Case Western Reserve University

The Cleveland Clinic Foundation

Robert G Salomon

John W Crabb

Joe G Hollyfield

Xiaorong Gu

Victor L Perez

Bela Anand-Apte

Quteba Ebrahem

Kutralanathan Reganathan

Yalun Cui

Wei Li

Nicholas D Tomko

Kutralanathan Renganathan

An isolated anti-carboxyethylpyrrole (anti-CEP) antibody or antigen binding portion thereof includes a heavy chain variable domain that includes three CDRs having at least 90% sequence identity to the three heavy chain CDRs of SEQ ID NO: 7, and a light chain variable domain that includes three CDRs having at least 90% sequence identity to the three light chain CDRs of SEQ ID NO: 8.

Anti-CEP antibody or fragment thereof

A method of measuring isolevuglandin and/or levuglandin adducts associated with oxidative injury in a subject includes obtaining a bodily sample from a subject suspected of including isolevuglandin and/or levuglandin phospholipid adducts, hydrolyzing isolevuglandin and/or levuglandin phospholipid adducts from the sample with an enzyme that forms isolevuglandin and/or levuglandin phospholipid derivatives, and determining the amount of isolevuglandin and/or levuglandin phospholipid derivatives by mass spectrometry.

Method of detecting isolevuglandin phospholipid adducts

The invention is directed to a method of producing a non-human mammal having one or more pathological characteristics of retinal degeneration and/or age-related macular degeneration. In particular, the invention provides a method of producing a non-human mammal having age-related macular degeneration (AMD). The invention is also directed to non-human animals produced by the methods described herein. Methods of identifying an agent for use in inhibiting one or more pathological characteristics of retinal degeneration and/or AMD is also encompassed by the invention. Also provided is a method of treating AMD in an individual in need thereof comprising, administering to the individual an agent identified herein.

Mouse model of retinal degeneration

The present invention pertains to methods of inhibiting angiogenesis in an individual in need thereof comprising administering to the individual an agent that inhibits one or more CEP protein adducts wherein the angiogenesis is the result of oxidative peptide modification of polyunsaturated fatty acids (PUFA) in the individual, and administration of the agent inhibits angiogenesis in the individual. In one embodiment, the invention is directed to methods of inhibiting ocular angiogenesis in an individual in need thereof comprising administering to the individual an agent that inhibits the angiogenic activity of one or more CEP protein adducts wherein administration of the. agent inhibits ocular angiogenesis in the individual. In another embodiment, the invention is directed to methods of inhibiting choroidal neovascularization in an individual in need thereof comprising administering to the individual an agent that inhibits the angiogenic activity of one or more CEP protein adducts wherein administration of the agent inhibits choroidal neovascularization in the individual.

Methods of reducing angiogenesis of age-related macular degeneration (AMD) or choroidal neovascularization by an anti-carboxyetheylpyrrole (CFP) antibody

Diagnostic methods for identifying a test subject who has or is at risk of developing age-related macular degeneration (AMD) or an analogous disease associated with oxidation of DHA-containing lipids are provided. In one aspect, the methods comprise: assaying for the presence of elevated levels of 2-(&#x3c9;-carboxyethyl) pyrrole (CEP) adducts in a bodily fluid which has been obtained from the test subject. In a preferred embodiment, such methods comprise providing an antibody that is immunospecific for CEP, contacting a bodily fluid from the subject with the anti-CEP antibody, and assaying for the formation of a complex between the antibody and an antigen in the sample. In another aspect, the methods comprise assaying for the presence of elevated levels of an antibody that binds to or is immunospecific for a CEP adduct in the bodily fluid of the test subject. The present invention also relates to CEP protein and peptide adducts, an antibody reactive with a CEP adduct and a diagnostic kit comprising such antibody.

Diagnostic methods for age related macular degeneration

Levuglandin (LG) derivatives are used as antigens for raising antibodies useful in diagnostic assays. The antibodies produced by LG-carrier protein adducts can be used to detect adducts of LGE.sub.2 with human low density lipoprotein (LDL). LGE.sub.2 -protein adduct immunoreactivity may be generated during in vitro free-radical oxidation of LDL. An enzyme-linked immunosorbent assay for detecting adducts of LGE.sub.2 with human LDL is also described.

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Cleveland, OH, United States of America

Robert G Salomon