METHODS OF TREATMENT USING ALPHA-1-ANTITRYPSIN COMPOSITIONS

摘要

A streamlined method for purifying alpha-1-antitrypsin (AAT) from an AAT-containing protein mixture, such as Coh fraction IV precipitate, is provided. In the method of the invention, contaminating proteins are destabilized by cleavage of disulfide bonds with a reducing reagent, such as dithiol, which does not affect AAT. The destabilized proteins are then preferentially adsorbed on a solid protein-adsorbing material, without the addition of a salt as a precipitante. Separation of the solid absorbent from the solution leaves a purified AAT solution that is directly suitable for chromatographic purification, without the need for extensive desalting as in prior art processes. A process incorporating this method, which provides pharmaceutical grade AAT in high yield on a commercial scale, is also described.

主权项

1. A method of treating alpha-1-antitrypsin (AAT) deficiency in a subject in need thereof, comprising administering to the subject a pharmaceutically effective amount of a pharmaceutical composition comprising alpha-1-antitrypsin (AAT) isolated or purified from plasma or fractions thereof, wherein said composition further comprises:
(a) less than 0.1% albumin; and (b) less than 0.1% apolipoprotein A1, and wherein percentages of albumin and apolipoprotein A1 are weight percentages based on total protein weight, and wherein total protein weight is measured using a Bradford assay or by absorbance at 280 nm using as an extinction coefficient E1cm, 280nm1%=5.3.