Stabilized Formulations Containing Anti-CTLA-4 Antibodies
AssigneeRegeneron Pharmaceuticals, Inc.
InventorsYuan CHENG, David B. LUDWIG, Xiaolin TANG
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Abstract
The present invention provides liquid and lyophilized pharmaceutical formulations comprising an antibody that specifically binds to human cytotoxic T-lymphocyte-associated protein 4 (hCTLA-4). The formulations may contain, in addition to an anti-CTLA-4 antibody, a buffer, at least one sugar, or at least one non-ionic surfactant. The pharmaceutical formulations of the present invention exhibit a substantial degree of antibody stability after storage for several months and after being subjected to thermal and other physical stresses.
Claims36
1-15. (canceled)
The stable pharmaceutical formulation of claim 27, wherein the antibody comprises a heavy chain comprising the amino acid sequence of residues 1-445 of SEQ ID NO:
- 9 and a light chain comprising the amino acid sequence of SEQ ID NO:
- 10.
The stable pharmaceutical formulation of claim 27, wherein the antibody comprises a heavy chain comprising the amino acid sequence of SEQ ID NO:
- 9 and a light chain comprising the amino acid sequence of SEQ ID NO:
- 10.
18-23. (canceled)
A stable liquid pharmaceutical formulation comprising, in an aqueous solution:
- (i) a human antibody that specifically binds to human cytotoxic T-lymphocyte-associated protein 4 (hCTLA-4) at a concentration of from 5±0.5 mg/ml to 150±15 mg/ml, wherein the antibody comprises a HCVR comprising HCDR1, HCDR2, and HCDR3 domains comprising the amino acid sequences of SEQ ID NOs:
- 3, 4, and 5, respectively, and LCDR1, LCDR2, and LCDR3 domains comprising the amino acid sequences of SEQ ID NOs:
- 6, 7, and 8, respectively;
- (ii) 5 mM to 25 mM histidine;
- (iii) 3% w/v to 12% w/v sucrose;
- and
- (iv) 0.05% w/v to 0.25% w/v polysorbate 20,
- wherein the aqueous solution has a pH of from 5.8 to 6.2.
A stable lyophilized pharmaceutical formulation of an antibody that specifically binds to human cytotoxic T-lymphocyte-associated protein 4 (hCTLA-4), made by lyophilizing an aqueous solution comprising:
- (i) a human antibody that specifically binds to human cytotoxic T-lymphocyte-associated protein 4 (hCTLA-4) at a concentration of from 5±0.5 mg/ml to 150±15 mg/ml, wherein the antibody comprises a HCVR comprising HCDR1, HCDR2, and HCDR3 domains comprising the amino acid sequences of SEQ ID NOs:
- 3, 4, and 5, respectively, and LCDR1, LCDR2, and LCDR3 domains comprising the amino acid sequences of SEQ ID NOs:
- 6, 7, and 8, respectively;
- (ii) 5 mM to 25 mM histidine;
- (iii) 3% w/v to 12% w/v sucrose;
- and
- (iv) 0.05% w/v to 0.25% w/v polysorbate 20,
- wherein the aqueous solution has a pH of from 5.8 to 6.2.
29-33. (canceled)
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38-39. (canceled)
41-45. (canceled)
47-50. (canceled)
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54-56. (canceled)
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66-67. (canceled)
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Dependencies are inferred from the claim text.