Antiproliferative agent

Abstract

The invention provides an antibody specific to the ANGPTL4 protein capable of neutralizing proliferation and methods of making and using the same. The antibody of the invention is further directed to the C terminal region of the protein and may be capable of neutralizing cell proliferation and treating cancer. The antibody may be monoclonal and or humanized antibody.

1 - 29 . (canceled) 
     
     
         30 . An antagonist to angiopoietin like 4 protein (ANGPTL4) that reduces cell proliferation and reduces a level of Reactive Oxygen Species in a cell, wherein the antagonist comprises an interfering RNA sequence or an antibody specific to angiopoietin like 4 protein (ANGPTL4). 
     
     
         31 . The antagonist of  claim 30  directed to the C terminal region of the protein. 
     
     
         32 . The antagonist of  claim 30  wherein the antibody is a monoclonal antibody, a humanized antibody or both. 
     
     
         33 . The anatagonist of  claim 30  wherein the interfering RNA sequence comprises that set out in SEQ ID 4, or SEQ ID NO. 5, or SEQ ID NO. 6, or SEQ ID NO. 7. 
     
     
         34 . A method of treating a patient to reduce cell proliferation and reduce a level of Reactive Oxygen Species in a cell, which comprises the step of: (a) contacting proliferating cell with an antagonist to angiopoietin like 4 protein (ANGPTL4) wherein the antagonist comprises an interfering RNA sequence or an antibody specific to angiopoietin like 4 protein (ANGPTL4). 
     
     
         35 . The method of  claim 34  wherein the antagonist is directed to the C terminal region of the protein. 
     
     
         36 . The method of  claim 34  wherein the interfering RNA sequence comprises that set out in SEQ ID 4, or SEQ ID NO. 5, or SEQ ID NO. 6, or SEQ ID NO. 7. 
     
     
         37 . A method of reducing cell proliferation and reducing a level of Reactive Oxygen Species in a cell, which comprises the step of: (a) contacting proliferating cell with an antagonist to angiopoietin like 4 protein (ANGPTL4) wherein the antagonist comprises an interfering RNA sequence or an antibody specific to angiopoietin like 4 protein (ANGPTL4). 
     
     
         38 . The method of  claim 37  wherein the antagonist is directed to the C terminal region of the protein. 
     
     
         39 . The method of  claim 37  wherein the cell is in vitro. 
     
     
         40 . The method of  claim 37  wherein the cell is in vivo, and the modulator is administered to a subject. 
     
     
         41 . The method of  claim 37  wherein the interfering RNA sequence comprises that set out in SEQ ID 4, or SEQ ID NO. 5, or SEQ ID NO. 6, or SEQ ID NO. 7. 
     
     
         42 . An antagonist to angiopoietin like 4 protein (ANGPTL4) for the treatment of a cancer wherein the antagonist comprises an interfering RNA sequenceor an antibody specific to angiopoietin like 4 protein (ANGPTL4) that reduces cell proliferation and reduces the level of Reactive Oxygen Species in a cell. 
     
     
         43 . The antagonist of  claim 42  directed to the C terminal region of the protein. 
     
     
         44 . The antagonist of  claim 42  wherein the antibody is a monoclonal antibody and or a humanized antibody. 
     
     
         45 . The anatagonist, of  claim 42  wherein the interfering RNA sequence comprises that set out in SEQ ID 4, or SEQ ID NO. 5, or SEQ ID NO. 6, or SEQ ID NO. 7. 
     
     
         46 . A composition comprising a therapeutically effective amount of an antagonist to angiopoietin like 4 protein (ANGPTL4) wherein the antagonist comprises an interfering RNA sequence or an antibody specific to angiopoietin like 4 protein (ANGPTL4) that reduces cell proliferation and reduces the level of Reactive Oxygen Species in a cell. 
     
     
         47 . The composition of  claim 46  wherein the antagonist is directed the C teminal region of the protein. 
     
     
         48 . The composition of  claim 46  wherein the antibody is a monoclonal antibody and or a humanized antibody. 
     
     
         49 . The composition of  claim 46  wherein the interfering RNA sequence comprises that set out in SEQ ID 4, or SEQ ID NO. 5, or SEQ ID NO. 6, or SEQ ID NO. 7. 
     
     
         50 . The antagonist or composition of  claim 46  wherein the antagonist is suitable for use in suppression of tumor growth. 
     
     
         51 . The method, antagonist or composition of  claim 46  wherein the antagonist is suitable for use in treating metastasis. 
     
     
         52 . A method of diagnosing an anoikis resistance proliferative disorder, comprising the steps of (a) determining an amount of the angiopoietin like 4 protein (ANGPTL4) protein in body fluids or tissue sampled from a person suspected of having a proliferative disorder using an antibody specific to angiopoietin like 4 protein (ANGPTL4); and (b) comparing the amount of the angiopoietin like 4 protein (ANGPTL4) from a person suspected of having a proliferative disorder with a second amount sampled from a healthy individual wherein elevated ANGPLT4 in the first sample compared with the second sample is indicative that an anoikis resistance proliferative disorder is present in the person suspected of having a proliferative disorder. 
     
     
         53 . The method of  claim 52  wherein the antibody is capable of binding selectively a sequence set out in SEQ ID 1, or SEQ ID NO. 2 or SEQ ID NO. 3. 
     
     
         54 . The method of  claim 52  wherein the state of tumor progression can be determined by the expression level of the angiopoietin like 4 protein (ANGPTL4) protein in body fluids or tissue sampled increasing from a benign state to a metastatic state.