Combinations of immunosupressive agents for the treatment or prevention of graft rejections

Abstract

A pharmaceutical composition useful in the treatment or prevention of transgenic xenograft rejection comprising immunosuppressant compounds selected from the group consisting of an IL-2 transcription inhibitor and immunosuppressant compounds that immunosuppress for B-cell-mediated or antibody-mediated rejection of xenografts, and pharmaceutically acceptable diluents or carriers, and a method of preventing hyperacute rejection, reducing early graft damage, improving early xenograft function and promoting long term survival of said transgenic xenografts comprising the steps of i) contacting the body fluid removed from a human recipient with a xenoantigenic material which is bound to a biocompatible solid support, ii) reintroducing the treated body fluid into the recipient, and iii) treating the recipient with said pharmaceutical composition.

1 . A pharmaceutical composition useful in the treatment or prevention of xenograft rejection comprising 
 (a) cyclosporin;    (b) an immunosuppressant compound selected from the group consisting of mycophenolic acid, a pharmaceutically acceptable salt of mycophenolic acid, and combinations thereof; and    (c) rapamycin and/or derivatives thereof.    
     
     
         2 . A pharmaceutical composition comprising 
 (a) cyclosporin;    (b) an immunosuppressant compound selected from the group consisting of mycophenolic acid, a pharmaceutically acceptable salt of mycophenolic acid, and combinations thereof; and    (c) rapamycin and/or derivatives thereof as a combined preparation for simultaneous, separate or sequential use in the treatment or prevention of xenograft rejection.    
     
     
         3 . A kit of parts comprising a pharmaceutical composition according to  claim 1  together with instructions for use in the treatment or prevention of xenograft rejection.  
     
     
         4 . Use of a pharmaceutical composition according to  claim 1  or  2  in the manufacture of a medicament for the treatment or prevention of xenograft rejection.  
     
     
         5 . A pharmaceutical composition according to  claim 1  or  2  wherein the pharmaceutically acceptable salt of mycophenolic acid is MPA sodium salt formulated as an enteric-coated solid oral dosage form.  
     
     
         6 . A method for the treatment or prevention of xenograft rejection comprising administering a pharmaceutical composition according to  claim 1  or  2 .  
     
     
         7 . A method for reducing early graft damage, improving early xenograft function or promoting long term survival of xenografts of transgenic organ in human recipients comprising: 
 (i) exposing body fluid removed from a human with a xenoantigenic material or anti-human mono- or polyclonal antibodies or another antibody adsorbent, which is bound to a biocompatible solid support;    (ii) reintroducing the treated body fluid into the human, and    (iii) treating the human with a composition comprising at least two immunosuppressant compounds selected from the group consisting of (a) IL-2 transcription inhibitors and (b) immunosuppressant compounds that immunosuppress for B-cell-mediated or antibody-mediated rejection of xenografts.    
     
     
         8 . A method for reducing early graft damage, improving early xenograft function or promoting long term survival of xenografts of an organ transgenic for hDAF in human recipients comprising: 
 (i) exposing body fluid removed from a human with a xenoantigenic material or anti-human mono- or polyclonal antibodies or another antibody adsorbent, which is bound to a biocompatible solid support;    (ii) reintroducing the treated body fluid into the human, and    (iii) treating the human with a composition comprising at least two immunosuppressant compounds selected from the group consisting of (a) IL-2 transcription inhibitors and (b) immunosuppressant compounds that immunosuppress for B-cell-mediated or antibody-mediated rejection of xenografts.    
     
     
         9 . The method according to  claim 7  wherein the steps (i) and (ii) are conducted postoperatively and in parallel with treatment with the composition.