Stable Formulations Comprising A Bispecific EGFR/C-Met Antibody
AssigneeJanssen Biotech, Inc.
InventorsJessica Kupec, Melissa Schreyer, Patrick Stahl, Satyen Torne
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Abstract
Provided herein are stable aqueous pharmaceutical compositions comprising formulations of a bispecific epidermal growth factor receptor (EGFR)/hepatocyte growth factor receptor (c-Met) antibody and methods of preparing the same. Also provided herein are methods of treating cancer in a subject in need thereof by administering to the subject the stable aqueous pharmaceutical compositions as disclosed herein. Further provided herein are kits and articles of manufacture comprising the stable aqueous pharmaceutical compositions as disclosed herein.
Claims33
A stable aqueous pharmaceutical composition comprising:
- a) about 44 mg/mL to about 56 mg/mL of a bispecific epidermal growth factor receptor (EGFR)/hepatocyte growth factor receptor (c-Met) antibody, the bispecific antibody comprising:
- a first heavy chain (HC1) comprising a HC1 variable region 1 (VH1);
- a first light chain (LC1) comprising a light chain variable region 1 (VL1);
- a second heavy chain (HC2) comprising a HC2 variable region 2 (VH2);
- and
- a second light chain (LC2) comprising a light chain variable region 2 (VL2),
- wherein the VH1 comprises a heavy chain complementarity determining region 1 (HCDR1), a HCDR2 and a HCDR3 amino acid sequences of SEQ ID NOs:
- 1, 2, and 3, respectively;
- the VL1 comprises a light chain complementarity determining region 1 (LCDR1), a LCDR2 and a LCDR3 amino acid sequences of SEQ ID NOs:
- 4, 5 and 6, respectively, the VH2 comprises the HCDR1, the HCDR2 and the HCDR3 amino acid sequences of SEQ ID NOs:
- 7, 8 and 9, respectively;
- and
- the VL2 comprises the LCDR1, the LCDR2 and the LCDR3 amino acid sequences of SEQ ID NOs:
- 10, 11 and 12, respectively;
- b) about 8 mM to about 12 mM of histidine and/or pharmaceutically acceptable histidine salt,
- c) about 6.8% (w/v) to about 10.2% (w/v) of sucrose,
- d) about 0.036% (w/v) to about 0.084% (w/v) of polysorbate 80 (PS80),
- e) about to 0.8 mg/mL to about 1.2 mg/mL of methionine,
- f) about 16 μg/mL to about 24 μg/mL of ethylenediaminetetraacetic acid (EDTA);
- and
- g) a pH from about 5.2 to about 6.2.
A method for preparing a stable aqueous pharmaceutical composition of a bispecific antibody targeting EGFR and cMet, the bispecific antibody targeting EGFR and cMet comprising a first heavy chain (HC1) comprising a HC1 variable region 1 (VH1);
- a first light chain (LC1) comprising a light chain variable region 1 (VL1);
- a second heavy chain (HC2) comprising a HC2 variable region 2 (VH2);
- and a second light chain (LC2) comprising a light chain variable region 2 (VL2), wherein the VH1 comprises a heavy chain complementarity determining region 1 (HCDR1), a HCDR2 and a HCDR3 comprising amino acid sequences of SEQ ID NOs:
- 1, 2, and 3, respectively;
- the VL1 comprises a light chain complementarity determining region 1 (LCDR1), a LCDR2 and a LCDR3 comprising amino acid sequences of SEQ ID NOs:
- 4, 5 and 6, respectively;
- the VH2 comprises HCDR1, HCDR2 and HCDR3 amino acid sequences of SEQ ID NOs:
- 7, 8 and 9, respectively;
- and the VL2 comprises LCDR1, LCDR2 and LCDR3 amino acid sequences of SEQ ID NOs:
- 10, 11 and 12, respectively;
- the method comprising:
- combining a composition comprising about 50 mg/mL of the bispecific antibody, about 10 mM histidine and/or pharmaceutically acceptable histidine salt, about 8.5% Sucrose, and about 1 mg/mL L-methionine with polysorbate 80 to a final concentration of about 0.06% (w/v) and EDTA to a final concentration of about 20 μg/mL, wherein the stable aqueous pharmaceutical composition has about pH 5.7.
Dependencies are inferred from the claim text.