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Antibodies to EGFL7 and methods for their use

An antibody and carrier technology, applied in the field of compositions for regulating vascular development, can solve the problems of unclear vascular steps and the like

Inactive Publication Date: 2009-05-27
GENENTECH INC
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0009] Despite many advances in the field of angiogenesis, some steps in the process of blood vessel formation remain poorly understood

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

Experimental program
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preparation example Construction

[0284] v. Preparation of antibody-drug conjugates

[0285] In the antibody-drug conjugate (ADC) of the present invention, the antibody (Ab) is conjugated to one or more drug moieties (D) via a linker (L), for example, about 1 to about 20 moieties per antibody. drug section. The ADC of general formula I can be prepared through several routes using organic chemical reactions, conditions and reagents known to those skilled in the art, including: (1) the nucleophilic group of the antibody reacts with a divalent linker reagent through a covalent bond to form Ab-L, which subsequently reacts with the drug moiety D; and (2) the nucleophilic group of the drug moiety reacts via a covalent bond with a divalent linker reagent to form D-L, which subsequently reacts with the nucleophilic group of the antibody. Additional methods for preparing ADCs are described herein.

[0286] Ab-(L-D)p I

[0287] A joint may consist of one or more joint components. Exemplary linker building blocks inc...

Embodiment 1

[0340] Example 1: Generation and Characterization of Monoclonal Antibodies to EGFL7

[0341] Production of monoclonal antibodies

[0342] EGFL7 was identified and cloned in a study aimed at discovering 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 disclosed eg in patent application US2003 / 0224948A1 (where EGFL7 is identified as PRO1449). hEGFL7 The serial number is NM_016215.

[0343] Egfl7 homozygous knockout mice (produced at Genentech) were immunized with E. coli-produced, His6-tagged recombinant human and mouse EGFL7 proteins diluted in Ribi adjuvant (Corixia, Hamilton, MT) twice a week , through the foot pads, 8 doses. B cells from lymph nodes were harvested from 10 mice exhibiting high serum titers and compared with mouse myeloma cells (X63.Ag8.653; American Type Culture Collection fusion. After 10-14 days, supernatants were screened ...

Embodiment 2

[0380] Example 2: Anti-EGFL7 monoclonal antibody inhibits tumor growth in vivo

[0381] In this example, the ability of anti-EGFL7 mAbs to inhibit tumor growth in vivo was tested in several models. We first tested mAbs in PBS in the Colo205 model (human colorectal cancer) and A673 model (human rhabdomyosarcoma model). We observed no single-agent effects of mAbs in PBS in these models.

[0382] We then tested the mAb alone and / or in combination with the anti-VEGF antibody B20.4.1 (described in WO 2005 / 012359). We tested the antibody 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 have been well established, such as described in 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 (control); B20.4 alo...

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Abstract

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

Description

field of invention [0001] In general, the present invention relates to compositions and methods useful for modulating vascular development. In particular, the invention relates to antibodies that bind epidermal growth factor-like domain 7 (EGFL7) polypeptides. The invention further relates to the diagnosis and treatment of disorders and diseases associated with angiogenesis. Background of the invention [0002] The development of vascular supply is an essential requirement for many physiological and pathological processes. Actively growing tissues such as embryos and tumors require an adequate blood supply. They meet this need by producing pro-angiogenic factors that promote the formation of new blood vessels through a process called angiogenesis. Tube formation of blood vessels is a complex but ordered biological event involving all or many of the following steps: a) proliferation of ECs from pre-existing endothelial cells (ECs) or differentiation of ECs from progenitor ...

Claims

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Application Information

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IPC IPC(8): C07K16/22A61P35/00A61P27/02
Inventor 叶伟兰梅克·施密特乔-安妮·杭戈吴雁
Owner GENENTECH INC
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