Stabilized liquid polypeptide-containing pharmaceutical compositions
AssigneeChiron Corporation
InventorsBao-Lu Chen, Maninder S. Hora
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Abstract
Stabilized liquid polypeptide-containing pharmaceutical compositions are provided. The compositions comprise an amino acid base, which serves as the primary stabilizing agent of the polypeptide, and an acid and/or its salt form to buffer the solution within an acceptable pH range for stability of the polypeptide. The compositions are near isotonic. Methods for increasing stability of a polypeptide in a liquid pharmaceutical composition and for increasing storage stability of such a pharmaceutical composition are also provided.
Claims46
A liquid pharmaceutical composition comprising tissue factor pathway inhibitor (TFPI) or variant thereof as a therapeutically active component, wherein said composition has been prepared by a method comprising the step of combining said TFPI or variant thereof with at least one amino acid and a buffering agent that is an acid substantially free of its salt form, wherein said amino acid is at least one of amino acids arginine in its free base form and lysine in its free base, said composition has a pH within a range of about pH 4.0 to about pH 9.0, and said variant thereof has at least 70% sequence identity with said TFPI as calculated using the ALIGN program with a PAM 120 weight residue table, a gap length penalty of 12, and a gap penalty of 4.
A method for preparing a liquid pharmaceutical composition comprising tissue factor pathway inhibitor (TFPI) or variant thereof, said method comprising combining said TFPI or variant thereof with at least one amino acid and a buffering agent that is an acid substantially free of its salt form, wherein said amino acid is at least one of amino acids arginine in its free base form and lysine in its free base, said composition having a pH within a range of about pH 4.0 to about pH 9.0, and said variant thereof has at least 70% sequence identity with said TFPI.
A method for preparing a liquid pharmaceutical composition comprising tissue factor pathway inhibitor (TFPI) or variant thereof, said method comprising combining said TFPI or variant thereof with arginine in its free base form and succinic acid substantially free of its salt form, wherein about 175 mM to about 325 mM arginine in its free base form and about 80 mM to about 190 mM succinic acid are combined with said TFPI or variant thereof, said variant thereof having at least 70% sequence identity with said TFPI.
A method for preparing a liquid pharmaceutical composition comprising tissue factor pathway inhibitor (TFPI) or variant thereof, said method comprising combining said TFPI or variant thereof with arginine in its free base form and citric acid substantially free of its salt form, wherein about 175 mM to about 400 mM arginine in its free base form and about 40 mM to about 200 mM citric acid are combined with said TFPI or variant thereof, said variant thereof having at least 70% sequence identity with said TFPI.
Dependencies are inferred from the claim text.