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Inhibiting her2 shedding with matrix metalloprotease antagonists

A matrix metal, antagonist technology, applied in the direction of immunoglobulin, anti-animal/human immunoglobulin, antibody, etc.

Inactive Publication Date: 2008-01-30
GENENTECH INC
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

p95 levels can now only be measured by Western blot

Method used

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  • Inhibiting her2 shedding with matrix metalloprotease antagonists
  • Inhibiting her2 shedding with matrix metalloprotease antagonists
  • Inhibiting her2 shedding with matrix metalloprotease antagonists

Examples

Experimental program
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Embodiment

[0253] The examples below investigate the role of matrix metalloproteinases (MMPs) in HER2 shedding.

[0254] Materials and methods

[0255] Cell Culture and Transfection

[0256] All cell lines used in this study were obtained from the American Type Culture Collection (ATCC, Manassas, VA). BT 474, MCF-7 and SKBR-3 cells were maintained in high glucose DMEM:Ham's F12 (50:50) supplemented with 10% heat-inactivated FBS and 2 mM L-glutamine. Cos-7 cells were maintained in high glucose DMEM supplemented with 10% heat-inactivated FBS and 2 mM L-glutamine. Cell lines were supplied with 5% CO 2 maintained at 37 °C in a humidified incubator. BT 474 and SKBR-3 cells using kit V according to the manufacturer's instructions (AMAXA TM ) the transient transfection described in the electroporation method. Cos-7 cells using LIPOFECTAMINE TM 2000 (Invitrogen) according to the manufacturer's recommendations for transfection as described.

[0257] Fo5 and f2:1282 mouse xenograft tumor ...

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Abstract

The present application describes the use of antagonists of matrix metalloproteinases (MMPs), especially MMP-15, to inhibit HER2 shedding.

Description

[0001] This non-provisional application claims priority under 35 USC §119 to provisional application 60 / 651,348, filed February 9, 2005, the entire disclosure of which is hereby incorporated by reference. field of invention [0002] The present invention focuses on the use of antagonists of matrix metalloproteinases (MMPs), especially MMP-15, to inhibit HER2 shedding. Background of the invention [0003] The HER family of receptor tyrosine kinases are important mediators of cell growth, differentiation and survival. This family of receptors includes four distinct members, including epidermal growth factor receptor (EGFR, ErbB1 or HER1), HER2 (ErbB2 or p185 neu ), HER3 (ErbB3) and HER4 (ErbB4 or tyro2). [0004] EGFR, encoded by the erbB1 gene, has been causally linked to human malignancies. Specifically, elevated EGFR expression was observed in breast, bladder, lung, head, neck, and gastric cancers, as well as glioblastoma. Increased expression of the EGFR receptor is oft...

Claims

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Application Information

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IPC IPC(8): C12N15/11C12N9/64A61K39/395G01N33/574A61P35/00C12N15/113
CPCG01N33/57488C12N2310/14G01N2333/96486C12N15/1137C12N2310/53C07K16/32A61K2039/505G01N33/574C07K2319/30C12N2310/111C07K16/30C07K2316/96C07K2317/73A61P35/00A61P43/00A61K39/395C12N9/64
Inventor 肯德尔·D·凯里拉尔夫·H·施瓦尔马克·X·斯利科夫斯基
Owner GENENTECH INC
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