Protein formulation
AssigneeGenentech, Inc.
InventorsJames Andya, Jeffrey L. Cleland, Chung C. Hsu, Xanthe M. Lam, David E. Overcashier, Steven J. Shire, Janet Yu-Feng Yang, Sylvia Sau-Yan Wu
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Abstract
A stable lyophilized protein formulation is described which can be reconstituted with a suitable diluent to generate a high protein concentration reconstituted formulation which is suitable for subcutaneous administration. For example, anti-IgE and anti-HER2 antibody formulations have been prepared by lyophilizing these antibodies in the presence of a lyoprotectant. The lyophilized mixture thus formed is reconstituted to a high protein concentration without apparent loss of stability of the protein.
Claims47
A stable isotonic reconstituted formulation comprising an antibody in an amount of about 50 mg/mL to about 400 mg/mL and a diluent, which reconstituted formulation has been prepared from a lyophilized mixture of the antibody and a lyoprotectant which prevents or reduces chemical or physical instability of the antibody upon lyophilization and subsequent storage, wherein the molar ratio of lyoprotectant:antibody is about 100-510 mole lyoprotectant:1 mole of antibody, and wherein the antibody concentration in the reconstituted formulation is about 2-40 times greater than the antibody concentration in the mixture before lyophilization.
A stable reconstituted formulation comprising an antibody in an amount of about 50 mg/mL to about 400 mg/mL and a diluent, which reconstituted formulation has been prepared from a lyophilized mixture of an antibody and a lyoprotectant which prevents or reduces chemical or physical instability of the antibody upon lyophilization and subsequent storage, wherein the molar ratio of lyoprotectant:antibody is about 100-510 mole lyoprotectant:1 mole of antibody, and wherein the antibody concentration in the reconstituted formulation is about 2-40 times greater than the antibody concentration in the mixture before lyophilization.
A method for preparing a stable isotonic reconstituted formulation comprising reconstituting a lyophilized mixture of an antibody and a lyoprotectant which prevents or reduces chemical or physical instability of the antibody upon lyophilization and subsequent storage, wherein the molar ratio of lyoprotectant:antibody is about 100-510 mole lyoprotectant:1 mole of antibody in a diluent such that the antibody concentration in the reconstituted formulation is at least 50 mg/mL, wherein the antibody concentration in the reconstituted formulation is about 2-40 times greater than the antibody concentration in the mixture before lyophilization.
A method for preparing a formulation comprising the steps of:
- (a) lyophilizing a mixture of an antibody and a lyoprotecting amount of a lyoprotectant which prevents or reduces chemical or physical instability of the antibody upon lyophilization and subsequent storage, wherein the molar ratio of lyoprotectant:antibody is about 100-510 mole lyoprotectant:1 mole of antibody;
- and
- (b) reconstituting the lyophilized mixture of step (a) in a diluent such that the reconstituted formulation is isotonic and stable and has an antibody concentration of about 80 mg/mL to about 400 mg/mL.
An article of manufacture comprising:
- (a) a container which holds a lyophilized mixture of an antibody and a lyoprotectant which prevents or reduces chemical or physical instability of the antibody upon lyophilization and subsequent storage, wherein the molar ratio of lyoprotectant:
- antibody is about 100-510 mole lyoprotectant:1 mole of antibody;
- and
- (b) instructions for reconstituting the lyophilized mixture with a diluent to an antibody concentration in the reconstituted formulation of about 80 mg/mL to about 400 mg/mL.
A formulation comprising a lyophilized mixture of an antibody and a lyoprotectant which prevents or reduces chemical or physical instability of the antibody upon lyophilization and subsequent storage, wherein the molar ratio of lyoprotectant:antibody is about 100-510 mole lyoprotectant:1 mole antibody.
A formulation comprising anti-HER2 antibody in amount from about 5-40 mg/mL, sucrose or trehalose in an amount from about 10-100 mM, a buffer and a surfactant.
A formulation comprising anti-IgE antibody in amount from about 5-40 mg/ML, sucrose or trehalose in an amount from about 80-300 mM, a buffer and a surfactant.
A stable reconstituted formulation comprising a monoclonal antibody in an amount of about 50 mg/mL to about 400 mg/mL and a diluent, which reconstituted formulation has been prepared from a lyophilized mixture of the monoclonal antibody and a sugar selected from the group consisting of sucrose and trehalose, wherein the molar ratio of sugar:monoclonal antibody is about 100-510 mole sugar:1 mole of monoclonal antibody, and wherein the monoclonal antibody concentration in the reconstituted formulation is about 2-40 times greater than the monoclonal antibody concentration in the mixture before lyophilization.
Dependencies are inferred from the claim text.