Anti-DR5 family antibodies, bispecific or multivalent anti-DR5 family antibodies and methods of use thereof
View Patent ↗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, a CDR3 of sequence SEQ ID NO: 15; and the VL chain contains a CDR1 of sequence SEQ ID NO: 16, a CDR2 of amino acid 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 amino acid 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;
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 a bispecific antibody comprising the amino acid sequence pair SEQ ID NO: 2 and 4 and the amino acid sequence pair SEQ ID NO: 6 and 8.
4. The composition of claim 1 comprising a bispecific antibody comprising the amino acid sequence pair SEQ ID NO: 35 and 37 and the amino acid sequence pair SEQ ID NO: 39 and 41.
5. The composition of claim 1 , wherein the polypeptide or polypeptides is/are selected from the group of an Fv, an Fab, an F(ab′)2, an scFv, and an antibody.
6. The composition of claim 5 , wherein the antibody is a monoclonal antibody.
7. The composition of claim 1 , wherein the first or second binding domain comprises the amino acid sequence pairs SEQ ID NO:2 and 4, or SEQ ID NO: 35 and 37.
8. The composition of claim 1 , wherein the first or second binding domain comprises the amino acid sequence pairs SEQ ID NO: 6 and 8, or SEQ ID NO: 39 and 41.
9. The composition of claim 1 , wherein one binding domain comprises the pair of amino acid sequences SEQ ID NO: 2 and 4, and the other binding domain comprises the pair of amino acid sequences SEQ ID NO: 6 and 8.
10. The composition of claim 1 , wherein one binding domain comprises the pair of amino acid sequences SEQ ID NO: 35 and 37, and the other binding domain comprises the pair of amino acid sequences SEQ ID NO: 39 and 41.
11. 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, 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 amino acid sequence FAS, a CDR3 of sequence SEQ ID NO: 17.
12. 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: 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 amino acid sequence RTS, a CDR3 of sequence SEQ ID NO: 21.
13. A bispecific or multivalent polypeptide binding specifically a DR5 receptor, which comprises:
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 amino acid 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 amino acid sequence RTS, a CDR3 of sequence SEQ ID NO: 21.
14. A composition comprising two polypeptides, or antibodies or fragments thereof, both having the capability to bind to DR5 receptor,
wherein a first polypeptide or antibody or fragment thereof, comprises a first antigen-biding 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, a CDR3 of sequence SEQ ID NO: 15; and the VL chain contains a CDR1 of sequence SEQ ID NO: 16, a CDR2 of amino acid sequence FAS, a CDR3 of sequence SEQ ID NO: 17, and
wherein a second polypeptide or antibody or fragment thereof, comprises a second antigen-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 amino acid sequence RTS, a CDR3 of sequence SEQ ID NO: 21.
15. A bispecific antibody, or fragment thereof, having the capability to bind to DR5 receptor, said antibody comprising a first antigen-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, a CDR3 of sequence SEQ ID NO: 15; and the VL chain contains a CDR1 of sequence SEQ ID NO: 16, a CDR2 of amino acid sequence FAS, a CDR3 of sequence SEQ ID NO: 17, and a second antigen-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 amino acid sequence RTS, a CDR3 of sequence SEQ ID NO: 21.
16. A method for treating a mammal having a disease or disorder in which DR5 is expressed, wherein the disease or disorder is selected from the group consisting of cancer, an autoimmune disease, an inflammatory condition, a viral infection, and a viral disease, wherein the method comprises the administration to the mammal of an effective amount of a composition according to claim 1 .
17. The method of claim 16 , wherein the disease or disorder is a solid cancer.
18. The method of claim 16 , wherein the composition comprises at least two polypeptides, and wherein the at least two polypeptides are administered simultaneously, separately, or sequentially to the mammal.
19. The method of claim 16 , wherein the mammal is a human.