Method for preparing prefilled syringe formulation
AssigneeChugai Seiyaku Kabushiki Kaisha
InventorsKengo Arai, Kazunori Hirayama, Kiichi Egami, Masakazu Fukuda
Life of this patent
Estimating the term…
Abstract
An object of the present invention is to reduce formation of visually detectable particles in a formulation for injection in which a solution containing a protein is filled in a container. The present invention provides a method for determining a protein having a high risk of forming particles.
Claims17
A method for determining, in a pharmaceutical formulation comprising a protein as an active ingredient in a solution, a protein having a high risk of forming particles in a solution, the method comprising:
- constructing a three-dimensional structure model of a protein based on an amino acid sequence of the protein by homology modeling or antibody modeling;
- specifying portions, on a surface of the obtained model, corresponding to a cluster of hydrophobic residues and corresponding to a cluster of residues with a charge as a hydrophobic patch and a charged patch, respectively, and calculating areas of the patches;
- calculating a sum of areas of top 5 hydrophobic patches ranked according to the area (X((angstrom)2)), and a total area of charged patches (Y((angstrom)2));
- and
- determining that a protein having a “X+Y×1.5” value of 1,700 or greater is a protein having a high risk of forming particles in a solution,
- wherein the particles have a particle size of 40 μm or greater.
A method for determining, in a pharmaceutical formulation comprising a protein as an active ingredient in a solution, a protein having a high risk of forming particles in a solution, the method comprising:
- constructing a three-dimensional structure model of a protein based on an amino acid sequence of the protein by homology modeling or antibody modeling;
- specifying a portion, on a surface of the obtained model, corresponding to a cluster of residues with a charge as a charged patch, and calculating a total area of charged patches (Y((angstrom)2);
- and
- determining that a protein having a Y value of 600 or greater is a protein having a high risk of forming particles in a solution,
- wherein the particles have a particle size of 40 μm or greater.
A system for determining, in a pharmaceutical formulation comprising a protein as an active ingredient in a solution, a protein having a high risk of forming particles in a solution, the system comprising:
- means for constructing a three-dimensional structure model of a protein based on an amino acid sequence of the protein by homology modeling or antibody modeling;
- means for specifying, in a surface of the obtained model, a portion where hydrophobic residues are accumulated in a cluster, and a portion where residues with a charge are accumulated in a cluster as a hydrophobic patch and a charged patch, respectively, and calculating areas of the patches;
- means for calculating a sum of areas of top 5 hydrophobic patches ranked according to the area (X((angstrom)2)), and a total area of charged patches (Y((angstrom)2));
- and
- means for determining that a protein having a “X+Y×1.5” value of 1,700 or greater is a protein having a high risk of forming particles in a solution,
- wherein the particles have a particle size of 40 μm or greater.
A system for determining, in a pharmaceutical formulation comprising a protein as an active ingredient in a solution, a protein having a high risk of forming particles in a solution, the system comprising:
- means for constructing a three-dimensional structure model of a protein based on an amino acid sequence of the protein by homology modeling or antibody modeling;
- means for specifying a portion, on a surface of the obtained model, corresponding to a cluster of residues with a charge as a charged patch, and calculating a total area of charged patches (Y((angstrom)2));
- and
- means for determining that a protein having a Y value of 600 or greater is a protein having a high risk of forming particles in a solution,
- wherein the particles have a particle size of 40 μm or greater.
Dependencies are inferred from the claim text.