ANTI-DR5 FAMILY ANTIBODIES, BISPECIFIC OR MULTIVALENT ANTI-DR5 FAMILY ANTIBODIES AND METHODS OF USE THEREOF
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 composition of claim 1 , for use in combination with another anti-cancer drug.
8 . A polypeptide binding specifically a DRS 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, a CDR2 of sequence SEQ ID NO: 14, 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; or 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.
9 - 10 . (canceled)
11 . An isolated nucleotide sequence comprising the nucleotide sequence SEQ ID NO: 1, 3, 5, 7, 34, 36, 38 or 40.
12 . An expression vector or a host cell comprising the nucleotide sequence according to claim 11 . 13 - 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 claim 1 .