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

• US 20050208043A1
• Filed: 01/27/2005
• Published: 09/22/2005
• Est. Priority Date: 06/25/1999
• Status: Active Grant

• Current Assignee: Genentech, Inc. (Roche Holding AG)
• Original Assignee: Genentech, Inc. (Roche Holding AG)
• Inventors: Sliwkowski, Mark, Presta, Leonard G., Adams, Camellia W.
• Granted Patent: US 7,862,817 B2
• Time in Patent Office: Days
• US Class Current: 424/141.100
• 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. An article of manufacture comprising a container and a composition contained therein, wherein the composition comprises an antibody which binds ErbB2, and further comprising a package insert indicating that the composition can be used to treat cancer which expresses epidermal growth factor receptor (EGFR).

2. An article of manufacture comprising a container and a composition contained therein, wherein the composition comprises an antibody which binds ErbB2 and blocks ligand activation of an ErbB receptor, and further comprising a package insert indicating that the composition can be used to treat cancer, wherein the cancer is not characterized by overexpression of the ErbB2 receptor.

3. An article of manufacture comprising a container and a composition contained therein, wherein the composition comprises an antibody which binds ErbB2 and blocks ligand activation of an ErbB receptor, and further comprising a package insert indicating that the composition can be used to treat a cancer selected from the group consisting of colon, rectal and colorectal cancer.

4. A humanized antibody which binds ErbB2 and blocks ligand activation of an ErbB receptor.

5. The humanized antibody of claim 4 which binds ErbB2 essentially as effectively as murine monoclonal antibody 2C4.

6. The humanized antibody of claim 4 comprising a variable heavy (V_H) domain which comprises nonhuman hypervariable region residues incorporated into a human V_H domain and further comprises a framework region (FR) substitution at a position selected from the group consisting of 69H, 71H and 73H, utilizing the numbering system set forth in Kabat (1991).

7. The humanized antibody of claim 6 comprising FR substitutions at positions 69H, 71H and 73H.

8. The humanized antibody of claim 4 comprising V_H domain complementarity determining region (CDR) residues GFTFTDYTMX (SEQ ID NO:

7);

DVNPNSGGSIYNQRFKG (SEQ ID NO;

8); and

NLGPSFYFDY (SEQ ID NO;

9).

9. The humanized antibody of claim 4 comprising the V_H domain amino acid sequence in SEQ ID NO:

4.

10. The humanized antibody of claim 4 comprising variable light (V_L) domain complementarity determining region (CDR) residues KASQDVSIGVA (SEQ ID NO:

10);

SASYXXX (SEQ ID NO;

11); and

QQYYIYPYT (SEQ ID NO;

     12).

11. The humanized antibody of claim 4 comprising the V_L domain amino acid sequence in SEQ ID NO:

3.

12. The humanized antibody of claim 4 which is an intact IgG1 antibody.

13. The humanized antibody of claim 4 which is an antibody fragment.

14. The humanized antibody of claim 13 which is a Fab fragment.

16. A composition comprising the humanized antibody of claim 4 and a pharmaceutically acceptable carrier.

17. An immunoconjugate comprising the humanized antibody of claim 4 conjugated with a cytotoxic agent.

15. An affinity matured antibody which binds ErbB2 and blocks ligand activation of an ErbB receptor.