Antibodies that bind to obm

Abstract

Novel proteins and polypeptides binding to osteoclastogenesis inhibitory factor (OCIF) (OCIF-binding molecules, OBMs) and nucleic acids encoding these proteins and polypeptides are provided. Processes for producing these proteins, polypeptides, and nucleic acid molecules by genetic engineering are provided. Medicinal compounds are provided which comprise proteins and nucleic acids according to the invention, as well as proteins which bind to OBM, including anti-OBM antibodies. These compounds may be used for the treatment of bone disease.

1 . A method of reducing bone resorption in a patient in need thereof, comprising administering to said patient a therapeutic amount of a monoclonal antibody that binds osteoclastogenesis inhibitory factor-binding molecule (OBM) with a K d  of less than 10 −9  M, wherein said therapeutic amount is effective to reduce bone resorption and wherein said OBM consists of the amino acid sequence of SEQ ID NO: 11 or SEQ ID NO: 17. 
     
     
         2 . The method of  claim 1 , wherein said antibody binds a protein consisting of the amino acid sequence of SEQ ID NO: 11. 
     
     
         3 . The method of  claim 2 , wherein said antibody does not bind a protein consisting of the amino acid sequence of SEQ ID NO: 1. 
     
     
         4 . The method of  claim 1 , wherein said antibody binds a protein consisting of the amino acid sequence of SEQ ID NO: 17. 
     
     
         5 . The method of  claim 4 , wherein said antibody does not bind a protein consisting of the amino acid sequence of SEQ ID NO: 1. 
     
     
         6 . The method of  claim 1 , wherein said antibody is an IgG class antibody. 
     
     
         7 . The method of  claim 6 , wherein said antibody is an IgG1 or IgG2 class antibody. 
     
     
         8 . The method of  claim 7 , wherein said antibody is an IgG2a or IgG2b class antibody. 
     
     
         9 . The method of  claim 1 , wherein said antibody has a kappa light chain. 
     
     
         10 . The method of  claim 1 , wherein said antibody is a human antibody. 
     
     
         11 . The method of  claim 1 , wherein said patient has at least one disease accompanying abnormal bone metabolism. 
     
     
         12 . The method of  claim 11 , wherein said at least one 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. 
     
     
         13 . A method of inhibiting osteoclast formation in a patient in need thereof, comprising administering to said patient a therapeutic amount of a monoclonal antibody that binds osteoclastogenesis inhibitory factor-binding molecule (OBM) with a K d  of less than 10 −9  M, 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. 
     
     
         14 . The method of  claim 13 , wherein said antibody binds a protein consisting of the amino acid of SEQ ID NO: 17. 
     
     
         15 . The method of  claim 14 , wherein said antibody does not bind a protein consisting of the amino acid of SEQ ID NO: 1. 
     
     
         16 . The method of  claim 13 , wherein said antibody binds a protein consisting of the amino acid sequence of SEQ ID NO: 11. 
     
     
         17 . The method of  claim 16 , wherein said antibody does not bind a protein consisting of the amino acid of SEQ ID NO: 1. 
     
     
         18 . The method of  claim 13 , wherein said antibody is a monoclonal antibody. 
     
     
         19 . The method of  claim 13 , wherein said antibody is an IgG class antibody. 
     
     
         20 . The method of  claim 19 , wherein said antibody is an IgG1 or IgG2 class antibody. 
     
     
         21 . The method of  claim 20 , wherein said antibody is an IgG2a or IgG2b class antibody. 
     
     
         22 . The method of  claim 13 , wherein said antibody has a kappa light chain. 
     
     
         23 . The method of  claim 13 , wherein said antibody is a human antibody. 
     
     
         24 . The method of  claim 13 , wherein said patient has at least one disease accompanying abnormal bone metabolism. 
     
     
         25 . The method of  claim 24 , wherein said at least one 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. 
     
     
         26 . A method of reducing bone resorption in a patient in need thereof, comprising administering to said patient a therapeutically effective amount of a monoclonal antibody that binds osteoclastogenesis inhibitory factor-binding molecule (OBM) with a K d  of less than 10 −9  M, wherein said antibody is obtained by the method comprising the steps (i) to (iv):
 (i) preparing an antibody that binds to OBM;   (ii) determining at least one of the activities:
 (a) an activity to reduce bone resorption; 
 (b) an activity to inhibit osteoclast formation; or 
 (c) an activity to inhibit the binding of OBM and osteoclastogenesis inhibitor factor; 
   (iii) isolating an antibody that binds to OBM and has at least one of the following activities:
 (a) an activity to reduce bone resorption; 
 (b) an activity to inhibit osteoclast formation; or 
 (c) an activity to inhibit the binding of OBM and osteoclastogenesis inhibitory factor; and 
   (iv) administering said antibody to said patient.   
     
     
         27 . A method for treating a disease accompanying abnormal bone metabolism comprising administering a therapeutic amount of a monoclonal antibody that binds osteoclastogenesis inhibitory factor-binding molecule (OBM) with a K d  of less than 10 −9  M, 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. 
     
     
         28 . The method of  claim 27 , wherein said disease is a disease selected from the group consisting of osteoporosis, hypercalcemia, Paget's disease, renal osteodystrophy, rheumatoid arthritis, and osteoarthritis. 
     
     
         29 . The method of  claim 1 , wherein said antibody binds OBM with a K d  of less than 10 −10  M. 
     
     
         30 . The method of  claim 13 , wherein said antibody binds OBM with a K d  of less than 10 −10  M. 
     
     
         31 . The method of  claim 27 , wherein said antibody binds OBM with a K d  of less than 10 −10  M.