Antibodies directed to HER-3 and uses thereof

Patent metadata

Field	Value
Publication number	US-9249230-B2
Application number	US-36578409-A
Country	US
Kind code	B2
Filing date	Feb 4, 2009
Priority date	Dec 30, 2005
Publication date	Feb 2, 2016
Grant date	Feb 2, 2016

Abstract

The present invention relates to binding proteins that bind to HER-3 and polynucleotides encoding the same. Expression vectors and host cells comprising the same for the production of the binding protein of the invention are also provided. In addition, the invention provides compositions and methods for diagnosing and treating diseases associated with HER-3 mediated signal transduction and/or its ligand heregulin.

First claim

The invention claimed is:

1. An isolated binding protein that binds to HER-3, comprising a heavy chain amino acid sequence that comprises a CDRH1 having the sequence of SEQ ID NO: 236, a CDRH2 having the sequence of SEQ ID NO: 258, and a CDRH3 having the sequence of SEQ ID NO: 283; and a light chain amino acid sequence that comprises a CDRL1 having the sequence of SEQ ID No: 320, a CDRL2 having the sequence of SEQ ID NO: 343, and a CDRL3 having the sequence of SEQ ID NO: 360.

2. An isolated binding protein that binds to HER-3, comprising a heavy chain amino acid sequence that comprises a CDRH1 having the sequence of SEQ ID NO: 236, a CDRH2 having the sequence of SEQ ID NO: 258, and a CDRH3 having the sequence of SEQ ID NO: 285; and a light chain amino acid sequence that comprises a CDRL1 having the sequence of SEQ ID No: 320, a CDRL2 having the sequence of SEQ ID NO: 343, and a CDRL3 having the sequence of SEQ ID NO: 360.

3. An isolated binding protein that binds to HER-3, comprising a heavy chain amino acid sequence that comprises a CDRH1 having the sequence of SEQ ID NO: 251, a CDRH2 having the sequence of SEQ ID NO: 278, and a CDRH3 having the sequence of SEQ ID NO: 309; and a light chain amino acid sequence that comprises a CDRL1 having the sequence of SEQ ID No: 334, a CDRL2 having the sequence of SEQ ID NO: 356, and a CDRL3 having the sequence of SEQ ID NO: 381.

4. An isolated binding protein that binds to HER-3, comprising a heavy chain amino acid sequence that comprises a CDRH1 having the sequence of SEQ ID NO: 252, a CDRH2 having the sequence of SEQ ID NO: 280, and a CDRH3 having the sequence of SEQ ID NO: 313; and a light chain amino acid sequence that comprises a CDRL1 having the sequence of SEQ ID No: 337, a CDRL2 having the sequence of SEQ ID NO: 351, and a CDRL3 having the sequence of SEQ ID NO: 385.

5. The isolated binding protein of claim 4 , wherein the binding protein is directed against the extracellular domain of HER-3.

6. The isolated binding protein of claim 4 , wherein the binding of the binding protein to HER-3 reduces HER-3-mediated signal transduction.

7. The isolated binding protein of claim 4 , wherein the binding of the binding protein to HER-3 reduces HER-3 phosphorylation.

8. The isolated binding protein of claim 4 , wherein the binding of the binding protein to HER-3 reduces cell proliferation.

9. The isolated binding protein of claim 4 , wherein the binding of the binding protein to HER-3 reduces cell migration.

10. The isolated binding protein of claim 4 , wherein the binding of the binding protein to HER-3 increases the downregulation of HER-3.

11. The isolated binding protein of claim 4 , which is an antibody.

12. The isolated binding protein of claim 11 , wherein the antibody is selected from the group consisting of a monoclonal antibody, a recombinant antibody, a humanized antibody, a chimeric antibody, a multispecific antibody, and an antibody fragment thereof.

13. The isolated binding protein of claim 12 , wherein the antibody fragment is selected from the group consisting of a Fab fragment, a Fab′ fragment, a F(ab′)2 fragment, a Fv fragment, a diabody, and a single chain antibody molecule.

14. The isolated binding protein of claim 11 , wherein antibody is selected from the group consisting of the IgG1-, IgG2-, IgG3- and IgG4-type.

15. The isolated binding protein of claim 11 , wherein the binding protein is coupled to a labelling group.

16. The isolated binding protein of claim 15 , wherein the labelling group is selected from the group consisting of a radioisotope or radionuclide, a fluorescent group, an enzymatic group, a chemiluminescent group, a biotinyl group, a leucine zipper pair sequence, a binding site for secondary antibodies, a metal binding domain and a epitope tag.

17. The isolated binding protein of claim 11 , wherein the binding protein is coupled to an effector group.

18. The isolated binding protein of claim 17 , wherein the effector group is selected from the group consisting of a radioisotope, a radionuclide, a toxin, a therapeutic group, and a chemotherapeutic group.

19. The isolated binding protein of claim 18 , wherein the therapeutic or chemotherapeutic group is selected from the group consisting of calicheamicin, auristatin-PE, geldanamycin, maytansine and derivatives thereof.

20. A pharmaceutical composition comprising as an active agent at least one isolated binding protein of claim 4 , and a pharmaceutically acceptable carrier, diluent or adjuvant.

21. The composition of claim 20 for therapeutic use.

22. The composition of claim 20 for diagnostic use.

23. A kit comprising the isolated binding protein of claim 4 .

24. The kit of claim 23 , comprising a further therapeutic agent.

25. The kit of claim 24 , wherein the further therapeutic agent is an antineoplastic agent.

26. The kit of claim 25 , wherein the anti-neoplastic agent is an anti-tumor antibody or a chemotherapeutic agent.

27. An isolated binding protein that binds to HER-3, comprising a heavy chain amino acid sequence that comprises a CDRH1 having the sequence of SEQ ID NO: 256, a CDRH2 having the sequence of SEQ ID NO: 282, and a CDRH3 having the sequence of SEQ ID NO: 315; and a light chain amino acid sequence that comprises a CDRL1 having the sequence of SEQ ID No: 340, a CDRL2 having the sequence of SEQ ID NO: 344, and a CDRL3 having the sequence of SEQ ID NO: 387.

28. The isolated binding protein of claim 27 , wherein the binding protein is directed against the extracellular domain of HER-3.

29. The isolated binding protein of claim 27 , wherein the binding of the binding protein to HER-3 reduces HER-3-mediated signal transduction.

30. The isolated binding protein of claim 27 , wherein the binding of the binding protein to HER-3 reduces HER-3 phosphorylation.

31. The isolated binding protein of claim 27 , wherein the binding of the binding protein to HER-3 reduces cell proliferation.

32. The isolated binding protein of claim 27 , wherein the binding of the binding protein to HER-3 reduces cell migration.

33. The isolated binding protein of claim 27 , wherein the binding of the binding protein to HER-3 increases the downregulation of HER-3.

34. The isolated binding protein of claim 27 , which is an antibody.

35. The isolated binding protein of claim 34 , wherein the antibody is selected from the group consisting of a monoclonal antibody, a recombinant antibody, a humanized antibody, a chimeric antibody, a multispecific antibody, and an antibody fragment thereof.

36. The isolated binding protein of claim 35 , wherein the antibody fragment is selected from the group consisting of a Fab fragment, a Fab′ fragment, a F(ab′)2 fragment, a Fv fragment, a diabody, and a single chain antibody molecule.

37. The isolated binding protein of claim 34 , wherein antibody is selected from the group consisting of the IgG1-, IgG2-, IgG3- and IgG4-type.

38. The isolated binding protein of claim 34 , wherein the binding protein is coupled to a labelling group.

39. The isolated binding protein of claim 38 , wherein the labelling group is selected from the group consisting of a radioisotope or radionuclide, a fluorescent group, an enzymatic group,

Assignees

• Rothe Mike
• Treder Martin
• Borges Eric
• Hartmann Susanne
• Green Larry L
• U3 Pharma Gmbh
• Amgen Inc

Inventors

• Rothe Mike
• Treder Martin
• Borges Eric
• Hartmann Susanne
• Green Larry L

Classifications

• A61P35/04

  specific for metastasis · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• A61P37/00

  Drugs for immunological or allergic disorders · CPC title

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• G01N33/575

  for cancer · CPC title