinant methods for producing Human G-protein Chemokine Receptor (CCR5) HDGNR10 and human anti-Human G-protein Chemokine Receptor (CCR5) HDGNR10 antibodies. The invention further relates to diagnostic and therapeutic methods useful for diagnosing and treating diseases, disorders, and/or conditions related to this novel human protein and these novel human antibodies.

Abstract: An anti-CD4 antibody which binds to CD4, has a high affinity and has a high effector activity, such as an antibody-dependent cellular cytotoxicity (ADCC activity) or complement-dependent cellular cytotoxicity (CDC activity), is required for a disease relating to a CD4-expressing cell. The present invention can provide a monoclonal antibody or an antibody fragment thereof, which binds to a CD4 extracellular region with high affinity and also exhibits a high ADCC activity or a high CDC activity; a hybridoma which produces the antibody; a DNA which encodes the antibody; a vector which contains the DNA; a transformant obtainable by introducing the vector; a process for producing an antibody or an antibody fragment thereof using the hybridoma or the transformant; and a therapeutic agent using the antibody or the antibody fragment thereof or a diagnostic agent using the antibody or the antibody fragment thereof.

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 relates to new indazole inhibitors of tyrosine kinase activity, pharmaceutical compositions thereof, and methods of use thereof.

Abstract: The present invention is directed to antibodies and binding fragments thereof, which bind with high affinity and specificity to human P-selectin glycoprotein ligand 1 (PSGL-1) and which block both selectin and chemokine binding to PSGL-1 expressed on leukocytes, lymphocytes and endothelial cells and thus which inhibit migration and/or rolling of these cells and to methods for screening for such antibodies and binding fragments thereof and to methods of therapeutic use thereof.

Abstract: Soluble, secreted tumor necrosis factor receptor polypeptides, polynucleotides encoding the polypeptides, and related compositions and methods are disclosed. The polypeptides comprise one cysteine-rich repeat that is homologous to other tumor necrosis factor receptors, such as transmembrane activator and CAML-interactor (TACI). The polypeptides may be used for detecting ligands, agonists and antagonists. The polypeptides may also be used in methods that modulate B cell activation.

Abstract: The present invention relates, in general, to human immunodeficiency virus (HIV) and, in particular, to a multicomponent vaccine and method of using same to protect against HTV-I infection.

Abstract: The present invention disclosed recombinant anti-VLA-4 antibody molecules, including humanized recombinant anti-VLA-4 antibody molecules. These antibodies are useful in the treatment of specific and non-specific inflammation, including asthma and inflammatory bowel disease. In addition, the humanized recombinant anti-VLA-4 antibodies disclosed can be useful in methods of diagnosing and localizing sites of inflammation.

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 present invention relates to methods and compositions for the prevention and treatment of cancer, inflammatory diseases and disorders or deficiencies of the immune system. The methods of the invention comprise administering a CD40 binding protein that potentiates the binding of CD40 to CD40 ligand.

Abstract: Particular members of the multisubunit immune recognition receptor (MIRR) family of receptors, specifically, the B cell antigen receptor (BCR), the pre-B cell receptor (pre-BCR), the pro-B cell receptor (pro-BCR), Ig Fc receptors (FcR), and NK receptors, can be physically uncoupled from their associated transducers. The invention describes regulatory compounds and methods for mimicking such dissociation/destabilization for the purposes of receptor desensitization and for treatment of conditions in which receptor desensitization or alternatively, enhanced or prolonged receptor sensitization, is desirable. Compounds and methods for enhancing or prolonging receptor sensitization are also disclosed, as are methods for identifying regulatory compounds suitable for use in the present methods.

Abstract: Methods of therapy for B-cell malignancies are provided. The methods comprise administering a therapeutically effective amount of an antagonist anti-CD40 antibody or antigen-binding fragment thereof to a patient in need thereof. The antagonist anti-CD40 antibody or antigen-binding fragment thereof is free of significant agonist activity when the antibody binds a CD40 antigen on a normal human B cell, exhibits antagonist activity when the antibody binds a CD40 antigen on a malignant human B cell, and can exhibit antagonist activity when the antibody binds a CD40 antigen on a normal human B cell. Antagonist activity of the anti-CD40 antibody or antigen-binding fragment thereof beneficially inhibits proliferation and/or differentiation of malignant human B cells.

Abstract: The present invention relates to a polypeptide construct comprising at least one CDR3 region, wherein at least one of the at least CDR3 regions comprises at least one substitution in the amino acid sequence YYDDHY (SEQ ID NO.1) and wherein the at least one substitution comprises: in the first position of SEQ ID NO.1 a substitution from Y to H; in the second position of SEQ ID NO. 1 a substitution from Y to S, from Y to N, from Y to F or from Y to H; in third position of SEQ ID NO. 1 a substitution from D to N or from D to E; in the forth position of SEQ ID NO. 1 a substitution from D to Q, from D to A, from D to V, from D to E or from D to G; in the fifth position of SEQ ID NO. 1 a substitution from H to Q, from H to P, from H to Y, from H to R or from H to N; or in the sixth position a substitution from Y to N.

Abstract: Methods are disclosed of treating rheumatoid arthritis in a human comprising administering to the human more than one intravenous dose of a therapeutically effective amount of rituximab and administering methotrexate to the human.

Abstract: Compositions and methods for treating or preventing a hematologic malignancy, such as AML, using an anti-alpha4 antibody are described.

Abstract: The invention relates to the use of a CD28-specific superagonistic monoclonal antibody (MAB) or of a mimetic compound of the same, for producing a pharmaceutical composition, wherein the dosage is below or above a defined dosage limit.

Abstract: The present invention provides compositions and methods for treating and preventing disease associated with ?v?5 integrin by blocking binding to ?v?5 integrin.

Abstract: A method of chronically reducing a patient's pathological inflammation via the administration of an agent that specifically binds to an alpha-4 integrin or a dimer comprising an alpha-4 integrin is disclosed. The agent provided must have a binding affinity such that administration is sufficient to suppress pathological inflammation, and the agent is administered chronically to provide long-term suppression of pathological inflammation.

Abstract: The present invention provides compositions and methods for the treatment of autoimmune diseases, in particular rheumatoid arthritis. Compounds which function as antagonists of Toll-like Receptor 2 are shown to suppress the immune response which result in the onset and progression of autoimmune disease. In particular monoclonal antibodies which have a binding specificity to Toll-like receptor 2 are disclosed for use in methods for the treatment and/or prophylaxis of autoimmune disease.

Abstract: The present invention relates, generally, to methods and compositions for increasing the efficiency of therapeutic antibodies. Their efficiency is enhanced through the increase of the ADCC mechanism. More particularly, the invention relates to the use of a therapeutic antibody in combination with compounds that block an inhibitory receptor or stimulate an activating receptor of an NK cell in order to enhance the efficiency of the treatment with therapeutic antibodies in human subjects.

Abstract: The invention relates to a method of directing selection of biological therapeutic molecules to specific functional domains of the target biologic molecule. Selection is directed by the use of closely related molecules, where one is a decoy and the other contains the targeted domain or epitope. The invention is based on the use of physical data, which may be combined with derived data, to ascertain that the decoy and the target differ only in the specific functional domain or epitope where the binding will be directed.

Abstract: Methods for preventing or treating an antibody-mediated disease in a patient are presented, the methods comprising administration of a monoclonal antibody capable of binding to a human CD40 antigen located on the surface of a human B cell, wherein the binding of the antibody to the CD40 antigen prevents the growth or differentiation of the B cell. Monoclonal antibodies useful in these methods, and epitopes immunoreactive with such monoclonal antibodies are also presented.

Abstract: The present invention comprises a composition with means to inhibit the function of the inflammatory cytokine IL-1 and methods for using this composition to treat inflammatory disease of ocular and adnexal tissues by topical administration. The present invention also discloses devices for delivering this composition to target tissues.

Abstract: The present invention provides soluble CTLA4 mutant molecules which bind with greater avidity to the CD80 and/or CD86 antigen than wild type CTLA4 or non-mutated CTLA4Ig. The soluble CTLA4 molecules have a first amino acid sequence comprising the extracellular domain of CTLA4, where certain amino acid residues within the S25-R33 region and M97-G107 region are mutated. The mutant molecules of the invention may also include a second amino acid sequence which increases the solubility of the mutant molecule.

Abstract: Fully human antibodies and antigen-binding portions thereof that bind to human 4-1BB and that allow binding of human 4-1BB to a human 4-1BB ligand. In one aspect, the antibody is an IgG4 antibody. Also provided is a method for treating a disease in a subject comprising administering a therapeutically effective amount of the antibody to said subject.

Abstract: Antagonists of ?4 integrin/?4 integrin ligand adhesion, which inhibit the biological effects of such adhesion are described and methods for their use are detailed. Such antagonists are useful in suppressing bone destruction associated with multiple myeloma. The homing of multiple myeloma cells to bone marrow and their ?4 integrin-dependent release of bone-resorbing factors, resulting in bone destruction in patients with multiple myeloma, is inhibited.

Abstract: This invention provides a method of reducing viral load in an HIV-1-infected human subject which comprises administering to the subject an effective HIV-1 viral load reducing dose of a CCR5 receptor antagonist, such as a humanized antibody designated PRO 140 or an anti-CCR5 receptor monoclonal antibody, wherein the viral load reducing dose achieves an average maximum decrease of viral load in the subject of at least 1.83 log10 to 2.5 log10 at about ten days following administration of the CCR5 receptor antagonist and wherein the viral load reducing dose further achieves a mean viral load reduction of 1.7 log10 at about nine days following administration of the CCR5 receptor antagonist.

Abstract: Disclosed herein are methods of depleting peripheral blood B cells in a human host comprising administering to the host an immunologically active anti-CD20 antibody in an amount effective to deplete peripheral blood B cells in the host.

Abstract: Human Death Receptor 4 (DR4) antibodies are provided. The human DR4 antibodies may be included in pharmaceutical compositions, articles of manufacture, or kits. Methods of treatment and diagnosis using the DR4 antibodies are also provided.

Abstract: Compounds that bind to P-Selectin Glycoprotein 1 (PSGL-1) on the surface of T cells or natural killer (NK) cells can be used to induce T cell or NK cell depletion and/or to induce T cell or NK cell apoptosis. The compounds and methods of the invention can be used to control unwanted T cell- or NK cell-mediated immune responses in conditions such as autoimmune diseases, transplant rejection, and allergic diseases.

Abstract: This invention provides monoclonal antibodies that recognize the Toll-like Receptor 4/MD-2 receptor complex, and monoclonal antibodies that recognize the TLR4/MD2 complex as well as TLR4 when not complexed with MD-2. The invention further provides methods of using the monoclonal antibodies as therapeutics. This invention also provides soluble chimeric proteins, methods of expressing and purifying soluble chimeric proteins, and methods of using soluble chimeric proteins as therapeutics, in screening assays and in the production of antibodies.

Abstract: The present invention provides humanized anti-CD20 antibodies comprising a human IgG1 Fc region comprising an isoleucine at position 247 and a glutamine at position 339 as well as nucleic acids encoding the antibodies and methods of using the antibodies for treating lymphoma. Furthermore, the invention provides compositions comprising the antibodies and methods of producing them.

Abstract: The present invention relates to the method for depleting in vivo regulatory T cell, the method for suppressing IL-10 producing activity of regulatory T cell, the method for treating diseases in which pathologic conditions are deteriorated by regulatory T cell and the method for enhancing tumor immunity which comprises administering to a patient a monoclonal antibody which specifically binds to human CC chemokine 4 (CCR4) or the antibody fragment thereof.

Abstract: Monoclonal antibodies prepared against platelet ?3 integrin useful in antithrombotic therapy or in models of thrombosis, thrombocytopenia, and anti-angiogenesis. The antibodies are prepared using ?3 integrin deficient (?3?/?) mice immunized against platelets or ?3 integrin fragments.

Abstract: The present invention provides anti-CD20 antibody fragments for use as in vivo imaging probes and as therapeutic moieties for the diagnosis and treatment of NHL.

Abstract: Methods for inducing antigen-specific T cell tolerance are disclosed. The methods involve contacting a T cell with: 1) a cell which presents antigen to the T cell, wherein a ligand on the cell interacts with a receptor on the surface of the T cell which mediates contact-dependent helper effector function; and 2) an antagonist of the receptor on the surface of the T cell which inhibits interaction of the ligand on the antigen presenting cell with the receptor on the T cell. In a preferred embodiment, the cell which presents antigen to the T cell is a B cell and the receptor on the surface of the T cell which mediates contact-dependent helper effector function is gp39. Preferably, the antagonist is an anti-gp39 antibody or a soluble gp39 ligand (e.g., soluble CD40). The methods of the invention can be used to induce T cell tolerance to a soluble antigen or to an allogeneic cell.

Abstract: An antibody or antibody fragment directed against the CD28 receptor which blocks the interaction between B7-1 or B7-2 and CD28. Methods for blocking activation via CD28, including CD28-dependent lymphocyte activation.

Abstract: The present invention relates to the field of immunology and hyperproliferative diseases. More specifically, the present invention relates to a method of detecting and monitoring therapeutic antibody:antigen complex, soluble antigen and soluble therapeutic antibody, wherein a patient has undergone at least one course of immunotherapy. Yet further, levels of therapeutic antibody:antigen complexes, soluble antigens or soluble therapeutic antibodies may be measured and used to stage or monitor a hyperproliferative disease.

Abstract: The present invention relates to new triazole modulators of aromatase activity, pharmaceutical compositions thereof, and methods of use thereof.