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Peptides and peptide mimetics to treat pathologies associated with eye disease

a technology of pathologies and peptides, applied in the field of atherosclerosis, can solve problems such as death and disability, affecting the quality of life, and affecting the ability to recognize faces and day-to-day tasks, and achieve the effects of reducing the risk of death and disability, and reducing the risk of eye diseas

Inactive Publication Date: 2011-07-28
UAB RES FOUND
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

This patent describes new compositions and methods for treating vascular conditions and inflammation-related diseases in mammals. The invention provides peptides that can reduce symptoms of atherosclerosis, a condition that causes the hardening and narrowing of arteries, and also protect phospholipids from oxidation. These peptides can be used alone or in combination with other peptides or other compounds to create new treatments for these conditions. The peptides are designed to form specific structures and can be modified to improve their effectiveness. Overall, this patent provides new tools to help develop better treatments for vascular and inflammatory diseases.

Problems solved by technology

However, heart attack and stroke remain the major cause of death and disability, particularly in the United States and in Western European countries.
For the patient it compromises dramatically quality of life, since they lose their ability to read, to recognize faces and day-to-day tasks become major obstacles.
It causes a rapid, irreversible vision loss due to leakage, bleeding, and scaring (Ambati et al.

Method used

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  • Peptides and peptide mimetics to treat pathologies associated with eye disease
  • Peptides and peptide mimetics to treat pathologies associated with eye disease
  • Peptides and peptide mimetics to treat pathologies associated with eye disease

Examples

Experimental program
Comparison scheme
Effect test

example 1

Use of ApoJ-Related Peptides to Mediate Symptoms of Atherosclerosis

Prevention of LDL-Induced Monocyte Chemotactic Activity

[0360]FIG. 1 illustrates a comparison of the effect of D-4F (Anantharamaiah et al. (2002) Circulation, 105: 290-292) with the effect of an apoJ peptide made from D amino acids (D-J336, Ac-L-L-E-Q-L-N-E-Q-F-N-W-V-S-R-L-A-N-L-T-Q-G-E-NH2, SEQ ID NO:1177)) on the prevention of LDL-induced monocyte chemotactic activity in vitro in a co-incubation. Human aortic endothelial cells were incubated with medium alone (no addition), with control human LDL (200 μg protein / ml) or control human LDL+ control human HDL (350 μg HDL protein / ml). D-J336 or D-4F was added to other wells in a concentration range as indicated plus control human LDL (200 μg protein / ml). Following overnight incubation, the supernatants were assayed for monocyte chemotactic activity. As shown in FIG. 1, the in vitro concentration of the apoJ variant peptide that prevents LDL-induced monocyte chemotactic a...

example 2

Oral G* Peptides Increase HDL Protective Capacity in Apo E Deficient Mice

[0373]Female, 4 month old apoE deficient mice (n=4 per group) were treated with G* peptides having the following amino acid sequences. Peptide 113-122=Ac-LVGRQLEEFL-NH2(SEQ ID NO. 9), Peptide 336-357=Ac-LLEQLNEQFNWVSRLANLTQGE-NH2 (SEQ ID NO. 17), and Peptide 377-390=Ac-PSGVTEVVVKLFDS-NH2 (SEQ ID NO. 19).

[0374]Each mouse received 200.mu.g of the peptide by stomach tube. Four hours later blood was obtained, plasma separated, lipoproteins fractionated and HDL (at 25 μg per ml) was assayed for protective capacity against the oxidation of LDL (at 100 μg per ml) in cultures of human artery wall cells. The data are shown in FIG. 8. The peptide afforded significant HDL-protective capacity in the mice.

[0375]In another experiment, female, 4 month old apoE deficient mice (n=4 per group) were treated with the 11 amino acid G* peptide 146-156 with the sequence: Ac-QQTHMLDVMQD-NH2. (SEQ ID NO:11). The mice received the pepti...

example 3

Solution Phase Chemistry for Peptide Synthesis

[0376]In certain embodiments, a solution-phase synthesis chemistry provides a more economical means of synthesizing peptides of this invention.

[0377]Prior to this invention synthesis was typically performed using an all-solid phase synthesis chemistry. The solid phase synthesis of peptides of less than 9 amino acids is much more economical than the solid phase synthesis of peptides of more than 9 amino acids. Synthesis of peptides of more than 9 amino acids results in a significant loss of material due to the physical dissociation of the elongating amino acid chain from the resin. The solid phase synthesis of peptides containing less than 9 amino acids is much more economical because the there is relatively little loss of the elongating chain from the resin.

[0378]In certain embodiments, the solution phase synthesis functions by converting the synthesis of the 18 amino acid apoA-I mimetic peptide, 4F (and other related peptides) from an a...

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Abstract

This invention provides novel active agents (e.g. peptides, small organic molecules, amino acid pairs, etc.) peptides that ameliorate one or more symptoms of eye disease and / or other pathologies characterized by an inflammatory response, hi certain embodiment, the peptides resemble a G* amphipathic helix of apolipoprotein J. The agents are highly stable and readily administered via an oral route or via intraocular injection.

Description

CROSS-REFERENCE TO RELATED PATENT APPLICATIONS[0001]This application claims priority to U.S. application Ser. No. 12 / 027,728, titled Peptides and Peptide Mimetics to Treat Pathologies Associated with Eye Disease, filed on Feb. 7, 2008, which is incorporated herein by reference in their entirety for all purposes.STATEMENT AS TO RIGHTS TO INVENTIONS MADE UNDER FEDERALLY SPONSORED RESEARCH AND DEVELOPMENT[0002]This invention was made with government support under Grant No: HL30568 and Grant No: ey 06109 awarded by the National Heart Blood Lung Institute of the National Institutes of Health and the National Eye Institute. The Government of the United States of America has certain rights in the invention.FIELD OF THE INVENTION[0003]This invention relates to the field of atherosclerosis and other conditions characterized by inflammation and / or the formation of various oxidized species. In particular, this invention pertains to the identification of classes of active agents that are orally...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): A61K38/10A61K38/16A61K39/395A61K38/20A61K38/21A61K38/22A61K38/19A61P27/02A61P27/06A61K9/14
CPCA61K9/0019A61K9/0048A61K45/06A61K38/16A61K38/1709A61K38/10A61P27/02A61P27/06
Inventor ANANTHARAMAIAH, GATTADAHALLI M.RUDOLF, MARTIN
Owner UAB RES FOUND
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