Abstract: The present invention is directed to a pharmaceutical composition comprising: (A) a type II anti-CD20 antibody with increased antibody dependent cellular cytotoxicity (ADCC); and (B) a chemotherapeutic agent selected from the group consisting of: cyclophosphamide, vincristine and doxorubicine. The present invention is also directed to a method for the treatment of a CD20 expressing cancer, comprising administering to a patient in need of such treatment (i) an effective first amount of a type II anti-CD20 antibody with increased antibody dependent cellular cytotoxicity; and (ii) an effective second amount of one or more chemotherapeutic agents selected from the group consisting of cyclophosphamide, vincristine and doxorubicine.

Abstract: Isolated ligands which bind a molecule expressed on the surface of T cells and induce antigen specific apoptosis in activated T cells are disclosed. Preferably, the T cell surface molecule is CTLA4 and the ligand is a monoclonal anti-CTLA4 antibody that binds to an epitope of CTLA4 distinct from the binding sites of B7-1 and B7-2. Upon binding of the antibody to CTLA4 on an activated T cell, in the presence of an antigenic signal, antigen specific apoptosis is induced. The invention also describes a novel natural CTLA4 ligand, distinct from B7-1 and B7-2, which mediates induction of apoptosis. Pharmaceutical compositions of anti-CTLA4 antibodies or other isolated CTLA4 ligands which can be administered to subjects to induce T cell apoptosis, thereby clonally deleting antigen specific T cells, such as alloreactive T cells in transplantation situations or autoreactive T cells in autoimmune disorders, are also disclosed.

Abstract: The present invention relates to a LO-CD2a antibody and methods of using such antibodies or molecules that bind to the same epitope (or a portion thereof) to prevent and inhibit an immune response in human patients, preferably, where the immune response is mediated by the activation and proliferation of T cells or natural killer cells. The administration of an effective amount of the LO-CD2a antibody to a human patient will prevent or inhibit graft rejection, graft versus host disease or autoimmune disease.

Abstract: The present invention relates to compositions and methods for modulating Toll-like receptors (TLRs) for enhancing survival of activated CD4+ T cells. The enhanced survival of activated CD4+ T cells provides a means for regulating an immune response.

Abstract: The invention is based in part on the finding that suppressing regulatory T cell function is needed in order to convert passive immunity into active antigen-specific immunity. Generally, the methods of the invention comprise at least the combination of: (1) increasing the amount of immune complexes in the subject, wherein the immune complex comprises a target antigen and a immunoglobulin molecule comprising (i) a variable region specific to the target antigen and (ii) a Fc receptor binding region; and (2) inhibiting regulatory T cell function or decreasing/depleting the regulatory T cell population in the subject.

Abstract: The present invention relates to binding molecules that specifically bind to the human Fc gamma receptor expressed on the surface of natural killer (NK) cells and macrophages (i.e. Fc?RIIIA), and in particular binding molecules that specifically bind the A form Fc?RIII but do not bind to the B form of Fc?RIII, as well as to the use of such binding molecules in the diagnosis and treatment of disease. The invention further extends to polynucleotides encoding such binding molecules, host cells comprising such polynucleotides and methods of producing binding molecules of the invention using such host cells.

Abstract: Methods for treating a human patient for an inflammatory or autoimmune disease 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 an inflammatory or autoimmune disease that is treatable with an anti-CD40 antibody and which is non-responsive or refractory to treatment with rituximab (Rituxan®), as well as methods and kits for selecting an antibody therapy for treatment of a human patient having an inflammatory or autoimmune disease that is non-responsive or refractory to treatment with rituximab (Rituxan®), are also provided.

Abstract: Binding members, especially antibody molecules, for interleukin (IL)-4 receptor alpha (IL-4R?), and their therapeutic use e.g. in treating or preventing disorders associated with IL-4R?, IL-4 and/or IL-13, examples of which are asthma and COPD.

Abstract: The invention provides nine oligonucleotides with sequences of SEQ ID NO: 1-9 or their functional homologues or a composition comprising the same and a method for treating B cell neoplasm by using the oligonucleotides or their functional homologues or the composition comprising the oligonucleotides. The oligonucleotides induce the apoptosis of B cell neoplastic cells, up-regulate CD40 on B cell neoplastic cells and stimulate the production of IL-10 from B cell neoplastic cells.

Abstract: The present invention relates in a first aspect to a B-cell depleting anti-CD20 antibody or a CD20-binding antibody fragment thereof for the treatment of chronic fatigue syndrome and myalgic encephalomyelitis. In particular, the present invention relates to the use of anti-CD20 monoclonal antibodies or fragments thereof which are preferably humanized for the treatment of chronic fatigue syndrome/myalgic encephalomyelitis in a subject afflicted with said disease.

Abstract: A test method that provides data useful in predicting the probability of onset of acute graft-versus-host disease (GVHD) is described along with a kit for performing the method, and a pharmaceutical preparation and a molecular targeted therapy for treating or preventing GVHD. The test method includes measuring the blood DNAM-1 concentration of a patient of hematopoietic stem cell transplantation from bone marrow or the like over a period after the transplantation to provide data concerning the transition of the concentration to an abnormally high level deviating from the normal range, whereby the probability of the development of acute graft-versus-host disease is predicted, the risk of the development is estimated, or therapeutic effects after the development are evaluated.

Abstract: This invention relates to anti-P-selectin antibodies and, in particular, to anti-P-selectin antibodies and variants thereof that contain an 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 critical limb ischemia or peripheral arterial occlusive disease (CLI/PAOD).

Abstract: Disclosed is a method and composition for treating tumors or infectious diseases, wherein the composition includes CD40 binding molecules together with CTL-activating peptides, e.g., tumor antigens. Such composition is useful for enhancing the anti-tumor effect of a peptide tumor vaccine, or for otherwise activating CTLs so that the activated CTLs can act against tumorous or infected cells. The CD40 binding molecules can include antibody molecules, as well as homologues, analogues and modified or derived forms thereof, including immunoglobulin fragments like Fab, (Fab?)2 and Fv, as well as other molecules including peptides, oligonucleotides, peptidomimetics and organic compounds which bind to CD40 and activate the CTL response.

Abstract: The present invention relates to antibodies and antigen-binding portions thereof that specifically bind to CD40, preferably human CD40, and that function as CD40 agonists. The invention also relates to human anti-CD40 antibodies and antigen-binding portions thereof. The invention also relates to antibodies that are chimeric, bispecific, derivatized, single chain antibodies or portions of fusion proteins. The invention also relates to isolated heavy and light chain immunoglobulins derived from human anti-CD40 antibodies and nucleic acid molecules encoding such immunoglobulins. The present invention also relates to methods of making human anti-CD40 antibodies, compositions comprising these antibodies and methods of using the antibodies and compositions for diagnosis and treatment. The invention also provides gene therapy methods using nucleic acid molecules encoding the heavy and/or light immunoglobulin molecules that comprise the human anti-CD40 antibodies.

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 CD40L. 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 CD40L, 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/CD40L interactions, the methods involving administering a monovalent anti-CD40L antibody polypeptide to the individual.

Abstract: The present invention relates to a pharmaceutical formulation comprising an anti-CD20 antibody. The formulation may additionally comprise a buffer, a surfactant and/or an isotonicity agent.

Abstract: Methods of treating, preventing and/or managing cancer as well as and diseases and disorders associated with, or characterized by, undesired angiogenesis are disclosed. Specific methods encompass the administration of an immunomodulatory compound alone or in combination with a second active ingredient. The invention further relates to methods of reducing or avoiding adverse side effects associated with chemotherapy, radiation therapy, hormonal therapy, biological therapy or immunotherapy which comprise the administration of an immunomodulatory compound. Pharmaceutical compositions, single unit dosage forms, and kits suitable for use in methods of the invention are also disclosed.

Abstract: The invention provides humanized and chimeric anti-CD20 antibodies for treatment of CD20 positive malignancies and autoimmune diseases.

Abstract: Antibodies against AILIM (also called ICOS and 8F4) were found to significantly suppress the onset of inflammatory bowel diseases (especially Crohn's disease and colitis (ulcerative colitis and such)), and exhibit a significant therapeutic effect against inflammatory bowel diseases.

Abstract: Disclosed are agonist anti-CD40 molecules, including monoclonal antibodies, which can bind to and stimulate professional and non-professional human antigen-presenting cells (“APCs”), enhance the stimulatory effect of CD40L on CD40 positive cells and/or induce phenotypical maturation of monocyte derived dendritic cells. Several such monoclonal antibodies are provided, and cell lines producing them have been deposited at the American Type Culture Collection.

Abstract: The present invention relates to methods and compositions designed for the treatment, management or prevention of cancer. The methods of the invention comprise the administration of an effective amount of one or more antagonists of Integrin ?V?3 alone or in combination with the administration of an effective amount of one or more other agents useful for cancer therapy. The invention also provides pharmaceutical compositions comprising one or more antagonists of Integrin ?V?3 and/or one or more other agents useful for cancer therapy. In particular, the invention is directed to methods of treatment and prevention of cancer by the administration of a therapeutically or prophylactically effective amount of one or more antagonists of Integrin ?V?3 alone or in combination with standard and experimental therapies for treatment or prevention of cancer. Also included are methods for screening for epitope-specific Integrin ?V?3 antagonists which can be used according to the methods of the invention.

Abstract: The present invention relates generally to methods for stimulating T cells, and more particularly, to methods to eliminate undesired (e.g., autoreactive, alloreactive, pathogenic) subpopulations of T cells from a mixed population of T cells, thereby restoring the normal immune repertoire of said T cells. The present invention also relates to compositions of cells, including stimulated T cells having restored immune repertoire and uses thereof.

Abstract: An antibody against AILIM (alternatively called JTT-1 antigen, JTT-2 antigen, ICOS and 8F4) was found to have a significant therapeutic effect on arthrosis, for example, rheumatoid arthritis and osteoarthritis, graft versus host disease, graft immune rejection, inflammation (hepatitis and inflammatory bowel diseases), diseased condition accompanied by the excessive production of an antibody against a foreign antigen triggered by immunological sensitization by the antigen.

Abstract: The present invention relates to methods and compositions for use in treatment of patients with autoantibody positive disease. In a specific embodiment, the present invention relates to a method of treating a patient that has an ANA titer of 1:80 or greater and/or greater than or equal to 30 IU/ml of anti-dsDNA antibodies in his/her blood plasma or serum comprising administering a therapeutically effective amount of an immunomodulatory agent, such as an antagonist of Neutrokine-alpha. Additionally provided is a method of reducing the frequency and/or quantity of corticosteroid administration to patients. In preferred embodiments, the patient has systemic lupus erythematosus. Methods for determining if a lupus patient is responding to medical treatment are also provided.

Abstract: Specific depletion or modulation of activity of CD4+ T cells is used to treat and/or prevent damage due to ischemia of kidneys, heart, brain. It also has been found to reduce rejection of transplanted organs. The donor, recipient, or isolated organ can be so treated.

Abstract: The present application describes therapy of ocular disorders using antagonists, such as antibodies, that bind to CD20.

Abstract: An improved method for selectively depleting hypoxic cells within the bone marrow is disclosed. The method can be used to enhance engraftment of hematopoietic stem cells (HSCs) in the bone marrow of a host subject. Also disclosed is a method for treating a cancer within the bone marrow of a host subject.

Abstract: The present invention relates, in general, to HIV and, in particular, to immunogens that present epitopes located in the membrane external proximal region (MPER) of HIV-I envelope gp41 in multivalent form and to methods of using same.

Abstract: The present invention provides compositions and methods for the prevention and treatment of primary and metastatic neoplastic diseases and infectious diseases, for stimulating an immune response in a subject, and for use as an alternative to interleukin-12 (IL-12) treatment. In particular, the present invention provides Apicomplexa-related proteins (ARPs) that have immune stimulatory activity and thus have uses in the treatment and prevention of cancer and infectious diseases and in immune modulation. Compositions comprising an ARP are provided. Methods of use of an ARP for the prevention and/or treatment of cancer and/or infectious diseases, for use as an alternative to interleukin-12 (IL-12) treatment, and for eliciting an immune response in a subject, are also provided.

Abstract: An antibody or a functional fragment thereof, acting agonistically or antagonistically on CD40.

Abstract: The present invention provides for novel compositions of anti-CTLA-4 antibodies comprising a chelating agent. Also provided are method of treating diseases and conditions with novel compositions of CTLA-4 antibodies, including various neoplasia conditions.

Abstract: The invention relates to the discovery of novel soluble neutral active Hyaluronidase Glycoproteins (sHASEGPs), methods of manufacture, and their use to facilitate administration of other molecules or to alleviate glycosaminoglycan associated pathologies. Minimally active polypeptide domains of the soluble, neutral active sHASEGP domains are described that include asparagine-linked sugar moieties required for a functional neutral active hyaluronidase domain. Included are modified amino-terminal leader peptides that enhance secretion of sHASEGP. The invention further comprises sialated and pegylated forms of a recombinant sHASEGP to enhance stability and serum pharmacokinetics over naturally occurring slaughterhouse enzymes. Further described are suitable formulations of a substantially purified recombinant sHASEGP glycoprotein derived from a eukaryotic cell that generate the proper glycosylation required for its optimal activity.

Abstract: The invention relates to humanized anti-B7-2 and anti-B7-1 antibodies, wherein each comprise a variable region of non-human origin and at least a portion of an immunoglobulin of human origin. The invention also pertains to methods of treatment for various autoimmune diseases, transplant rejection, inflammatory disorders and infectious diseases by administering humanized anti-B7-2 and/or anti-B7-1 antibodies.

Abstract: Resistin antagonists, including antibodies reactive with defined epitopes, are disclosed. Methods of utilizing resistin antagonists to treat or alleviate the symptoms of the diseases with aberrant fibroblast activity including interstitial lung diseases, hypertrophic scarring, keloid scarring and scleroderma are also disclosed. Antigens useful for raising antibodies against human resistin are also disclosed.

Abstract: Compositions of CD3 antibody and gastrin and uses thereof in the prevention and intervention of diabetes.

Abstract: The present invention relates to nucleic acid molecules encoding Neutrokine-alpha and/or Neutrokine-alphaSV polypeptides, including soluble forms of the extracellular domain. Neutrokine-alpha and/or Neutrokine-alphaSV polypeptides are also provided as are vectors, host cells and recombinant methods for producing the same. The invention further relates to antibodies or portions thereof that specifically bind Neutrokine-alpha and/or Neutrokine-alphaSV and diagnostic and therapeutic methods using these antibodies. Also provided are diagnostic methods for detecting immune system-related disorders and therapeutic methods for treating immune system-related disorders using the compositions of the invention.

Abstract: The present invention relates to polypeptide compositions which bind to cell surface epitopes and, in multivalent forms, cause or lead to the killing of cells including lymphoid tumor cells, and in the case of monovalent forms, cause immunosuppression or otherwise inhibit activation of lymphocytes. The invention further relates to nucleic acids encoding the polypeptides, methods for the production of the polypeptides, methods for killing cells, methods for immunosuppressing a patient, pharmaceutical, diagnostic and multivalent compositions and kits comprising the polypeptides and uses of the polypeptides.

Abstract: The present invention is directed to a combination therapy involving a type II anti-CD20 antibody and an anti-Bcl-2 active agent for the treatment of a patient suffering from cancer, particularly a CD20-expressing cancer. An aspect of the invention is a composition comprising a type II anti-CD20 antibody and an anti-Bcl-2 active agent. Another aspect of the invention is a kit comprising a type II anti-CD20 antibody and an anti-Bcl-2 active agent. Yet another aspect of the invention is a method for the treatment of a patient suffering from cancer comprising co-administering, to a patient in need of such treatment) a type II anti-CD20 antibody and an anti-Bcl-2 active agent.

Abstract: Methods for treating or preventing hyperproliferating diseases, e.g., cancer, are described. A method may comprise administering to a subject in need thereof a therapeutically effective amount of a nucleic acid encoding an MHC class I and/or II activator and optionally a nucleic acid encoding an antigen.

Abstract: The present invention relates to the identification of antibodies which are specific to human B7.1 antigen (CD80) and which are capable of inhibiting the binding of B7.1 to a CD28 receptor and which are not capable of inhibiting the binding of B7.1 to a CTLA-4 receptor. Two of these antibodies, 16C10 and 7C10, significantly inhibit the production of IL-2, in spite of the existence of a second activating ligand B7.2 (CD86). Blocking of the primary activation signal between CD28 and B7.1 (CD80) with these antibodies while allowing the unimpaired or coincident interaction of CTLA-4 and B7.1 and/or B7.2 represents a combined antagonistic effect on positive co-stimulation with an agonistic effect on negative signalling. These antibodies may be used as specific immunosuppressants, e.g., for the treatment of autoimmune diseases and to prevent organ transplant rejection.

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: The present invention relates to the identification of antibodies which are specific to human B7.1 antigen (CD80) and which are capable of inhibiting the binding of B7.1 to a CD28 receptor and which are not capable of inhibiting the binding of B7.1 to a CTLA-4 receptor. Two of these antibodies, 16C10 and 7C10, significantly inhibit the production of IL-2, in spite of the existence of a second activating ligand B7.2 (CD86). Blocking of the primary activation signal between CD28 and B7.1 (CD80) with these antibodies while allowing the unimpaired or coincident interaction of CTLA-4 and B7.1 and/or B7.2 represents a combined antagonistic effect on positive co-stimulation with an agonistic effect on negative signalling. These antibodies may be used as specific immunosuppressants, e.g., for the treatment of autoimmune diseases and to prevent organ transplant rejection.

Abstract: Compositions and methods for regulating an immune response in a subject are described. More particularly, described are human antibodies that regulate the activity of NK cells and allow a potentiation of NK cell cytotoxicity in mammalian subjects, and antibodies having antigen-binding properties similar to those of human monoclonal antibody 1-7F9 or 1-4F1. Described also are also fragments and derivatives of such antibodies, as well as pharmaceutical compositions comprising the same and their uses, particularly for use in therapy, to increase NK cell activity or cytotoxicity in subjects.

Abstract: Small animal models for assessing immunomodulatory effects of compounds are provided.

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

Abstract: Materials and Methods for using 4-1BB agonists to treat or prevent autoimmune disorders, lymphoproliferative diseases, and allergies are provided.

Abstract: The present invention provides compositions and methods for targeting stem cells to injured cardiac tissue.

Abstract: Methods for inducing T cell tolerance to a tissue or organ graft in a transplant recipeint are disclosed. The methods involve administering to a subject: 1) an allogeneic or xenogeneic cell which expresses donor antigens and which has a ligand on the cell surface which interacts with a receptor on the surface of a recipient T cell which mediates contact-dependent helper effector function; and 2) an antagonist of the receptor which inhibits interaction of the ligand with the receptor. In a preferred embodiment, the allogeneic or xenogeneic cell is a B cell, preferably a resting B cell, and the molecule on the surface of the T cell which mediates contact-dependent helper effector function is gp39. A preferred gp39 antagonist is an anti-gp39 antibody. The allogeneic or xenogeneic cell and the gp39 antagonist are typically administered to a transplant recipient prior to transplantation of the tissue or organ.

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: The present invention is based upon the surprising discovery that exposure of a non-resistant HIV to a first entry inhibitor, such as an anti-CD4 antibody or a co-receptor inhibitor, which like all current HIV drugs selects for mutations that result in a resistant HIV, surprisingly results in HIV viruses much more susceptible to neutralization by a second entry inhibitor, such as soluble CD4 (sCD4) or an HIV gp41 inhibitor. Therefore, the present invention provides methods and compositions for inhibiting HIV-1 infection in a subject that overcomes the problem of drug resistance.