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Antibodies to egfl7 and methods for their use

Inactive Publication Date: 2010-08-12
GENENTECH INC
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

[0019]In some embodiments, the invention provides a method for reducing or inhibiting angiogenesis in a subject having a pathological condition associated with angiogenesis, comprising administering to the subject an effective amount of the anti-EGFL7 antibody of the invention or a pharmaceutical composition comprising an anti-EGFL7 antibody of the invention. In some embodiments, the pathological condition is a neoplasm, e.g. a carcinoma. In some embodiments, the pathological condition is associated with the eye, e.g. an intraocular neovascular disease. In some embodiments, an anti-angiogenic agent is administered to the subject in addition to an anti-EGFL7 antibody of the invention. In some embodiments, the anti-angiogenic agent is an antagonist of vascular endothelial growth factor (VEGF), e.g. an anti-VEGF antibody (including bevacizumab and ranibizumab). In some embodiments, the anti-angiogenic agent is administered prior to or subsequent to the administration of the anti-EGFL7 antibody. In some embodiments, the anti-angiogenic agent is administered concurrently with the anti-EGFL7 antibody.
[0020]In some embodiments, the invention provides

Problems solved by technology

Despite the many advances in the field of angiogenesis, some of the steps during vessel tube formation are still poorly defined.

Method used

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  • Antibodies to egfl7 and methods for their use
  • Antibodies to egfl7 and methods for their use
  • Antibodies to egfl7 and methods for their use

Examples

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example 1

Production and Characterization of Monoclonal Antibodies to EGFL7

[0334]Production of Monoclonal Antibodies

[0335]EGFL7 was identified and cloned in an effort to discover novel human secreted and transmembrane proteins, particularly those involved in the regulation of vascular development. Details of the cloning and expression of human EGFL7 are described in, for example, patent application US2003 / 0224948A1 (in which EGFL7 is identified as PRO1449). The GenBank® accession number for human EGFL7 is NM—016215.

[0336]Egfl7 homozygous knockout mice (generated at Genentech) were immunized with E. coli produced His6-tagged recombinant human and mouse EGFL7 proteins, diluted in Ribi adjuvant (Corixia, Hamilton, Mont.) twice a week, via footpad, eight doses. B cells from lymph nodes were harvested from ten mice demonstrating high serum titers and were fused with mouse myeloma cells (X63.Ag8.653; American Type Culture Collection® (ATCC®)). After 10-14 days, the supernatants were screened for an...

example 2

Anti-EGFL7 Mabs Inhibit Tumor Growth In Vivo

[0351]In this example, anti-EGFL7 Mabs were tested for their ability to inhibit tumor growth in vivo in several models. We first tested the Mabs in PBS in the Colo205 model (human colorectal cancer) and the A673 model (human rhabdomyosarcoma model). We did not observe an effect in these models with the Mabs in PBS as single agents.

[0352]We then tested the Mabs alone and / or in combination with an anti-VEGF antibody, B20.4.1 (described in WO 2005 / 012359). We tested the antibodies in three models: a Her2 human breast cancer model (“Fo5 model”), a human lung cancer (NSCLC) model (“H1299”) and another human breast cancer model (“MDA-MB231”). These tumor models are well established and are described in, e.g., Lee et al., Clin Cancer Res. 11(16):6065-74 (2005); Cameron et al., Cancer Cell Int.5:23 (2005); Finkle et al., Clinical Cancer Res. 10:2499-251 (2004). Each animal was treated with anti-ragweed Mab (control); B20.4 alone; 18F7 alone; or B2...

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Abstract

The invention provides anti-EGFL7 antibodies, and compositions comprising and methods of using these antibodies.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS[0001]This application is a National Stage of PCT / US2007 / 064242, filed Mar. 16, 2007 and claims priority under 35 USC §119 to U.S. Provisional Application No. 60 / 783,686, filed Mar. 16, 2006, and U.S. Provisional Application No. 60 / 812,569, filed Jun. 9, 2006, the entire contents of which are hereby incorporated by reference.FIELD OF THE INVENTION[0002]The present invention relates generally to compositions and methods that are useful for modulating vascular development. Specifically, the present invention relates to antibodies that bind to the Epidermal Growth Factor-Like Domain 7 (EGFL7) polypeptide. The present invention further relates to the diagnosis and treatment of conditions and diseases associated with angiogenesis.BACKGROUND OF THE INVENTION[0003]Development of a vascular supply is a fundamental requirement for many physiological and pathological processes. Actively growing tissues such as embryos and tumors require adequate blood su...

Claims

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Application Information

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IPC IPC(8): A61K39/395C07K16/22C07H21/04A61P35/04A61P35/00A61P27/06A61P37/06A61P17/06A61P9/10C12N15/74C12N1/21C12N5/10C12P21/00
CPCA61K2039/505A61K2039/507C07K2317/565C07K2316/96C07K2317/56C07K16/22C07K2317/73A61P17/06A61P19/02A61P27/00A61P27/02A61P27/06A61P35/00A61P35/04A61P37/06A61P43/00A61P9/00A61P9/10
Inventor YE, WEILANSCHMIDT, MAIKEHONGO, JO-ANNEWU, YAN
Owner GENENTECH INC
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