Composition for treating il-6-related diseases

Abstract

The present invention provides a pharmaceutical composition for treating IL-6-related diseases containing an IL-6 inhibitor as an active ingredient, wherein the pharmaceutical composition is routinely administered after a short-interval dosing period where the same dose as the routine dose is administered at a shorter interval than the routine dosing interval.

1 - 15 . (canceled) 
     
     
         16 . A method of treating an IL-6-related disease with an IL-6 inhibitor, the method comprising:
 during a first dosing period (“the short-interval dosing period”), administering multiple sequential doses of the IL-6 inhibitor to a human patient who has the IL-6-related disease, wherein the amount of each dose administered to the patient during the short-interval dosing period is a routine dosage, and the interval of time between sequential doses is shorter than a routine dosing interval;   after the final administration of the short-interval dosing period, waiting the routine dosing interval and then administering the IL-6 inhibitor to the patient at the routine dosage, spaced by an interval of time between consecutive doses that is the routine dosing interval, thereby treating the patient's IL-6-related disease.   
     
     
         17 . The method of  claim 16 , wherein multiple consecutive doses are administered after the final administration of the short-interval dosing period, and are spaced by the routine dosing interval. 
     
     
         18 . The method of  claim 16 , wherein the IL-6 inhibitor is an antibody. 
     
     
         19 . The method of  claim 18 , wherein the antibody comprises a heavy-chain variable region comprising the amino acid sequence of SEQ ID NO: 1 and a light-chain variable region comprising the amino acid sequence of SEQ ID NO: 2. 
     
     
         20 . The method of  claim 18 , wherein the antibody comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 3 and a light chain comprising the amino acid sequence of SEQ ID NO: 4. 
     
     
         21 . The method of  claim 18 , wherein the antibody is SA237. 
     
     
         22 . The method of  claim 16 , wherein the routine dosing interval is an interval of time within the range of three to five weeks. 
     
     
         23 . The method of  claim 16 , wherein the routine dosing interval is four weeks. 
     
     
         24 . The method of  claim 16 , wherein the interval of time between sequential doses administered during the short-interval dosing period is one half the length of the routine dosing interval. 
     
     
         25 . The method of  claim 16 , wherein the interval of time between sequential doses administered during the short-interval dosing period is in the range of one to two weeks. 
     
     
         26 . The method of  claim 16 , wherein the interval of time between sequential doses administered during the short-interval dosing period is two weeks. 
     
     
         27 . The method of  claim 16 , wherein the time from the initial administration to the final administration of the short-interval dosing period is one to eight weeks. 
     
     
         28 . The method of  claim 16 , wherein the time from the initial administration to the final administration of the short-interval dosing period is four weeks. 
     
     
         29 . The method of  claim 28 , wherein a total of three doses are administered during the short-interval dosing period, spaced by two-week intervals of time. 
     
     
         30 . The method of  claim 18 , wherein the routine dosage is a dosage amount in the range of 50 mg to 800 mg per administration. 
     
     
         31 . The method of  claim 18 , wherein the routine dosage is 120 mg per administration. 
     
     
         32 . The method of  claim 16 , wherein the IL-6 inhibitor is administered intravenously. 
     
     
         33 . The method of  claim 16 , wherein the IL-6 inhibitor is administered subcutaneously. 
     
     
         34 . The method of  claim 16 , wherein the IL-6-related disease is selected from: rheumatoid arthritis, juvenile idiopathic arthritis, systemic-onset juvenile idiopathic arthritis, Castleman's disease, systemic lupus erythematosus (SLE), lupus nephritis, Crohn's disease, lymphoma, ulcerative colitis, anemia, vasculitis, Kawasaki disease, Still's disease, amyloidosis, multiple sclerosis, transplantation, age-related macular degeneration, ankylosing spondylitis, psoriasis, psoriatic arthritis, chronic obstructive pulmonary disease (COPD), IgA nephropathy, osteoarthritis, asthma, diabetic nephropathy, graft-versus-host disease (GVHD), endometriosis, hepatitis (NASH), myocardial infarction, arteriosclerosis, sepsis, osteoporosis, diabetes, multiple myeloma, prostate cancer, kidney cancer, B-cell non-Hodgkin's lymphoma, pancreatic cancer, lung cancer, esophageal cancer, colon cancer, cancer cachexia, cancer nerve invasion, myocardial infarction, myopic choroidal neovascularization, idiopathic choroidal neovascularization, uveitis, chronic thyroiditis, delayed hypersensitivity, contact dermatitis, atopic dermatitis, mesothelioma, polymyositis, dermatomyositis, panuveitis, anterior uveitis, intermediate uveitis, scleritis, keratitis, orbital inflammation, optic neuritis, diabetic retinopathy, proliferative vitreoretinopathy, dry eye, post-operative inflammation, neuromyelitis optica, myasthenia gravis, and pulmonary hypertension. 
     
     
         35 . A method of treating an IL-6-related disease with an antibody comprising a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 1 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 2, the method comprising:
 during a period of time (“the short-interval dosing period”), administering two to five sequential doses of the antibody to a human patient who has the IL-6-related disease, wherein the amount of each dose administered to the patient during the short-interval dosing period is a routine dosage and the interval of time between each two sequential doses during the short-interval dosing period is an interval with a length in the range of one to two weeks (the “short interval”); and   after the final administration of the short-interval dosing period, waiting an interval of time that is twice the length of the short interval, and then administering the IL-6 inhibitor to the patient at the routine dosage, spaced by an interval of time between consecutive doses that is twice as long as the short interval,   
       thereby treating the patient's IL-6-related disease. 
     
     
         36 . The method of  claim 35 , wherein multiple consecutive doses are administered after the final administration of the short-interval dosing period, and are spaced by an interval of time that is twice as long as the short interval. 
     
     
         37 . The method of  claim 35 , wherein the antibody comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 3 and a light chain comprising the amino acid sequence of SEQ ID NO: 4. 
     
     
         38 . The method of  claim 35 , wherein the short-interval dosing period is four weeks in length and the short interval is two weeks in length. 
     
     
         39 . The method of  claim 35 , wherein the IL-6-related disease is rheumatoid arthritis or juvenile idiopathic arthritis. 
     
     
         40 . A method for treating an IL-6 related disease, the method comprising:
 administering a pharmaceutical composition comprising an anti-IL-6 receptor antibody subcutaneously to a human patient who has an IL-6 related disease, wherein the pharmaceutical composition is administered to the patient three times with two-week intervals between sequential administrations; and   after the third administration, the pharmaceutical composition is administered to the patient with a four-week interval between administrations.   
     
     
         41 . The method of  claim 40 , wherein the pharmaceutical composition is administered to the patient multiple times after the third administration, spaced at four-week intervals. 
     
     
         42 . The method of  claim 40 , wherein the antibody comprises a heavy chain comprising the sequence of SEQ ID NO:3 and a light chain comprising the sequence of SEQ ID NO:4. 
     
     
         43 . The method of  claim 40 , wherein the amount of the antibody in the pharmaceutical composition that is administered to the patient in each administration is 120 mg. 
     
     
         44 . A method of treating an IL-6-related disease with an IL-6 inhibitor, the method comprising:
 during a first dosing period, administering multiple sequential doses of the IL-6 inhibitor to a patient who has the IL-6-related disease, wherein the amount of each dose administered to the patient during the first dosing period is a given dosage and the interval of time between sequential doses is a first dosing interval;   after the final administration of the first dosing period, waiting an interval of time (“the second dosing interval”) that is longer than the first dosing interval and then administering the IL-6 inhibitor at the given dosage, wherein any consecutive doses of the IL-6 inhibitor after the final administration of the first dosing period are spaced by the second dosing interval, wherein the method treats the patient's IL-6-related disease.   
     
     
         45 . The method of  claim 44 , wherein multiple consecutive doses of the IL-6 inhibitor are administered after the final administration of the first dosing period, and are spaced by the second dosing interval.