Anti Aβ antibody formulation
View Patent ↗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.
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.
2. The formulation of claim 1 , wherein the antibody is present at a concentration of from about 17 mg/ml to about 23 mg/ml.
3. The formulation of claim 2 , wherein the histidine is present at a concentration of from 8 mM to 12 mM.
4. The formulation of claim 3 , wherein the mannitol is present in an amount of from 3% w/v to 5% w/v.
5. The formulation of claim 4 , wherein the methionine is present at a concentration of from 8 mM to 12 mM.
6. The formulation of claim 5 , wherein the polysorbate is present in an amount of from 0.003% w/v to 0.007% w/v.
7. The formulation of claim 6 , wherein the pH is from 5.8 to 6.2.
8. A stable unit dosage form, 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.
9. The unit dosage form of claim 8 , wherein the antibody is present in an amount of from 80 mg to 120 mg.
10. The unit dosage form of claim 9 , wherein the histidine is present at a concentration of from 8 mM to 12 mM.
11. The unit dosage form of claim 10 , wherein the mannitol is present in an amount of from 3% w/v to 5% w/v.
12. The unit dosage form of claim 11 , wherein the methionine is present at a concentration of from 8 mM to 12 mM.
13. The unit dosage form of claim 12 , wherein the polysorbate is present in an amount of from 0.003% w/v to 0.007% w/v.
14. The unit dosage form of claim 13 , wherein the pH is from 5.8 to 6.2.
15. The unit dosage form of claim 8 , wherein the 3D6 antibody is present at a concentration of from about 17 mg/ml to about 23 mg/ml.
16. A pharmaceutical product, comprising:
(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.
17. The pharmaceutical product of claim 16 , wherein the antibody is present in an amount of from 80 mg to 120 mg.
18. The pharmaceutical product of claim 17 , wherein the histidine is present at a concentration of from 8 mM to 12 mM.
19. The pharmaceutical product of claim 18 , wherein the mannitol is present in an amount of from 3% w/v to 5% w/v.
20. The pharmaceutical product of claim 19 , wherein the methionine is present at a concentration of from 8 mM to 12 mM.
21. The pharmaceutical product of claim 20 , wherein the polysorbate is present in an amount of from 0.003% w/v to 0.007% w/v.
22. The pharmaceutical product of claim 21 , wherein the pH is from 5.8 to 6.2.
23. The pharmaceutical product of claim 22 , wherein the dose is from about 0.5 mg to about 3 mg per kg of patient body weight.
24. The pharmaceutical product of claim 23 , wherein the dose is from about 1 mg to about 2 mg per kg of patient body weight.
25. The pharmaceutical product of claim l 6 , wherein the 3D6 antibody is present at a concentration of from about 17 mg/ml to about 23 mg/ml.
26. A stable formulation, comprising:
(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.
27. A stable unit dosage form, 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 about 6.0.
28. A pharmaceutical product, comprising:
(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.