United States Patent:  6,057,293

Assignee:  Xoma Corporation (Berkeley, CA)

Filed:  April 26, 1999

Bactericidal/permeability increasing protein (BPI) and biologically active fragments, analogs and variants thereof are solubilized by lipid carriers including phospholipids, liposomes and nonionic detergents and stabilized against particle formation by poloxamer surfactants.

SUMMARY OF THE INVENTION

The present invention provides compositions comprising a bactericidal/permeability-increasing protein (BPI) or a biologically active polypeptide fragment, analog or variant thereof (produced by recombinant or nonrecombinant means) and a lipid carrier, particularly a nonionic detergent lipid carrier, where the BPI polypeptide is solubilized in the lipid carrier. Useful nonionic detergent lipid carriers include octoxynol-9 (TRITON X-100, Rohm & Haas), polysorbate 80 (TWEEN 80, ICI Americas, Inc., Wilmington Del..), polysorbate 20 (TWEEN 20, ICI Americas, Inc.) and laureth-4 (BRIJ 30, ICI Americas, Inc.). The nonionic detergent lipid carriers, such as polysorbate 80 solubilize/stabilize BPI polypeptides by altering (generally lowering) the surface tension of the polypeptide solution. The invention also provides a method of solubilizing/stabilizing such BPI polypeptides by contacting the polypeptide with a lipid carrier under conditions such that the polypeptide is solubilized.

The invention additionally relates to the discovery that a poloxamer surfactant is particularly useful for the solubilization/stabilization of compositions comprising an aqueous solution of BPI protein or biologically active fragments, analogs, or variants of BPI protein. The invention provides a method of solubilizing/stabilizing such polypeptides without altering the surface tension by contacting the polypeptide solution with a poloxamer surfactant, for example, poloxamer 188. The poloxamer surfactant component is preferably present in a concentration of from about 0.01% to about 1% by weight with a concentration of 0.1% to 0.2% by weight being preferred to stabilize protein solutions comprising less than or equal to 2 mg/mL.

The invention further relates to compositions comprising a bactericidal/permeability-increasing protein (BPI) or a biologically active polypeptide fragment, analog or variant thereof and a phospholipid or liposome lipid carrier wherein the polypeptide is solubilized.

Claim 1 of 3 Claims

1. A composition comprising a bactericidal/permeability-increasing protein or a biologically active BPI fragment, BPI analog or BPI variant thereof and a nonionic detergent lipid carrier wherein the BPI or biologically active BPI fragment, BPI analog or BPI variant thereof is solubilized in the lipid carrier

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