48 results about "Anti-IL-6" patented technology

The present invention relates to at least one novel chimeric, humanized or CDR-grafted anti-IL-6 antibodies derived from the murine CLB-8 antibody, including isolated nucleic acids that encode at least one such anti-IL-6 antibody, vectors, host cells, transgenic animals or plants, and methods of making and using thereof, including therapeutic compositions, methods and devices.

The present inventors succeeded in discovering specific amino acid mutations in the variable region, framework region, and constant region of TOCILIZUMAB, and this enables to reduce immunogenicity risk and the heterogeneity originated from disulfide bonds in the hinge region, as well as to improve antigen binding activity, pharmacokinetics, stability under acidic conditions, and stability in high concentration preparations.

An anti-IL-6 antibody, including isolated nucleic acids that encode at least one anti-IL-6 antibody, vectors, host cells, transgenic animals or plants, and methods of making and using thereof have applications in diagnostic and / or therapeutic compositions, methods and devices.

A preventive and / or therapeutic agent for systemic lupus erythematosus comprising an anti-interleukin-6 (IL-6) receptor antibody as an active ingredient.

A therapeutic agent for myeloma comprising a combined use of a nitrogen mustard anticancer agent and anti-IL-6 receptor antibody. Thus, a therapeutic agent for myeloma comprising anti-IL-6 receptor antibody for use in combination with a nitrogen mustard anticancer agent; a therapeutic agent for myeloma comprising a nitrogen mustard anticancer agent for use in combination with anti-IL-6 receptor antibody; and a therapeutic agent for myeloma comprising a nitrogen mustard anticancer agent and anti-IL-6 receptor antibody.

An anti-IL-6 antibody, including isolated nucleic acids that encode at least one anti-IL-6 antibody, vectors, host cells, transgenic animals or plants, and methods of making and using thereof have applications in diagnostic and / or therapeutic compositions, methods and devices.

The present inventors assessed the effect of anti-IL-6 receptor antibodies in suppressing chronic rejection reaction. They assessed the effect of anti-mouse IL-6 receptor antibody (MR16-1) administration in suppressing the chronic rejection reaction using a mouse model for post-heart-transplantation chronic rejection. The result of histopathological analysis of transplanted hearts extirpated 60 days after transplantation revealed that fibrosis of myocardium and vascular stenotic lesions, which are pathological conditions characteristic of the chronic rejection reaction, were significantly suppressed in the MR16-1-treated group as compared to the control group. Thus, MR16-1 administration was demonstrated to have the effect of suppressing chronic rejection reaction. Specifically, the present inventors discovered for the first time that the rejection reaction in the chronic phase after organ transplantation was suppressed by administering an anti-IL-6 receptor antibody.

The present inventors investigated the antitumor effects of anti-IL-6 receptor antibodies against prostate cancer. The result showed that the anti-IL-6 receptor antibodies had both in vivo and in vitro antitumor effects against prostate cancer. It was also revealed that the hPM1 antitumor effect is via IL-6 receptor.

The present application discloses methods for treating an IL-6-mediated disorder such as rheumatoid arthritis (RA), juvenile idiopathic arthritis (JIA), systemic JIA (sJIA), polyarticular course JIA (pcJIA), systemic sclerosis, or giant cell arteritis (GCA), with subcutaneously administered antibody that binds interleukin-6 receptor (anti-IL-6R antibody). In particular, it relates to identification of a fixed dose of anti-IL-6R antibody, e.g. tocilizumab, which is safe and effective for subcutaneous administration in patients with IL-6-mediated disorders. In addition, formulations and devices useful for subcutaneous administration of an anti-IL-6R antibody are disclosed.

The present invention is directed to therapeutic methods using IL-6 antagonists such as anti-IL-6 antibodies and fragments thereof having binding specificity for IL-6 to prevent or treat anemia (e.g., anemia associated with chemotherapy) including persons on a treatment regimen with a drug or chemotherapy and / or radiation for cancer (e.g., head and neck cancer) that is associated with increased risk of anemia.

The effect of anti-IL-6 receptor antibodies in suppressing cytotoxic T cell induction was examined. The results showed that CTL activity against alloantigens was statistically significantly reduced in mice treated with anti-IL-6 receptor antibodies as compared to mice not treated with antibodies and mice treated with a control antibody. The anti-IL-6 receptor antibody was also administered to recipients of a mouse model for allogenic heart transplantation. As a result, histopathological findings showed that inflammatory cell infiltration into transplanted hearts was suppressed and the survival period of transplanted hearts was significantly prolonged. Thus, the present inventors for the first time discovered that administration of anti-IL-6 receptor antibodies could suppress cytotoxic T cell induction and thereby suppress acute rejection after transplantation.

The present invention relates to at least one novel chimeric, humanized or CDR-grafted anti-IL-6 antibodies derived from the murine CLB-8 antibody, including isolated nucleic acids that encode at least one such anti-IL-6 antibody, vectors, host cells, transgenic animals or plants, and methods of making and using thereof, including therapeutic compositions, methods and devices.

The present inventors investigated the effects of anti-IL-6 receptor antibodies on improving the condition of infarcted areas in myocardial infarction, and on suppressing left ventricular remodeling after myocardial infarction. As a result, the administration of anti-IL-6 receptor antibodies significantly suppressed the increase of MPO activity in the infarcted area and suppressed myocardial MCP-1 expression in both the infarcted area and the non-infarcted area. Furthermore, echocardiography and histological examinations revealed that cardiac hypertrophy is also suppressed.

The present inventors focused on the fact that inflammation at the subretinal macular area enhances choroidal neovascularization, and developed pharmaceutical agents that suppress initiation or advancement of neovascularization by angiogenic factors such as VEGF. More specifically, the present inventors revealed that administering anti-IL-6 receptor monoclonal antibodies to mice treated with laser photocoagulation inhibits the development of choroidal neovascularization.

The present inventors used a model of intrasplenically induced liver metastasis to determine whether or not NF-κB activation in the liver is involved in the onset of metastatic tumors. When IKKβ was deleted from both liver cells and hematopoietically-derived cells, the onset of tumors was reduced remarkably. Tumor cells activated neighboring bone marrow cells (Kupffer cells) and produced mitogens such as interleukin (IL)-6, and this promoted angiogenesis and growth of tumors. The mitogen production depended on NF-κB in hematopoietically-derived Kupffer cells. Furthermore, treatment with an anti-IL-6 receptor antibody decreased the degree of metastatic tumor development. That is, the present inventors showed that tumor metastasis depends on inflammation, and proinflammatory intervention that targets Kupffer cells is useful for chemical prevention of metastatic tumors. Furthermore, it was shown that inhibition of the IKKβ / NF-κB signal transduction pathway, in particular IL-6 inhibition, can be utilized for anti-metastasis agents.

The present inventors investigated anti-IL-6 receptor antibodies for their effect in suppressing damage to transplanted islets after islet transplantation. As a result, they found that anti-IL-6 receptor antibodies reduced damage to transplanted islets, improved islet survival, and corrected hyperglycemia in recipients. Further, they revealed that administration of the anti-IL-6 receptor antibodies of the present invention suppressed the production of inflammatory cytokines by infiltrating cells after transplantation. Specifically, the present inventors discovered for the first time that damage to transplanted islets after islet transplantation can be suppressed by using anti-IL-6 receptor antibodies according to the present invention.

The present invention provides pharmaceutical compositions comprising second-generation molecules that are superior than TOCILIZUMAB, by altering the amino acid sequences of the variable and constant regions of TOCILIZUMAB, which is a humanized anti-IL-6 receptor IgG1 antibody, to enhance the antigen-neutralizing ability and increase the pharmacokinetics, so that the therapeutic effect is exerted with a less frequency of administration, and the immunogenicity, safety and physicochemical properties (stability and homogeneity) are improved. The present invention also provides methods for producing these pharmaceutical compositions. The present inventors have successfully generated second-generation molecules that are superior to TOCILIZUMAB by appropriately combining amino acid sequence alterations in the CDR domains, variable regions, and constant regions.

The invention provides methods of treating anemia in patients in need thereof, particularly in patients having anemia associated with chronic and / or inflammatory conditions such as cancers and arthritic conditions by administering antibodies or antibody fragments that bind IL-6. The treatment methods result in increased hemoglobin.

The present invention provides pharmaceutical compositions comprising second-generation molecules that are superior than TOCILIZUMAB, by altering the amino acid sequences of the variable and constant regions of TOCILIZUMAB, which is a humanized anti-IL-6 receptor IgG1 antibody, to enhance the antigen-neutralizing ability and increase the pharmacokinetics, so that the therapeutic effect is exerted with a less frequency of administration, and the immunogenicity, safety and physicochemical properties (stability and homogeneity) are improved. The present invention also provides methods for producing these pharmaceutical compositions.The present inventors have successfully generated second-generation molecules that are superior to TOCILIZUMAB by appropriately combining amino acid sequence alterations in the CDR domains, variable regions, and constant regions.

The present inventors investigated anti-IL-6 receptor antibodies for their effect in suppressing damage to transplanted islets after islet transplantation. As a result, they found that anti-IL-6 receptor antibodies reduced damage to transplanted islets, improved islet survival, and corrected hyperglycemia in recipients. Further, they revealed that administration of the anti-IL-6 receptor antibodies of the present invention suppressed the production of inflammatory cytokines by infiltrating cells after transplantation. Specifically, the present inventors discovered for the first time that damage to transplanted islets after islet transplantation can be suppressed by using anti-IL-6 receptor antibodies according to the present invention.

The invention relates inter alia to a bivalent, bispecific construct comprising an anti-IL-6 antibody, or derivative thereof, and an anti-IL-23 antibody, or derivative thereof and its use in therapy. The invention also relates to useful anti-IL-6 antibodies and anti-IL-23 antibodies.

The present invention provides human anti-IL-6 antibodies with extended in vivo half-life. The invention further relates to pharmaceutical compositions, therapeutic compositions, and methods using therapeutic antibodies that bind to IL-6 and that has an extended in vivo half-life for the treatment and prevention of IL-6 mediated diseases and disorders, such as, but not limited to, inflammatory diseases and disorders, autoimmune diseases and disorders and tumors.

The present inventors focused on the fact that inflammation at the subretinal macular area enhances choroidal neovascularization, and developed pharmaceutical agents that suppress initiation or advancement of neovascularization by angiogenic factors such as VEGF. More specifically, the present inventors revealed that administering anti-IL-6 receptor monoclonal antibodies to mice treated with laser photocoagulation inhibits the development of choroidal neovascularization.

The effect of anti-IL-6 receptor antibodies in suppressing cytotoxic T cell induction was examined. The results showed that CTL activity against alloantigens was statistically significantly reduced in mice treated with anti-IL-6 receptor antibodies as compared to mice not treated with antibodies and mice treated with a control antibody. The anti-IL-6 receptor antibody was also administered to recipients of a mouse model for allogenic heart transplantation. As a result, histopathological findings showed that inflammatory cell infiltration into transplanted hearts was suppressed and the survival period of transplanted hearts was significantly prolonged. Thus, the present inventors for the first time discovered that administration of anti-IL-6 receptor antibodies could suppress cytotoxic T cell induction and thereby suppress acute rejection after transplantation.

The present application discloses methods for treating an IL-6-mediated disorder such as rheumatoid arthritis (RA), juvenile idiopathic arthritis (JIA), systemic JIA (sJIA), polyarticular course JIA (pcJIA), systemic sclerosis, or giant cell arteritis (GCA), with subcutaneously administered antibody that binds interleukin-6 receptor (anti-IL-6R antibody). In particular, it relates to identification of a fixed dose of anti-IL-6R antibody, e.g. tocilizumab, which is safe and effective for subcutaneous administration in patients with IL-6-mediated disorders. In addition, formulations and devices useful for subcutaneous administration of an anti-IL-6R antibody are disclosed.

The present inventors investigated the effects of anti-IL-6 receptor antibodies on improving the condition of infarcted areas in myocardial infarction, and on suppressing left ventricular remodeling after myocardial infarction. As a result, the administration of anti-IL-6 receptor antibodies significantly suppressed the increase of MPO activity in the infarcted area and suppressed myocardial MCP-1 expression in both the infarcted area and the non-infarcted area. Furthermore, echocardiography and histological examinations revealed that cardiac hypertrophy is also suppressed.

The present invention provides novel monoclonal antibodies that bind specifically to IL-6. The antibodies of the invention comprise a variable heavy chain (VH) region selected from any of the VH regions disclosed herein as well as amino acid variants thereof, and / or a variable light chain (VL) region selected from any of the VL regions disclosed herein as well as amino acid variants thereof. The invention also provides methods of treating diseases and disorders associated with IL-6 expression and / or activity.

The present invention relates generally to compositions and methods using mammalian, dsDNA (Double Stranded Deoxyribonucleic Acid) vaccination for the induction and maintenance of regulator suppressor T cells resulting in suppression of non infectious, and post infectious, inflammatory, allergic, auto-immune, vasculitic, certain degenerative vascular, and graft versus host diseases, with or without the use of IL-10, and with or without the use or TGFβ, with or without the use of anti-IL 6 receptor antibody, anti TNF antibody and or Plasmapheresis, IVIG, Corticosteroids, Methotrexate, Bromocriptine, and or vitamin D analogues.