Stable protein formulations comprising a molar excess of sorbitol
AssigneesBiocon Limited, Mylan Inc.
InventorsKala Chandramouli, Rohan Pai
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Abstract
A stable pharmaceutical formulation comprising a protein of interest, sorbitol and polyethylene glycol (PEG). The sorbitol and protein is present in a molar ratio of 550 to 700 mole of sorbitol:1 mole of protein and the PEG to protein is present in the molar ratio of 2-50:1. The formulation optionally comprising buffer. The formulation in lyophilised form is stable for at least 4 years at 2-8° C. Also provided is a process for preparing the composition and a pharmaceutical kit comprising the same.
Claims17
A stable pharmaceutical formulation comprising an anti-HER2 antibody in a molar concentration of 0.10 mM to 0.25 mM, a sugar alcohol consisting of sorbitol, a histidine buffer comprising from 1.0 mM to 3.0 mM L-histidine and from 1.5 mM to 3.0 mM L-histidine hydrochloride and polyethylene glycol (PEG), wherein the PEG has a molecular weight from 2000 g/mol to 5000 g/mol and wherein the sorbitol and the anti-HER2 antibody is present in a molar ratio of 550 to 700 mole of sorbitol:1 mole of the anti-HER2 antibody;
- wherein the PEG is present in a molar ratio of 5 to 15 mole PEG:1 mole of the anti-HER2 antibody, wherein the stable pharmaceutical formulation has a pH of 5.0-7.5.
A process for preparing a stable formulation, comprising the steps of:
- a) mixing an anti-HER2 antibody in a molar concentration of 0.10 mM to 0.25 mM and a sugar alcohol consisting of sorbitol in the molar ratio of 550-700 mole sorbitol:1 mole of the anti-HER2 antibody, a histidine buffer comprising from 1.0 mM to 3.0 mM L-histidine and from 1.5 mM to 3.0 mM L-histidine hydrochloride and polyethylene glycol PEG in the molar ratio of 5 to 15 mole PEG:1 mole of the anti-HER2 antibody, wherein the PEG has a molecular weight from 2000 g/mol to 5000 g/mol and wherein the stable formulation has a pH of 5.0-7.5;
- b) lyophilizing the mixture;
- and optionally
- c) reconstituting the lyophilized mixture of step (b) in a diluent such that the anti-HER2 antibody concentration is from 5 mg/ml to 50 mg/ml.
A pharmaceutical kit comprising:
- a) a container which holds a lyophilized mixture of an anti-HER2 antibody in a molar concentration of 0.10 mM to 0.25 mM, and a sugar alcohol consisting of sorbitol in a molar ratio of 550-700 mole sorbitol:1 mole of the anti-HER2 antibody, and polyethylene glycol PEG in a molar ratio of 5 to 15 mole PEG:1 mole of the anti-HER2 antibody, wherein the PEG has a molecular weight from 2000 g/ml to 5000 g/ml, wherein the mixture before lyophilization is buffered with a histidine buffer comprising from 1.0 mM to 3.0 mM L-histidine and from 1.5 mM to 3.0 mM L-histidine hydrochloride, wherein the mixture before lyophilization has a pH of 5.0-7.5;
- and
- b) instruction for reconstituting the lyophilized mixture with a diluent.
Dependencies are inferred from the claim text.