Compositions and Methods of Use for Therapeutic Low Density Lipoprotein-related protein 6 (LRP6) Antibodies

Abstract

The present invention relates to antibodies targeting LRP6 and compositions and methods of use thereof.

1 - 11 . (canceled) 
     
     
         11 . The antibody or fragment of  claim 61 , wherein said antibody or fragment is a monoclonal antibody. 
     
     
         12 . The antibody or fragment of  claim 61 , wherein said antibody is a human or humanized antibody. 
     
     
         13 . The antibody or fragment of  claim 61 , wherein said antibody or fragment is a chimeric antibody. 
     
     
         14 . The antibody or fragment of  claim 61 , wherein said antibody or fragment comprises a human heavy chain constant region and a human light chain constant region. 
     
     
         15 . The antibody or fragment of  claim 61 , wherein said antibody or fragment is a single chain antibody. 
     
     
         16 . The antibody or fragment of  claim 61 , wherein said antibody is a Fab fragment. 
     
     
         17 . The antibody or fragment of  claim 61 , wherein said antibody or fragment is a scFv. 
     
     
         18 . The antibody or fragment of  claim 61 , wherein said antibody or fragment binds to both human LRP6 and cynomologus LRP6. 
     
     
         19 . The antibody or fragment of  claim 61 , wherein said antibody or fragment is an IgG isotype. 
     
     
         20 - 48 . (canceled) 
     
     
         49 . An isolated antibody or fragment thereof that binds to a low density lipoprotein-related 6 (LRP6) or fragment thereof wherein the antibody or fragment thereof comprises a VH comprising SEQ ID NO: 82 and a VL comprising SEQ ID NO: 81, wherein the antibody or fragment thereof is monovalent or bivalent. 
     
     
         50 . An isolated antibody or fragment thereof to LRP6 that binds to a low density lipoprotein-related 6 (LRP6) or fragment thereof wherein the antibody or fragment thereof comprises a VH comprising SEQ ID NO: 90 and a VL comprising SEQ ID NO: 89, wherein the antibody or fragment thereof is monovalent or bivalent. 
     
     
         51 - 60 . (canceled) 
     
     
         61 . An isolated antibody or fragment thereof that binds to a low density lipoprotein-related 6 (LRP6) or fragment thereof wherein the antibody or fragment thereof comprises a heavy chain variable region CDR1 of SEQ ID NO: 69; a heavy chain variable region CDR2 of SEQ ID NO: 70; a heavy chain variable region CDR3 of SEQ ID NO: 71; a light chain variable region CDR1 of SEQ ID NO: 72; a light chain variable region CDR2 of SEQ ID NO: 73; and a light chain variable region CDR3 of SEQ ID NO: 74, wherein the antibody or fragment thereof is monovalent or bivalent. 
     
     
         62 - 65 . (canceled) 
     
     
         66 . The A fragment of the antibody of any previous  claim 61  that binds with LRP6 selected from the group consisting of; Fab, F(ab 2 )′, F(ab) 2 ′, scFV, VHH, VH, VL, dAbs, wherein the fragment is monovalent or bivalent. 
     
     
         67 . A pharmaceutical composition comprising the antibody of  claim 61  and a pharmaceutically acceptable carrier. 
     
     
         68 - 72 . (canceled) 
     
     
         73 . A method of treating a cancer comprising the steps of:
 (a) selecting a subject having an LRP6 expressing cancer, and   (b) administering to said subject an effective amount of a composition comprising an antibody of  claim 61  or fragment thereof, wherein the administration of the antibody treats that cancer in the subject having an LRP6 expressing cancer.   
     
     
         74 . (canceled) 
     
     
         75 . The method of  claim 73 , wherein said cancer is selected from the group consisting of breast cancer, lung cancer, multiple myeloma, ovarian cancer, liver cancer, bladder cancer, gastric cancer, prostate cancer, acute myeloid leukemia, chronic myeloid leukemia, osteosarcoma, squamous cell carcinoma, and melanoma. 
     
     
         76 - 85 . (canceled) 
     
     
         86 . The AR antibody or fragment of  claim 61 , having a VH of SEQ ID NO: 82 and a VL of SEQ ID NO: 81. 
     
     
         87 - 98 . (canceled) 
     
     
         99 . The Ala antibody or fragment of  claim 61 , having VH of SEQ ID NO: 82 and VL of SEQ ID NO: 81 for use as a drug, wherein the antibody is monovalent or bivalent. 
     
     
         100 - 108 . (canceled)