Composition comprising material for inhibiting SCF or receptor thereof for treating or preventing diseases associated with vascular permeability

Inventors

Suh, Won Hee • Kim, Ji Yeon

Assignees

Novelty Nobility Inc

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Publication Number

US-9528112-B2

Patent

Publication Date

2016-12-27

Expiration Date


Abstract

The present invention relates to a composition comprising a material for inhibiting stem cell factor (SCF) or the receptor thereof for treating or preventing vascular permeability related diseases. Also, the present invention relates to a method for screening for an agent for treating vascular permeability related diseases, comprising the steps of: (a) treating a sample from a patient suspected of having a disease associated with vascular permeability with a candidate material; and (b) comparing the level of expression of the SCF or the receptor thereof with that of a control group. The present invention verifies SCF as a novel target for regulating vascular permeability. When the present invention is used, vascular permeability is decreased in diseases of the eye involving increased vascular permeability, thereby effectively treating or preventing vascular permeability related diseases. Also, vascular permeability can be effectively regulated using the composition. Further, the present invention can be provided as an effective means for screening an agent for treating vascular permeability related diseases by measuring the regulation of the expressions of SCF and c-Kit.

Core Innovation

The disclosure centers on stem cell factor (SCF) and the SCF receptor C-Kit (CD117) as a novel target for regulating vascular permeability in vascular endothelial cells. It reports that SCF increases endothelial or retinal vascular permeability through phosphorylation of C-Kit and downstream Akt/eNOS signaling, resulting in nitric oxide (NO) production and downstream effects on vascular endothelial junctions, including endocytosis of VE-cadherin.

The disclosure further reports that inhibiting SCF or C-Kit decreases vascular permeability. Evidence is described as including in vitro experiments and animal models, and the effects are reported in contexts including diabetic retinopathy.

A related approach described in the disclosure is to identify agents that reduce SCF/C-Kit activity or expression. The disclosure outlines measuring SCF or C-Kit, including optional C-Kit phosphorylation, in patient samples after treatment with candidate agents, and then selecting candidate agents that reduce SCF/C-Kit activity or expression.

Claims Coverage

The independent claims cover three core activities: treating or preventing vascular permeability related diseases by inhibiting SCF or its receptor in a selected patient, regulating vascular permeability by in vivo regulating SCF or receptor expression using an inhibiting composition, and screening candidate agents by comparing SCF or receptor expression in treated patient samples versus untreated controls. Across these independent claims, the inventive features repeatedly focus on SCF (stem cell factor) and the receptor thereof, with dependent refinements specifying C-Kit (CD117) and optional C-Kit phosphorylation as a readout.

Inhibiting SCF or the receptor thereof to treat or prevent vascular permeability related diseases

A method for treating or preventing vascular permeability related diseases comprising selecting a patient in need of treating or preventing the diseases and administering a composition comprising a material for inhibiting SCF (stem cell factor) or the receptor thereof to the patient.

Regulating expression of SCF or the receptor thereof in vivo by inhibition

A method for regulating vascular permeability comprising selecting a patient in need of regulating vascular permeability related diseases and regulating the expression of SCF or the receptor thereof in vivo in the patient by using a composition comprising a material for inhibiting SCF or the receptor thereof.

Screening an agent by comparing SCF or receptor expression versus untreated control

A method for screening an agent for treating vascular permeability related diseases comprising treating a sample from a patient with a candidate material, comparing the expression level of SCF or the receptor thereof with an untreated control group, and identifying a candidate material showing decreased expression level of SCF or the receptor thereof as an agent for treating vascular permeability related diseases.

Overall, the claim set ties vascular permeability regulation and therapeutic or screening decisions to SCF (stem cell factor) and its receptor thereof. The independent claims rely on inhibiting SCF or receptor activity or expression and, for screening, selecting agents that decrease SCF or receptor expression versus untreated controls; dependent claims refine the receptor to C-Kit (CD117) and include optional comparison of C-Kit phosphorylation.

Stated Advantages

Decreases vascular permeability.

Provides a method for treating or preventing vascular permeability related diseases.

Enables regulation of vascular permeability by in vivo regulating expression of SCF or the receptor thereof.

Identifies a candidate material showing decreased expression level of SCF or the receptor thereof as an agent for treating vascular permeability related diseases.

Documented Applications

Treating or preventing vascular permeability related diseases selected from non-proliferative diabetic retinopathy, ROP (retinopathy of prematurity), age-related macular degeneration, corneal dystrophy, retinoschises, Stargardt's disease, autosomal dominant druzen, Best's macular dystrophy, cystoid macular edema, ischemic retinopathy, inflammation-induced retinal degenerative disease, X-linked juvenile retinoschisis, Malattia Leventinese (ML), Doyne honeycomb retinal dystrophy, and vascular endothelial cell related inflammatory disease.

Regulating vascular permeability related diseases in vivo by regulating expression of SCF or the receptor thereof using a composition comprising a material for inhibiting SCF or the receptor thereof, for the listed disease group including non-proliferative diabetic retinopathy and ROP.

Screening an agent for treating vascular permeability related diseases by treating a patient sample with a candidate material and identifying agents that decrease the expression level of SCF or the receptor thereof versus an untreated control group.

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