Anti-dr5 family antibodies, bispecific or multivalent anti-dr5 family antibodies and methods of use thereof

Abstract

Anti-DR5 family member antibodies and bispecific antibodies comprising one or more anti-DR5 family member antibodies are disclosed. These antibodies can be used to trigger cell death on DR5 positive cells.

1 . A composition comprising at least one or two polypeptides binding specifically a DR5 receptor, wherein the at least one or two polypeptides comprise two immunoglobulin binding domains comprising:
 a first binding domain comprising a pair of VH and VL chains wherein the VH chain contains a CDR1 of sequence SEQ ID NO: 13, a CDR2 of sequence SEQ ID NO: 14 CDR1, a CDR3 of sequence SEQ ID NO: 15; and the VL chain contains a CDR1 of sequence SEQ ID NO: 16, a CDR2 of sequence FAS, a CDR3 of sequence SEQ ID NO: 17, and   a second binding domain comprising a pair of VH and VL chains wherein the VH chain contains a CDR1 of sequence SEQ ID NO: 18, a CDR2 of sequence SEQ ID NO: 14, a CDR3 of sequence SEQ ID NO: 19; and the VL chain contains a CDR1 of sequence SEQ ID NO: 20, a CDR2 of sequence RTS, a CDR3 of sequence SEQ ID NO: 21,   wherein
 the at least one polypeptide comprises both immunoglobulin binding domains, or 
 the at least two polypeptides comprise a first polypeptide comprising the first binding domain and a second polypeptide comprising the second binding domain for a simultaneous, separate or sequential administration to a mammal, including man, 
   
       and a pharmaceutically carrier, diluent or excipient. 
     
     
         2 . The composition of  claim 1 , comprising:
 one or more of amino acid sequence pairs SEQ ID NO: 2 and 4 and SEQ ID NO: 6 and 8,   the pair of amino acid sequences SEQ ID NO: 2 and 4,   the pair of amino acid sequences SEQ ID NO: 6 and 8, or   both amino acid sequence pairs SEQ ID NO: 2 and 4 and SEQ ID NO: 6 and 8; or   one or more of amino acid sequence pairs SEQ ID NO: 35 and 37 and SEQ ID NO: 39 and 41,   the pair of amino acid sequences SEQ ID NO: 35 and 37,   the pair of amino acid sequences SEQ ID NO: 39 and 41, or   both amino acid sequence pairs SEQ ID NO: 35 and 37 and SEQ ID NO: 39 and 41.   
     
     
         3 . The composition of  claim 1  comprising the amino acid sequence pair SEQ ID NO: 2 and 4, an antibody comprising the amino acid sequence pair SEQ ID NO: 6 and 8. 
     
     
         4 . The composition of  claim 1  comprising the amino acid sequence pair SEQ ID NO: 35 and 37, an antibody comprising the amino acid sequence pair SEQ ID NO: 39 and 41. 
     
     
         5 . The composition of  claim 1 , wherein the polypeptide or polypeptides is/are Fv, Fab, F(ab′)2, scFv, antibody, preferably a monoclonal antibody. 
     
     
         6 . The composition of  claim 1 , for use as a medicament to induce apoptosis of a tumour cell and/or to treat cancer, preferably a solid cancer. 
     
     
         7 . The method of  claim 15 , wherein the polypeptide is for use in combination with another anti-cancer drug. 
     
     
         8 . A polypeptide binding specifically a DR5 receptor, comprising one or two binding domains comprising a pair of VH and VL chains wherein the VH chain contains a CDR1 of sequence SEQ ID NO: 13 or SEQ ID NO: 18, a CDR2 of sequence SEQ ID NO: 14 or SEQ ID NO: 14, a CDR3 of sequence SEQ ID NO: 15 or SEQ ID NO: 19; and the VL chain contains a CDR1 of sequence SEQ ID NO: 16 or SEQ ID NO: 20, a CDR2 of sequence FAS or a CDR2 sequence of RTS, a CDR3 of sequence SEQ ID NO: 17 or SEQ ID NO:21. 
     
     
         9 . (canceled) 
     
     
         10 . A biparatopic, bispecific our multivalent polypeptide binding specifically a DR5 receptor, which comprises:
 a first binding domain that binds to a first epitope of said DR5 receptor, comprising a pair of VH and VL chains, wherein the VH chain contains a CDR1 of sequence SEQ ID NO: 13, a CDR2 of sequence SEQ ID NO: 14 CDR1, a CDR3 of sequence SEQ ID NO: 15; and the VL chain contains a CDR1 of sequence SEQ ID NO: 16, a CDR2 of sequence FAS, a CDR3 of sequence SEQ ID NO: 17, and   a second binding domain that binds to a second epitope of said DR5 receptor, comprising a pair of VH and VL chains wherein the VH chain contains a CDR1 of sequence SEQ ID NO: 18, a CDR2 of sequence SEQ ID NO: 14, a CDR3 of sequence SEQ ID NO: 19; and the VL chain contains a CDR1 of sequence SEQ ID NO: 20, a CDR2 of sequence RTS, a CDR3 of sequence SEQ ID NO: 21.   
     
     
         11 . (canceled) 
     
     
         12 . An expression vector or a host cell comprising the nucleotide sequence according to  claim 11 . 
     
     
         13 . The composition of  claim 6  for a simultaneous, separate or sequential administration to a mammal, including man. 
     
     
         14 . (canceled) 
     
     
         15 . A method for the treatment or the prevention of a cancer, an autoimmune disease, an inflammatory condition, a viral infection or a viral disease, comprising the administration to a mammal including human, of an effective amount of a composition or polypeptide of  claim 1 .