Anti-alpha-v integrin antibody for the treatment of fibrosis and/or fibrotic disorders

A technology of fibrosis and integrin, applied in the direction of antibodies, chemical instruments and methods, biochemical equipment and methods, etc., can solve problems such as inapplicability

Pending Publication Date: 2018-08-31
MERCK PATENT GMBH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0054] 2. These guidelines do not apply to patients with systemic sclerosis-like conditions that better explain their presentation, such as: nephrosclerotic fibrosis, diabetic scleredema, sclerosing myxedema, acral erythema ( erythromyalgia), porphyria, lichen sclerosus, graft-versus-host disease, and diabetic chierarthropathy

Method used

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  • Anti-alpha-v integrin antibody for the treatment of fibrosis and/or fibrotic disorders
  • Anti-alpha-v integrin antibody for the treatment of fibrosis and/or fibrotic disorders
  • Anti-alpha-v integrin antibody for the treatment of fibrosis and/or fibrotic disorders

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0315] Myofibroblast differentiation is induced in epithelial-fibroblast co-cultures and inhibited by atezolizumab

[0316] list of abbreviations

[0317] αSMA: alpha smooth muscle actin

[0318] BSA: bovine serum albumin

[0319] Cy5: Anthocyanin 5

[0320] DAPI: 4’,6-diamidino-2-phenylindole

[0321] ECM: extracellular matrix

[0322] FGM: Fibroblast Growth Medium

[0323] FMT: Fibroblast to Myofibroblast Transition

[0324] FITC: Fluorescent isothiocyanate

[0325] IXM: Image Xpress Micro Screening System

[0326] ug: microgram

[0327] mg: milligram

[0328] mL: milliliter

[0329] ng: nanogram

[0330] NHDF: normal human dermal fibroblast

[0331] NHLF: normal human lung fibroblasts

[0332] PBS: Phosphate-buffered saline

[0333] TGF-β1: transforming growth factor-β1

[0334] ELISA: enzyme-linked immunosorbent assay

[0335] FBS: fetal bovine serum

[0336] IL interleukin

[0337] overview

[0338] TGF-β1 is a potent mediator of fibroblast-to-myofibrob...

Embodiment 2

[0405] Effect of atezolizumab on TGF-β-induced FMT in human lung fibroblasts

[0406] List of icons

[0407] Figure 3: TGF-β increases integrin expression in human lung fibroblasts

[0408] Figure 4: TGF-β increases the expression of aSMA, IL-6, and other myofibroblast marker genes in lung fibroblasts

[0409] Figure 5: Atetizumab treatment of fibroblast cultures reduces TGF-β-induced increases in aSMA and IL-6

[0410] Figure 6: Atezolizumab Treatment Reduces TGF-β-Induced Collagen Gel Contraction

[0411] list of abbreviations

[0412] αSMA: alpha smooth muscle actin

[0413] BSA: bovine serum albumin

[0414] Cy5: Anthocyanin 5

[0415] DAPI: 4’,6-diamidino-2-phenylindole

[0416] ECM: extracellular matrix

[0417] FGM: Fibroblast Growth Medium

[0418] FMT: Fibroblast to Myofibroblast Transition

[0419] FITC: Fluorescent isothiocyanate

[0420] IXM: Image Xpress Micro Screening System

[0421] ug: microgram

[0422] mg: milligram

[0423] mL: milliliter ...

Embodiment 3

[0508] The effect of atezolizumab on the binding of αvβ6 to latent-associated peptide (LAP)

[0509] list of abbreviations

[0510] αSMA: alpha smooth muscle actin

[0511] ECM: extracellular matrix

[0512] ug: microgram

[0513] mg: milligram

[0514] mL: milliliter

[0515] LAP: Latent-associated peptide (LAP)

[0516] LTBP: latent TGF-beta binding protein

[0517] ng: nanogram

[0518] TGF-β1: transforming growth factor-β1

[0519] ELISA: enzyme-linked immunosorbent assay

[0520] h: human

[0521] IL: interleukin

[0522] Overview αvβ3, αvβ3, αvβ6 and αvβ8 can control the activation of TGF-β

[0523] TGF-β1 is a major pro-fibrotic cytokine that plays an important role in the development of tissue fibrosis in various organs. TGF-β1 promotes fibrosis by promoting the differentiation of tissue fibroblasts into myofibroblasts. Myofibroblasts produce extracellular matrix (ECM) proteins and are the main drivers of ECM expansion and contraction during fibrosis. TGF...

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Abstract

The invention relates to the prophylaxis and / or treatment of fibrosis and / or fibrotic diseases by means of antibodies. Above all, the invention relates to the administration of an anti-alpha-v integrin (receptor) antibody to patients suffering from fibrosis and / or fibrotic diseases, including but not limited to systemic sclerosis (SSc). More specifically, the instant invention relates to the treatment of fibrotic diseases of the skin, lung, heart, liver and / or kidney by means of said antibody. Even more specifically, the instant invention relates to the administration of a recombinant, de- immunized monoclonal antibody targeting av-integrins patients suffering from systemic sclerosis, including, but not limited to systemic sclerosis of the skin, lung, heart and / or kidney by means of the anti-alpha-v integrin antibody DI17E6 and structural mutants or modifications thereof.

Description

field of invention [0001] The present invention relates to the treatment of fibrosis and / or fibrotic diseases by antibodies. The invention further relates to the prevention of fibrosis and / or fibrotic diseases by antibodies. First, the present invention relates to the administration of anti-αv integrin (receptor) antibodies to patients suffering from fibrosis and / or fibrotic diseases, including but not limited to systemic sclerosis (SSc). More specifically, the present invention relates to the treatment of fibrotic diseases of the skin, lung, heart, liver and / or kidney by said antibodies, and / or their prevention. Even more specifically, the present invention relates to the administration of recombinant deimmunized monoclonal antibodies targeting αv integrin to patients suffering from systemic sclerosis, including but not limited to systemic sclerosis of the skin, lung, heart and / or kidney . In particular, the present invention relates to the treatment of said patients by th...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07K16/28
CPCA61K39/395C07K16/2839C12Q1/25C12Q3/00G01N33/54366A61K2039/505C07K2317/76C07K2317/73A61P1/00A61P1/16A61P11/00A61P13/12A61P17/00A61P17/02A61P29/00A61P35/00A61P43/00A61P7/00A61P9/00A61P9/14A61P3/10A61K31/343A61K45/06C12Q1/6883G01N33/6893A61K2300/00C12Q2600/158
Inventor I·策利克E·施陶布M·乌尔班S·拉布E·萨米A·本德尔G·希金博特姆Y·吴D·徐
Owner MERCK PATENT GMBH
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