JP2008515999A5 - - Google Patents

Claims (55)

A composition for use in the prevention or treatment of eye conditions complement-associated, containing complement inhibitor, composition. 2. The composition of claim 1, wherein the complement inhibitor is a selective inhibitor of an alternative complement pathway. 3. The composition of claim 2, wherein the complement inhibitor is a CRIg polypeptide or an agonist thereof . 4. The composition of claim 3, wherein the CRIg polypeptide is selected from the group consisting of the CRIg polypeptide of SEQ ID NOs: 2, 4, 6, 8, and the extracellular domain (ECD) of the polypeptide. 5. The composition of claim 4, wherein the CRIg polypeptide is an ECD of a CRIg polypeptide of SEQ ID NO: 2, 4, 6, or 8. 6. The composition of claim 5, wherein the CRIg polypeptide is an ECD of a CRIg polypeptide of SEQ ID NO: 4 or 6. 4. The composition of claim 3, wherein the CRIg polypeptide is fused to an immunoglobulin sequence. 8. The composition of claim 7, wherein the immunoglobulin sequence is an immunoglobulin constant region sequence. 9. The composition of claim 8, wherein the immunoglobulin constant region sequence is that of an immunoglobulin heavy chain. 10. The immunoglobulin heavy chain constant region sequence is fused to the extracellular region of the CRIg polypeptide of SEQ ID NO: 2, 4, 6, or 8 so that a CRIg-Ig fusion protein is produced. Composition . 11. The composition of claim 10, wherein the immunoglobulin heavy chain constant region sequence is that of IgG. The composition according to claim 11, wherein the IgG is IgG-1 or IgG-3. The composition according to claim 12, wherein the IgG-1 heavy chain constant region sequence includes at least a hinge region , a CH2 region , and a CH3 region. 13. The composition of claim 12, wherein the IgG-1 heavy chain constant region sequence includes a hinge region , a CH1 region , a CH2 region , and a CH3 region. 11. The composition of claim 10, wherein the CRIg-Ig fusion protein includes a linker between the CRIg sequence and the Ig sequence. 11. The composition of claim 10, wherein the CRIg-Ig fusion protein is encoded by a nucleic acid selected from the group consisting of SEQ ID NOs: 20, 21, 25, 26, 27, and 28. Retinopathy in which the complement symptoms are related to age-related macular degeneration (AMD), chronic choroidal neovascularization (CNV), uveitis, diabetic retinopathy and other ischemia Selected from the group consisting of: endophthalmitis, diabetic macular edema, pathological myopia, von Hippel-Lindau disease, ocular histoplasmosis, central retinal vein occlusion (CRVO), corneal neovascularization, and retinal neovascularization, The composition of claim 1. 18. The composition of claim 17, wherein the eye disease to which the complement is related is age-related macular degeneration (AMD) or chronic choroidal neovascularization (CNV). Ru der intended for use in preventing C NV, The composition according to claim 18. Ru der intended for use in the prevention of progression A MD, composition according to claim 18. Ru der intended for use in the prevention of progression to CNV of A MD, composition according to claim 20. Composition for use in preventing the onset or progression of AMD in a subject at risk of developing age-related macular degeneration (AMD) in at least one eye or diagnosed with AMD in at least one eye a is, it contains C RIG polypeptides or agonists, compositions. 23. The composition of claim 22, wherein the CRIg polypeptide is as defined in any one of claims 5-7 . Said fusion polypeptide, fused to an immunoglobulin heavy chain constant region sequences, are included extracellular domain of SEQ ID NO: 4 or 6 of the polypeptide composition according to claim 2 3. The fusion polypeptide, SEQ ID NO: 20,21,25,26,27, and the nucleotide sequences of 28 selected from the group consisting of the fusion polypeptides encoded composition of claim 2 4. 26. The composition according to any one of claims 22 to 25 , wherein the subject is a human. 27. The composition of claim 26 , wherein the human subject has been diagnosed with AMD in at least one eye. The AMD is a dry 燥型 AMD Category 3 or Category 4 A composition according to claim 2 7. 30. The composition of claim 28 , wherein the subject has been identified as being at risk of developing CNV. 30. The composition of claim 29 , wherein the subject is genetically at risk of developing CNV. 30. The composition of claim 28 , wherein the human subject has been diagnosed as having AMD in both eyes. It said human subject has an AMD category 3 or category 4 in both eyes, the composition according to claim 3 1. Slow the progression of A MD, composition according to claim 2 6. We slow the progression to CNV of A MD, The composition of claim 28. A composition according to progression to CNV in A MD hinder, to claim 2 6. The human subject is diagnosed as having AMD only one eye, the composition according to claim 2 7. Ru slow racemase the occurrence of AMD in the other side of the eye, the composition of claim 3 6. Hinder the development of AMD in the other side of the eye, the composition of claim 3 6. Formulated for administration by nitric child intravitreal injection composition according to claim 2 6. 27. The composition of claim 26 , formulated for administration with an additional agent for prevention or treatment of AMD or CNV. The additional agent is an anti-VEGF-A antibody composition of claim 4 0. A composition for use in the prophylactic or therapeutic treatment of dry 燥型 age-related macular degeneration (AMD), containing the C RIG polypeptides or agonists, compositions. 43. The composition of claim 42, wherein the CRIg polypeptide is as defined in any one of claims 4-14. A composition for use in the prophylaxis or treatment of a disease or condition involving complement , comprising a CRIg polypeptide or an agonist thereof . 45. The composition of claim 44 , wherein the CRIg polypeptide is selected from the group consisting of CRIg polypeptides of SEQ ID NOs: 2, 4, 6, 8, and the extracellular region of such polypeptides. 46. The composition of claim 45 , wherein the CRIg polypeptide is fused to an immunoglobulin sequence according to any one of claims 7-14 . 45. The composition of claim 44 , wherein the complement-related disease is an inflammatory disease or an autoimmune disease. Diseases with which the complement is concerned include rheumatoid arthritis (RA), adult respiratory distress syndrome (ARDS), distant tissue injury after ischemia reperfusion, complement activation during cardiopulmonary bypass surgery, dermatomyositis , Pemphigus, lupus nephritis and resulting glomerulonephritis and vasculitis, cardiopulmonary bypass surgery, coronary artery endothelial dysfunction induced by heart failure, type II membranoproliferative glomerulonephritis, IgA nephropathy, acute renal failure , Cryoglobulinemia, antiphospholipid syndrome, age-related macular degeneration, uveitis, diabetic retinopathy, allograft, hyperacute rejection, hemodialysis, chronic obstructive pulmonary distress syndrome (COPD), asthma, aspiration Selected from the group consisting of pneumonia, urticaria, chronic idiopathic urticaria, hemolytic uremic syndrome, endometriosis, cardiogenic shock, ischemia reperfusion injury, and multiple sclerosis (MS), Item 47 A composition according to 1 . Diseases related to the complement include inflammatory bowel disease (IBD), systemic lupus erythematosus, rheumatoid arthritis, juvenile chronic arthritis, spondyloarthropathy, systemic sclerosis (scleroderma), idiopathic inflammatory muscle Disease (dermatomyositis, polymyositis), Sjogren's syndrome, systemic vasculitis, sarcoidosis, autoimmune hemolytic anemia (immune pancytopenia, paroxysmal nocturnal hemoglobinuria) autoimmune thrombocytopenia (idiopathic) Thrombocytopenic purpura, immune thrombocytopenia), thyroiditis (Graves' disease, Hashimoto's disease thyroiditis, juvenile lymphocytic thyroiditis, atrophic thyroiditis), diabetes mellitus, immune kidney disease (glomerulonephritis, tubulointerstitial nephritis), central nervous system and peripheral nervous system demyelinating diseases (such as multiple sclerosis, idiopathic polyneuropathy), hepatobiliary diseases (e.g., infectious hepatitis (a hepatitis, hepatitis B, C hepatitis Hepatitis D, E hepatitis, and other non-liver-tropic virus)), autoimmune chronic active hepatitis, primary biliary cirrhosis, granulomatous hepatitis, and sclerosing cholangitis, inflammatory and fibrotic lung Diseases (eg, cystic fibrosis), gluten-sensitive bowel disease, Whipple disease, autoimmune or immune skin diseases (including vesicular skin disease, erythema multiforme, and contact dermatitis), psoriasis, lungs Allergic diseases (eg, eosinophilic pneumonia, idiopathic pulmonary fibrosis, and hypersensitivity pneumonia), transplant-related diseases (including transplant rejection and graft-versus-host disease), Alzheimer's disease, paroxysmal nocturnal hemoglobin 48. The composition of claim 47 , selected from the group consisting of urinary disease, hereditary angioedema, and atherosclerosis. 46. The composition of claim 45 , wherein the subject is a mammal. Wherein the mammal is a human, the composition according to claim 5 0. A composition for use in inhibiting the production of a C3b complement fragment in a mammal , comprising a CRIg polypeptide or an agonist thereof . The CRIg polypeptide, CRIg polypeptide of SEQ ID NO: 2, 4, 6, 8, and are selected from the group consisting of the extracellular regions of such polypeptides, composition according to claim 5 2. The CRIg polypeptide is fused to an immunoglobulin sequence of any one of claims 7 to 14, composition according to claim 3. A composition for selective inhibition of an alternative complement pathway in a mammal , comprising a CRIg polypeptide or an agonist thereof .