Amino acid sequences that modulate the interaction between cells of the immune system

Abstract

The present invention relates to amino acid sequences that block the interaction between (a target on) an antigen presenting cell (APC) and (a target on) a T-cell. More particularly, the present invention relates to amino acid sequences that are directed against (as defined herein) a target on an APC (also referred to herein as “APC target”) or a target on a T-cell (also referred to herein as “T-cell target”). The invention further relates to compounds or constructs, and in particular proteins and polypeptides, that comprise or essentially consist of one or more such amino acid sequences.

1 . An antibody polypeptide that binds the same epitope as domain antibody (dAb) 1 h-239-891(D70C) (SEQ ID NO: 543). 
     
     
         2 . The antibody polypeptide of  claim 1 , wherein said antibody polypeptide is a dAb. 
     
     
         3 . The antibody polypeptide of  claim 2 , wherein the dAb is 1 h-239-891(D70C) (SEQ ID NO: 543). 
     
     
         4 . The antibody polypeptide of  claim 2 , wherein the dAb comprises a first single variable domain having a binding specificity to a first antigen and a second single variable domain having a binding activity to a second antigen, wherein the first antigen is CD28, and wherein the second antigen is an antigen other than CD28. 
     
     
         5 . The antibody polypeptide of  claim 4 , wherein the second antigen is an antigen presenting cell surface antigen or a T cell surface antigen. 
     
     
         6 . The antibody polypeptide of  claim 4 , wherein the second antigen is a cytokine. 
     
     
         7 . A domain antibody (dAb) comprising an amino acid sequence that differs from that of SEQ ID NO:58, SEQ ID NO:59, SEQ ID NO:60, SEQ ID NO:61, SEQ ID NO:62, SEQ ID NO:63, SEQ ID NO:64, SEQ ID NO:65, SEQ ID NO:66, SEQ ID NO:67, SEQ ID NO:68, SEQ ID NO:272, SEQ ID NO:273, SEQ ID NO:274, SEQ ID NO:275, SEQ ID NO:276, SEQ ID NO:472, SEQ ID NO:473, SEQ ID NO:474, SEQ ID NO:475, SEQ ID NO:476, SEQ ID NO:477, SEQ ID NO:478, SEQ ID NO:479, SEQ ID NO:480, SEQ ID NO:481, SEQ ID NO:482, SEQ ID NO:483, SEQ ID NO: 534, SEQ ID NO: 535, SEQ ID NO: 536, SEQ ID NO: 537, SEQ ID NO: 539, SEQ ID NO: 540, SEQ ID NO: 542, SEQ ID NO: 543, SEQ ID NO: 545, SEQ ID NO: 547, SEQ ID NO: 548, SEQ ID NO: 550, SEQ ID NO: 551, SEQ ID NO: 553, SEQ ID NO: 562, SEQ ID NO: 567, SEQ ID NO: 570, SEQ ID NO: 575, SEQ ID NO: 576, SEQ ID NO: 577, SEQ ID NO: 578, SEQ ID NO: 580, SEQ ID NO: 599, SEQ ID NO: 600, SEQ ID NO: 607, SEQ ID NO: 611, SEQ ID NO: 617, or SEQ ID NO: 622 by no more than 25 amino acids, wherein the dAb binds to CD28. 
     
     
         8 . The dAb of  claim 7 , wherein the dAb comprises an amino acid sequence that differs from that of said SEQ ID NO. by 20 or fewer amino acid positions. 
     
     
         9 . The dAb of  claim 8 , wherein the dAb comprises an amino acid sequence that differs from that of said SEQ ID NO. by 10 or fewer amino acid positions. 
     
     
         10 . The dAb of  claim 9 , wherein the dAb comprises an amino acid sequence that differs from that of said SEQ ID NO. by 5 or fewer amino acid positions. 
     
     
         11 . The dAb of  claim 10 , wherein the dAb comprises an amino acid sequence that differs from that of said SEQ ID NO. by one amino acid position. 
     
     
         12 . A pharmaceutical composition comprising a therapeutically-effective amount of an antibody polypeptide of  claim 1  and a pharmaceutically acceptable carrier. 
     
     
         13 . The pharmaceutical composition of  claim 12 , further comprising an immunosuppressive/immunomodulatory and/or anti-inflammatory agent. 
     
     
         14 . A method of treating or alleviating an immune disease in an individual in need of such treatment, comprising administering to the individual a therapeutically effective amount of the pharmaceutical composition of  claim 12 , wherein the immune disease is treated or alleviated. 
     
     
         15 . The method of  claim 14 , wherein the immune disease is an autoimmune disease or a graft-related disease. 
     
     
         16 . The method of  claim 14 , wherein the pharmaceutical composition is administered in combination with an immunosuppressive/immunomodulatory and/or anti-inflammatory agent.