Use of an antibody specific for BDCA 2 for ligation and removal of dendritic cells in the treatment systemic lupus erythematosis

Abstract

The invention provides humanized antibody and other antigen-binding fragments that are specific for the newly identified dendritic cell marker BDCA-2. These agents may be used for treatment of conditions caused or mediated by dendritic cells, including but not limited to systemic lupus erythematosus (SLE). The invention includes pharmaceutical compositions that contain a means for specifically binding BDCA-2, methods of preparing therapeutic products, and their use in therapy. Methods are also provided for screening, manufacture, and use of specific antibodies that identify other dendritic cell markers.

1 .- 8 . (canceled) 
     
     
         9 . A pharmaceutical composition for treating an inflammatory disorder in a subject in need thereof,
 wherein the composition comprises an effective amount of a means for binding blood dendritic cell antigen 2 (BDCA-2) combined in a formulation with a pharmaceutically acceptable excipient,
 wherein the composition is formulated and prepared in a manner so as to be suitable for administration to a human, and 
 wherein the amount of the means for binding BDCA-2 and the formulation of the composition configure the composition to be effective for treating the inflammatory disorder without causing undue side effects in the subject. 
   
     
     
         10 . The pharmaceutical composition of  claim 9 , wherein the means for binding BDCA-2 is an antibody or an antigen binding fragment that is specific for BDCA-2. 
     
     
         11 . The pharmaceutical composition of  claim 9 , wherein the means for binding blood dendritic cell antigen 2 (BDCA-2) is a humanized monoclonal antibody that is specific for BDCA-2. 
     
     
         12 . The pharmaceutical composition of  claim 9 , wherein the inflammatory disorder is an autoimmune disease. 
     
     
         13 . The pharmaceutical composition of  claim 9 , wherein the inflammatory disorder is systemic lupus erythematosus (SLE). 
     
     
         14 . The pharmaceutical composition of  claim 9 , wherein the BDCA-2 is encoded by exons 1-6; exons 1 and 3-6; exons 1-2 and 4-6; or exons 1-3 and 5-6 of SEQ ID NO:1. 
     
     
         15 . A product comprising a pharmaceutical composition according to  claim 9 , packaged with information about the use of the composition for treatment of systemic lupus erythematosus (SLE). 
     
     
         16 . A method of treating an inflammatory condition in a patient in need thereof, comprising administering to the patient a pharmaceutical composition according to  claim 9 . 
     
     
         17 . The method of  claim 15 , wherein the means for binding blood dendritic cell antigen 2 (BDCA-2) is a humanized monoclonal antibody that is specific for BDCA-2. 
     
     
         18 . The method of  claim 15 , wherein the inflammatory condition is systemic lupus erythematosus (SLE). 
     
     
         19 . A method of removing dendritic cells from a subject in need thereof, comprising contacting the dendritic cells in the subject with a means for binding blood dendritic cell antigen 2 (BDCA-2). 
     
     
         20 . The method of  claim 19 , wherein the contacting is consequent to administering the means for binding BDCA-2 to the subject by intravenous, subcutaneous, or intramuscular injection. 
     
     
         21 . A method of treating systemic lupus erythematosus (SLE) in a subject in need thereof, comprising removing dendritic cells from the subject according to the method of  claim 19 . 
     
     
         22 . The method of  claim 21 , wherein the means for binding BDCA-2 is a humanized antibody that is specific for BDCA-2. 
     
     
         23 . A method of ligating BDCA-2 protein on a dendritic cell, comprising:
 contacting the dendritic cell with an antibody or antigen-binding fragment under conditions where the antibody or antigen-binding fragment will ligate to BDCA-2 protein on the dendritic cell;   wherein said antibody or antigen-binding fragment comprises a polypeptide domain that specifically binds a BDCA-2 protein encoded by SEQ ID NO:1.   
     
     
         24 . A method of determining whether an antibody or antigen binding fragment can specifically recognize a dendritic cell or a dendritic cell marker and is therefore suitable for compounding as a pharmaceutical composition according to claim  2 ,
 wherein the method comprises contacting the antibody or antigen binding fragment with BDCA-2 protein in vitro, and determining that the antibody or antigen binding fragment can specifically recognize a dendritic cell or a dendritic cell marker if it binds to the BDCA-2 protein in preference to other proteins.   
     
     
         25 . A method of preparing a pharmaceutical composition according to  claim 9 , comprising:
 obtaining an antibody that specifically binds BDCA-2;   obtaining a pharmaceutically acceptable excipient; and   combining a predetermined amount of the antibody with a predetermined amount of the excipient in a formulation that is suitable for administration to a human;   wherein the amount of the antibody and the formulation of the composition configure the composition to be effective for treating the inflammatory disorder without causing undue side effects in a subject in need thereof.   
     
     
         26 . The method of  claim 25 , wherein the antibody is a humanized monoclonal antibody and the inflammatory condition is systemic lupus erythematosus (SLE). 
     
     
         27 . The method of  claim 25 , wherein the antibody is a humanized from of an antibody selected from AC144, AD5-13A11, and AD5-5B8. 
     
     
         28 . A method of manufacturing a pharmaceutical product, comprising obtaining a pharmaceutical composition that has been prepared according to the method of  claim 25 , and packaging the composition with information about the use of the antibody or antigen binding fragment in the treatment of systemic lupus erythematosus (SLE).