The Rockefeller University

Amgen Inc.

Mark M Wurfel

Samuel D Wright

Peter Eric Hailman

Henri Stephen Lichenstein

David Edwin Lyons

The present invention relates to compositions and methods for neutralizing lipopolysaccharide, and treatment of gram-negative sepsis based therein. Accordingly, the invention is directed to a composition of homogeneous particles comprising phospholipids and a lipid exchange protein, such as phospholipid transfer protein or LPS binding protein. The lipid exchange protein is characterized by being capable of facilitating an exchange protein of lipopolysaccharide into the particles. In a specific embodiment, exemplified herein, the lipid particles are high density lipoprotein particles comprising apolipoprotein A-I (apo A-I), a phospholipid, and cholesterol or a lipid bilayer binding derivative thereof. In a specific example, the phospholipid is phosphatidylcholine (PC). In a specific example, the ratio of phosphatidylcholine:cholesterol:apolipoprotein A-I is approximately 80:4:1. The levels of LPS exchange protein activity in a sample from a patient provides a diagnostic, monitoring, or prognostic indicator for a subject with endotoxemia, gram-negative sepsis, or septic shock.

Compositions for neutralization of lipopolysaccharides

The invention relates to a novel human serum protein and nucleic acid referred to as AFM, which has one or more activities in common with human serum albumin, human a-fetoprotein, or human vitamin D binding protein and which has an apparent molecular weight by SDS-PAGE of 87 kd; variants thereof; and related genes, vectors, cells and methods.

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New York, NY, United States of America

Mark M Wurfel