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

Materials and methods for treating ocular-related disorders

a technology for ocular disorders and materials, applied in the field of materials and methods for treating ocular disorders, can solve the problems of severe vision loss and blindness, damage to and insufficient regulation of the vasculature of the ey

Inactive Publication Date: 2007-05-03
GEN VEC INC
View PDF34 Cites 10 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

The present invention provides a method for preventing or treating ocular-related disorders such as neovascularization and age-related macular degeneration. This is achieved by contacting an ocular cell with an expression vector containing a nucleic acid sequence encoding an inhibitor of angiogenesis and / or a neurotrophic agent. The nucleic acid sequence can be the same or different. The invention also provides a viral vector containing a nucleic acid sequence encoding PEDF or a therapeutic fragment thereof. The viral vector can also contain other therapeutic substances. The technical effect of this invention is the production of the inhibitor of angiogenesis and / or the neurotrophic agent to treat ocular-related disorders.

Problems solved by technology

Ocular-related disorders, while often not life threatening, necessitate life-style changes that jeopardize the independence of the afflicted individual.
Leading causes of severe vision loss and blindness are ocular-related disorders wherein the vasculature of the eye is damaged or insufficiently regulated.
Damage of the retina, i.e., retinal detachment, retinal tears, or retinal degeneration, is directly connected to vision loss.
While a common cause of retinal detachment, retinal tears, and retinal degeneration is abnormal, i.e., uncontrolled, vascularization of various ocular tissues, this is not always the case.
Atrophic complications associated with age-related macular degeneration, nonproliferative diabetic retinopathy, and inflammatory ocular damage are not associated with neovascularization, but can result in severe vision loss if not treated.
Disorders associated with both neovascular and atrophic components, such as age-related macular degeneration and diabetic retinopathy, are particularly difficult to treat due to the emergence of a wide variety of complications.
Age-related macular degeneration is the leading cause of blindness in patients over 65 years of age.
Prolonged periods of vascular leakage ultimately lead to thickening of the basement membrane and formation of soft and hard exudates.
Retinal neovascularization is the leading cause of vision loss associated with proliferative diabetic retinopathy.
For many ocular-related disorders, no efficient therapeutic options currently are available.
However, laser treatment may cause permanent blind spots corresponding to the treated areas.
Laser treatment may also cause persistent or recurrent hemorrhage, increase the risk of retinal detachment, or induce neovascularization or fibrosis.
With respect to age-related macular degeneration, many patients eventually experience severe vision loss in spite of treatment.
However, in most cases, all available treatment options have limited therapeutic effect, require repeated, costly procedures, and / or are associated with dangerous side-effects.

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

Examples

Experimental program
Comparison scheme
Effect test

example 1

[0092] This example illustrates a preferred method of obtaining expression of a factor comprising both anti-angiogenic and neurotrophic activity from an adenoviral vector in in vivo retina.

[0093] An adenoviral vector deficient in one or more essential gene functions of the E1, E3, and E4 regions of the adenoviral genome and comprising a PEDF gene (Ad.PEDF) is preferably constructed as set forth in WO 99 / 15686 (McVey et al.). However, the method of the present invention is not dependent on the method of vector construction employed and previously described methods of vector construction are also suitable. Several in vivo models of ocular neovascularization are available. Neovascularization of the retina is obtained in, for example, neonatal animals, i.e., neonatal mice, by exposing the mice to hypoxic conditions shortly after birth. Several days later, the neonatal mice are exposed to standard atmospheric conditions, resulting in ischemia-induced neovascularization of the retina.

[0...

example 2

[0096] This example demonstrates a preferred method of obtaining expression of a factor comprising both anti-angiogenic and neurotrophic activity from an adenoviral vector in in vivo choroid. The following example further provides methods for determining the effect of PEDF on neovascularization.

[0097] An adenoviral vector deficient in one or more essential gene functions of the E1, E3, and E4 regions of the adenoviral genome and comprising a PEDF gene (Ad.PEDF) is constructed as set forth in WO 99 / 15686 (McVey et al.).

[0098] An in vivo model of choroidal neovascularization can be obtained by detaching the retina of an eye of, for example, a mouse or rabbit, and debriding the pigmented epithelia. Choriocapillary regeneration is monitored in both treated and untreated eyes. Ad.PEDF is administered prior to perturbing the retinal pigment epithelial (RPE) to determine the effect of the present inventive method in preventing choroidal neovascularization. Of course, Ad.PEDF is administe...

example 3

[0100] This example demonstrates the utility of adenoviral vectors to deliver multiple doses of an exogenous nucleic acid to the eye.

[0101] Adenoviral vectors comprising the luciferase gene (Ad.L) or control adenoviral vectors comprising no transgene (Ad.null) were injected into the intravitreal space of C57BL6 mouse eyes (Day 0). One day following injection of the adenoviral vectors (Day 1), eyes infected with Ad.L were enucleated and frozen (1st administration). The eyes infected with Ad.null were divided into three groups. In Group I, Ad.L vectors were injected into the intravitreal space of the eye at Day 14 (fourteen days following the initial dose of Ad.null). Group I eyes were enucleated and frozen the day following the second administration of adenoviral vectors (Day 15, 2nd administration). Group II eyes were injected intravitreally with Ad.null at Day 14, and injected intravitreally with Ad.L vectors four weeks following the initial injection with Ad.null (Day 28, 3rd adm...

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
pHaaaaaaaaaa
areaaaaaaaaaaa
transparentaaaaaaaaaa
Login to View More

Abstract

The present invention is directed to a method of prophylactically or therapeutically treating an animal for at least one ocular-related disorder, e.g., ocular neovascularization or age-related macular degeneration. The method comprises contacting an ocular cell with an expression vector comprising a nucleic acid sequence encoding an inhibitor of angiogenesis and the same or different nucleic acid sequence encoding a neurotrophic agent. The method also can comprise contacting an ocular cell with different expression vectors, each comprising a nucleic acid sequence encoding an inhibitor of angiogenesis and / or a nucleic acid sequence encoding a neurotrophic agent. In addition, the present invention provides a viral vector comprising a nucleic acid sequence encoding pigment epithelium-derived factor (PEDF) or a therapeutic fragment thereof.

Description

CROSS-REFERENCE TO RELATED PATENT APPLICATIONS [0001] This patent application is a continuation of copending U.S. patent application Ser. No. 10 / 211,701, filed Aug. 2, 2002, which is a continuation of International Patent Application No. PCT / US01 / 04203, filed Feb. 9, 2001, which designates the U.S., and which claims the benefit of U.S. Provisional Patent Application No. 60 / 228,337, filed Aug. 28, 2000, and which also claims the benefit of U.S. Provisional Patent Application No. 60 / 181,743, filed Feb. 11, 2000, and which also is a continuation-in-part of U.S. patent application Ser. No. 09 / 599,997, filed Jun. 23, 2000, which claims the benefit of U.S. Provisional Patent Application No. 60 / 181,743, filed Feb. 11, 2000.BACKGROUND OF THE INVENTION [0002] An overwhelming majority of the world's population will experience some degree of vision loss in their lifetime. Vision loss affects virtually all people regardless of age, race, economic or social status, or geographical location. Ocul...

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): A61K48/00A61K35/76A61P27/02C12N15/09C07K14/71C07K14/81C12N15/861
CPCA61K48/00A61K48/005A61K48/0075C07K14/71C07K14/811C12N15/86C12N2710/10343C12N2799/022A61P27/02C12N15/85
Inventor KOVESDI, IMREBROUGH, DOUGLAS E.WEI, LISAMCVEY, DUNCAN L.
Owner GEN VEC 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