Back to results
US 2014/0274902 A1Published application
Recombinant fviii formulations
AssigneeBayer HealthCare LLC
InventorsDeqian Wang, Xinghang Ma, Nelly Tsvetkova
Life of this patent
Estimating the term…
Abstract
Provided are liquid and lyophilized rFVIII formulations, including full-length rFVIII (FL-rFVIII) formulations, B-domain deleted rFVIII (BDD-rFVIII) formulations, and BDD-rFVIII mutant (BDD-rVIII mutant) formulations. Also provided are liquid and lyophilized PEGylated rFVIII (PEG-rFVIII) formulations, including PEGylated full-length rFVIII (PEG-FL-rFVIII) formulations, PEGylated B-domain deleted rFVIII (PEG-BDD-rFVIII) formulations, and PEGylated BDD-rFVIII mutant (PEG-BDD-rFVIII mutant) formulations.
Claims74
A full-length rFVIII (FL-rFVIII) formulation, comprising:
- a. from about 0 mM to about 20 mM or about 50 mM histidine;
- b. from about 0 mM to about 29 mM, or about 34 mM, or about 58 mM, or about 100 mM, or about 300 mM of a sugar or sugar alcohol;
- c. from about 1 mM to about 2 mM, or about 2.5 mM, or about 5 mM, or about 10 mM, or about 15 mM calcium chloride;
- d. from about 100 mM to about 150 mM, or about 200 mM, or about 220 mM, or about 250 mM sodium chloride;
- e. from about 20 ppm to about 50 ppm, or about 80 ppm, or about 100 ppm, or about 120 ppm, or about 200 ppm of a non-ionic surfactant;
- and
- f. from about 0.1 μg/ml to about 300 μg/ml, or from about 1.0 μg/ml to about 200 μg/ml, or from about 10 μg/ml to about 125 μg/ml of a FL-rFVIII;
- wherein said FL-rFVIII formulation has a pH from about pH 6.0 to about pH 6.5, or about pH 7.0, or about pH 7.5.
5 more elements
A B-domain deleted rFVIII (BDD-rFVIII) formulation, comprising:
- a. from about 0 mM to about 20 mM or about 50 mM histidine;
- b. from about 0 mM to about 29 mM, or about 34 mM, or about 58 mM, or about 100 mM, or about 300 mM of a sugar or sugar alcohol;
- c. from about 1 mM to about 2 mM, or about 2.5 mM, or about 5 mM, or about 10 mM, or about 15 mM calcium chloride;
- d. from about 100 mM to about 150 mM, or about 200 mM, or about 220 mM, or about 250 mM sodium chloride;
- e. from about 20 ppm to about 50 ppm, or about 80 ppm, or about 100 ppm, or about 120 ppm, or about 200 ppm of a non-ionic surfactant;
- and
- f. from about 0.1 μg/ml to about 300 μg/ml, or from about 1.0 μg/ml to about 200 μg/ml, or from about 10 μg/ml to about 125 μg/ml of a BDD-rFVIII;
- wherein said BDD-rFVIII formulation has a pH from about pH 6.0 to about pH 6.5, or about pH 7.0, or about pH 7.5.
5 more elements
A B-domain deleted rFVIII mutant (BDD-rFVIII-mutant) formulation, comprising:
- a. from about 0 mM to about 20 mM or about 50 mM histidine;
- b. from about 0 mM to about 29 mM, or about 34 mM, or about 58 mM, or about 100 mM, or about 300 mM of a sugar or sugar alcohol;
- c. from about 1 mM to about 2 mM, or about 2.5 mM, or about 5 mM, or about 10 mM, or about 15 mM calcium chloride;
- d. from about 100 mM to about 150 mM, or about 200 mM, or about 220 mM, or about 250 mM sodium chloride;
- e. from about 20 ppm to about 50 ppm, or about 80 ppm, or about 100 ppm, or about 120 ppm, or about 200 ppm of a non-ionic surfactant;
- and
- f. from about 0.1 μg/ml to about 300 μg/ml, or from about 1.0 μg/ml to about 200 μg/ml, or from about 10 μg/ml to about 125 μg/ml of a BDD-rFVIII-mutant;
- wherein said BDD-rFVIII-mutant formulation has a pH from about pH 6.0 to about pH 6.5, or about pH 7.0, or about pH 7.5.
5 more elements
A PEGylated full-length rFVIII (PEG FL-rFVIII) formulation, comprising:
- a. from about 0 mM to about 20 mM or about 50 mM histidine;
- b. from about 0 mM to about 29 mM, or about 34 mM, or about 58 mM, or about 100 mM, or about 300 mM of a sugar or sugar alcohol;
- c. from about 1 mM to about 2 mM, or about 2.5 mM, or about 5 mM, or about 10 mM, or about 15 mM calcium chloride;
- d. from about 100 mM to about 150 mM, or about 200 mM, or about 220 mM, or about 250 mM sodium chloride;
- e. from about 20 ppm to about 50 ppm, or about 80 ppm, or about 100 ppm, or about 120 ppm, or about 200 ppm of a non-ionic surfactant;
- and
- f. from about 0.1 μg/ml to about 300 μg/ml, or from about 1.0 μg/ml to about 200 μg/ml, or from about 10 μg/ml to about 125 μg/ml of a PEG FL-rFVIII;
- wherein said PEG FL-rFVIII formulation has a pH from about pH 6.0 to about pH 6.5, or about pH 7.0, or about pH 7.5.
5 more elements
A PEGylated B-domain deleted rFVIII (PEG-BDD-rFVIII) formulation, comprising:
- a. from about 0 mM to about 20 mM or about 50 mM histidine;
- b. from about 0 mM to about 29 mM, or about 34 mM, or about 58 mM, or about 100 mM, or about 300 mM of a sugar or sugar alcohol;
- c. from about 1 mM to about 2 mM, or about 2.5 mM, or about 5 mM, or about 10 mM, or about 15 mM calcium chloride;
- d. from about 100 mM to about 150 mM, or about 200 mM, or about 220 mM, or about 250 mM sodium chloride;
- e. from about 20 ppm to about 50 ppm, or about 80 ppm, or about 100 ppm, or about 120 ppm, or about 200 ppm of a non-ionic surfactant;
- and
- f. from about 0.1 μg/ml to about 300 μg/ml, or from about 1.0 μg/ml to about 200 μg/ml, or from about 10 μg/ml to about 125 μg/ml of a PEG-BDD-rFVIII;
- wherein said PEG-BDD-rFVIII formulation has a pH from about pH 6.0 to about pH 6.5, or about pH 7.0, or about pH 7.5.
5 more elements
A PEG BDD-rFVIII-mutant formulation, comprising:
- a. from about 0 mM to about 20 mM or about 50 mM histidine;
- b. from about 0 mM to about 29 mM, or about 34 mM, or about 58 mM, or about 100 mM, or about 300 mM of a sugar or sugar alcohol;
- c. from about 1 mM to about 2 mM, or about 2.5 mM, or about 5 mM, or about 10 mM, or about 15 mM calcium chloride;
- d. from about 100 mM to about 150 mM, or about 200 mM, or about 220 mM, or about 250 mM sodium chloride;
- e. from about 20 ppm to about 50 ppm, or about 80 ppm, or about 100 ppm, or about 120 ppm, or about 200 ppm of a non-ionic surfactant;
- and
- f. from about 0.1 μg/ml to about 300 μg/ml, or from about 1.0 μg/ml to about 200 μg/ml, or from about 10 μg/ml to about 125 μg/ml of a PEG BDD-rFVIII-mutant;
- wherein said PEG BDD-rFVIII-mutant formulation has a pH from about pH 6.0 to about pH 6.5, or about pH 7.0, or about pH 7.5.
5 more elements
A full-length rFVIII (FL-rFVIII) formulation, comprising:
- a. from about 0 mM to about 20 mM or about 50 mM MOPS;
- b. from about 0 mM to about 29 mM, or about 34 mM, or about 58 mM, or about 100 mM, or about 300 mM of a sugar or sugar alcohol;
- c. from about 1 mM to about 2 mM, or about 2.5 mM, or about 5 mM, or about 10 mM, or about 15 mM calcium chloride;
- d. from about 100 mM to about 150 mM, or about 200 mM, or about 220 mM, or about 250 mM sodium chloride;
- e. from about 20 ppm to about 50 ppm, or about 80 ppm, or about 100 ppm, or about 120 ppm, or about 200 ppm of a non-ionic surfactant;
- and
- f. from about 0.1 μg/ml to about 300 μg/ml, or from about 1.0 μg/ml to about 200 μg/ml, or from about 10 μg/ml to about 125 μg/ml of a FL-rFVIII;
- wherein said FL-rFVIII formulation has a pH from about pH 6.0 to about pH 6.5, or about pH 7.0, or about pH 7.5.
5 more elements
A B-domain deleted rFVIII (BDD-rFVIII) formulation, comprising:
- a. from about 0 mM to about 20 mM or about 50 mM MOPS;
- b. from about 0 mM to about 29 mM, or about 34 mM, or about 58 mM, or about 100 mM, or about 300 mM of a sugar or sugar alcohol;
- c. from about 1 mM to about 2 mM, or about 2.5 mM, or about 5 mM, or about 10 mM, or about 15 mM calcium chloride;
- d. from about 100 mM to about 150 mM, or about 200 mM, or about 220 mM, or about 250 mM sodium chloride;
- e. from about 20 ppm to about 50 ppm, or about 80 ppm, or about 100 ppm, or about 120 ppm, or about 200 ppm of a non-ionic surfactant;
- and
- f. from about 0.1 μg/ml to about 300 μg/ml, or from about 1.0 μg/ml to about 200 μg/ml, or from about 10 μg/ml to about 125 μg/ml of a BDD-rFVIII;
- wherein said BDD-rFVIII formulation has a pH from about pH 6.0 to about pH 6.5, or about pH 7.0, or about pH 7.5.
5 more elements
A B-domain deleted rFVIII mutant (BDD-rFVIII-mutant) formulation, comprising:
- a. from about 0 mM to about 20 mM or about 50 mM MOPS;
- b. from about 0 mM to about 29 mM, or about 34 mM, or about 58 mM, or about 100 mM, or about 300 mM of a sugar or sugar alcohol;
- c. from about 1 mM to about 2 mM, or about 2.5 mM, or about 5 mM, or about 10 mM, or about 15 mM calcium chloride;
- d. from about 100 mM to about 150 mM, or about 200 mM, or about 220 mM, or about 250 mM sodium chloride;
- e. from about 20 ppm to about 50 ppm, or about 80 ppm, or about 100 ppm, or about 120 ppm, or about 200 ppm of a non-ionic surfactant;
- and
- f. from about 0.1 μg/ml to about 300 μg/ml, or from about 1.0 μg/ml to about 200 μg/ml, or from about 10 μg/ml to about 125 μg/ml of a BDD-rFVIII-mutant;
- wherein said BDD-rFVIII-mutant formulation has a pH from about pH 6.0 to about pH 6.5, or about pH 7.0, or about pH 7.5.
5 more elements
A PEGylated full-length rFVIII (PEG FL-rFVIII) formulation, comprising:
- a. from about 0 mM to about 20 mM or about 50 mM MOPS;
- b. from about 0 mM to about 29 mM, or about 34 mM, or about 58 mM, or about 100 mM, or about 300 mM of a sugar or sugar alcohol;
- c. from about 1 mM to about 2 mM, or about 2.5 mM, or about 5 mM, or about 10 mM, or about 15 mM calcium chloride;
- d. from about 100 mM to about 150 mM, or about 200 mM, or about 220 mM, or about 250 mM sodium chloride;
- e. from about 20 ppm to about 50 ppm, or about 80 ppm, or about 100 ppm, or about 120 ppm, or about 200 ppm of a non-ionic surfactant;
- and
- f. from about 0.1 μg/ml to about 300 μg/ml, or from about 1.0 μg/ml to about 200 μg/ml, or from about 10 μg/ml to about 125 μg/ml of a PEG FL-rFVIII;
- wherein said PEG FL-rFVIII formulation has a pH from about pH 6.0 to about pH 6.5, or about pH 7.0, or about pH 7.5.
5 more elements
A PEGylated B-domain deleted rFVIII (PEG-BDD-rFVIII) formulation, comprising:
- a. from about 0 mM to about 20 mM or about 50 mM MOPS;
- b. from about 0 mM to about 29 mM, or about 34 mM, or about 58 mM, or about 100 mM, or about 300 mM of a sugar or sugar alcohol;
- c. from about 1 mM to about 2 mM, or about 2.5 mM, or about 5 mM, or about 10 mM, or about 15 mM calcium chloride;
- d. from about 100 mM to about 150 mM, or about 200 mM, or about 220 mM, or about 250 mM sodium chloride;
- e. from about 20 ppm to about 50 ppm, or about 80 ppm, or about 100 ppm, or about 120 ppm, or about 200 ppm of a non-ionic surfactant;
- and
- f. from about 0.1 μg/ml to about 300 μg/ml, or from about 1.0 μg/ml to about 200 μg/ml, or from about 10 μg/ml to about 125 μg/ml of a PEG-BDD-rFVIII;
- wherein said PEG-BDD-rFVIII formulation has a pH from about pH 6.0 to about pH 6.5, or about pH 7.0, or about pH 7.5.
5 more elements
A PEGylated B-domain deleted rFVIII-mutant (PEG BDD-rFVIII-mutant) formulation, comprising:
- a. from about 0 mM to about 20 mM or about 50 mM MOPS;
- b. from about 0 mM to about 29 mM, or about 34 mM, or about 58 mM, or about 100 mM, or about 300 mM of a sugar or sugar alcohol;
- c. from about 1 mM to about 2 mM, or about 2.5 mM, or about 5 mM, or about 10 mM, or about 15 mM calcium chloride;
- d. from about 100 mM to about 150 mM, or about 200 mM, or about 220 mM, or about 250 mM sodium chloride;
- e. from about 20 ppm to about 50 ppm, or about 80 ppm, or about 100 ppm, or about 120 ppm, or about 200 ppm of a non-ionic surfactant;
- and
- f. from about 0.1 μg/ml to about 300 μg/ml, or from about 1.0 μg/ml to about 200 μg/ml, or from about 10 μg/ml to about 125 μg/ml of a PEG BDD-rFVIII-mutant;
- wherein said PEG BDD-rFVIII-mutant formulation has a pH from about pH 6.0 to about pH 6.5, or about pH 7.0, or about pH 7.5.
5 more elements
A FL-rFVIII formulation, comprising:
- a. from about 0 mM to about 20 mM or about 50 mM histidine;
- b. from about 0 mM to about 29 mM, or about 34 mM, or about 58 mM, or about 100 mM, or about 300 mM of a sugar or sugar alcohol;
- c. from about 1 mM to about 2 mM, to about 2.5 mM, to about 5 mM calcium chloride;
- d. from about 0 mM to about 10 mM, or about 20 mM, or about 30 mM, or about 40 mM, or about 50 mM sodium chloride;
- e. from about 20 ppm to about 50 ppm, or about 80 ppm, or about 100 ppm, or about 120 ppm, or about 200 ppm of a non-ionic surfactant;
- f. from about 0 mM to about 50 mM, or about 100 mM, or about 150 mM, or about 293 mM, or about 400 mM glycine;
- and
- g. from about 0.1 μg/ml to about 300 μg/ml, or about 1.0 μg/ml to about 200 μg/ml, or about 10 μg/ml to about 125 μg/ml of a FL-rFVIII;
- wherein said FL-rFVIII formulation has a pH from about pH 6.0 to about pH 6.5, or about pH 7.0, or about pH 7.5.
6 more elements
A PEG-FL-rFVIII formulation, comprising:
- a. from about 0 mM to about 20 mM or about 50 mM histidine;
- b. from about 0 mM to about 29 mM, or about 34 mM, or about 58 mM, or about 100 mM, or about 300 mM of a sugar or sugar alcohol;
- c. from about 1 mM to about 2 mM, to about 2.5 mM, to about 5 mM calcium chloride;
- d. from about 0 mM to about 10 mM, or about 20 mM, or about 30 mM, or about 40 mM, or about 50 mM sodium chloride;
- e. from about 20 ppm to about 50 ppm, or about 80 ppm, or about 100 ppm, or about 120 ppm, or about 200 ppm of a non-ionic surfactant;
- f. from about 0 mM to about 50 mM, or about 100 mM, or about 150 mM, or about 293 mM, or about 400 mM glycine;
- and
- g. from about 0.1 μg/ml to about 300 μg/ml, or about 1.0 μg/ml to about 200 μg/ml, or about 10 μg/ml to about 125 μg/ml of a PEG-FL-rFVIII;
- wherein said PEG-FL-rFVIII formulation has a pH from about pH 6.0 to about pH 6.5, or about pH 7.0, or about pH 7.5.
6 more elements
A PEG-BDD-rFVIII formulation, comprising:
- a. from about 0 mM to about 20 mM or about 50 mM histidine;
- b. from about 0 mM to about 29 mM, or about 34 mM, or about 58 mM, or about 100 mM, or about 300 mM of a sugar or sugar alcohol;
- c. from about 1 mM to about 2 mM, to about 2.5 mM, to about 5 mM calcium chloride;
- d. from about 0 mM to about 10 mM, or about 20 mM, or about 30 mM, or about 40 mM, or about 50 mM sodium chloride;
- e. from about 20 ppm to about 50 ppm, or about 80 ppm, or about 100 ppm, or about 120 ppm, or about 200 ppm of a non-ionic surfactant;
- f. from about 0 mM to about 50 mM, or about 100 mM, or about 150 mM, or about 293 mM, or about 400 mM glycine;
- and
- g. from about 0.1 μg/ml to about 300 μg/ml, or about 1.0 μg/ml to about 200 μg/ml, or about 10 μg/ml to about 125 μg/ml of a PEG-BDD-rFVIII;
- wherein said PEG-BDD-rFVIII formulation has a pH from about pH 6.0 to about pH 6.5, or about pH 7.0, or about pH 7.5.
6 more elements
A PEG BDD-rFVIII-mutant formulation, comprising:
- a. from about 0 mM to about 20 mM or about 50 mM histidine;
- b. from about 0 mM to about 29 mM, or about 34 mM, or about 58 mM, or about 100 mM, or about 300 mM of a sugar or sugar alcohol;
- c. from about 1 mM to about 2 mM, to about 2.5 mM, to about 5 mM calcium chloride;
- d. from about 0 mM to about 10 mM, or about 20 mM, or about 30 mM, or about 40 mM, or about 50 mM sodium chloride;
- e. from about 20 ppm to about 50 ppm, or about 80 ppm, or about 100 ppm, or about 120 ppm, or about 200 ppm of a non-ionic surfactant;
- f. from about 0 mM to about 50 mM, or about 100 mM, or about 150 mM, or about 293 mM, or about 400 mM glycine;
- and
- g. from about 0.1 μg/ml to about 300 μg/ml, or about 1.0 μg/ml to about 200 μg/ml, or about 10 μg/ml to about 125 μg/ml of a PEG BDD-rFVIII-mutant;
- wherein said PEG BDD-rFVIII-mutant formulation has a pH from about pH 6.0 to about pH 6.5, or about pH 7.0, or about pH 7.5.
6 more elements
A FL-rFVIII formulation, comprising:
- a. from about 0 mM to about 20 mM or about 50 mM MOPS;
- b. from about 0 mM to about 29 mM, or about 34 mM, or about 58 mM, or about 100 mM, or about 300 mM of a sugar or sugar alcohol;
- c. from about 1 mM to about 2 mM, to about 2.5 mM, to about 5 mM calcium chloride;
- d. from about 0 mM to about 10 mM, or about 20 mM, or about 30 mM, or about 40 mM, or about 50 mM sodium chloride;
- e. from about 20 ppm to about 50 ppm, or about 80 ppm, or about 100 ppm, or about 120 ppm, or about 200 ppm of a non-ionic surfactant;
- f. from about 0 mM to about 50 mM, or about 100 mM, or about 150 mM, or about 293 mM, or about 400 mM glycine;
- and
- g. from about 0.1 μg/ml to about 300 μg/ml, or about 1.0 μg/ml to about 200 μg/ml, or about 10 μg/ml to about 125 μg/ml of a FL-rFVIII;
- wherein said FL-rFVIII formulation has a pH from about pH 6.0 to about pH 6.5, or about pH 7.0, or about pH 7.5.
6 more elements
A PEG-FL-rFVIII formulation, comprising:
- a. from about 0 mM to about 20 mM or about 50 mM MOPS;
- b. from about 0 mM to about 29 mM, or about 34 mM, or about 58 mM, or about 100 mM, or about 300 mM of a sugar or sugar alcohol;
- c. from about 1 mM to about 2 mM, to about 2.5 mM, to about 5 mM calcium chloride;
- d. from about 0 mM to about 10 mM, or about 20 mM, or about 30 mM, or about 40 mM, or about 50 mM sodium chloride;
- e. from about 20 ppm to about 50 ppm, or about 80 ppm, or about 100 ppm, or about 120 ppm, or about 200 ppm of a non-ionic surfactant;
- f. from about 0 mM to about 50 mM, or about 100 mM, or about 150 mM, or about 293 mM, or about 400 mM glycine;
- and
- g. from about 0.1 μg/ml to about 300 μg/ml, or about 1.0 μg/ml to about 200 μg/ml, or about 10 μg/ml to about 125 μg/ml of a PEG-FL-rFVIII;
- wherein said PEG-FL-rFVIII formulation has a pH from about pH 6.0 to about pH 6.5, or about pH 7.0, or about pH 7.5.
6 more elements
A PEG-BDD-rFVIII formulation, comprising:
- a. from about 0 mM to about 20 mM or about 50 mM MOPS;
- b. from about 0 mM to about 29 mM, or about 34 mM, or about 58 mM, or about 100 mM, or about 300 mM of a sugar or sugar alcohol;
- c. from about 1 mM to about 2 mM, to about 2.5 mM, to about 5 mM calcium chloride;
- d. from about 0 mM to about 10 mM, or about 20 mM, or about 30 mM, or about 40 mM, or about 50 mM sodium chloride;
- e. from about 20 ppm to about 50 ppm, or about 80 ppm, or about 100 ppm, or about 120 ppm, or about 200 ppm of a non-ionic surfactant;
- f. from about 0 mM to about 50 mM, or about 100 mM, or about 150 mM, or about 293 mM, or about 400 mM glycine;
- and
- g. from about 0.1 μg/ml to about 300 μg/ml, or about 1.0 μg/ml to about 200 μg/ml, or about 10 μg/ml to about 125 μg/ml of a PEG-BDD-rFVIII;
- wherein said PEG-BDD-rFVIII formulation has a pH from about pH 6.0 to about pH 6.5, or about pH 7.0, or about pH 7.5.
6 more elements
A PEG BDD-rFVIII-mutant formulation, comprising:
- a. from about 0 mM to about 20 mM or about 50 mM MOPS;
- b. from about 0 mM to about 29 mM, or about 34 mM, or about 58 mM, or about 100 mM, or about 300 mM of a sugar or sugar alcohol;
- c. from about 1 mM to about 2 mM, to about 2.5 mM, to about 5 mM calcium chloride;
- d. from about 0 mM to about 10 mM, or about 20 mM, or about 30 mM, or about 40 mM, or about 50 mM sodium chloride;
- e. from about 20 ppm to about 50 ppm, or about 80 ppm, or about 100 ppm, or about 120 ppm, or about 200 ppm of a non-ionic surfactant;
- f. from about 0 mM to about 50 mM, or about 100 mM, or about 150 mM, or about 293 mM, or about 400 mM glycine;
- and
- g. from about 0.1 μg/ml to about 300 μg/ml, or about 1.0 μg/ml to about 200 μg/ml, or about 10 μg/ml to about 125 μg/ml of a PEG BDD-rFVIII-mutant;
- wherein said PEG BDD-rFVIII-mutant formulation has a pH from about pH 6.0 to about pH 6.5, or about pH 7.0, or about pH 7.5.
6 more elements
Dependencies are inferred from the claim text.