Humanized anti-ErbB2 antibodies and treatment with anti-ErbB2 antibodies

A humanized antibody, antibody technology, applied in the direction of antibodies, drug combinations, anti-tumor drugs, etc.

Inactive Publication Date: 2007-10-03
GENENTECH INC
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0011] Although EGF and TGFα do not bind ErbB2, EGF stimulates EGFR and ErbB2 to form a heterodimer, which activates EGFR and leads to transphosphorylation of ErbB2 in the heterodimer

Method used

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  • Humanized anti-ErbB2 antibodies and treatment with anti-ErbB2 antibodies
  • Humanized anti-ErbB2 antibodies and treatment with anti-ErbB2 antibodies
  • Humanized anti-ErbB2 antibodies and treatment with anti-ErbB2 antibodies

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Experimental program
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Effect test

preparation example

[0261] Controlled release formulations may also be prepared. Suitable examples of controlled release formulations include semipermeable matrices of solid hydrophobic polymers containing the antibody in shaped articles such as membranes or microcapsules. Examples of controlled release formulations include polyesters, hydrogels such as poly(2-hydroxyethyl-methacrylate) or poly(vinyl alcohol), polylactide (US Patent 3,773,919), L-glutamic acid and gamma ethyl -Copolymers of L-glutamate, non-degradable ethylene ethyl acetate, degradable lactic acid-glycolic acid copolymers such as LUPRONDEPOT TM (injectable microspheres composed of lactic-co-glycolic acid and leuprolide acetate), and poly-D-(-)-3-hydroxybutyric acid.

[0262] Preparations for in vivo administration must be sterile. This is easily accomplished by filtration through a sterile filter.

[0263] V. Treatment with anti-ErbB2 antibodies

[0264] According to the present invention, anti-ErbB2 antibodies can be used to...

Embodiment 1

[0324] Preparation and Identification of Monoclonal Antibody 2C4

[0325]Murine monoclonal antibodies 2C4, 7F3 and 4D5, which specifically bind to the extracellular domain of ErbB2, were prepared as described in Fendly et al., Cancer Res. 50: 1550-1558 (1990). Briefly, NIH 3T3 / HER2-3 prepared as described by Hudziak et al. (Proc. 400 cells (approximately expressing 1×10 5 ErbB2 molecule / cell), and immunized BALB / c mice with it. At 0, 2, 5 and 7 weeks, mice were intraperitoneally injected with 10 7 cells (in 0.5ml PBS). Specific antiserum (which can be compared with 32 P-labeled ErbB2 immunoprecipitation) mice were intraperitoneally injected with wheat germ agglutinin-Sepharose (WGA) purified ErbB2 membrane extracts. Afterwards 0.1 ml of ErbB2 preparation was injected intravenously, and the splenocytes were fused with the mouse myeloma cell line X63-Ag8.653.

[0326] Hybridoma cell supernatants were screened for ErbB2 binding by ELISA and radioimmunoprecipitation.

[032...

Embodiment 2

[0337] Monoclonal antibody 2C4 blocks the HRG-dependent binding of ErbB2 to ErbB3

[0338] The ability of ErbB3 to combine with ErbB2 was detected by co-immunoprecipitation assay. will be 1.0×10 6 MCF7 or SK-BR-3 cells were seeded in 6-well tissue culture plates and allowed to adhere overnight in 50:50 DMEM / Ham's F12 containing 10% fetal bovine serum (FBS) and 10 mM HEPES (pH 7.2) base (growth medium). The cells were starved for 2 hours in serum-free growth medium before the start of the experiment.

[0339]The cells were briefly washed with PBS and then either diluted with 100 nM of the indicated antibodies (diluted in 0.2% w / v bovine serum albumin (BSA) RPMI medium (pH 7.2) (binding buffer) containing 10 mM HEPES) or only with The cells were incubated with binding buffer (control). After 1 hour at room temperature, HRG was added to half of the wells at a final concentration of 5 nM (+). A similar volume of binding buffer (-) was added to the other wells. The incubation...

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Abstract

This application describes humanized anti-ErbB2 antibodies, and methods of treating cancer with anti-ErbB2 antibodies, such as humanized anti-ErbB2 antibodies.

Description

field of invention [0001] The present invention relates to humanized anti-ErbB2 antibodies and methods of treating cancer with anti-ErbB2 antibodies, such as humanized anti-ErbB2 antibodies. Background of the invention [0002] The ErbB family of receptor tyrosine kinases are important mediators in cell growth, differentiation and survival. This receptor family includes 4 different members, namely epidermal growth factor receptor (EGFR or ErbB1), HER2 (ErbB2 or p185 neu ), HER3 (ErbB3) and HER4 (ErbB4 or tyro2). [0003] There is evidence that EGFR, encoded by the erbB1 gene, is associated with human malignancies. The increased expression of EGFR is especially observed in tumors such as breast cancer, bladder cancer, lung cancer, head tumor, neck tumor, gastric cancer and glioblastoma. Increased expression of the EGFR receptor is often associated with increased production of the EGFR ligand, transforming growth factor alpha (TGF-α), in the same canc...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07K16/32A61K47/48A61P35/00A61K45/00A61K31/337A61K31/429A61K31/437A61K31/4985A61K31/513A61K31/555A61K33/243A61K39/395A61P43/00
CPCC07K2317/24A61K2039/507A61K47/48407C07K2316/96A61K2039/505C07K16/32C07K2317/73C07K2317/76A61K47/6809A61P35/00A61P43/00A61K39/395
Inventor 卡梅利亚·W·亚当斯伦纳德·G·普雷斯塔马克·斯利科斯基
Owner GENENTECH INC
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