Anti-ROBO4 antibodies and uses therefor

• US 7,834,154 B2
• Filed: 02/08/2008
• Issued: 11/16/2010
• Est. Priority Date: 02/09/2007
• Status: Expired due to Fees

• Current Assignee: Genentech, Inc. (Roche Holding AG)
• Original Assignee: Genentech, Inc. (Roche Holding AG)
• Inventors: Peale, Franklin V. Jr., Carano, Richard, Koch, Alexander W., Wu, Yan, Watts, Ryan J., Stawicki, Scott
• Primary Examiner(s): GUSSOW, ANNE
• Application Number:
  US12/028,124
• Publication Number:
  US 20080247951A1
• Time in Patent Office: 1,012 Days
• Field of Search: None
• US Class Current: 530/387.1
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: A61P 17/06 Antipsoriatics
• CPC Class Codes: A61P 19/02 for joint disorders, e.g. arthritis, arthrosis
• CPC Class Codes: A61P 27/02 Ophthalmic agents
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 35/04 specific for metastasis
• CPC Class Codes: A61P 37/06 Immunosuppressants, e.g. drugs for graft rejection
• CPC Class Codes: A61P 9/10 for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
• CPC Class Codes: C07K 16/2803 against the immunoglobulin superfamily
• CPC Class Codes: C07K 16/30 from tumour cells
• CPC Class Codes: C07K 2317/55 Fab or Fab'
• CPC Class Codes: C07K 2317/565 Complementarity determining region [CDR]
• CPC Class Codes: C07K 2317/76 Antagonist effect on antigen, e.g. neutralization or inhibition of binding
• CPC Class Codes: C07K 2317/77 Internalization into the cell
• CPC Class Codes: C07K 2317/92 Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value

Abstract

The invention provides anti-Robo4 antibodies, and compositions comprising the antibodies and methods of using these antibodies, including diagnostic and therapeutic methods.

Claims

1. An isolated anti-Robo4 antibody comprising:

(i) an HVR-L1 comprising sequence A1-A11, wherein A1-A11 is RASQDVSTAVA (SEQ ID NO;

1)

(ii) an HVR-L2 comprising sequence B1-B7, wherein B1-B7 is SASFLYS (SEQ ID NO;

2)

(iii) an HVR-L3 comprising sequence C1-C9, wherein C1-C9 is QQSYTTPPT (SEQ ID NO;

3)

(iv) an HVR-H1 comprising sequence D1-D10, wherein D1-D10 is GFTINGYYIH (SEQ ID NO;

17)

(v) an HVR-H2 comprising sequence E1-E18, wherein E1-E18 is GFIYPAGGDTDYADSVKG (SEQ ID NO;

18); and

(vi) an HVR-H3 comprising sequence F1-F17 wherein F1-F17 is ARLIGNKFGWSSYGMDY (SEQ ID NO;

19).

5. The antibody of any one of claims 1-3 and 4, wherein the antibody is humanized.

6. The antibody of any one of claims 1-3 and 4, wherein the antibody is selected from the group consisting of a Fab, a Fab′

, and a (Fab′

)₂.

7. The antibody of any one of claims 1-3 and 4, further comprising a cytotoxic agent.

8. The antibody of claim 7, wherein the cytotoxic agent is selected from the group consisting of:

N²′

-deacetyl-N-²′

(3-mercapto-1-oxopropyl)-maytansine (DM1), monomethyl auristatin E (MMAE), monomethyl auristatin F (MMAF), and combinations thereof.

9. The antibody of claim 8, further comprising a detectable label.

10. The antibody of claim 9, wherein the detectable label is selected from the group consisting of:

biotin, a fluorescent dye, a radionuclide, chelating agent 1, 4, 7, 10-tetraazacyclododecane-N, N′

, N″

, N′

″

-tetraacetic acid (DOTA), a microbubble, a perfluorocarbon nanoparticle emulsion, a metallic particle, and combinations thereof.

11. The antibody of claim 9, wherein the detectable label is covalently attached to the antibody at a cysteine residue.

12. The antibody of claim 11, wherein the cysteine residue is at position 118 of the heavy chain Fc region according to EU numbering.

2. An isolated anti-Robo4 antibody comprising a light chain variable domain comprising an amino acid sequence selected from the group consisting of:

SEQ ID NOS;

72-97 as shown in FIGS. 1A and 2A.

3. An isolated anti-Robo4 antibody comprising a heavy chain variable domain comprising an amino acid sequence selected from the group consisting of:

SEQ ID NOS;

140-165 as shown in FIGS. 1B and 2B.

4. An isolated anti-Robo4 antibody comprising

(i) a light chain variable domain comprising

an HVR-L1 comprising SEQ ID NO:

1,

an HVR-L2 comprising SEQ ID NO;

2, and

an HVR-L3 comprising QQSRSDHPT (SEQ ID NO;

20); and

(ii) a heavy chain variable domain comprising

an HVR-H1 comprising SEQ ID NO;

17,

an HVR-H2 comprising SEQ ID NO;

18, and

an HVR-H3 comprising SEQ ID NO;

19.