Protein formulation
DCFirst Claim
1. 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.
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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.
694 Citations
47 Claims
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1. 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. - View Dependent Claims (2, 3, 4, 5, 6, 7, 34, 35, 36, 37, 38, 39, 40, 41)
- antibody is about 100-510 mole lyoprotectant;
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8. 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. - View Dependent Claims (9, 10, 11, 12)
- antibody is about 100-510 mole lyoprotectant;
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13. 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. - View Dependent Claims (14, 15, 16)
- antibody is about 100-510 mole lyoprotectant;
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17. A method for preparing a formulation comprising the steps of:
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(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. - View Dependent Claims (18, 19, 20)
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21. An article of manufacture comprising:
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(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. - View Dependent Claims (22, 23, 24, 42, 43)
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25. 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. - View Dependent Claims (44, 45, 46)
- antibody is about 100-510 mole lyoprotectant;
- 26. 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.
- 32. 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.
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47. 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.
- monoclonal antibody is about 100-510 mole sugar;
Specification