Back to results
US 6,320,029 B1Granted
Methods of production and use of liquid formulations of plasma proteins
AssigneesAmerican National Red Cross, The Coalition for Hemophilia B
InventorsShirley I. Miekka, William N. Drohan, Thomas R. Jameson, John R. Taylor, Jr., Manish S. Singh
Life of this patent
Estimating the term…
Abstract
The present invention relates to the preparation and use of liquid formulations of plasma proteins, particularly blood coagulation factors. More specifically, the present invention relates to stable liquid formulations of Factor VIII and Factor IX that can be administered by injection or infusion to provide a constant level of the coagulation factor in the blood.
Claims22
A method of delivering a plasma protein to a mammal in need thereof, said method comprising the steps of:
- (a) preparing a stable (at least 30 days at 37° C.) liquid formulation of at least one plasma protein selected from the group consisting of:
- (i) a stable aqueous liquid formulation of at least one plasma protein, (ii) a stable non-aqueous liquid formulation of at least one plasma protein, and (iii) a stable mixed aqueous and non-aqueous liquid formulation of at least one plasma protein;
- (b) incorporating said stable liquid formulation of at least one plasma protein into a continuous administration system;
- and
- (c) introducing said continuous administration system into amammal in need of said plasma protein,
- wherein said plasma protein is delivered from said continuous administration system into said mammal, and
- wherein said stable aqueous liquid formulation of at least one plasma protein is selected from the group consisting of:
- (i) a stable aqueous liquid formulation comprising:
- (a) a plasma protein;
- (b) a pH buffering compound;
- (c) a source of calcium ions;
- (d) an osmotic modulating agent in a concentration of 1-500 mM;
- and (e) water;
- (ii) a stable aqueous liquid formulation comprising:
- (a) aplasma protein;
- (b) a pH buffering compound;
- (c) calcium chloride in a concentration of 0. 1-40 mM;
- (d) an osmotic modulating agent;
- and (e) water;
- and
- (iii) a stable aqueous liquid formulation comprising:
- (a) a plasma protein;
- (b) a pH buffering compound in a concentration of 0.1-100 mM;
- (c) a source of calcium ions;
- (d) an osmotic modulating agent;
- and (e) water, and
- wherein said stable non-aqueous liquid formulation comprises:
- (a) a plasma protein;
- and (b) a non-aqueous liquid, and contains substantially no water, and
- wherein said stable mixed aqueous and non-aqueous liquid formulation of a plasma protein comprises:
- (a) a plasma protein;
- (b) a non-aqueous liquid selected from the group consisting of:
- glycerol, dimethyl sulfoxide (DM SO), ethylene glycol, diethylene glycol, triethylene glycol, PEG 200, PEG 300, PEG 400, dipropylene glycol, tripropylene glycol, PPG 425, PPG 725, PPG 1000, PPG 2000, PPG 3000 and PPG 4000;
- and (c) water.
31 more elements
The method according to claim 1, wherein said non-aqueous liquid is a hydrophilic non-aqueous liquid.
- 13.The method according to claim 12, wherein said hydrophilic non-aqueous liquid is a polyethylene glycol or a polypropylene glycol.
A method of delivering a plasma protein to a mammal in need thereof, said method comprising the steps of:
- (a) preparing a stable (at least 30 days at 37° C.) liquid formulation of at least one plasma protein selected from the group consisting of:
- (i) a stable aqueous liquid formulation of at least one plasma protein, (ii) a stable non-aqueous liquid formulation of at least one plasma protein, and (iii) a stable mixed aqueous and non-aqueous liquid formulation of at least one plasma protein;
- and
- (b) introducing said stable liquid formulation of at least one plasma protein into a mammal in need thereof,
- wherein said plasma protein is delivered into said mammal, and
- wherein said stable aqueous liquid formulation of at least one plasma protein is selected from the group consisting of:
- (i) a stable aqueous liquid formulation comprising:
- (a) a plasma protein;
- (b) a pH buffering compound;
- (c) a source of calcium ions;
- (d) an osmotic modulating agent in a concentration of 1-500 mM;
- and (e) water;
- (ii) a stable aqueous liquid formulation comprising:
- (a) a plasma protein;
- (b) a pH buffering compound;
- (c) calcium chloride in a concentration of 0. 1-40 mM;
- (d) an osmotic modulating agent;
- and (e) water;
- and
- (iii) a stable aqueous liquid formulation comprising:
- (a) a plasma protein;
- (b) a pH buffering compound in a concentration of 0.1-100 mM;
- (c) a source of calcium ions;
- (d) an osmotic modulating agent;
- and (e) water, and
- wherein said stable non-aqueous liquid formulation comprises:
- (a) a plasma protein;
- and (b) a non-aqueous liquid, and contains substantially no water, and
- wherein said stable mixed aqueous and non-aqueous liquid formulation of a plasma protein comprises:
- (a) a plasma protein;
- (b) a non-aqueous liquid selected from the group consisting of:
- glycerol, dimethyl sulfoxide (DM SO), ethylene glycol, diethylene glycol, triethylene glycol, PEG 200, PEG 300, PEG 400, dipropylene glycol, tripropylene glycol, PPG 425, PPG 725, PPG 1000, PPG 2000, PPG 3000 and PPG 4000;
- and (c) water.
30 more elements
Dependencies are inferred from the claim text.