Antibodies to opgl

Abstract

Antibodies that interact with osteoprotegerin ligand (OPGL) are described. Methods of treating osteopenic disorders by administering a pharmaceutically effective amount of antibodies to OPGL are described. Methods of detecting the amount of OPGL in a sample using antibodies to OPGL are described.

We claim: 
     
         1 . An antibody, comprising a heavy chain and a light chain, wherein the heavy chain comprises an amino acid sequence as set forth in SEQ ID NO: 2 or a fragment thereof, and the light chain comprises an amino acid sequence as set forth in SEQ ID NO: 4 or a fragment thereof. 
     
     
         2 . An antibody, comprising a heavy chain and a light chain, wherein the heavy chain comprises a variable region comprising an amino acid sequence as set forth in SEQ ID NO: 13 or a fragment thereof, and wherein the light chain comprises a variable region comprising an amino acid sequence as set forth in SEQ ID NO: 14 or a fragment thereof. 
     
     
         3 . The antibody of  claim 2 , wherein the heavy chain and the light chain are connected by a flexible linker to form a single-chain antibody. 
     
     
         4 . The antibody of  claim 3 , which is a single-chain Fv antibody. 
     
     
         5 . The antibody of  claim 2 , which is a Fab antibody. 
     
     
         6 . The antibody of  claim 2 , which is a Fab′ antibody. 
     
     
         7 . The antibody of  claim 2 , which is a (Fab′)2 antibody. 
     
     
         8 . The antibody of  claim 2 , which is fully human. 
     
     
         9 . The antibody of  claim 2 , wherein the antibody inhibits binding of OPGL to an osteoclast differentiation and activation receptor (ODAR). 
     
     
         10 . An antibody, comprising a heavy chain and a light chain,
 (a) wherein the heavy chain comprises a first variable region, and wherein the first variable region comprises a sequence that has at least 90% identity to the amino acid sequence set forth in SEQ ID NO: 13, and   (b) wherein the light chain comprises a second variable region, and wherein the second variable region comprises a sequence that has at least 90% identity to the amino acid sequence set forth in SEQ ID NO: 14, and   (c) wherein the antibody interacts with an osteoprotegerin ligand (OPGL).   
     
     
         11 . A pharmaceutical composition comprising an antibody of  claim 10 . 
     
     
         12 . The pharmaceutical composition of  claim 11 , further comprising at least one therapeutic agent selected from a bone morphogenic factor, transforming growth factor-β (TGF-β), an interleukin-1 (IL-1) inhibitor, IL-1ra, Kineret™, a TNFα inhibitor, a soluble TNFα receptor, Enbrel™, an anti-TNFα antibody, Remicade™, a D2E7 antibody, a parathyroid hormone, an analog of a parathyroid hormone, a parathyroid hormone related protein, an analog of a parathyroid hormone related protein, a prostaglandin, a bisphosphonate, an alendronate, fluoride, calcium, a non-steroidal anti-inflammatory drug (NSAID), a COX-2 inhibitor, Celebrex™, Vioxx™; an immunosuppressant, methotrexate, leflunomide, a serine protease inhibitor, a secretory leukocyte protease inhibitor (SLPI), an IL-6 inhibitor, an antibody to IL-6, an IL-8 inhibitor, an antibody to IL-8, an IL-18 inhibitor, an IL-18 binding protein, an IL-18 antibody, an Interleukin-1 converting enzyme (ICE) modulator, a fibroblast growth factor (FGF), an FGF modulator, a PAF antagonist, a keratinocyte growth factor (KGF), a KGF-related molecule, a KGF modulator; a matrix metalloproteinase (MMP) modulator, a nitric oxide synthase (NOS) modulator, a modulator of glucocorticoid receptor, a modulator of glutamate receptor, a modulator of lipopolysaccharide (LPS) levels, a noradrenaline, a noradrenaline mimetic, and a noradrenaline modulator. 
     
     
         13 . A method of treating an osteopenic disorder in a patient, comprising administering the pharmaceutical composition of  claim 11 . 
     
     
         14 . A method of treating rheumatoid arthritis in a patient, comprising administering the pharmaceutical composition of  claim 12 .