Bispecific, bivalent anti-VEGF/anti-ANG-2 antibodies

• US 8,945,552 B2
• Filed: 03/24/2011
• Issued: 02/03/2015
• Est. Priority Date: 03/26/2010
• Status: Active Grant

• Current Assignee: Hoffmann-La Roche Incorporated (Roche Holding AG)
• Original Assignee: Hoffmann-La Roche Incorporated (Roche Holding AG)
• Inventors: Baehner, Monika, Imhof-Jung, Sabine, Kavlie, Anita, Kettenberger, Hubert, Klein, Christian, Stubenrauch, Kay-Gunnar, Thomas, Markus, Thomas, Joerg, Schaefer, Wolfgang
• Primary Examiner(s): BRISTOL, LYNN ANNE
• Application Number:
  US13/071,127
• Publication Number:
  US 20110236388A1
• Time in Patent Office: 1,412 Days
• Field of Search: None
• US Class Current: 424/136.1
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system
• CPC Class Codes: C07K 16/22 against growth factors ; against growth regulators
• CPC Class Codes: C07K 16/3015 Breast
• CPC Class Codes: C07K 16/3046 Stomach, Intestines
• CPC Class Codes: C07K 16/468 Immunoglobulins having two or more different antigen binding sites, e.g. multifunctional antibodies
• CPC Class Codes: C07K 2317/31 multispecific
• CPC Class Codes: C07K 2317/35 Valency
• CPC Class Codes: C07K 2317/52 Constant or Fc region; Isotype
• CPC Class Codes: C07K 2317/522 CH1 domain
• CPC Class Codes: C07K 2317/56 variable (Fv) region, i.e. VH and/or VL
• CPC Class Codes: C07K 2317/66 comprising a swap of domains, e.g. CH3-CH2, VH-CL or VL-CH1
• 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: C07K 2317/92 Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value
• CPC Class Codes: C07K 2317/94 Stability, e.g. half-life, pH, temperature or enzyme-resistance

Abstract

The present invention relates to bispecific, bivalent antibodies against human vascular endothelial growth factor (VEGF/VEGF-A) and against human angiopoietin-2 (ANG-2), methods for their production, pharmaceutical compositions containing said antibodies, and uses thereof.

Claims

1. A purified bispecific, bivalent antibody comprising a first antigen-binding site that specifically binds to human VEGF and a second antigen-binding site that specifically binds to human ANG-2, wherein the antibody comprises the amino acid sequences of SEQ ID NO:

5, SEQ ID NO;

6, SEQ ID NO;

7, and SEQ ID NO;

8.

2. The purified bispecific antibody according to claim 1 for the treatment of colorectal cancer.

3. A pharmaceutical composition comprising the antibody of claim 1.

4. The bispecific antibody of claim 1, obtained by culturing a host cell comprising a nucleic acid encoding the bispecific antibody under conditions to express the bispecific antibody encoded by the nucleic acid;

and then purifying the expressed bispecific antibody.

5. A purified bispecific, bivalent antibody comprising a first antigen-binding site that specifically binds to human VEGF and a second antigen-binding site that specifically binds to human ANG-2, wherein the antibody comprises the amino acid sequences of SEQ ID NO:

9, SEQ ID NO;

10, SEQ ID NO;

11, and SEQ ID NO;

12.

6. The purified bispecific antibody according to claim 5 for the treatment of colorectal cancer.

7. A pharmaceutical composition comprising the antibody of claim 5.

8. The bispecific antibody of claim 5, obtained by culturing a host cell comprising a nucleic acid encoding the bispecific antibody under conditions to express the bispecific antibody encoded by the nucleic acid;

and then purifying the expressed bispecific antibody.

9. A purified bispecific, bivalent antibody comprising a first antigen-binding site that specifically binds to human VEGF and a second antigen-binding site that specifically binds to human ANG-2, wherein the antibody comprises the amino acid sequences of SEQ ID NO:

13, SEQ ID NO;

14, SEQ ID NO;

15, and SEQ ID NO;

16.

10. The purified bispecific antibody according to claim 9 for the treatment of colorectal cancer.

11. A pharmaceutical composition comprising the antibody of claim 9.

12. The bispecific antibody of claim 9, obtained by culturing a host cell comprising a nucleic acid encoding the bispecific antibody under conditions to express the bispecific antibody encoded by the nucleic acid;

and then purifying the expressed bispecific antibody.