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Biodegradable microparticles for sustained delivery of Anti-angiogenic peptide

An anti-angiogenesis, microparticle technology, applied in the direction of cardiovascular system diseases, peptides, drug combinations, etc., can solve the problems of unfavorable patient compliance, discomfort, and low frequency of injections

Inactive Publication Date: 2020-06-19
ASCLEPIX THERAPEUTICS LLC +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Such intravitreal injections are uncomfortable to say the least, which is detrimental to patient compliance, especially when regular intravitreal injections are performed frequently, such as once a month
Therefore, there is a need for a treatment for wet AMD and other ocular disorders that provides effective but prolonged effectiveness with each treatment; thus requiring less frequent intravitreal injections

Method used

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  • Biodegradable microparticles for sustained delivery of Anti-angiogenic peptide
  • Biodegradable microparticles for sustained delivery of Anti-angiogenic peptide
  • Biodegradable microparticles for sustained delivery of Anti-angiogenic peptide

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0097] Example 1: Microparticles with Higher Lactic to Glycolic Acid Ratio Have Longer Peptide Release Relative to Microparticles with Lower Lactic to Glycolic Acid Ratio

[0098] Preparation of poly(lactide-co-glycolide) containing poly(lactide-co-glycolide) with various ratios of lactic acid (LA) to glycolic acid (GA) (LA:GA ratio) and loaded with AXT107 peptide (which has the amino acid sequence of SEQ ID NO:3) ester) "PLGA" microparticles. As an example, low lactic acid microparticles (LMP) comprising a 65:35 LA:GA ratio, medium lactic acid microparticles (MMP) comprising a 75:25 LA:GA ratio, and 85:15 LA:GA ratio were evaluated in this example. High Lactic Acid Microparticles (HMP) with a GA ratio; see figure 1 . When not elongated at a temperature above its polymer transition temperature (see figure 1 ), LMP and HMP loaded with 5% peptide were found to be roughly spherical (see Figure 2A and Figure 2B ), and has an average diameter of about 5 microns (see Figure...

Embodiment 2

[0102] Example 2: AXT107-containing microparticles reduce neovascularization and vascular leakage in vivo

[0103] The ability of AXT107-containing microparticles to treat and / or alleviate symptoms of choroidal neovascularization (CNV) and subretinal neovascularization (subretinal NV) was evaluated. CNV and subretinal NV are associated with age-related macular degeneration (AMD), and particularly "wet" AMD. Here, basically image 3 Mouse models of CNV or subretinal NV were evaluated as shown in .

[0104] Such as Figure 4A As shown in , AXT107-containing microparticles were as effective as aflibercept, an FDA-approved therapeutic agent for wet macular degeneration, in inhibiting laser-induced CNV; A). Notably, the combination of aflibercept and AXT107-containing microparticles (A+AXT107) showed additional inhibition over either treatment alone. Figure 4B AXT107-containing microparticles were shown to promote CNV regression in a dose-dependent manner.

[0105] Similarly,...

Embodiment 3

[0108] Example 3: AXT107-containing HMPs provide longer-lasting in vivo effectiveness than AXT107-containing LMPs

[0109] Such as Figure 5A As shown in, AXT107-containing HMPs provide long-term (at least until 16 weeks post-injection) in vivo efficacy in inhibiting laser-induced CNV; they promote in vivo regression of CNV following laser induction; see Figure 5B . Such as Figure 5C As shown in , AXT107-containing LMPs provided prolonged (at least until 8 weeks post-injection) in vivo efficacy in inhibiting laser-induced CNV. At 12 weeks post-injection, there appeared to be little difference between LMPs containing AXT107 and empty LMPs. Like AXT107-containing HMPs, AXT107-containing LMPs promote regression in vivo following laser induction; see Figure 5D .

[0110] Finally, AXT107-Containing HMPs Effectively Treat Vascular Leakage in Transgenic rhoVEGF Mice, a Mouse Model of Subretinal NV; see Figure 5E and Figure 5F .

[0111] These data suggest that microparti...

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Abstract

The present invention provides microparticle compositions comprising antiangiogenic peptides, as well as methods of treatment, including for macular degeneration. In various aspects and embodiments, the present invention provides microparticle compositions providing extended release of anti-angiogenic peptides. The microparticle of the present invention comprises poly(lactide-co-glycolide) (PLGA)having a having lactic acid (LA) to glycolic acid (GA) ratio (LVG) of more than 1:1; the microparticle further comprises, e.g., encapsulates, an anti-angiogenic peptide derived from the alpha 5 fibrilof type IV collagen.

Description

[0001] Cross References to Related Applications [0002] This application claims the benefit of U.S. Provisional Application No. 62 / 502,913, filed May 8, 2017, the contents of which are hereby incorporated by reference in their entirety. [0003] Federally funded research or development [0004] This invention was made with Government support under R21-EY023148 ​​awarded by the National Institutes of Health (NIH). The US Government has certain rights in this invention. Background technique [0005] Age-related macular degeneration (AMD) is currently the leading cause of vision loss. It affects more than 10 million Americans, which is more than cataracts and glaucoma combined. Wet AMD involves the growth of new blood vessels in the choroid layer behind the retina. New blood vessels tend to leak fluid, lipids, and blood. Leakage can cause scar tissue to form and stop retinal cells from functioning. Currently, the most common and effective clinical treatment for wet AMD is ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K9/16A61K38/00A61K38/04A61K38/08A61K38/10A61K38/39A61P27/02A61P9/10
CPCA61K9/0024A61K9/0051A61K9/1647A61K38/08A61K38/10A61K38/39C07K7/06C07K7/08A61K9/1617A61P27/02
Inventor 乔丹·J·格林尼兰詹·潘迪亚历山大·S·波佩尔彼得·A·坎波基亚罗金滋荣席尔瓦拉克尔·利马E罗恩·史慕丽亚当·米兰多
Owner ASCLEPIX THERAPEUTICS LLC
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