Antigen binding proteins that bind delta-like 4 (DLL-4)

Patent metadata

Field	Value
Publication number	US-10174107-B2
Application number	US-201313903793-A
Country	US
Kind code	B2
Filing date	May 28, 2013
Priority date	May 31, 2012
Publication date	Jan 8, 2019
Grant date	Jan 8, 2019

Abstract

There is disclosed compositions and methods relating to or derived from anti-DLL-4 antibodies. More specifically, there is disclosed fully human antibodies that bind DLL-4, DLL-4-binding fragments and derivatives of such antibodies, and DLL-4-binding polypeptides comprising such fragments. Further still, there is disclosed nucleic acids encoding such antibodies, antibody fragments and derivatives and polypeptides, cells comprising such polynucleotides, methods of making such antibodies, antibody fragments and derivatives and polypeptides, and methods of using such antibodies, antibody fragments and derivatives and polypeptides, including methods of treating or diagnosing subjects having DLL-4 related disorders or conditions, including various inflammatory disorders and various cancers.

First claim

We claim:

1. An antibody that binds to a Delta-like 4 (DLL-4) epitope, the antibody comprising: a heavy chain variable domain sequence that is at least 95% identical to an amino acid sequence selected from the group consisting of SEQ ID NO. 1, SEQ ID NO. 5, and SEQ ID NO. 7; and that has a light chain variable domain sequence that is at least 95% identical to an amino acid sequence selected from the group consisting of SEQ ID NO. 2, SEQ ID NO. 6, and SEQ ID NO. 8.

2. The antibody of claim 1 , wherein the antibody has comprises a heavy chain/light chain variable domain sequence selected from the group consisting of SEQ ID NO. 1/SEQ ID NO. 2, SEQ ID NO. 5/SEQ ID NO. 6, and SEQ ID NO. 7/SEQ ID NO. 8.

3. The antibody of claim 1 , wherein the antibody is selected from the group consisting of a Fab, a Fab′, a F(ab′) 2 , an Fv, a domain antibody (dAb), a single-chain antibody, a chimeric antibody, a diabody, a triabody, a tetrabody, a fully human antibody, a humanized antibody, and a chimeric antibody.

4. The antibody of claim 3 , wherein the antibody is an IgG.

5. An antibody Fab fragment that binds to a DLL-4 epitope, the Fab fragment comprising: a heavy chain variable domain sequence that is at least 95% identical to an amino acid sequence selected from the group consisting of SEQ ID NO. 1, SEQ ID NO. 5, and SEQ ID NO. 7, and a light chain variable domain sequence that is at least 95% identical to an amino acid sequence selected from the group consisting of SEQ ID NO. 2, SEQ ID NO. 6, and SEQ ID NO. 8.

6. The Fab fragment of claim 5 , wherein the Fab fragment comprises a heavy chain/light chain variable domain sequence selected from the group consisting of SEQ ID NO. 1/SEQ ID NO. 2, SEQ ID NO. 5/SEQ ID NO. 6, and SEQ ID NO. 7/SEQ ID NO. 8.

7. A single chain antibody, or fragment thereof, that binds to a DLL-4 epitope, the single chain antibody comprising: a heavy chain variable domain sequence that is at least 95% identical to an amino acid sequence selected from the group consisting of SEQ ID NO. 1, SEQ ID NO. 5, and SEQ ID NO. 7, and a light chain variable domain sequence that is at least 95% identical to an amino acid sequence selected from the group consisting of SEQ ID NO. 2, SEQ ID NO. 6, and SEQ ID NO. 8, wherein the heavy chain variable domain and the light chain variable domain are connected by a peptide linker.

8. The single chain antibody of claim 7 , wherein the single chain antibody comprises a heavy chain/light chain variable domain sequence selected from the group consisting of SEQ ID NO. 1/SEQ ID NO. 2, SEQ ID NO. 5/SEQ ID NO. 6, and SEQ ID NO. 7/SEQ ID NO. 8.

9. An antibody that binds to a DLL-4 epitope, the antibody comprising:
(a) a heavy chain variable domain comprising CDR1, CDR2 and CDR3 region amino acid sequences set forth in SEQ ID NO. 1, 5, or 7; and
(b) a light chain variable domain comprising CDR1, CDR2 and CDR3 region amino acid sequences set forth in SEQ ID NO. 2, 6, or 8.

10. The antibody of claim 9 , wherein the antibody comprises
a heavy chain variable domain comprising CDR1, CDR2 and CDR3 region amino acid sequences set forth in SEQ ID NO. 1; and
a light chain variable domain comprising CDR1, CDR2 and CDR3 region amino acid sequences set forth in SEQ ID NO. 2.

11. The antibody of claim 9 , wherein the antibody comprises:
a heavy chain variable domain comprising CDR1, CDR2 and CDR3 region amino acid sequences set forth in SEQ ID NO. 5; and
a light chain variable domain comprising CDR1, CDR2 and CDR3 region amino acid sequences set forth in SEQ ID NO. 6.

12. The antibody of claim 9 , wherein the antibody comprises:
a heavy chain variable domain comprising CDR1, CDR2 and CDR3 region amino acid sequences set forth in SEQ ID NO. 7; and
a light chain variable domain comprising CDR1, CDR2 and CDR3 region amino acid sequences set forth in SEQ ID NO. 8.

13. The antibody of claim 9 , wherein the antibody is selected from the group consisting of a Fab, a Fab′, a F(ab′) 2 , an Fv, a domain antibody (dAb), a single-chain antibody, a chimeric antibody, a diabody, a triabody, a tetrabody, a fully human antibody, a humanized antibody, and a chimeric antibody.

14. The antibody of claim 13 , wherein the antibody is a Fab.

15. The antibody of claim 13 , wherein the antibody is a single chain antibody.

16. The antibody of claim 13 , wherein the antibody is an IgG.

17. An antibody that binds to a DLL-4 epitope, the antibody comprising a heavy chain variable domain comprising an amino acid sequence selected from the group consisting of SEQ ID NO. 1, 5, and 7, and further comprising a light chain.

18. The antibody of claim 17 , wherein the heavy chain variable domain comprises the amino acid sequence set forth in SEQ ID NO. 1.

19. The antibody of claim 17 , wherein the heavy chain variable domain comprises the amino acid sequence set forth in SEQ ID NO. 5.

20. The antibody of claim 17 , wherein the heavy chain variable domain comprises the amino acid sequence set forth in SEQ ID NO. 7.

21. An antibody that binds to a DLL-4 epitope, the antibody comprising a light chain variable domain comprising an amino acid sequence selected from the group consisting of SEQ ID NO. 2, 6, and 8, and further comprising a heavy chain.

22. The antibody of claim 21 , wherein the light chain variable domain comprises the amino acid sequence set forth in SEQ ID NO. 2.

23. The antibody of claim 21 , wherein the light chain variable domain comprises the amino acid sequence set forth in SEQ ID NO. 6.

24. The antibody of claim 21 , wherein the light chain variable domain comprises the amino acid sequence set forth in SEQ ID NO. 8.

25. An antibody that binds to a DLL-4 epitope, the antibody comprising a heavy chain/light chain variable domain sequence selected from the group consisting of SEQ ID NO. 1/SEQ ID NO. 2, SEQ ID NO. 5/SEQ ID NO. 6, and SEQ ID NO. 7/SEQ ID NO. 8.

26. The antibody of claim 25 , wherein the heavy chain/light chain variable domain sequence is SEQ ID NO. 1/SEQ ID NO. 2.

27. The antibody of claim 25 , wherein the heavy chain/light chain variable domain sequence is SEQ ID NO. 5/SEQ ID NO. 6.

28. The antibody of claim 25 , wherein the heavy chain/light chain variable domain sequence is SEQ ID NO. 7/SEQ ID NO. 8.

Assignees

• Sorrento Therapeutics Inc

Inventors

• Gros Edwige
• Zhang Yanliang
• Zhou Heyue
• Gastwirt Randy

Classifications

• C07K2317/92

  Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value · CPC title

• C07K16/22 Primary

  against growth factors {; against growth regulators} · CPC title

• C07K2317/76

  Antagonist effect on antigen, e.g. neutralization or inhibition of binding · CPC title

• C07K2317/21

  from primates, e.g. man · CPC title

• A61P35/00

  Antineoplastic agents · CPC title