Humanized anti-ErbB2 antibodies and treatment with anti-ErbB2 antibodies

• US 6,949,245 B1
• Filed: 06/23/2000
• Issued: 09/27/2005
• Est. Priority Date: 06/25/1999
• Status: Expired due to Term

• Current Assignee: Genentech, Inc. (Roche Holding AG)
• Original Assignee: Genentech, Inc. (Roche Holding AG)
• Inventors: Sliwkowski, Mark
• Primary Examiner(s): Harris, Alana M.
• Assistant Examiner(s): Holleran, Anne L.
• Application Number:
  US09/602,812
• Time in Patent Office: 1,922 Days
• Field of Search: 424/143.1, 424/130.1, 424/133.1, 424/135.1, 424/136.1, 424/138.1, 424/141.1, 424/142.1, 424/172.1, 424/174.1, 424/178.1, 424/800, 424/801, 424/152.1, 424/155.1, 424/137.1
• US Class Current: 424/143.1
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/282 Platinum compounds
• CPC Class Codes: A61K 31/337 having four-membered rings, e.g. taxol
• CPC Class Codes: A61K 31/525 Isoalloxazines, e.g. riboflavins, vitamin B2
• CPC Class Codes: A61K 31/7072 having two oxo groups directly attached to the pyrimidine ring, e.g. uridine, uridylic acid, thymidine, zidovudine
• CPC Class Codes: A61K 33/24 Heavy metals; Compounds thereof
• CPC Class Codes: A61K 33/243 Platinum; Compounds thereof
• CPC Class Codes: A61K 39/395 Antibodies agglutinins A61K38/36 ; as drug carriers A61K47/50; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61K 47/6809 Antibiotics, e.g. antitumor antibiotics anthracyclins, adriamycin, doxorubicin or daunomycin
• CPC Class Codes: A61K 51/10 Antibodies or immunoglobulins; Fragments thereof , the carrier being an antibody, an immunoglobulin or a fragment thereof, e.g. a camelised human single domain antibody or the Fc fragment of an antibody
• CPC Class Codes: A61P 31/00 Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 35/04 specific for metastasis
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system
• CPC Class Codes: C07K 16/32 against translation products of oncogenes
• CPC Class Codes: C07K 2317/24 containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
• CPC Class Codes: C07K 2317/55 Fab or Fab'
• CPC Class Codes: C07K 2317/73 Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation
• CPC Class Codes: C07K 2317/76 : Antagonist effect on antigen, e.g. neutralization or inhibition of binding
• CPC Class Codes: Y10S 424/80 : Antibody or fragment thereof whose amino acid sequence is disclosed in whole or in part
• CPC Class Codes: Y10S 424/801 : involving antibody or fragment thereof produced by recombinant dna technology

Abstract

The present application describes humanized anti-ErbB2 antibodies and methods for treating cancer with anti-ErbB2 antibodies, such as humanized anti-ErbB2 antibodies.

Claims

1. A method of treating cancer in a human, wherein the cancer expresses epidermal growth factor receptor (EGFR) and ErbB2, comprising administering to the human a therapeutically effective amount of an antibody which binds ErbB2 and blocks by 50% or greater binding of monoclonal antibody 2C4 (ATCC HB-12697) to ErbB2.

2. The method of claim 1 wherein the antibody blocks ligand activation of an ErbB receptor.

3. The method of claim 1 wherein the cancer is characterized by excessive activation of EGFR.

4. The method of claim 3 wherein the cancer overexpresses an ErbB ligand.

6. The method of claim 1 wherein the antibody blocks TGF-α

activation of mitogen-activated protein kinase (MAPK).

7. The method of claim 1 wherein the cancer is not characterized by overexpression of ErbB2 receptor.

8. The method of claim 1 wherein the cancer is selected from the group consisting of colon, rectal and colorectal cancer.

9. The method of claim 1 wherein the cancer is lung cancer.

10. The method of claim 9 wherein the cancer is non-small cell lung cancer.

11. The method of claim 1 wherein the antibody has a biological characteristic of monoclonal antibody 2C4 (ATCC HB-12697).

12. The method of claim 1 wherein the antibody is an antibody fragment.

13. The method of claim 12 wherein the antibody fragment is a Fab fragment.

14. The method of claim 1 wherein the antibody is not conjugated with a cytotoxic agent.

15. The method of claim 12 wherein the antibody fragment is not conjugated with a cytotoxic agent.

16. The method of claim 1 wherein the antibody is conjugated with a cytotoxic agent.

17. The method of claim 1 comprising administering at least one dose of the antibody to the human in an amount from about 0.5 mg/kg to about 10 mg/kg.

18. The method of claim 17 comprising administering the dose about every week.

19. The method of claim 17 comprising administering the dose about every three weeks.

5. The method of claim, 5 wherein the ErbB ligand is transforming growth factor alpha (TGF-α

).

20. A method of treating cancer in a human, wherein the cancer expresses but does not overexpress ErbB2 receptor, comprising administering to the human a therapeutically effective amount of an antibody which binds to ErbB2 and blocks ligand activation of an ErbB receptor more effectively than humanized monoclonal antibody huMAb4D5-8.

21. The method of claim 20 wherein the cancer is breast cancer.

22. The method of claim 21 wherein the cancer is metastatic breast cancer.

23. A method of treating cancer in a human, wherein the cancer is selected from the group consisting of colon, rectal and colorectal cancer which express but do not overexpress ErbB2, comprising administering to the human a therapeutically effective amount of an antibody which binds ErbB2 and blocks ligand activation of an ErbB receptor more effectively than humanized monoclonal antibody huMAb4D5-8.

24. A method of treating cancer in a human, wherein the cancer expresses epidermal growth factor receptor (EGFR) and ErbB2, comprising administering to the human a therapeutically effective amount of a humanized form of monoclonal antibody 2C4 (ATCC HB-12697).