217 results about "Organ transplant rejection" patented technology

The present invention relates to the identification of macaque antibodies to human B7.1 and B7.2 by screening of phage display libraries or monkey heterohybridomas obtained using B lymphocytes from B7.1 and / or B7.2 immunized monkeys. More specifically, the invention provides four monkey monoclonal antibodies 7B6, 16C10, 7C10 and 20C9 which inhibit the B7:CD28 pathway and thereby function as effective immunosuppressants. The invention further provides the complete DNA and amino acid sequences of the light and heavy chain of three primatized antibodies derived from those monkey monoclonal antibodies which bind B7.1 and possibly B7.2, primatized 7C10, primatized 7B6 and primatized 16C10. These primatized and monkey antibodies may be used as specific immunosuppressants, e.g., for the treatment of autoimmune diseases and to prevent organ transplant rejection.

The invention relates to cell stimulatory fusion proteins and DNA sequences, vectors comprising at least two agonists of TNF / TNFR super family, immunoglobulin super family, cytokine family proteins and optional antigen combination. Instructions for use of these proteins and DNA constructs as immune adjuvants and vaccines for treatment of various chronic diseases such as viral infection are also provided. Additionally, the use of these protein and DNA constructs as immune suppressant for treatment of various chronic diseases, such as autoimmunity and organ transplant rejection, is also illustrated.

The invention relates to a method of treating or monitoring / diagnosing a disease state mediated by activated macrophages. The method comprises the step of administering to a patient suffering from a macrophage mediated disease state an effective amount of a composition comprising a conjugate or complex of the general formulaAb−Xwhere the group Ab comprises a ligand capable of binding to activated macrophages, and when the conjugate is being used for treatment of the disease state, the group X comprises an immunogen, a cytotoxin, or a compound capable of altering macrophage function, and when the conjugate is being used for monitoring / diagnosing the disease state, X comprises an imaging agent. The method is useful for treating a patient suffering from a disease selected from the group consisting of rheumatoid arthritis, ulcerative colitis, Crohn's disease, inflammation, infections, osteomyelitis, atherosclerosis, organ transplant rejection, pulmonary fibrosis, sarcoidosis, and systemic sclerosis.

The invention relates to a method of treating or monitoring / diagnosing a disease state mediated by activated macrophages. The method comprises the step of administering to a patient suffering from a macrophage mediated disease state an effective amount of a composition comprising a conjugate or complex of the general formula Ab-X where the group Ab comprises a ligand capable of binding to activated macrophages, and when the conjugate is being used for treatment of the disease state, the group X comprises an immunogen, a cytotoxin, or a compound capable of altering macrophage function, and when the conjugate is being used for monitoring / diagnosing the disease state, X comprises an imaging agent. The method is useful for treating a patient suffering from a disease selected from the group consisting of rheumatoid arthritis, ulcerative colitis, Crohn's disease, inflammation, infections, osteomyelitis, atherosclerosis, organ transplant rejection, pulmonary fibrosis, sarcoidosis, and systemic sclerosis.

[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.

The present invention relates to methods and compositions for the prevention and treatment and prevention of immune system disorders, including cancer, AIDS, asthmatic disorders, autoimmune diseases, organ transplant rejection and chronic viral diseases such as HCV or HBV infections. The therapeutic methods of the invention comprise administering molecules that modulate the activity of 8F4, thereby modulating costimulation of T cells. The present invention further provides monoclonal antibodies against the 8F4 molecule and hybridoma cells which produce said monoclonal antibodies. Pharmaceutical compositions comprising molecules that modulate the activity of 8F4 are also provided.

The present invention relates to antiviral compounds of formula (I),compositions containing these compounds, processes for their preparation, intermediates in their synthesis, and their use as therapeutics for prevention of organ transplantation rejection, the treatment of immune disorders and inflammation, and treatment of viral (particularly hepatitis C viral) infection.

The invention relates to an indoleamine2,3-dioxygenase inhibitor having a structure as shown in a formula (I), as well as a preparation method and application thereof. The IDO inhibitor is (Z)-N'-hydroxyl-N-benzoate derivative, has high inhibiting activity for IDO, can be used for effectively inhibiting the IDO activity and inhibiting immunosuppression of patients, can be widely applied to treatment or prevention of cancer or tumors, virus infection, depression, neural degeneration disease, trauma, age related cataract, organ transplant rejection or autoimmune disease, and is expected to be developed into a new generation of immunosuppressors.

The present invention provides compositions and methods of treatment of HCV infected subjects that are not sensitive to interferon treatment. Further, compositions and methods are provided for prevention of organ transplant rejection. The compositions of the invention comprise an anti microRNA-122 oligonucleotide, and are made for administration to a primate.

The present invention is directed to a composition comprising a nanoparticulate cyclosporine having improved bioavailability. The nanoparticulate cyclosporine particles of the composition have an effective average particle size of less than about 2000 nm in diameter and are useful in the prevention and treatment of organ transplant rejection and autoimmune diseases such as psoriasis, rheumatoid arthritis, and other related diseases. The invention also relates to a controlled release composition comprising a cyclosporine or a nanoparticulate cyclosporine that in operation delivers the drug in a pulsed or bimodal manner for the prevention and treatment of organ transplant rejection and autoimmune diseases such as psoriasis, rheumatoid arthritis, and other related diseases.

The present invention relates to substituted fused tricyclic compounds of formula (I) or (Ia), their tautomers, polymorphs, stereoisomers, prodrugs, solvates, co-crystals, pharmaceutically acceptable salts, pharmaceutical compositions containing them and methods of treating conditions and diseases that are mediated by JAK activity. The compounds of the present invention are useful in the treatment, prevention or suppression of diseases and disorders mediated by JAK activity. Such conditions include, but not limited to, arthritis, Alzheimer's disease, autoimmune thyroid disorders, cancer, diabetes, leukemia, T-cell prolymphocytic leukemia, lymphoma, myleoproliferation disorders, lupus, multiple myeloma, multiple sclerosis, osteoarthritis, sepsis, psoriatic arthritis, prostate cancer, T-cell autoimmune disease, inflammatory diseases, chronic and acute allograft transplant rejection, bone marrow transplant, stroke, asthma, chronic obstructive pulmonary disease, allergy, bronchitis, viral diseases, or Type I diabetes, complications from diabetes, rheumatoid arthritis, asthma, Crohn's disease, dry eye, uveitis, inflammatory bowel disease, organ transplant rejection, psoriasis and ulcerative colitis. The present disclosure also relates to process for the preparation of such compounds, and to pharmaceutical compositions containing them.

The present invention provides cyclosporin analogues of formula I,and compositions comprising these compounds, as well as processes for their preparation, intermediates in their synthesis, and methods of use thereof for prevention of organ transplantation rejection, the treatment of immune disorders and inflammation, and treatment of viral (particularly hepatitis C viral) infection.

The present invention provides methods of characterizing organ transplant rejection or inflammatory conditions associated with organ transplant rejection using gene expression profiling.

The present invention provides to an isoxazoline derivative of formula (I), the pharmaceutically acceptable salts, esters and stereochemically isomeric forms thereof, and the use of the derivative in inhibiting the activity of caspases. The present invention also provides a pharmaceutical composition for preventing inflammation and apoptosis which comprise the isoxazoline derivative, pharmaceutically acceptable salts, esters and stereochemically isomeric forms thereof and the process for preparing the same. The derivative according to the present invention can be effectively used in treating diseases due to caspases, such as, for example the disease in which cells are abnormally died, dementia, cerebral stroke, AIDS, diabetes, gastric ulcer, hepatic injury by hepatitis, sepsis, organ transplantation rejection reaction and anti-inflammation.

The present invention provides a compound of the formula or a pharmaceutically acceptable salt or solvate thereof, wherein R<1>, R<2>, R<3>, R<9>, R<10>, A and B are as defined in the specification. The present invention also provides pharmaceutical compositions containing the compound of this invention, and methods of treatment using the compound of this invention. The invention also relates to the use of a combination of a compound of this invention and one or more antiviral or other agents useful in the treatment of Human Immunodeficiency Virus (HIV). The invention further relates to the use of a compound of this invention, alone or in combination with another agent, in the treatment of solid organ transplant rejection, graft v. host disease, arthritis, rheumatoid arthritis, inflammatory bowel disease, atopic dermatitis, psoriasis, asthma, allergies or multiple sclerosis.

This invention describes an ICE inhibitor prodrug (I) having good bioavailabilityCompound I is useful for treating IL-1 mediated diseases such as rheumatoid arthritis, inflammatory bowel disease, Crohn's disease, ulcerative colitis, inflammatory peritonitis, septic shock, pancreatitis, traumatic brain injury, organ transplant rejection, osteoarthritis, asthma, psoriasis, Alzheimer's disease, myocardial infarction, congestive heart failure, Huntington's disease, atherosclerosis, atopic dermatitis, leukemias and related disorders, myelodysplastic syndrome, uveitis or multiple myeloma.

The invention discloses a new class of propylene glycol derivatives represented by the general formula (I), a preparation method thereof, a pharmaceutical composition containing them, and their use as medicines, especially immunomodulatory medicines. This kind of compound with excellent curative effect and low toxicity can be used for immune disorder and immunosuppression; and can be used for treatment and / or low immunity, rejection after organ transplantation and autoimmune disease. General formula (I)

The present invention relates to a cyclosporin analog of the following formula (I) or a pro-drug or pharmaceutically acceptable salt thereof:whereinA is of the formula:where Q, W, X, Y, and Z are defined herein. In a second embodiment, the present invention relates to pharmaceutical compositions comprising pro-drugs or pharmaceutically acceptable salts of the compounds of the present invention and the use thereof for treating autoimmune diseases or for the prevention of organ transplantation rejection in a subject. In a third embodiment, the present invention relates to processes for the production of novel cyclosporin analogs of the present invention.

The present invention provides a compound of the formula or a pharmaceutically acceptable salt or solvate thereof, wherein R<1>, R<2>, R<3>, R<9>, R<10>, A and B are as defined in the specification. The present invention also provides pharmaceutical compositions containing the compound of this invention, and methods of treatment using the compound of this invention. The invention also relates to the use of a combination of a compound of this invention and one or more antiviral or other agents useful in the treatment of Human Immunodeficiency Virus (HIV). The invention further relates to the use of a compound of this invention, alone or in combination with another agent, in the treatment of solid organ transplant rejection, graft v. host disease, arthritis, rheumatoid arthritis, inflammatory bowel disease, atopic dermatitis, psoriasis, asthma, allergies or multiple sclerosis.

The invention relates to an indoleamine 2,3-dioxygenase inhibitor with a structure represented by the formula (I) and a preparation method and applications thereof. The indoleamine 2,3-dioxygenase (IDO) inhibitor is the derivative of (Z)-N'-hydroxyl-N-phenyl formamidine, has an extremely high activity on inhibiting IDO, can effectively inhibit the activity of IDO, and can be used to inhibit the immunity inhibition of patients. The inhibitor can be widely used to treat or prevent cancer / tumor, viral infection, depression, neurodegenerative diseases, wounds, age related cataract, organ-graft refection, and autoimmune disease, and can be advantageously to be used as a novel immune-suppressor.

The invention relates to an in vitro amplification and low-temperature storage method for regulatory T cells of umbilical cord blood. The method comprises the following steps of: separating a CD4+CD25+T cell group rich in the regulatory T cells from the umbilical cord blood; amplifying the enriched CD4+CD25+T cell group to obtain high-purity regulatory T cells; and storing the amplified regulatory T cells in liquid nitrogen at a low temperature to serve as third-party unrelated donor regulatory T cells for treating clinical diseases. The method has the advantages that: a large quantity of regulatory T cells can be obtained from the umbilical cord blood and stored for a long term in the liquid nitrogen, can meet the requirements of clinic for regulatory T cell products, and are used for treating graft versus host disease, organ transplantation rejection and autoimmune disease.

The present invention provides methods of treating a disease or disorder, in which increasing the number of regulatory T cell (Treg) is beneficial, by administering to a subject suffering from such a disease or disorder a therapeutically effective amount of DII4 antagonists that block DII4-Notch signal pathways, thereby increasing the number of Treg. Diseases or disorders treatable by the methods of the invention include autoimmune diseases or disorders, such as multiple sclerosis (MS), diabetes, and the like. Suitable DII4 antagonists for the invention include antibodies or antibody fragments that specifically bind DII4 and block DII4-Notch interactions, the extracellular domain of DII4, and the like. The invention also provides methods of preventing an occurrence or recurrence of such diseases or disorders in a subject predisposed or susceptible to developing such diseases or disorders. Furthermore, the methods of the invention are useful in preventing or treating organ transplant rejections or graft-versus-host disease.

A novel [1,2,4]triazolo[1,5-a]pyridine compound is disclosed that has a formula represented by the following:This compound may be prepared as a pharmaceutical composition, and may be used for the prevention and treatment of a variety of conditions in mammals including humans, including by way of non-limiting example, diseases involving cartilage degradation, bone and / or joint degradation, for example osteoarthritis; and / or conditions involving inflammation or immune responses, such as Crohn's disease, rheumatoid arthritis, psoriasis, allergic airways disease (e.g. asthma, rhinitis), juvenile idiopathic arthritis, colitis, inflammatory bowel diseases, endotoxin-driven disease states (e.g. complications after bypass surgery or chronic endotoxin states contributing to e.g. chronic cardiac failure), diseases involving impairment of cartilage turnover (e.g. diseases involving the anabolic stimulation of chondrocytes), congenital cartilage malformations, diseases associated with hypersecretion of IL6 and transplantation rejection (e.g. organ transplant rejection) and proliferative diseases.

The present invention concerns a molecule binding to LAG-3 protein and causing depletion of LAG-3 + activated T cells particularly said molecule is a cytotoxic anti-LAG-3 monoclonal antibody or fragment thereof. It also concerns a method of treating or preventing organ transplant rejection or autoimmune diseases in a mammal comprising administering to said mammal a therapeutically effective amount of said antibody.

Disclosed is an isoxazole derivative that inhibits the activity of the Janus kinases (JAKs), the structure thereof as presented in formula I, formula II, formula IX, and formula XI. The substituent groups in the formulas are described in the description. Also disclosed are the pharmaceutical composition of the compound and a related use in medicine preparation.

Compounds of formula (I)for clinical treatment of autoimmune diseases, inflammatory diseases, organ transplant rejection and malignant neoplasia. A pharmaceutical composition comprising a compound of formula (I) in an amount giving a daily dosage of from 0.005 mg / kg to 10 mg / kg body weight, in particular from 0.025 mg / kg to 2 mg / kg body weight.

The invention relates to polymer-modified bioactive synthetic chemokines and to methods for their production and use. The bioactive synthetic chemokines of the invention comprises a polymer modified polypeptide chemokine backbone. The compounds and methods or the invention are useful for the treatment of disorders involving naturally occurring chemokines, such as for the treatment of HIV and AIDS related disorders and for the treatment of asthma, allergic rhinitis, atopic dermatitis, atheroma / atherosclerosis, organ transplant rejection, and rheumatoid arthritis.