Anti-HER antibodies

• US 9,327,035 B2
• Filed: 10/29/2013
• Issued: 05/03/2016
• Est. Priority Date: 03/20/2009
• Status: Active Grant

• Current Assignee: Genentech, Inc. (Roche Holding AG)
• Original Assignee: Genentech, Inc. (Roche Holding AG)
• Inventors: Fuh, Germaine, Haber, Lauric, Schaefer, Gabriele, Sliwkowski, Mark X.
• Primary Examiner(s): BRISTOL, LYNN ANNE
• Application Number:
  US14/066,258
• Publication Number:
  US 20140056899A1
• Time in Patent Office: 917 Days
• Field of Search: 424/136.1, 530/387.3
• US Class Current: 1/1
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: A61K 2039/507 Comprising a combination of two or more separate antibodies
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 35/04 specific for metastasis
• CPC Class Codes: C07K 16/28 against receptors, cell surface antigens or cell surface determinants
• CPC Class Codes: C07K 16/2863 against receptors for growth factors, growth regulators
• CPC Class Codes: C07K 16/32 against translation products of oncogenes
• CPC Class Codes: C07K 2317/31 multispecific
• CPC Class Codes: C07K 2317/56 variable (Fv) region, i.e. VH and/or VL
• CPC Class Codes: C07K 2317/565 Complementarity determining region [CDR]
• CPC Class Codes: C07K 2317/73 Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation
• CPC Class Codes: C07K 2317/732 Antibody-dependent cellular cytotoxicity [ADCC]
• CPC Class Codes: C07K 2317/92 Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value

Abstract

The invention provides anti-HER antibodies, including multispecific anti-HER antibodies, compositions comprising and methods of using these antibodies. Also provided herein are EGFR/HER3 multispecific antibodies that are less toxic than traditional EGFR antagonists.

Claims

1. A method of treating an individual having cancer comprising administering to the individual an effective amount of a multispecific antibody comprising an antigen-binding domain that specifically binds to EGFR and HER3, wherein the antibody comprises (a) HVR-H1 comprising the amino acid sequence of LSGDWIH (SEQ ID NO:

48);

(b) HVR-H2 comprising the amino acid sequence of VGEISAAGGYTD (SEQ ID NO;

     51); and

(c) HVR-H3 comprising the amino acid sequence of ARESRVSFEAAMDY (SEQ ID NO;

     53); and

(d) HVR-L1 comprising the amino acid sequence of NIATDVA (SEQ ID NO;

     55);

(e) HVR-L2 comprising the amino acid sequence of SASF (SEQ ID NO;

     56); and

(f) HVR-L3 comprising the amino acid sequence of SEPEPYT (SEQ ID NO;

     57), and wherein the cancer comprises cells that express EGFR and HER3.

2. The antibody of claim 1, wherein the cancer is selected from the group consisting of breast cancer, colorectal cancer, pancreatic cancer, head and neck cancer, melanoma, ovarian cancer, prostate cancer, and non-small lung cell cancer.

3. The method of claim 1, wherein the antibody comprises (a) a heavy chain variable domain having at least 95% sequence identity to the amino acid sequence of SEQ ID NO:

30;

(b) a light chain variable domain having at least 95% sequence identity to the amino acid sequence of SEQ ID NO;

29;

or (c) a heavy chain variable domain as in (a) and a light chain variable domain as in (b).

4. The method of claim 1, wherein the antibody comprises a heavy chain variable domain comprising SEQ ID NO:

30.

5. The method of claim 1, wherein the antibody comprises a light chain variable domain sequence comprising SEQ ID NO:

29.

6. The method of claim 1, wherein the antibody is a full length IgG1 antibody.

7. The method of claim 6, wherein the antibody exhibits ADCC activity.

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

9. A method of treating an individual having cancer comprising administering to the individual an effective amount of a multispecific antibody comprising an antigen-binding domain that specifically binds to EGFR and HER3, wherein the antibody comprises a heavy chain variable domain sequence comprising SEQ ID NO:

30 and a light chain variable domain sequence comprising SEQ ID NO;

29, and wherein the cancer comprises cells that express EGFR and HER3.

10. The method of claim 9, wherein the antibody is a full length IgG1 antibody.

11. The method of claim 10, wherein the antibody exhibits ADCC activity.

12. The method of claim 9, wherein the antibody is conjugated with a cytotoxic agent.

13. The antibody of claim 9, wherein the cancer is selected from the group consisting of breast cancer, colorectal cancer, pancreatic cancer, head and neck cancer, melanoma, ovarian cancer, prostate cancer, and non-small lung cell cancer.