Compositions and methods of use for antibodies of dickkopf-1

Abstract

Antibodies and fragments that bind to the protein target Dickkopf (DKK1) are provided, as are methods of use and kits, for treating a target cell, in particular, a cell associated with an osteolytic condition.

What is claimed is: 
     
         1 . A method for inhibiting the binding of DKK1 protein to the DKK1 receptor in a subject,
 wherein the method comprises the step of:   administering to the subject an effective amount of a composition comprising an isolated antibody or a functional fragment thereof comprising:
 a. CDR sequences of a variable heavy chain comprising: CDR1 with a sequence comprising amino acids 22 to 35 of SEQ ID NO: 11, CDR2 with a sequence comprising amino acids 47 to 66 of SEQ ID NO: 11, and CDR3 with a sequence comprising amino acids 99 to 105 of SEQ ID NO: 11, and 
 b. CDR sequences of a variable light chain comprising: CDR1 with a sequence comprising amino acids 23 to 36 of SEQ ID NO: 30, CDR2 with a sequence comprising amino acids 48 to 58 of SEQ ID NO: 30, and CDR3 with a sequence comprising amino acids 91 to 100 of SEQ ID NO: 30, 
   wherein the antibody or functional fragment thereof specifically binds to human DKK1.   
     
     
         2 . The method according to  claim 1 , wherein the subject is human. 
     
     
         3 . The method according to  claim 1 , wherein the subject has a disorder or condition associated with DKK1. 
     
     
         4 . The method according to  claim 3 , wherein the disorder or condition is selected from: osteolytic lesions; osteolytic lesions associated with a myeloma; osteolytic lesions associated with a multiple myeloma, or cancers of the bone, breast, colon, melanocytes, hepatocytes, epithelium, esophagus, brain, lung, prostate or pancreas or metastasis thereof; bone loss associated with transplantation; osteosarcoma; prostate cancer; hepatocellular carcinoma (HCC); myeloma including multiple myeloma; diabetes; obesity; muscle wasting; Alzheimer's disease; osteoporosis; osteopenia; rheumatism; colitis; and unwanted hair loss. 
     
     
         5 . The method according to  claim 1 , wherein the method further comprises administering an additional therapeutic agent. 
     
     
         6 . The method according to  claim 5 , wherein the additional therapeutic agent is Zometa. 
     
     
         7 . The method according to  claim 5 , wherein the additional therapeutic agent is selected from the group consisting of: an anti-cancer agent; an antimetabolic agent; an anti-diabetic agent; an anti-osteoporotic agent; an antibiotic; an anti-inflammatory agent; a growth factor; and a cytokine. 
     
     
         8 . The method according to  claim 5 , wherein the antibody or functional fragment thereof comprises a scaffold selected from an IgM and an IgG, wherein the IgG is selected from an IgG1, an IgG2, and IgG3 or an IgG4. 
     
     
         9 . The method according to  claim 5 , wherein the antibody or functional fragment thereof is selected from: a whole immunoglobulin or Fab fragment or scFv antibody fragment thereof, a heavy chain antibody, and an antigen-binding region thereof on a non-immunoglobulin scaffold. 
     
     
         10 . The method according to  claim 5 , wherein the composition further comprises a pharmaceutically acceptable carrier or excipient. 
     
     
         11 . A method for inhibiting the binding of DKK1 protein to the DKK1 receptor in a subject,
 wherein the method comprises the step of:   administering to the subject an effective amount of a composition comprising an immunoconjugate comprising an isolated antibody or a functional fragment thereof comprising:
 a. CDR sequences of a variable heavy chain comprising: CDR1 with a sequence comprising amino acids 22 to 35 of SEQ ID NO: 11, CDR2 with a sequence comprising amino acids 47 to 66 of SEQ ID NO: 11, and CDR3 with a sequence comprising amino acids 99 to 105 of SEQ ID NO: 11, and 
 b. CDR sequences of a variable light chain comprising: CDR1 with a sequence comprising amino acids 23 to 36 of SEQ ID NO: 30, CDR2 with a sequence comprising amino acids 48 to 58 of SEQ ID NO: 30, and CDR3 with a sequence comprising amino acids 91 to 100 of SEQ ID NO: 30, 
   wherein the antibody or functional fragment thereof specifically binds to human DKK1.   
     
     
         12 . The method according to  claim 11 , wherein the subject is human. 
     
     
         13 . The method according to  claim 11 , wherein the subject has a disorder or condition associated with DKK1. 
     
     
         14 . The method according to  claim 13 , wherein the disorder or condition is selected from: osteolytic lesions; osteolytic lesions associated with a myeloma; osteolytic lesions associated with a multiple myeloma, or cancers of the bone, breast, colon, melanocytes, hepatocytes, epithelium, esophagus, brain, lung, prostate or pancreas or metastasis thereof; bone loss associated with transplantation; osteosarcoma; prostate cancer; hepatocellular carcinoma (HCC); myeloma including multiple myeloma; diabetes; obesity; muscle wasting; Alzheimer's disease; osteoporosis; osteopenia; rheumatism; colitis; and unwanted hair loss. 
     
     
         15 . The method according to  claim 11 , wherein the method further comprises administering an additional therapeutic agent. 
     
     
         16 . The method according to  claim 15 , wherein the additional therapeutic agent is Zometa. 
     
     
         17 . The method according to  claim 15 , wherein the additional therapeutic agent is selected from the group consisting of: an anti-cancer agent; an antimetabolic agent; an anti-diabetic agent; an anti-osteoporotic agent; an antibiotic; an anti-inflammatory agent; a growth factor; and a cytokine.