Agonistic antibody to cd27

Abstract

The invention relates to a binding compound, which binds the same epitope of human CD27 as monoclonal antibody hCD27.15, produced by hybridoma hCD27.15 which was deposited with the ATCC in on Jun. 2, 2010 under number PTA-11008. In particular the invention relates to such a binding compound of claim 1 which may comprise: an antibody heavy chain variable region which may comprise at least one CDR selected from the group consisting of SEQ ID NOs : 5, 6 and 7, or a variant of any of said sequences; and/or an antibody light chain variable region which may comprise at least one CDR selected from the group consisting of SEQ ID NOs: 8, 9 and 10, or a variant of any of said sequences.

1 - 20 . (canceled) 
     
     
         21 . A human or humanized antibody or antigen-binding fragment thereof comprising the following characteristics:
 (i) competes for binding to human CD27 with a second antibody or antigen-binding fragment comprising an antibody heavy chain variable region comprising the CDRs of SEQ ID NOs: 5, 6 and 7; and an antibody light chain variable region comprising the CDRs of SEQ ID NOs: 8, 9 and 10;   (ii) blocks binding of human CD27 to human CD70; and   (iii) binds human CD27 with a KD of about 100 nM or lower.   
     
     
         22 . A human or humanized antibody or antigen-binding fragment thereof comprising the following characteristics:
 (i) competes for binding to human CD27 with a second antibody or antigen-binding fragment comprising an antibody heavy chain variable region comprising the CDRs of SEQ ID NOs: 5, 6 and 7; and an antibody light chain variable region comprising the CDRs of SEQ ID NOs: 8, 9 and 10;   (ii) blocks binding of human CD27 to human CD70;   (iii) co-stimulates human CD8+T cells more effectively than the CD27 ligand CD70.   
     
     
         23 . The human or humanized antibody or antigen-binding fragment thereof of  claim 21 , which is selected from the group consisting of Fab, Fab′, Fab′-SH, Fv, scFv, F(ab′) 2 , bispecific mAb and a diabody. 
     
     
         24 . The human or humanized antibody or antigen-binding fragment thereof of  claim 22 , which is selected from the group consisting of Fab, Fab′, Fab′-SH, Fv, scFv, F(ab′) 2 , bispecific mAb and a diabody. 
     
     
         25 . A polynucleotide encoding the human or humanized antibody or antigen-binding fragment thereof of  claim 21 . 
     
     
         26 . A polynucleotide encoding the human or humanized antibody or antigen-binding fragment thereof of  claim 22 . 
     
     
         27 . An expression vector comprising the polynucleotide of  claim 25 . 
     
     
         28 . An expression vector comprising the polynucleotide of  claim 26 . 
     
     
         29 . A host cell comprising the expression vector of  claim 27 . 
     
     
         30 . A host cell comprising the expression vector of  claim 28 . 
     
     
         31 . A method of producing an antibody or antigen-binding fragment thereof, which method comprises:
 a) culturing a host cell comprising an expression vector that comprises a polynucleotide encoding the human or humanized antibody or antigen-binding fragment thereof of  claim 21  under the control of suitable regulatory sequences in culture medium under conditions wherein the polynucleotide is expressed, thereby producing polypeptides comprising the light and heavy chain variable regions; and   b) recovering the polypeptides from the host cell or culture medium.   
     
     
         32 . A method of producing an antibody or antigen-binding fragment thereof, which method comprises:
 a) culturing a host cell comprising an expression vector that comprises a polynucleotide encoding the human or humanized antibody or antigen-binding fragment thereof of  claim 22  under the control of suitable regulatory sequences in culture medium under conditions wherein the polynucleotide is expressed, thereby producing polypeptides comprising the light and heavy chain variable regions; and   b) recovering the polypeptides from the host cell or culture medium.   
     
     
         33 . A method of stimulating the proliferation and/or survival of CD27+ cells comprising administering to a subject in need thereof a human or humanized antibody or antigen-binding fragment thereof comprising the following characteristics:
 (i) competes for binding to human CD27 with a second antibody or antigen-binding fragment comprising an antibody heavy chain variable region comprising the CDRs of SEQ ID NOs: 5, 6 and 7; and an antibody light chain variable region comprising the CDRs of SEQ ID NOs: 8, 9 and 10;   (ii) blocks binding of human CD27 to human CD70; and   (iii) binds human CD27 with a KD of about 100 nM or lower.   
     
     
         34 . A method of stimulating the proliferation and/or survival of CD27+ cells comprising administering to a subject in need thereof a human or humanized antibody or antigen-binding fragment thereof comprising the following characteristics:
 (i) competes for binding to human CD27 with a second antibody or antigen-binding fragment comprising an antibody heavy chain variable region comprising the CDRs of SEQ ID NOs: 5, 6 and 7; and an antibody light chain variable region comprising the CDRs of SEQ ID NOs: 8, 9 and 10;   (ii) blocks binding of human CD27 to human CD70; and   (iii) co-stimulates human CD8+T cells more effectively than the CD27 ligand CD70.   
     
     
         35 . The method of  claim 33 , wherein the human or humanized antibody or antigen-binding fragment thereof is selected from the group consisting of Fab, Fab′, Fab′-SH, Fv, scFv, F(ab′) 2 , bispecific mAb and a diabody. 
     
     
         36 . The method of  claim 34 , wherein the human or humanized antibody or antigen-binding fragment thereof is selected from the group consisting of Fab, Fab′, Fab′-SH, Fv, scFv, F(ab′) 2 , bispecific mAb and a diabody. 
     
     
         37 . The method of  claim 33 , wherein the CD27+ cell is a CD27+ T cell. 
     
     
         38 . The method of  claim 34 , wherein the CD27+ cell is a CD27+ T cell. 
     
     
         39 . The human or humanized antibody or antigen-binding fragment thereof of  claim 22  that co-stimulates human CD8+ T cells in solution more effectively than the CD27 ligand CD70. 
     
     
         40 . The human or humanized antibody or antigen-binding fragment thereof of  claim 34  that co-stimulates human CD8+ T cells in solution more effectively than the CD27 ligand CD70.