1411 results about "Immunologic disorders" patented technology

A CD20-binding polypeptide composition of the invention comprises at least one polypeptide selected from the group consisting of a polypeptide having the amino acid residue sequence of SEQ ID NO: 1 (Vh of 2B8 antibody), but which includes at least one amino acid residue substitution in SEQ ID NO: 1 selected from the group consisting of V12K, A14P, M20V, I48T, A68T, Q82E, T87R, S91T, and T106W; a polypeptide having the amino acid residue sequence of SEQ ID NO: 4 (Vk of 2B8 antibody), but which includes at least one amino acid residue substitution in SEQ ID NO: 4 selected from the group consisting of L11I, S12T, S27T, V29A, G40T, V59S, S69T, L72M, R76S, and V77L; a polypeptide having the amino acid residue sequence of SEQ ID NO: 9 (Vh of Leu16 antibody), but which includes at least one amino acid residue substitution in SEQ ID NO: 9 selected from the group consisting of V12K, M20V, A68T, Q82E, T87R, S91T, D93V, and A114T; and a polypeptide having the amino acid residue sequence of SEQ ID NO: 11 (Vk of Leu16 antibody), but which includes at least one amino acid residue substitution in SEQ ID NO: 11 selected from the group consisting of L11I, S12T, A59S, S69T, L72M, R76S, and V77L. The compositions are useful for diagnosis and treatment of autoimmune diseases.

Substituted bicyclic heteroaryls and compositions containing them, for the treatment of general inflammation, arthritis, rheumatic diseases, osteoarthritis, inflammatory bowel disorders, inflammatory eye disorders, inflammatory or unstable bladder disorders, psoriasis, skin complaints with inflammatory components, chronic inflammatory conditions, including but not restricted to autoimmune diseases such as systemic lupus erythematosis (SLE), myestenia gravis, rheumatoid arthritis, acute disseminated encephalomyelitis, idiopathic thrombocytopenic purpura, multiples sclerosis, Sjoegren's syndrome and autoimmune hemolytic anemia, allergic conditions including all forms of hypersensitivity, The present invention also enables methods for treating cancers that are mediated, dependent on or associated with p110δ activity, including but not restricted to leukemias, such as Acute Myeloid leukaemia (AML) Myelo-dysplastic syndrome (MDS) myelo-proliferative diseases (MPD) Chronic Myeloid Leukemia (CML) T-cell Acute Lymphoblastic leukaemia (T-ALL) B-cell Acute Lymphoblastic leukaemia (B-ALL) Non Hodgkins Lymphoma (NHL) B-cell lymphoma and solid tumors, such as breast cancer.

The present invention provides novel purinone and related derivatives useful for the prevention and treatment of autoimmune diseases, inflammatory disease, mast cell mediated disease and transplant rejection. The compounds are of the general formula III:

Disclosed herein are methods of treatment of autoimmune diseases such as systemic lupus erythematosus (SLE) as well as clinical assays for detection of autoimmune disease activity in patients utilizing the involving a PD1 ligand.

The present invention relates to humanized FcγRIIB antibodies, fragments, and variants thereof that bind human FcγRIIB with a greater affinity than said antibody binds FcγRIIA. The invention encompasses the use of the humanized antibodies of the invention for the treatment of any disease related to loss of balance of Fc receptor mediated signaling, such as cancer, autoimmune and inflammatory disease. The invention provides methods of enhancing the therapeutic effect of therapeutic antibodies by administering the humanized antibodies of the invention to enhance the effector function of the therapeutic antibodies. The invention also provides methods of enhancing the efficacy of a vaccine composition by administering the humanized antibodies of the invention. The invention encompasses methods for treating an autoimmune disease and methods for elimination of cancer cells that express FcγRIIB.

The compound represented by formula (I), a salt thereof, an N-oxide thereof, a solvate thereof, or a prodrug thereof specifically binds CCR5, so it is useful for preventing and / or treating CCR5-related diseases, for example, various inflammatory diseases (asthma, nephritis, nephropathy, hepatitis, arthritis, rheumatoid arthritis, rhinitis, conjunctivitis, ulcerative colitis, etc.), immunological diseases (autoimmune diseases, rejection in organ transplantation, immunosuppression, psoriasis, multiple sclerosis, etc.), infectious diseases (infection with human immunodeficiency virus, acquired immunodeficiency syndrome, etc.), allergic diseases (atopic dermatitis, urticaria, allergic bronchopulmonary aspergillosis, allergic eosinophilic gastroenteritis, etc.), ischemic reperfusion injury, acute respiratory distress syndrome, shock accompanying bacterial infection diabetes cancer metastasis and so on.Wherein all symbols in formula are as defined in the specification

The present invention concerns CAR, CAR-T and CAR-NK constructs, preferably comprising a scFv antibody fragment against a disease-associated antigen or a hapten. More preferably, the antigen is a TAA, such as Trop-2. The constructs may be administered to a subject with a disease, such as cancer, autoimmune disease, or immune dysfunction disease, to induce an immune response against disease-associated cells. Where the constructs bind to a hapten, the subject is first treated with a hapten-conjugated antibody that binds to a disease associated antigen. Therapy may be supplemented by other treatments, such as debulking procedures (e.g., surgery, chemotherapy, radiation therapy) or coadministration of other agents. More preferably, administration of the construct is preceded by predosing with an unconjugated antibody that binds to the same disease-associated antigen. Most preferably, an antibody against CD74 or HLA-DR is administered to reduce systemic immunotoxicity induced by the constructs.

The present invention is directed to a method for delivering cytokines to the central nervous system and the lymphatic system by way of a tissue innervated by the trigeminal nerve and / or olfactory nerve. Cytokines include tumor necrosis factors, interleukins, interferons, particularly interferon-β and its muteins such as IFN-βser17. Such a method of delivery can be useful in the treatment of central nervous system disorders, brain disorders, proliferative, viral, and / or autoimmune disorders such as Sjogren's disorder.

The present invention relates to antibodies or fragments thereof that specifically bind FcγRIIB, particularly human FcγRIIB, with greater affinity than said antibodies or fragments thereof bind FcγRIIA, particularly human FcγRIIA. The present invention also provides the use of an anti-FcγRIIB 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.

The present invention relates to Fc region-containing polypeptides that exhibit improved effector function due to alterations of the extent of fucosylation, and to methods of using such polypeptides for treating or preventing cancer and other diseases. The Fc region-containing polypeptides of the present invention are preferably immunoglobulins (e.g., antibodies), in which the Fc region comprises at least one amino acid substitution relative to the corresponding amino acid sequence of a wild type Fc region, and which is sufficient to attenuate post-translational fucosylation and mediate improved binding to an activating Fc receptor and reduced binding to an inhibitory Fc receptor. The methods of the invention are particularly useful in preventing, treating, or ameliorating one or more symptoms associated with a disease, disorder, or infection where either an enhanced efficacy of effector cell function mediated by FcγR is desired (e.g., cancer, infectious disease) or an inhibited effector cell response mediated by FcγR is desired (e.g., inflammation, autoimmune disease).

Substituted bicyclic heteroaryls and compositions containing them, for the treatment of general inflammation, arthritis, rheumatic diseases, osteoarthritis, inflammatory bowel disorders, inflammatory eye disorders, inflammatory or unstable bladder disorders, psoriasis, skin complaints with inflammatory components, chronic inflammatory conditions, including but not restricted to autoimmune diseases such as systemic lupus erythematosis (SLE), myestenia gravis, rheumatoid arthritis, acute disseminated encephalomyelitis, idiopathic thrombocytopenic purpura, multiples sclerosis, Sjoegren's syndrome and autoimmune hemolytic anemia, allergic conditions including all forms of hypersensitivity. The present invention also enables methods for treating cancers that are mediated, dependent on or associated with p110δ activity, including but not restricted to leukemias, such as Acute Myeloid leukaemia (AML) Myelo-dysplastic syndrome (MDS) myelo-proliferative diseases (MPD) Chronic Myeloid Leukemia (CML) T-cell Acute Lymphoblastic leukaemia (T-ALL) B-cell Acute Lymphoblastic leukaemia (B-ALL) Non Hodgkins Lymphoma (NHL) B-cell lymphoma and solid tumors, such as breast cancer.

The present invention provides novel purinones and purines useful for the prevention and treatment of autoimmune diseases, inflammatory disease, mast cell mediated disease and transplant rejection. The compounds are of the general formulae I and II:

Methods and compositions for immunotherapy of inflammatory and immune-dysregulatory diseases, using multispecific antagonists that target at least two different markers are disclosed. The different targets include (i) proinflammatory effectors of the innate immune system, (ii) coagulation factors, and (iii) targets specifically associated with an inflammatory or immune-dysregulatory disorder, with a pathologic angiogenesis or cancer, or with an infectious disease, wherein the targets included in group (iii) are neither a proinflammatory effector of the immune system nor a coagulation factor. When the multispecific antagonist reacts specifically with a target associated with an inflammatory or immune-dysregulatory disorder, with a pathologic angiogenesis or cancer, or with an infectious disease, it also binds specifically with at least one proinflammatory effector of the immune system or at least one coagulation factor. Thus, the multispecific antagonist contains at least one binding specificity related to the diseased cell or condition being treated and at least one specificity to a component of the immune system, such as a receptor or antigen of B cells, T cells, neutrophils, monocytes and macrophages, and dendritic cells, a modulator of coagulation, or a proinflammatory cytokine. The multispecific antagonists are used in the treatment of various diseases that are generated or exacerbated by, or otherwise involve, proinflammatory effectors of the innate immune system or coagulation factors. Such diseases more particularly include acute and chronic inflammatory disorders, autoimmune diseases, giant cell arteritis, septicemia and septic shock, coagulopathies (including diffuse intravascular coagulation), neuropathies, graft versus host disease, infectious diseases, acute respiratory distress syndrome, granulomatous diseases, transplant rejection, asthma, cachexia, myocardial ischemia, and atherosclerosis. Other diseases also responsive to these therapies include cancers and conditions with pathological angiogenesis.

The present invention relates to methods of treating or preventing cancer and other diseases using molecules, particularly polypeptides, more particularly immunoglobulins (e.g., antibodies), comprising a variant Fc region, wherein said variant Fc region comprises at least one amino acid modification relative to a wild-type Fc region, which variant Fc region binds an FcγR that activates a cellular effector (“FcγRActivating,” such as FcγRIIA or FcγRIIIA) and an FcγR that inhibits a cellular effector (“FcγRInhibiting,” such as FcγRIIA) with an altered Ratio of Affinities relative to the respective binding affinities of such FcγR for the Fc region of the wild-type immunoglobulin. The methods of the invention are particularly useful in preventing, treating, or ameliorating one or more symptoms associated with a disease, disorder, or infection where either an enhanced efficacy of effector cell function mediated by FcγR is desired (e.g., cancer, infectious disease) or an inhibited effector cell response mediated by FcγR is desired (e.g., inflammation, autoimmune disease).

There is a need for improved methods for determining the diagnosis and prognosis of patients with conditions, including autoimmune disease and cancer, especially lymphoid neoplasms, such as lymphomas and leukemias. Provided herein are methods for using DNA sequencing to identify personalized, or patient-specific biomarkers in patients with lymphoid neoplasms, autoimmune disease and other conditions. Identified biomarkers can be used to determine and / or monitor the disease state for a subject with an associated lymphoid disorder or autoimmune disease or other condition. In particular, the invention provides a sensitive method for monitoring lymphoid neoplasms that undergo clonal evolutions without the need to development alternative assays for the evolved or mutated clones serving as patient-specific biomarkers.

Invented is a method of inhibiting the activity / function of PI3 kinases using quinoline derivatives. Also invented is a method of treating one or more disease states selected from: autoimmune disorders, inflammatory diseases, cardiovascular diseases, neurodegenerative diseases, allergy, asthma, pancreatitis, multiorgan failure, kidney diseases, platelet aggregation, cancer, sperm motility, transplantation rejection, graft rejection and lung injuries by the administration of quinoline derivatives.

The present invention relates to immunogenic compositions for modulating the immune system, comprising a therapeutically effective quantity of two or more immuno-active antigenic agents with pathogen-associated molecular patterns (PAMPs) and / or danger-associated molecular patterns (DAMPs) and one or more physiologically acceptable carriers, excipients, diluents or solvents. The immunogenic compositions according to the present invention are used for producing medicaments for preventing and / or treating, and for preventing and / or treating infectious diseases, auto-immune diseases, allergic diseases, inflammation, arthritis, inflammatory diseases, transplant rejection, affections caused by vascular disorders, diseases caused by haemorrhagic or ischaemic cardiovascular accidents, ischaemia, heart attack and haemorrhagia leading to tissue destruction, heart, kidney, respiratory or liver insufficiency, cancer, malign and benign tumours and neoplasia. The present invention further relates to methods for inducing the regeneration of cells, tissues, organs and organic systems such as the circulatory, nervous and endocrine systems. Finally, the present invention relates to methods for restoring immune response in an animal, in particular a human being.

Substituted bicyclic heteroaryls and compositions containing them, for the treatment of general inflammation, arthritis, rheumatic diseases, osteoarthritis, inflammatory bowel disorders, inflammatory eye disorders, inflammatory or unstable bladder disorders, psoriasis, skin complaints with inflammatory components, chronic inflammatory conditions, including but not restricted to autoimmune diseases such as systemic lupus erythematosis (SLE), myestenia gravis, rheumatoid arthritis, acute disseminated encephalomyelitis, idiopathic thrombocytopenic purpura, multiples sclerosis, Sjoegren's syndrome and autoimmune hemolytic anemia, allergic conditions including all forms of hypersensitivity, The present invention also enables methods for treating cancers that are mediated, dependent on or associated with p110δ activity, including but not restricted to leukemias, such as Acute Myeloid leukaemia (AML) Myelo-dysplastic syndrome (MDS) myelo-proliferative diseases (MPD) Chronic Myeloid Leukemia (CML) T-cell Acute Lymphoblastic leukaemia (T-ALL) B-cell Acute Lymphoblastic leukaemia (B-ALL) Non Hodgkins Lymphoma (NHL) B-cell lymphoma and solid tumors, such as breast cancer.

The present invention relates to HSP90 inhibitors containing fused amino pyridine core that are useful as inhibitors of HSP90 and their use in the treatment of HSP90 related diseases and disorders such as cancer, an autoimmune disease, or a neurodegenerative disease.

The present invention relates to humanized FcγRIIB antibodies, fragments, and variants thereof that bind human FcγRIIB with a greater affinity than said antibody binds FcγRIIA. The invention encompasses the use of the humanized antibodies of the invention for the treatment of any disease related to loss of balance of Fc receptor mediated signaling, such as cancer (preferably a B-cell malignancy, particularly, B-cell chronic lymphocytic leukemia or non-Hodgkin's lymphoma), autoimmune disease, inflammatory disease or IgE-mediated allergic disorder. The present invention also encompasses the use of a humanized FcγRIIB antibody or an antigen-binding fragment thereof, in combination with other cancer therapies. The invention provides methods of enhancing the therapeutic effect of therapeutic antibodies by administering the humanized antibodies of the invention to enhance the effector function of the therapeutic antibodies. The invention also provides methods of enhancing the efficacy of a vaccine composition by administering the humanized antibodies of the invention with a vaccine composition.

[Object]A novel and excellent method for preventing or treating rejection in the transplantation of various organs, allergy diseases, autoimmune diseases, hematologic tumor, or the like, based on a PI3Kδ-selective inhibitory action and / or an IL-2 production inhibitory action, and / or a B cell proliferation inhibitory action (including an activation inhibitory action), is provided[Means for Solution]It was found that a 3-substituted triazine or 3-substituted pyrimidine derivative exhibits a PI3Kδ-selective inhibitory action, and / or an IL-2 production inhibitory action, and / or a B cell proliferation inhibitory action (including an activation inhibitory action), and can be an agent for preventing or treating rejection in the transplantation of various organs, allergy diseases (asthma, atopic dermatitis, etc.), autoimmune diseases (rheumatoid arthritis, psoriasis, ulcerative colitis, Crohn's disease, systemic lupus erythematosus, etc.), hematologic tumor (leukemia etc.), or the like, thereby completing the present invention.

This invention discloses methods and compositions for modulating immune responses, which involve particulate delivery of agents to immune cells, wherein the agents comprise an inhibitor of the NF-kappa B signaling pathway and an antigen that corresponds to a target antigen. The methods and compositions of the present invention are particularly useful in the treatment or prophylaxis of an undesirable immune response associated with the target antigen, including autoimmune diseases, allergies and transplantation associated diseases.

The present invention provides methods for the prediction and diagnosis of autoimmune diseases including Systemic Lupus Erythematosus using a panel of single nucleotide polymorphisms (SNPs).

The invention belongs to the technical field of medicaments, and in particular relates to a hetero-aromatic ring shown by a general formula (I) as well as a derivative type tyrosine kinase inhibitor, a pharmaceutically acceptable salt or a stereoisomer thereof, wherein X, Z, W, R1, R2, R3, L1, L2, a, b, c, d, e, p, q, A and B are as defined in the specification. The invention also relates to preparation methods of these compounds, a pharmaceutical preparation containing these compounds, and important functions of these compounds in preparation of medicaments for treating B cell related leukemia (such as B cell chronic lymphocytic carcinoma and non-hodgkin lymphoma) and autoimmune diseases (such as rheumatoid arthritis, systemic lupus erythematosus and the like).