Formulations that inhibit protein aggregation
AssigneeAmgen Inc.
InventorsStephen Brych, Masazumi Matsumura
Life of this patent
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Abstract
Disclosed is a stable pharmaceutically acceptable formulation containing a pharmaceutically acceptable amount of a protein. Also disclosed are methods for preparing such formulations and methods for inhibiting protein aggregate formation induced by physical stresses associated with processing, manufacture, shipping, and storing protein formulations, particularly freeze/thaw stress.
Claims31
A formulation comprising:
- a) a pharmaceutically acceptable amount of an antibody selected from the group consisting of antibody A, antibody B, antibody C, antibody D, antibody E, or fragments thereof;
- b) a buffer;
- and
- c) an inhibitor of insoluble aggregate formation.
A method for stabilizing a protein formulation against aggregate formation induced by one or more freeze/thaw cycles comprising:
- (a) selecting a buffer system, prior to the at least one freeze/thaw cycle;
- (b) contacting the buffer system of (a) with an amount of an inhibitor of insoluble aggregate formation effective to inhibit insoluble aggregate formation, prior to the at least one freeze/thaw cycle;
- and
- (c) contacting the buffer system and inhibitor of insoluble aggregate formation of (b), with an amount of a protein or protein fragment, prior to the at least one freeze/thaw cycle.
A method for inhibiting protein aggregate formation in a protein solution that is subjected to one or more freeze/thaw cycles comprising:
- (a) selecting a buffer system, prior to the at least one freeze/thaw cycle;
- (b) contacting the buffer system of (a) with an amount of an inhibitor of insoluble aggregate formation effective to inhibit insoluble aggregate formation, prior to the at least one freeze/thaw cycle;
- and
- (c) contacting the buffer system and inhibitor of insoluble aggregate formation of (b), with an amount of a protein or protein fragment, prior to the at least one freeze/thaw cycle.
A method for inhibiting protein aggregate formation induced by one or more freeze/thaw cycles comprising contacting a solution comprising a protein or protein fragment with an amount of an inhibitor of insoluble aggregate formation prior to, during, or after the at least one freeze/thaw cycle.
A method for preparing a protein formulation stabilized against protein aggregate formation induced by one or more freeze/thaw cycles comprising:
- (a) selecting a buffer system;
- (b) contacting the buffer system of (a) with an amount of an inhibitor of insoluble aggregate formation effective to inhibit insoluble aggregate formation;
- and
- (c) contacting the buffer system and inhibitor of insoluble aggregate formation of (b), with an amount of a protein or protein fragment, prior to the at least one freeze/thaw cycle.
A protein formulation having increased stability against insoluble aggregate formation induced by one or more freeze/thaw cycles, comprising:
- a) a protein or protein fragment;
- b) an amount effective to inhibit insoluble aggregate formation of an inhibitor of insoluble aggregate formation selected from MgCl2, propylene glycol, Pluronic-F68, Poloxamer 188, or ethanol;
- and
- c) a buffer system.
A method for stabilizing a protein formulation against aggregate formation induced by agitation stress comprising:
- (a) selecting a buffer system, prior to the agitation stress;
- (b) contacting the buffer system of (a) with an amount of an inhibitor of insoluble aggregate formation effective to inhibit insoluble aggregate formation, prior to the agitation stress;
- and
- (c) contacting the buffer system and inhibitor of insoluble aggregate formation of (b), with an amount of a protein or protein fragment, prior to the agitation stress.
A method for inhibiting protein aggregate formation in a protein solution that is subjected to agitation stress comprising:
- (a) selecting a buffer system, prior to the agitation stress;
- (b) contacting the buffer system of (a) with an amount of an inhibitor of insoluble aggregate formation effective to inhibit insoluble aggregate formation, prior to the agitation stress;
- and
- (c) contacting the buffer system and inhibitor of insoluble aggregate formation of (b), with an amount of a protein or protein fragment, prior to the agitation stress.
A method for inhibiting protein aggregate formation induced by agitation stress comprising contacting a solution comprising a protein or protein fragment with an amount of an inhibitor of insoluble aggregate formation prior to, during, or after the agitation stress.
A method for preparing a protein formulation stabilized against protein aggregate formation induced by agitation stress comprising:
- (a) selecting a buffer system;
- (b) contacting the buffer system of (a) with an amount of an inhibitor of insoluble aggregate formation effective to inhibit insoluble aggregate formation;
- and
- (c) contacting the buffer system and inhibitor of insoluble aggregate formation of (b), with an amount of a protein or protein fragment, prior to the agitation stress.
A protein formulation having increased stability against insoluble aggregate formation induced by agitation stress, comprising:
- a) a protein or protein fragment;
- b) an amount effective to inhibit insoluble aggregate formation of an inhibitor of insoluble aggregate formation selected from MgCl2, propylene glycol, Pluronic-F68, Poloxamer 188, or ethanol;
- and
- c) a buffer system.
Dependencies are inferred from the claim text.