Compositions and methods of tolerizing a primate to an antigen

Abstract

Inducing tolerance in a primate by use of a compound, or a combination of at least two compounds, that has certain characteristics when tested in vitro. The compound, alone or in combination, is preferably TRX1 antibody and the compound or combination is preferably used in accordance with a specified dosing regimen.

1 . A process for treating a primate to induce tolerance to at least one antigen comprising:
 treating a primate by administering to a primate a compound, or a combination of at least two compounds, said compound being a compound or combination that in a primary mixed lymphocyte reaction in vitro reduces the amount of CD4+CD25+ cells produced in said mixed lymphocyte reaction and that generates in said primary mixed lymphocyte reaction a cell population that reduces at least one of (x) the amount of CD4+CD25+ cells produced in vitro in at least one of a primary and secondary mixed lymphocyte reaction, and (y) the amount of at least one of IL-2, IL-4, and IL-12 in a secondary mixed lymphocyte reaction, said compound or said combination being administered in an amount and for a time effective to induce tolerance against said at least one antigen, said compound or said combination being present in said primate when said at least one antigen is present in said primate.   
     
     
         2 - 17 . (canceled) 
     
     
         18 . A process for inducing tolerance to an antigen in a patient, comprising:
 administering to said patient an effective amount of an antibody that binds to the same epitope as a humanized antibody selected from the group consisting of the humanized antibody shown in  FIG. 1 ; the humanized antibody shown in  FIG. 2 ; the humanized antibody shown in  FIG. 3 ; and the humanized antibody shown in  FIG. 4 .   
     
     
         19 . The process of  claim 18  wherein said patient has a reduced immune response to said antigen. 
     
     
         20 . The process of  claim 19  wherein said reduced immune response is maintained after the administered antibody no longer is detectable in the serum of said patient and said patient is not otherwise immunocompromised. 
     
     
         21 . The process of  claim 18  and further comprising at least one follow-up administration of said antibody to said patient. 
     
     
         22 . The process of  claim 19  and further comprising at least one follow-up administration of said antibody to said patient. 
     
     
         23 . The process of  claim 20  and further comprising at least one follow-up administration of said antibody to said patient. 
     
     
         24 . The process of  claim 18  wherein said antigen is a therapeutic agent. 
     
     
         25 . A process for inducing tolerance to a foreign antigen in a primate, comprising:
 administering to the primate a therapeutically effective amount of at least one non-depleting anti-CD4 antibody or non-depleting anti-CD4 antibody fragment and introducing at least one foreign antigen to the primate, wherein said non-depleting anti-CD4 antibody or said non-depleting anti-CD4 antibody fragment has been modified to reduce binding to an Fc.gamma. receptor as compared to said antibody without the further modification.   
     
     
         26 . The process of  claim 25  wherein said primate has a reduced immune response to said at least one foreign antigen. 
     
     
         27 . The process of  claim 26  wherein said reduced immune response is maintained after said non-depleting anti-CD4 antibody or said non-depleting anti-CD4 antibody fragment no longer is detectable in the serum of said primate and said primate is not otherwise immunocompromised. 
     
     
         28 . The process of  claim 25  and further comprising at least one follow-up administration of said non-depleting anti-CD4 antibody or said non-depleting anti-CD4 antibody fragment to said primate. 
     
     
         29 . The process of  claim 26  and further comprising at least one follow-up administration of said non-depleting anti-CD4 antibody or said non-depleting anti-CD4 antibody fragment to said primate. 
     
     
         30 . The process of  claim 27  and further comprising at least one follow-up administration of said non-depleting anti-CD4 antibody or said non-depleting anti-CD4 antibody fragment to said primate. 
     
     
         31 . The process of  claim 25  wherein said foreign antigen is a therapeutic agent. 
     
     
         32 . A process for reducing an immune response to a foreign antigen in a primate, comprising:
 administering to the primate a therapeutically effective amount of at least one non-depleting anti-CD4 antibody or non-depleting anti-CD4 antibody fragment and introducing at least one foreign antigen to the primate, wherein said non-depleting anti-CD4 antibody or said non-depleting anti-CD4 antibody fragment has been modified to reduce binding to an Fc.gamma. receptor as compared to said antibody without the further modification.   
     
     
         33 . The process of  claim 32  wherein said reduced immune response to said at least one foreign antigen is maintained after said non-depleting anti-CD4 antibody or said non-depleting anti-CD4 antibody fragment no longer is detectable in the serum of said primate and said primate is not otherwise immunocompromised. 
     
     
         34 . The process of  claim 32  and further comprising at least one follow-up administration of said non-depleting anti-CD4 antibody or said non-depleting anti-CD4 antibody fragment to said primate. 
     
     
         35 . The process of  claim 32  and further comprising at least one follow-up administration of said non-depleting anti-CD4 antibody or said non-depleting anti-CD4 antibody fragment to said primate. 
     
     
         36 . The process of  claim 32  wherein said foreign antigen is a therapeutic agent.