Multispecific anti-HER antibodies

• US 8,597,652 B2
• Filed: 03/19/2010
• Issued: 12/03/2013
• Est. Priority Date: 03/20/2009
• Status: Active Grant

• Current Assignee: F Hoffmann-La Roche AG (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:
  US12/728,052
• Publication Number:
  US 20100255010A1
• Time in Patent Office: 1,355 Days
• Field of Search: 424/171.1, 424/172.1, 530/387.1, 530/387.3, 530/391.7
• US Class Current: 424/171.1
• 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. An isolated multispecific antibody comprising a heavy chain variable domain sequence of SEQ ID NO:

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

29, wherein the antibody specifically binds to EGFR and HER3.

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

3. The antibody of claim 2, wherein the antibody exhibits ADCC activity.

4. An immunoconjugate comprising the antibody of claim 1 and a cytotoxic agent.

5. A pharmaceutical formulation comprising the antibody of claim 1 and a pharmaceutically acceptable carrier.

6. An isolated 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).

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

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

9. The antibody of claim 6, wherein the antibody comprises a heavy chain comprising the amino acid sequence of SEQ ID NO:

14 and a light chain comprising the amino acid sequence of SEQ ID NO;

13.

10. The antibody of claim 9, wherein the antibody exhibits ADCC activity.

11. An immunoconjugate comprising the antibody of claim 6 and a cytotoxic agent.

12. A pharmaceutical formulation comprising the antibody of claim 6 and a pharmaceutically acceptable carrier.

13. An immunoconjugate comprising the antibody of claim 9 and a cytotoxic agent.

14. A pharmaceutical formulation comprising the antibody of claim 9 and a pharmaceutically acceptable carrier.