ANTI-DR5 FAMILY ANTIBODIES, BISPECIFIC OR MULTIVALENT ANTI-DR5 FAMILY ANTIBODIES AND METHODS OF USE THEREOF

• US 20150139997A1
• Filed: 07/09/2013
• Published: 05/21/2015
• Est. Priority Date: 07/09/2012
• Status: Active Grant

• Current Assignee: Genmab BV (Genmab A/S)
• Original Assignee: International Drug Development Biotech
• Inventors: Vermot-Desroches, Claudine Brigitte Fernande, Subiger, Olivier Frdric, Bourdin, Laurence Franoise Jeanne-Marie
• Granted Patent: US 9,611,327 B2
• Time in Patent Office: Days
• US Class Current: 424/136.1
• CPC Class Codes: A61K 2039/507 Comprising a combination of two or more separate antibodies
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 31/12 Antivirals
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 37/06 Immunosuppressants, e.g. drugs for graft rejection
• CPC Class Codes: C07K 16/2878 against the NGF-receptor/TNF-receptor superfamily, e.g. CD27, CD30, CD40, CD95
• CPC Class Codes: C07K 2317/24 containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
• CPC Class Codes: C07K 2317/31 multispecific
• CPC Class Codes: C07K 2317/35 Valency
• CPC Class Codes: C07K 2317/54 F(ab')2
• CPC Class Codes: C07K 2317/55 Fab or Fab'
• CPC Class Codes: C07K 2317/56 variable (Fv) region, i.e. VH and/or VL
• CPC Class Codes: C07K 2317/565 Complementarity determining region [CDR]
• CPC Class Codes: C07K 2317/569 Single domain, e.g. dAb, sdAb, VHH, VNAR or nanobody®
• CPC Class Codes: C07K 2317/75 Agonist effect on antigen

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.

Claims

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 H) 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 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 Fv, Fab, F(ab′

)2, scFv, antibody, preferably a monoclonal antibody.

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 according to claim 1.

16. The composition of claim 1, comprising an antibody comprising the amino acid sequence pairs SEQ ID NO:

2 and 4, or 35 and 37.

17. The composition of claim 1, comprising an antibody comprising the amino acid sequence pairs SEQ ID NO:

6 and 8, or 39 and 41.

18. The composition of claim 1, comprising a polypeptide binding specifically a DR5 receptor, said polypeptide comprising the pair of amino acid sequences SEQ ID NO:

2 and 4, and another polypeptide binding specifically a DR5 receptor, said polypeptide comprising the pair of amino acid sequences SEQ ID NO;

6 and 8.

19. The composition of claim 1, comprising a polypeptide binding specifically a DR5 receptor, said polypeptide comprising the pair of amino acid sequences SEQ ID NO:

35 and 37, and another polypeptide binding specifically a DR5 receptor, said polypeptide comprising the pair of amino acid sequences SEQ ID NO;

39 and 41.

20. The method of claim 15, for the treatment or prevention of a solid cancer.

6. (canceled)

7. (canceled)

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, 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.

9. 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 sequence RTS, a CDR3 of sequence SEQ ID NO;

21.

10. A biparatopic, bispecific our 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 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.

11. (canceled)

12. (canceled)

13. A composition comprising two polypeptides, or antibodies or fragment thereof, both having the capability to bind to DR5, a first polypeptide or antibody comprising a first antigen-binding site that binds to a first epitope of said DR5, this first epitope being the one to which specifically binds a 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 polypeptide or antibody comprising a second different antigen-binding site that binds to a second epitope of said DR5, this epitope being the one to which specifically binds a 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, for a simultaneous, separate or sequential administration to a mammal, including man.

14. A bispecific antibody, or fragment thereof, having the capability to bind to DR5, said antibody comprising a first antigen-binding site that binds to a first epitope of said DR5, this first epitope being the one to which specifically binds a 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 different antigen-binding site that binds to a second epitope of said DR5, this epitope being the one to which specifically binds a 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.