773 results about "Multiple myeloma" patented technology

Antibodies, humanized antibodies, resurfaced antibodies, antibody fragments, derivatized antibodies, and conjugates of same with cytotoxic agents, which specifically bind to CD38, are capable of killing CD38+ cells by apoptosis, antibody-dependent cell-mediated cytotoxicity (ADCC), and / or complement-dependent cytotoxicity (CDC). Said antibodies and fragments thereof may be used in the treatment of tumors that express CD38 protein, such as multiple myeloma, chronic lymphocytic leukemia, chronic myelogenous leukemia, acute myelogenous leukemia, or acute lymphocytic leukemia, or the treatment of autoimmune and inflammatory diseases such as systemic lupus, rheumatoid arthritis, multiple sclerosis, erythematosus, and asthma. Said derivatized antibodies may be used in the diagnosis and imaging of tumors that express elevated levels of CD38. Also provided are cytotoxic conjugates comprising a cell binding agent and a cytotoxic agent, therapeutic compositions comprising the conjugate, methods for using the conjugates in the inhibition of cell growth and the treatment of disease, and a kit comprising the cytotoxic conjugate. In particular, the cell binding agent is a monoclonal antibody, and epitope-binding fragments thereof, that recognizes and binds the CD38 protein.

Isolated human monoclonal antibodies which bind to human CD38, and related antibody-based compositions and molecules, are disclosed. Also disclosed are pharmaceutical compositions comprising the human antibodies, and therapeutic and diagnostic methods for using the human antibodies.

The present invention provides monoclonal antibodies which interfere with the interactions between FDCs and B cells, thereby suppressing the proliferation and / or differentiation of B cells in lymphoid follicles. The monoclonal antibodies of the present invention are useful for treating follicular lymphomas, multiple myeloma as well as autoimmune diseases.

The invention provides an isolated and purified nucleic acid sequence encoding a chimeric antigen receptor (CAR) directed against B-cell Maturation Antigen (BCMA). The invention also provides host cells, such as T-cells or natural killer (NK) cells, expressing the CAR and methods for destroying multiple myeloma cells.

The present invention provides antigen binding proteins that specifically bind to Wilms' tumor protein (WT1), including humanized, chimeric and fully human antibodies against WT1, antibody fragments, chimeric antigen receptors (CARs), fusion proteins, and conjugates thereof. The antigen binding proteins and antibodies bind to HLA-A0201-restricted WT1 peptide. Such antibodies, fragments, fusion proteins and conjugates thereof are useful for the treatment of WT1 associated cancers, including for example, breast cancer, ovarian cancer, prostate cancer, chronic myelocytic leukemia, multiple myeloma, acute lymphoblastic leukemia (ALL), acute myeloid / myelogenous leukemia (AML) and myelodysplastic syndrome (MDS). In more particular embodiments, the anti-WT1 / A antibodies may comprise one or more framework region amino acid substitutions designed to improve protein stability, antibody binding and / or expression levels.

Methods of inhibiting fibroblast growth factor receptor 3 and treating various conditions mediated by fibroblast growth factor receptor 3 are provided that include administering to a subject a compound of Structure I, a pharmaceutically acceptable salt thereof, a tautomer thereof, or a pharmaceutically acceptable salt of the tautomer. Compounds having the Structure I have the following structure where and have the variables described herein. Such compounds may be used to prepare medicaments for use in inhibiting fibroblast growth factor receptor 3 and for use in treating conditions mediated by fibroblast growth factor receptor 3 such as multiple myeloma.

In certain aspects, the present invention provides compositions and methods for promoting bone growth and increasing bone density, as well as for the treatment of multiple myeloma.

The invention provides an isolated and purified nucleic acid sequence encoding a chimeric antigen receptor (CAR) directed against B-cell Maturation Antigen (BCMA). The invention also provides host cells, such as T-cells or natural killer (NK) cells, expressing the CAR and methods for destroying multiple myeloma cells.

The present invention is drawn to diagnosis, prognosis and treatment of multiple myeloma. In this regard, the present invention discloses importance of down-regulation of TP3 gene in multiple myeloma and its use as an independent progostic indicator of multiple myeloma. Additionally, the present invention also discloses novel-TP53 associated genes and demonstrates the clinical relevance of these alterations to disease progression.

The present invention provides recombinant antigen-binding regions and antibodies and functional fragments containing such antigen-binding regions that are specific for CD38, which plays an integral role in various disorders or conditions. These antibodies, accordingly, can be used to treat, for example, hematological malignancies such as multiple myeloma. Antibodies of the invention also can be used in the diagnostics field, as well as for investigating the role of CD38 in the progression of disorders associated with malignancies. The invention also provides nucleic acid sequences encoding the foregoing antibodies, vectors containing the same, pharmaceutical compositions and kits with instructions for use. The invention also provides isolated novel epitopes of CD38 and methods of use therefore

Isolated human monoclonal antibodies which bind to human CD38, and related antibody-based compositions and molecules, are disclosed. Also disclosed are pharmaceutical compositions comprising the human antibodies, and therapeutic and diagnostic methods for using the human antibodies.

Isolated human monoclonal antibodies which bind to human CD38, and related antibody-based compositions and molecules, are disclosed. Also disclosed are pharmaceutical compositions comprising the human antibodies, and therapeutic and diagnostic methods for using the human antibodies.

Anti-angiogenic peptides that inhibit activation or proliferation of endothelial cells are disclosed. Such peptides may be used to inhibit VEGF binding to the VEGFR2 receptor (also known as the kinase domain receptor or KDR) and bFGF binding to its receptor. Such peptides may also be used to inhibit, VEGF, bFGF, or integrin activation of endothelial cells in angiogenesis-associated diseases such as cancer, leukemia, multiple myeloma, inflammatory diseases, eye diseases and skin disorders.

In certain aspects, the present invention provides compositions and methods for promoting bone growth and increasing bone density, as well as for the treatment of multiple myeloma. Methods for dosing a patient with an ActRIIb antagonist are also provided.

This invention relates, in part, to methods and products for the detection of cancer, such as prostate cancer or multiple myeloma. This invention also relates, in part, to methods and products for the detection of prostate disease, such as benign prostatic hyperplasia (BPH). This invention further relates, in part, to methods and products for the detection of specific glycans in one or more samples, such as, for example, methods whereby specific glycans are detected and their amounts analyzed. Such methods can be used to determine relative ratios and / or threshold values for the specific glycans described herein. The relative ratios and / or threshold values can be used in the methods provided.

The combination of an interleukin-6 (IL-6) antagonist and an antiproliferative drug is described. In its preferred embodiment, the present invention describes the combination of an IL-6 superantagonist, particularly a superantagonist totally incapable of binding gp130 and an antiproliferative drug belonging to the glucocorticoid class (SANT-7 and dexamethasone). The combination according to the present invention has shown surprising synergism in an animal model of multiple myeloma and the ability to overcome the resistance to the antiproliferative drug developed by myeloid cells. The combination according to the present invention is useful for the preparation of a medicament for the treatment of tumours, particularly IL-6-dependent tumours.

The present invention relates to therapeutic targets for cancer. In particular, the present invention relates to small molecules and nucleic acids that target EZH2 expression in cancer (e.g., prostate cancer, breast cancer, other solid tumors, multiple myeloma).

Provided herein, in some embodiments, are methods of using certain cereblon-associated proteins, such as Aiolos, Ikaros, interferon (IFN), and IFN pathway proteins, casein kinase 1, alpha 1 (CSNK1A1), and ZFP9, as biomarkers for use in predicting and monitoring clinical sensitivity and therapeutic response to certain compounds in patients having various diseases and disorders, such as cancers (e.g., diffuse large B-cell lymphoma (DLBCL), multiple myeloma (MM), myelodysplasia syndromes (MDS) and acute myeloid leukemia (AML)) and IFN-associated disorders. Also provided herein, in certain embodiments, are methods of determining the efficacy of an immunomodulatory compound.

The present invention encompasses methods and compositions for enhancing the growth of adult marrow stromal cells. The present invention also encompasses methods and compositions for regulating the effects of Dkk-1. Methods and compositions for treatment of osteolytic lesions in multiple myeloma and enhancing osteogenesis are also included.

In certain aspects, the present invention provides compositions and methods for promoting bone growth and increasing bone density, as well as for the treatment of multiple myeloma.

Disclosed is a therapeutic method comprising administering a TIM-3 antibody to a subject who is suspected to be suffering from blood tumor and in whom TIM-3 has been expressed in a Lin(−)CD34(+)CD38(−) cell fraction of bone marrow or peripheral blood or a subject who has been received any treatment for blood tumor. Also disclosed is a composition for preventing or treating blood tumor, which comprises a TIM-3 antibody as an active ingredient. Conceived diseases include those diseases which can be treated through the binding or targeting of the TIM-3 antibody to blood tumor cells (AML cells, CML cells, MDS cells, ALL cells, CLL cells, multiple myeloma cells, etc.), helper T cell (e.g., Th1 cells, Th17 cells), and antigen-presenting cells (e.g., dendritic cells, monocytes, macrophages, and cells resembling to the aforementioned cells (hepatic stellate cells, osteoclasts, microglial cells, intraepidermal macrophages, dust cells (alveolar macrophages), etc)), all of which are capable of expressing TIM-3. The diseases for which the therapeutic use is to be examined include blood diseases in which the expression of TIM-3 is observed in bone marrow or peripheral blood, particularly blood tumor.

The present disclosure concerns an antibody that specifically binds CD38 which is capable of killing a CD38+ cell by induction of apoptosis, antibody-dependent cell-mediated cytotoxicity (ADCC), and complement-dependent cytotoxicity. The disclosed antibody may be used as a medicament or in the making of a medicament, wherein the antibody is to be administered to a human subject in a safe therapeutic dose of about 20 mg / kg or below. In one embodiment, the medicament is for treating CD38+ multiple Myeloma in humans.

Methods of therapy for treating a subject for multiple myeloma 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, but exhibits antagonist activity when the antibody binds a CD40 antigen on a human CD40-expressing cell. Antagonist activity of the anti-antibody or antigen-binding fragment thereof beneficially inhibits proliferation and / or differentiation of human CD40 expressing multiple myeloma cells.

The present invention relates to pyridines, pyrimidines and derivatives thereof, and pharmaceutically acceptable salts thereof. Also included is a method of treatment of inflammation, rheumatoid arthritis, Pagets disease, osteoporosis, multiple myeloma, uveititis, acute or chronic myelogenous leukemia, pancreatic β cell destruction, osteoarthritis, rheumatoid spondylitis, gouty arthritis, inflammatory bowel disease, adult respiratory distress syndrome (ARDS), psoriasis, Crohn's disease, allergic rhinitis, ulcerative colitis, anaphylaxis, contact dermatitis, asthma, muscle degeneration, cachexia, Reiter's syndrome, type I diabetes, type II diabetes, bone resorption diseases, graft vs. host reaction, Alzheimer's disease, stroke, myocardial infarction, ischemia reperfusion injury, atherosclerosis, brain trauma, multiple sclerosis, cerebral malaria, sepsis, septic shock, toxic shock syndrome, fever, myalgias due to HIV-1, HIV-2, HIV-3, cytomegalovirus (CMV), influenza, adenovirus, the herpes viruses or herpes zoster infection in a mammal comprising administering an effective amount a compound as described above.

In certain aspects, the present invention provides compositions and methods for promoting bone growth and increasing bone density, as well as for the treatment of multiple myeloma.

Provided is pyrazole derivatives as a TNIK (Traf2- and NCK-interacting kinase), IKKε (I-kappa-B kinase epsilon) and TBK1 (TANK-binding kinase 1) inhibitor; the pyrazole derivative according to the present invention effectively inhibits TNIK, IKKε and TBK1, and thus is useful not only as an anticancer agent for the treatment of various cancers including colorectal cancer, breast cancer, CNS cancer, colon cancer, non-small cell lung cancer, kidney cancer, prostate cancer, ovarian cancer, uterus cancer, stomach cancer, liver cancer, skin cancer, lung cancer, brain cancer, bladder cancer, esophageal cancer, pancreatic cancer, thyroid cancer, head and neck cancer, squamous cell carcinoma, osteosarcoma, B-cell or T-cell lymphoma, acute or chronic leukemia and multiple myeloma, but as a therapeutic agent for chronic inflammation.

The present invention relates to compounds of Formula (I),methods for preparing these compounds, compositions, intermediates and derivatives thereof and for treating a condition including but not limited to ankylosing spondylitis, artherosclerosis, arthritis (such as rheumatoid arthritis, infectious arthritis, childhood arthritis, psoriatic arthritis, reactive arthritis), bone-related diseases (including those related to bone formation), breast cancer (including those unresponsive to anti-estrogen therapy), cardiovascular disorders, cartilage-related disease (such as cartilage injury / loss, cartilage degeneration, and those related to cartilage formation), chondrodysplasia, chondrosarcoma, chronic back injury, chronic bronchitis, chronic inflammatory airway disease, chronic obstructive pulmonary disease, diabetes, disorders of energy homeostasis, gout, pseudogout, lipid disorders, metabolic syndrome, multiple myeloma, obesity, osteoarthritis, osteogenesis imperfecta, osteolytic bone metastasis, osteomalacia, osteoporosis, Paget's disease, periodontal disease, polymyalgia rheumatica, Reiter's syndrome, repetitive stress injury, hyperglycemia, elevated blood glucose level, and insulin resistance.