Antibodies to OCIF-binding molecules

Abstract

A novel protein which binds to Osteoclastogenesis Inhibitory Factor (OCIF-binding molecule; OBM), a process for preparing the same, DNA encoding said protein, a protein having an amino acid sequence encoded by this DNA, a method for producing said protein by genetic engineering technique, and a pharmaceutical composition containing said protein. Screening methods for a substance for controlling expression of said protein using said protein and the DNA, a substance which inhibits or modulates the biological activity of said protein, or a receptor which transmits the action of said protein through binding to said protein, the substance obtained by the screening methods, and a pharmaceutical composition which contains this substance. An antibody for said protein, a process for preparing the same, a measuring method of said protein using the antibody, and a medicine comprising this antibody.

1 - 64 . (canceled)  
     
     
         65 . A method of reducing bone resorption in a patient in need thereof, comprising administering to said patient a therapeutic amount of a human monoclonal antibody that binds osteoclastogenesis inhibitory factor-binding molecule (OBM), wherein said therapeutic amount is effective to reduce bone resorption and said OBM consists of the amino acid sequence of SEQ ID NO:11 or SEQ ID NO:17.  
     
     
         66 . The method of  claim 65 , wherein said OBM does not consist of SEQ ID NO:16.  
     
     
         67 . The method of  claim 66 , wherein said OBM does not consist of SEQ ID NO:1.  
     
     
         68 . The method of  claim 65 , wherein said monoclonal antibody exhibits a dissociation constant in an order of 1×10 −9  (M) for said OBM.  
     
     
         69 . The method of  claim 65 , wherein said monoclonal antibody exhibits a high affinity for said OBM.  
     
     
         70 . The method of  claim 65 , wherein said monoclonal antibody exhibits an affinity for said OBM equal to the affinity osteoclast inhibitory factor (OCIF) exhibits for said OBM.  
     
     
         71 . The method of  claim 65 , wherein said monoclonal antibody exhibits a dissociation constant for said OBM of 1×10 −9  (M) or less.  
     
     
         72 . The method of  claim 65 , wherein said monoclonal antibody exhibits a dissociation constant for said OBM between an order of 1×10 −11  (M) and an order of 1×10 −10  (M).  
     
     
         73 . The method of  claim 65 , wherein said monoclonal antibody exhibits a dissociation constant for said OBM between an order of 1×10 −11  (M) and an order of 1×10 −8  (M).  
     
     
         74 . The method of  claim 65 , wherein said monoclonal antibody exhibits a dissociation constant for said OBM between an order of 1×10 −9  (M) and an order of 1×10 −8  (M).  
     
     
         75 . A method of inhibiting osteoclast formation in a patient in need thereof, comprising administering to said patient a therapeutic amount of an antibody that binds osteoclastogenesis inhibitory factor-binding molecule (OBM), wherein said therapeutic amount is effective to inhibit osteoclast formation, and wherein said OBM consists of the amino acid sequence of SEQ ID NO:11 or SEQ ID NO:17 and said antibody exhibits a dissociation constant for said OBM between 1×10 −11  (M) and 1×10 −8  (M).  
     
     
         76 . The method of  claim 75 , wherein said dissociation constant for said OBM is between 1×10 −9  (M) and 1×10 −8  (M).  
     
     
         77 . The method of  claim 75 , wherein said antibody has a high affinity for said OBM.  
     
     
         78 . A method for treating a disease accompanying abnormal bone metabolism comprising administering a therapeutic amount of an antibody that binds osteoclastogenesis inhibitory factor-binding molecule (OBM), wherein said therapeutic amount is effective to reduce bone resorption or inhibit osteoclast formation, and wherein said OBM consists of the amino acid sequence of SEQ ID NO:11 or SEQ ID NO:17 and said antibody does not bind a protein consisting of the amino acid sequence of SEQ ID NO:16.  
     
     
         79 . The method of  claim 78 , wherein said disease accompanying abnormal bone metabolism is a disease selected from the group consisting of osteoporosis, hypercalcemia, Paget's disease, renal osteodystrophy, rheumatoid arthritis, and osteoarthritis.  
     
     
         80 . The method of  claim 78 , wherein said disease accompanying abnormal bone metabolism is osteoporosis.  
     
     
         81 . The method of  claim 78 , wherein said disease accompanying abnormal bone metabolism is hypercalcemia.  
     
     
         82 . The method of  claim 78 , wherein said disease accompanying abnormal bone metabolism is Paget's disease.  
     
     
         83 . The method of  claim 78 , wherein said disease accompanying abnormal bone metabolism is renal osteodystrophy.  
     
     
         84 . The method of  claim 78 , wherein said disease accompanying abnormal bone metabolism is rheumatoid arthritis.  
     
     
         85 . The method of  claim 78 , wherein said disease accompanying abnormal bone metabolism is osteoarthritis.  
     
     
         86 . A method for treating a disease accompanying abnormal bone metabolism comprising administering a therapeutic amount of a human monoclonal antibody that binds osteoclastogenesis inhibitory factor-binding molecule (OBM), wherein said therapeutic amount is effective to reduce bone resorption or inhibit osteoclast formation, and wherein said OBM consists of the amino acid sequence of SEQ ID NO:11 or SEQ ID NO:17.  
     
     
         87 . The method of  claim 86 , wherein said disease accompanying abnormal bone metabolism is osteoporosis.  
     
     
         88 . The method of  claim 86 , wherein said disease accompanying abnormal bone metabolism is hypercalcemia.  
     
     
         89 . The method of  claim 86 , wherein said disease accompanying abnormal bone metabolism is Paget's disease.  
     
     
         90 . The method of  claim 86 , wherein said disease accompanying abnormal bone metabolism is renal osteodystrophy.  
     
     
         91 . The method of  claim 86 , wherein said disease accompanying abnormal bone metabolism is rheumatoid arthritis.  
     
     
         92 . The method of  claim 86 , wherein said disease accompanying abnormal bone metabolism is osteoarthritis.  
     
     
         93 . A human monoclonal antibody which specifically binds to osteoclastogenesis inhibitory factor binding molecule (OBM), wherein said OBM consists of the amino acid sequence of SEQ ID NO:11 or SEQ ID NO:17 and said antibody inhibits bone resorption or inhibits the formation of osteoclasts.  
     
     
         94 . The human monoclonal antibody of  claim 93 , wherein said anibody exhibits a dissociation constant for said OBM of 1×10 −9  (M) or less.  
     
     
         95 . The human monoclonal antibody of  claim 93 , wherein said antibody does not bind a protein consisting of the amino acid sequence of SEQ ID NO:16.  
     
     
         96 . The human monoclonal antibody of  claim 93 , wherein said monoclonal antibody exhibits a dissociation constant for said OBM between an order of 1×10 −11  (M) and an order of 1×10 −10  (M).  
     
     
         97 . The human monoclonal antibody of  claim 93 , wherein said human monoclonal antibody exhibits an affinity for said OBM equal to the affinity osteoclast inhibitory factor (OCIF) exhibits for said OBM.  
     
     
         98 . A monoclonal antibody which specifically binds to osteoclastogenesis inhibitory factor binding molecule (OBM), wherein said OBM consists of the amino acid sequence of SEQ ID NO:11 or SEQ ID NO:17 and said antibody inhibits bone resorption or inhibits the formation of osteoclasts and exhibits a dissociation constant for said OBM between an order of 1×10 −9  (M) and an order of 1×10 −8  (M).