Anti Aβ antibody formulation
First Claim
1. A stable formulation, comprising:
- (a) a humanized version of monoclonal antibody 3D6 at a concentration of from about 1 mg/ml, to about 50 mg/ml, wherein the humanized 3D6 antibody comprises a light chain comprising the amino acid sequence of SEQ ID NO;
1 and a heavy chain comprising the amino acid sequence of residues 1-448 of SEQ ID NO;
2;
(b) histidine at a concentration of from about 5 mM to about 15 mM;
(c) mannitol in an amount of from about 2% w/v to about 6% w/v;
(d) methionine at a concentration of from about 5 mM to about 15 mM; and
(e) polysorbate in an amount of from about 0.001% w/v to about 0.01% w/v, wherein the formulation has a pH of from about 5.5 to about 6.5.
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Abstract
The present invention provides formulations for maintaining the stability of Aβ binding polypeptides, for example, Aβ antibodies. Exemplary formulations include a tonicity agent such as mannitol and a buffering agent or amino acid such as histidine. Other exemplary formulations include an antioxidant in a sufficient amount as to inhibit by-product formation, for example, the formation of high molecular weight polypeptide aggregates, low molecular weight polypeptide degradation fragments, and mixtures thereof. The formulations of the invention optionally comprise a tonicity agent, such as mannitol, and a buffering agent or amino acid such as histidine. The formulations are suitable for several different routes of administration.
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Citations
28 Claims
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1. A stable formulation, comprising:
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(a) a humanized version of monoclonal antibody 3D6 at a concentration of from about 1 mg/ml, to about 50 mg/ml, wherein the humanized 3D6 antibody comprises a light chain comprising the amino acid sequence of SEQ ID NO;
1 and a heavy chain comprising the amino acid sequence of residues 1-448 of SEQ ID NO;
2;(b) histidine at a concentration of from about 5 mM to about 15 mM; (c) mannitol in an amount of from about 2% w/v to about 6% w/v; (d) methionine at a concentration of from about 5 mM to about 15 mM; and (e) polysorbate in an amount of from about 0.001% w/v to about 0.01% w/v, wherein the formulation has a pH of from about 5.5 to about 6.5. - View Dependent Claims (2, 3, 4, 5, 6, 7)
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8. A stable unit dosage form, comprising:
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(a) a humanized version of monoclonal antibody 3D6 in an amount of from about 10 mg to about 250 mg, wherein the humanized 3D6 antibody comprises a light chain comprising the amino acid sequence of SEQ ID NO;
1 and a heavy chain comprising the amino acid sequence of residues 1-448 of SEQ ID NO;
2;(b) histidine at a concentration of from about 5 mM to about 15 mM; (c) mannitol in an amount of from about 2% w/v to about 6% w/v; (d) methionine at a concentration of from about 5 mM to about 15 mM; and (e) polysorbate in an amount of from about 0.001% w/v to about 0.01% w/v, wherein the formulation has a pH of from about 5.5 to about 6.5. - View Dependent Claims (9, 10, 11, 12, 13, 14, 15)
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16. A pharmaceutical product, comprising:
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(i) a glass vial comprising a stable humanized 3D6 antibody formulation, the formulation comprising; (a) a humanized version of monoclonal antibody 3D6 in an amount of from about 10 mg to about 250 mg, wherein the humanized 3D6 antibody comprises a light chain comprising the amino acid sequence of SEQ ID NO;
1 and a heavy chain comprising the amino acid sequence of residues 1-448 of SEQ ID NO;
2;(b) histidine at a concentration of from about 5 mM to about 15 mM; (c) mannitol in an amount of from about 2% w/v to about 6% w/v; (d) methionine at a concentration of from about 5 mM to about 15 mM; and (e) polysorbate in an amount of from about 0.001% w/v to about 0.01% w/v, wherein the formulation has a pH of from about 5.5 to about 6.5; and (ii) labeling for use comprising instructions to use the appropriate volume of the antibody formulation necessary to achieve a dose of from about 0.15 mg to about 5 mg per kg of patient body weight. - View Dependent Claims (17, 18, 19, 20, 21, 22, 23, 24)
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25. The pharmaceutical product of claim l6, wherein the 3D6 antibody is present at a concentration of from about 17 mg/ml to about 23 mg/ml.
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26. A stable formulation, comprising:
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(a) a humanized version of monoclonal antibody 3D6 at a concentration of about 20 mg/ml, wherein the humanized 3D6 antibody comprises a light chain comprising the amino acid sequence of SEQ ID NO;
1 and a heavy chain comprising the amino acid sequence of residues 1-448 of SEQ ID NO;
2;(b) L-histidine at a concentration of about 10 mM; (c) D-mannitol in an amount of about 4% w/v; (d) methionine at a concentration of about 10 mM; and (e) polysorbate-80 in an amount of about 0.005% w/v, wherein the formulation has a pH of about 6.0.
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27. A stable unit dosage form, comprising:
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(a) a humanized version of monoclonal antibody 3D6 in an amount of about 100 mg, wherein the humanized 3D6 antibody comprises a light chain comprising the amino acid sequence of SEQ ID NO;
1 and a heavy chain comprising the amino acid sequence of residues 1-448 of SEQ ID NO;
2;(b) L-histidine at a concentration of about 10 mM; (c) D-mannitol in an amount of about 4% w/v; (d) methionine at a concentration of about 10 mM; and (e) polysorbate-80 in an amount of about 0.005% w/v, wherein the formulation has a pH of about 6.0.
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28. A pharmaceutical product, comprising:
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(i) a glass vial comprising a stable humanized 3D6 antibody formulation, the formulation comprising; (a) a humanized version of monoclonal antibody 3D6 in an amount of about 100 mg, wherein the humanized 3D6 antibody comprises a light chain comprising the amino acid sequence of SEQ ID NO;
1 and a heavy chain comprising the amino acid sequence of residues 1-448 of SEQ ID NO;
2;(b) L-histidine at a concentration of about 10 mM; (c) D-mannitol in an amount of about 4% w/v; (d) methionine at a concentration of about 10 mM; and (e) polysorbate-80 in an amount of about 0.005% w/v, wherein the formulation has a pH of from about 5.5 to about 6.5;
and(ii) labeling for use comprising instructions to use the appropriate volume of the antibody formulation necessary to achieve a dose of from about 0.5 mg to about 3 mg per kg of patient body weight.
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Specification