Looking for breakthrough ideas for innovation challenges? Try Patsnap Eureka!

Methods and formulations for treating vascular eye diseases

Inactive Publication Date: 2017-03-23
REGENERON PHARM INC
View PDF4 Cites 3 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

The present invention provides methods for reducing the dependence and treatment burden of frequent intravitreal injections in subjects with vascular eye disease or disorder. This is achieved by sequentially administering an initial dose followed by one or more secondary doses of a pharmaceutical composition comprising an Ang-2 inhibitor in combination with a VEGF antagonist to the subject. Additionally, a stable liquid pharmaceutical formulation comprising a VEGF antagonist, an antibody or antigen-binding fragment thereof that specifically binds to Ang-2, a buffer, a non-ionic detergent, a tonicity agent, and a stabilizer is also provided.

Problems solved by technology

However, in AMD, although ˜95% of patients maintained their vision, only approximately 30% of patients achieved an improvement of 15 or more letters in best corrected visual acuity (BCVA) at 1 year.

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Methods and formulations for treating vascular eye diseases
  • Methods and formulations for treating vascular eye diseases
  • Methods and formulations for treating vascular eye diseases

Examples

Experimental program
Comparison scheme
Effect test

example 1

Effects of Combined Inhibition of VEGF and Ang2 Using Aflibercept (VEGF Trap) and Anti-Ang2 Antibody on the Developing Retinal Angiogenesis in Mice

[0140]Introduction: VEGF is the key modulator of angiogenesis in normal and pathological angiogenesis. However, other growth factors are also involved in angiogenesis and are able to mediate blood vessel resistance to anti-VEGF therapies. Angiopoietin-2 (Ang2) was shown to be involved in blood vessel growth and regression in various circumstances in a context-dependent manner. In this study we tested the effects of VEGF blockade using aflibercept alone and in combination with Ang2 inhibition with an anti-Ang2 antibody on blood vessel growth and regression in a normal retinal vascular development (RVD) model.

[0141]Human anti-Ang-2 antibodies were generated as described in US Patent Application Publication No. US20110027286. The exemplary anti-Ang-2 antibody used in the present and following Examples is the human anti-Ang-2 antibody designa...

example 2

Effect of IVT injection of co-formulated mAb1 and aflibercept on DL-alpha-aminoadipic acid (DL-alpha-AAA)—induced retinal neovascularization (RNV) in rabbit eyes

[0147]The glial toxin DL-alpha—AAA targets retinal Muller cells and astrocytes and leads to neovascularization and chronic vascular leak lasting at least 12 months (Kato et al 1993; Neuroscience 57: 473). The purpose of this study was to evaluate the effects of IVT injection of co-formulated Anti-Ang2 and aflibercept on RNV induced by DL-alpha-AAA.

[0148]Methods: Male New Zealand White Rabbits (>2kg body weight) were treated with a single intravitreal injection of DL-alpha-AAA to induce RNV. The leak was monitored and quantitated non-invasively using fluorescein angiography (FA). Pathological vasculature and a relatively invariable leakage area were established over 13 weeks post injection. Upon disease establishment, the subjects were split into three groups for treatment, as shown below:

[0149]Group I: 125 μg / 50 μl of aflibe...

example 3

Systemic administration of mAb1 alone or co-treatment with VEGF Trap-Eye IVT on DL-AAA induced retinal neo-vascular leak in rabbit eyes

[0154]The purpose of this study was to evaluate the effects of co-treatment of Anti-Ang2 antibody and aflibercept on RNV induced by DL-alpha-AAA, wherein the intravitreal administration of aflibercept was followed by systemic administrations of mAb1. The rationale of this study was to try and maintain the suppression of leakage over longer periods of time with an initial IVT injection of aflibercept and follow up with systemic injections once in two weeks (q2w) of anti-Ang 2 antibody.

[0155]As disclosed in Example 2, retinal neovascularization was induced in male New Zealand rabbits with a single intravitreal injection of DL-alpha-AAA. Stable retinal neovascularization and vascular leak was established 10 weeks post induction. After ten weeks of disease establishment, the subjects were split into four groups with balanced leakage severity and treatmen...

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

PUM

PropertyMeasurementUnit
concentrationaaaaaaaaaa
concentrationaaaaaaaaaa
concentrationaaaaaaaaaa
Login to View More

Abstract

The present invention provides methods for treating, preventing or reducing the severity of an eye disease. The methods of the present invention comprise administering to a subject in need thereof a therapeutic composition comprising an angiopoietin-2 (Ang-2) inhibitor such as an anti-Ang-2 antibody in combination with a vascular endothelial growth factor (VEGF) antagonist (e.g., aflibercept).

Description

FIELD OF THE INVENTION[0001]The present invention relates to methods of treating or ameliorating at least one symptom or indication of a vascular eye disease comprising administering a pharmaceutical formulation comprising an angiopoietin-2 (Ang-2) inhibitor and a vascular endothelial growth factor (VEGF) antagonist to a subject in need thereof.BACKGROUND[0002]Vascular eye diseases are the leading cause of vision loss in today's aging population. These diseases are characterized by abnormal ‘leaky’ blood vessels growing into the retina. Two of the largest contributors to this patient population are diabetic retinopathy and exudative age-related macular degeneration.[0003]Diabetic retinopathy (DR) is a major cause of visual impairment in the United States (Klein et al 1984, Ophthalmology 91:1464-1474; Moss et al 1998, Ophthalmology 105:998-1003). Diabetic retinopathy results from microvascular decompensation beginning with basement membrane thickening (Ruggiero et al 1997, Diabetes M...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

Application Information

Patent Timeline
no application Login to View More
Patent Type & Authority Applications(United States)
IPC IPC(8): A61K39/395A61K9/00A61K47/26C07K16/46C07K14/71A61K47/02A61K38/17C07K16/22
CPCA61K39/3955A61K2039/505A61K9/0048C07K16/22C07K16/46C07K14/71A61K47/02A61K47/26A61K39/39591C07K2319/30C07K2319/32C07K2317/565C07K2317/21C07K2317/76A61K38/179A61K2039/54A61P27/02A61P9/10A61P3/10A61K2300/00
Inventor VITTI, ROBERT L.ERICKSON, KRISTINE A.CHU, KAREN W.WIEGAND, STANLEY J.CAO, JINGTAILOBOV, IVAN B.WADHWA, SAURABHGRAHAM, KENNETH S.DIX, DANIEL
Owner REGENERON PHARM INC
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Patsnap Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Patsnap Eureka Blog
Learn More
PatSnap group products

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic, Popular Technical Reports.

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap|About US| Contact US: help@patsnap.com