Antibody Therapeutics that Bind CTLA4

Abstract

There is disclosed compositions and methods relating to or derived from anti-CTLA4 antibodies. More specifically, there is disclosed fully human antibodies that bind CTLA4, CTLA4-antibody binding fragments and derivatives of such antibodies, and CTLA4-binding polypeptides comprising such fragments. Further still, there is disclosed nucleic acids encoding such antibodies, antibody fragments and derivatives and polypeptides, cells comprising such polynucleotides, methods of making such antibodies, antibody fragments and derivatives and polypeptides, and methods of using such antibodies, antibody fragments and derivatives and polypeptides, including methods of treating a disease requiring either stimulation of immune responses or suppression. Stimulation is achieved using antibodies that block binding of human CTLA4 to human B7 and diseases amenable to treatment by stimulation and augmentation of prolonging of immune responses include cancers of the prostate, kidney, colon, lung or breast; pathogenic infections; diseases associated with the CNS e.g. amyloidogenic diseases including Alzheimer's disease; and diseases with inflammatory or allergic components. Diseases amenable to treatment include graft versus host disease, host versus graft disease, allergy, autoimmune diseases and other inflammatory diseases.

1 .- 20 . (canceled) 
     
     
         21 . An isolated anti-CTLA4 antibody, or antigen-binding fragment thereof, comprising a heavy chain variable domain comprising complementarity determining regions (CDRs) as set forth in a heavy chain variable region amino acid sequence of SEQ ID NO: 35 and a light chain variable region comprising CDRs as set forth in a light chain variable region amino acid sequence of SEQ ID NO. 36. 
     
     
         22 . The antibody of  claim 21 , which is a fully human anti-CTLA4 antibody of an IgG class. 
     
     
         23 . The antibody or antigen-binding fragment thereof of  claim 21 , wherein the antibody has a heavy chain variable region sequence having at least 95% identity to SEQ ID NO. 35 and a light chain variable region sequence having at least 95% identity to SEQ ID NO. 36. 
     
     
         24 . The antibody or antigen-binding fragment thereof of  claim 21 , wherein the antibody has a heavy chain variable region sequence of SEQ ID NO. 35 and a light chain variable region sequence of SEQ ID NO. 36. 
     
     
         25 . The antibody of  claim 22 , wherein the antibody has a heavy chain variable region sequence of SEQ ID NO. 35 and a light chain variable region sequence of SEQ ID NO. 36. 
     
     
         26 . The antigen-binding fragment of  claim 21 , wherein the fragment is a Fab fragment or a single chain antibody comprising a heavy chain variable domain and a light chain variable domain which are connected by a peptide linker. 
     
     
         27 . The antigen-binding fragment of  claim 26 , wherein the antibody fragment has a heavy chain variable region sequence of SEQ ID NO. 35 and a light chain variable region sequence of SEQ ID NO. 36. 
     
     
         28 . A method of treating cancer or another disease requiring either stimulation of an immune response or suppression in a subject in need thereof, the method comprising administering an effective amount of the antibody of  claim 21 , such that the cancer or other disease is treated. 
     
     
         29 . The method of  claim 28 , wherein the cancer comprises bladder cancer, blood cancer, brain cancer, breast cancer, colon cancer, fibrosarcoma, lung cancer, ovarian cancer, prostate cancer, melanoma, lymphoma, mesothelioma, or plasmacytoma. 
     
     
         30 . The method of  claim 28 , wherein the antibody has a heavy chain variable region sequence of SEQ ID NO. 35 and a light chain variable region sequence of SEQ ID NO. 36. 
     
     
         31 . The method of  claim 28 , wherein the cancer comprises a cancer of the prostate, kidney, colon, lung, or breast. 
     
     
         32 . The method of  claim 28 , wherein the other disease comprises a pathogenic infection; a disease associated with the central nervous system; amyloidogenic Alzheimer's disease; a disease with inflammatory or allergic components; graft versus host disease; host versus graft disease; allergy; an autoimmune disease; or another inflammatory disease. 
     
     
         33 . The method of  claim 28 , wherein the other disease comprises a pathogenic infection. 
     
     
         34 . An isolated nucleic acid encoding an anti-CTLA4 antibody, or antigen-binding fragment thereof, comprising a heavy chain variable domain comprising complementarity determining regions (CDRs) as set forth in a heavy chain variable region amino acid sequence of SEQ ID NO: 35 and a light chain variable region comprising CDRs as set forth in a light chain variable region amino acid sequence of SEQ ID NO. 36. 
     
     
         35 . The nucleic acid of  claim 34 , wherein the antibody has a heavy chain variable region sequence of SEQ ID NO. 35 and a light chain variable region sequence of SEQ ID NO. 36. 
     
     
         36 . An expression vector comprising the nucleic acid of  claim 34 . 
     
     
         37 . A host cell comprising the nucleic acid of  claim 34 . 
     
     
         38 . A method of making an anti-CTLA4 antibody, comprising culturing the host cell of  claim 37  under conditions wherein the antibody is expressed.