Methods for treating bone gap defects

Abstract

The invention provides a method of enhancing bone gap defect healing involving administering a sclerostin inhibitor.

1 . A method for treating a bone gap defect in a subject, the method comprising administering to a subject suffering from a gap of at least 0.5 cm between two segments of bone an effective amount of an anti-sclerostin antibody
 wherein the anti-sclerostin antibody is an antibody that demonstrates a binding affinity for sclerostin of SEQ ID NO: 1 of less than or equal to 1×10 −7  M;   wherein the anti-sclerostin antibody is administered over a treatment period lasting at least 28 weeks resulting in bridging the gap between the two segments of bone and does not result in a substantial increase in cortical porosity in the bridged bone of the subject, and   the subject is not receiving a bone graft, bone scaffold, prosthesis or a metal stabilizer.   
     
     
         2 . (canceled) 
     
     
         3 . The method of  claim 1 , wherein the bone gap defect is selected from the group consisting of a comminuted fracture, a non-union fracture, a segmental skeletal defect, a surgically created bone defect, a surgically treated bone defect, and a bone defect created from traumatic injury to the bone or disease. 
     
     
         4 . The method of  claim 3 , wherein the bone gap defect is produced by removal of infected sections of bone or the removal of cancer from the bone. 
     
     
         5 . The method of  claim 1 , wherein the subject is undergoing oral or maxillofacial surgery. 
     
     
         6 . The method of  claim 1 , further comprising administering a second bone-enhancing therapeutic selected from the group consisting of parathyroid hormone, a bisphosphonate, a RANKL antibody and a DKK-1 antibody. 
     
     
         7 . The method of any one of  claims 1 - 6 , wherein the anti-sclerostin antibody is administered in an amount of 30 mg/kg per week. 
     
     
         8 . The method of any one of  claims 1 - 7 , wherein the anti-sclerostin antibody is administered once a week for the duration of the treatment period. 
     
     
         9 . (canceled) 
     
     
         10 . The method of any one of  claims 1 - 9 , wherein the anti-sclerostin antibody is administered subcutaneously. 
     
     
         11 . The method of any one of  claims 1 - 10 , wherein the anti-sclerostin antibody is an immunoglobulin comprising a heavy chain and a light chain. 
     
     
         12 - 15 . (canceled) 
     
     
         16 . The method of any one of  claims 1 - 11 , wherein the anti-sclerostin antibody binds to a sclerostin polypeptide comprising the amino acid sequence set forth in SEQ ID NO: 1, wherein said anti-sclerostin antibody binds to the sequence of at least one of SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5. 
     
     
         17 . The method of any one of  claims 1 - 11 , wherein the anti-sclerostin antibody binds to a sclerostin polypeptide comprising the amino acid sequence set forth in SEQ ID NO: 1, wherein said anti-sclerostin antibody binds to the sequence of at least one of SEQ ID NO: 70, SEQ ID NO: 71, SEQ ID NO: 72, or SEQ ID NO: 73. 
     
     
         18 . The method of any one of  claims 1 - 11 , where the anti-sclerostin antibody cross-blocks the binding of at least one of antibodies Ab-A, Ab-B, Ab-C, Ab-D, Ab-1, Ab-2, Ab-3, Ab-4, Ab-5, Ab-6, Ab-7, Ab-8, Ab-9, Ab-10, Ab-11, Ab-12, Ab-13, Ab-14, Ab-15, Ab-16, Ab-17, Ab-18, Ab-19, Ab-20, Ab-21, Ab-22, Ab-23, and Ab-24 to sclerostin and/or is cross-blocked from binding to sclerostin by at least one of antibodies Ab-A, Ab-B, Ab-C, Ab-D, Ab-1, Ab-2, Ab-3, Ab-4, Ab-5, Ab-6, Ab-7, Ab-8, Ab-9, Ab-10, Ab-11, Ab-12, Ab-13, Ab-14, Ab-15, Ab-16, Ab-17, Ab-18, Ab-19, Ab-20, Ab-21, Ab-22, Ab-23, and Ab-24. 
     
     
         19 . The method of any one of  claims 1 - 11 , wherein the anti-sclerostin antibody comprises a CDR-H1 of SEQ ID NO:245, a CDR-H2 of SEQ ID NO:246, a CDR-H3 of SEQ ID NO:247, a CDR-L1 of SEQ ID NO:78, a CDR-L2 of SEQ ID NO:79 and a CDR-L3 of SEQ ID NO:80. 
     
     
         20 - 21 . (canceled) 
     
     
         22 . The method of any one of  claims 1 - 11 , wherein the anti-sclerostin antibody comprises CDRs of SEQ ID NOs: 20-25 of International Patent Publication No. WO 2008/115732 (SEQ ID NOs: 416-421), CDRs of SEQ ID NOs: 26-31 of International Patent Publication No. WO 2008/115732 (SEQ ID NOs: 422-427), or CDRs of SEQ ID NOs: 32-37 of International Patent Publication No. WO 2008/115732 (SEQ ID NOs: 428-433). 
     
     
         23 . The method of any one of  claims 1 - 11 , wherein the anti-sclerostin antibody comprises CDRs of SEQ ID NOs: 4, 15, 26, 37, 48, and 59 of International Patent Publication No. WO 2009/047356 (SEQ ID NOs: 443, 454, 465, 476, 487, and 498, respectively). 
     
     
         24 . The method of any one of  claims 1 - 11 , wherein the anti-sclerostin antibody comprises the amino acid sequence of at least one of SEQ ID NOs: 135-143, 153-161, or 171-179 of International Patent Publication No. WO 2010/130830 (SEQ ID NOs: 745-753, 763-771, 781-789, respectively).