Methods for blocking an interaction between notch-1 and delta-like 4 (DLL-4) by administering a DDL-4 antibody
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.
1. A method for blocking an interaction between Notch-1 and DLL-4, comprising administering an effective amount of an antibody that binds to a Delta-like 4 (DLL-4) epitope, the antibody comprising: a heavy chain variable domain sequence comprising SEQ ID NO. 1, SEQ ID NO. 5, or SEQ ID NO. 7; and a light chain variable domain sequence comprising SEQ ID NO. 2, SEQ ID NO. 6, or SEQ ID NO. 8.
2. The method of claim 1 , wherein the 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.
3. The method 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 method of claim 3 , wherein the antibody is an IgG.
5. A method for blocking an interaction between Notch-1 and DLL-4, comprising administering an effective amount of an antibody Fab fragment that binds to a DLL-4, epitope, the Fab fragment comprising: a heavy chain variable domain sequence comprising SEQ ID NO. 1, SEQ ID NO. 5, or SEQ ID NO. 7, and a light chain variable domain sequence comprising SEQ ID NO. 2, SEQ ID NO. 6, or SEQ ID NO. 8.
6. The method 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 method for blocking an interaction between Notch-1 and DLL-4, comprising administering an effective amount of 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 comprising SEQ ID NO. 1, SEQ ID NO. 5, or SEQ ID NO. 7, and a light chain variable domain sequence comprising SEQ ID NO. 2, SEQ ID NO. 6, or SEQ ID NO. 8, wherein the heavy chain variable domain and the light chain variable domain are connected by a peptide linker.
8. The method of claim 7 , wherein the single-chain antibody, or fragment thereof, 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. A method for blocking an interaction between Notch-1 and DLL-4, comprising administering an effective amount of 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 method of claim 9 , wherein the antibody comprises:
(a) a heavy chain variable domain comprising CDR1, CDR2 and CDR3 region amino acid sequences set forth in SEQ ID NO. 1; and
(b) a light chain variable domain comprising CDR1, CDR2 and CDR3 region amino acid sequences set forth in SEQ ID NO. 2.
11. The method of claim 9 , wherein the antibody comprises:
(a) a heavy chain variable domain comprising CDR1, CDR2 and CDR3 region amino acid sequences set forth in SEQ ID NO. 5; and
(b) a light chain variable domain comprising CDR1, CDR2 and CDR3 region amino acid sequences set forth in SEQ ID NO. 6.
12. The method of claim 9 , wherein the antibody comprises:
(a) a heavy chain variable domain comprising CDR1, CDR2 and CDR3 region amino acid sequences set forth in SEQ ID NO. 7; and
(b) a light chain variable domain comprising CDR1, CDR2 and CDR3 region amino acid sequences set forth in SEQ ID NO. 8.
13. The method 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 method of claim 13 , wherein the antibody is a Fab.
15. The method of claim 13 , wherein the antibody is a single-chain antibody.
16. The method of claim 13 , wherein the antibody, wherein the antibody is an IgG.
17. A method for blocking an interaction between Notch-1 and DLL-4, comprising administering an effective amount of 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 method of claim 17 , wherein the heavy chain variable domain comprises the amino acid sequence set forth in SEQ ID NO. 1.
19. The method of claim 17 , wherein the heavy chain variable domain comprises the amino acid sequence set forth in SEQ ID NO. 5.
20. The method of claim 17 , wherein the heavy chain variable domain comprises the amino acid sequence set forth in SEQ ID NO. 7.
21. A method for blocking an interaction between Notch-1 and DLL-4, comprising administering an effective amount of 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 method of claim 21 , wherein the light chain variable domain comprises the amino acid sequence set forth in SEQ ID NO. 2.
23. The method of claim 21 , wherein the light chain variable domain comprises the amino acid sequence set forth in SEQ ID NO. 6.
24. The method of claim 21 , wherein the light chain variable domain comprises the amino acid sequence set forth in SEQ ID NO. 8.
25. A method for blocking an interaction between Notch-1 and DLL-4, comprising administering an effective amount of an antibody that binds to a DLL-4 epitope, wherein the 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.
26. The method of claim 25 , wherein the the heavy chain/light chain variable domain sequence is SEQ ID NO. 1/SEQ ID NO. 2.
27. The method of claim 25 , wherein the the heavy chain/light chain variable domain sequence is SEQ ID NO. 5/SEQ ID NO. 6.
28. The method of claim 25 , wherein the the heavy chain/light chain variable domain sequence is SEQ ID NO. 7/SEQ ID NO. 8.