Stable IgG4 based binding agent formulations
The present invention provides stable pharmaceutical antibody formulations, including liquid drug product formulations and lyophilized drug product formulations, comprising an IgG4 binding agent and a citrate buffer, wherein the pH of the formulation is at or below both pH 6 and the pI of the binding agent. The formulations can be used in the treatment of chronic bowel diseases or rheumatoid arthritis.
1. An antibody formulation comprising:
a) about 20 mg/mL of a humanized IgG4 anti-CXCR5 (C-X-C chemokine receptor type 5) antibody comprising a heavy chain variable region comprising complementary determining regions (CDRs) comprising the amino acid sequences of SEQ ID NOS: 15, 16, and 17, and a light chain variable region comprising CDRs comprising the amino acid sequences of SEQ ID NOS: 18, 19, and 20;
b) about 10 mM citrate buffer;
c) about 0.02% polysorbate 20;
d) about 6% sucrose; and
e) about 0.2% sodium chloride;
wherein the pH of the formulation is at or below the lower of about pH 6.0 and the pI of the binding agent.
2. An antibody formulation comprising:
a) about 100 mg/mL of a humanized IgG4 anti-CXCR5 (C-X-C chemokine receptor type 5) antibody comprising a heavy chain variable region comprising complementary determining regions (CDRs) comprising the amino acid sequences of SEQ ID NOS: 15, 16, and 17, and a light chain variable region comprising CDRs comprising the amino acid sequences of SEQ ID NOS: 18, 19, and 20;
b) about 10 mM citrate buffer;
c) about 0.01% polysorbate 20;
d) about 4.5% sucrose;
e) about 0.2% sodium chloride; and
f) about 1% arginine;
wherein the pH of the formulation is at or below the lower of about pH 6.0 and the pI of the binding agent.
3. An antibody formulation comprising:
a) about 5 mg/mL to about 280 mg/mL of a humanized IgG4 anti-CXCR5 (C-X-C chemokine receptor type 5) antibody comprising a heavy chain variable region comprising complementary determining regions (CDRs) comprising the amino acid sequences of SEQ ID NOS: 15, 16, and 17, and a light chain variable region comprising CDRs comprising the amino acid sequences of SEQ ID NOS: 18, 19, and 20;
b) about 10 mM citrate buffer;
c) about 0.01% polysorbate 20;
d) about 4.5% sucrose;
e) about 0.2% sodium chloride; and
f) about 1% arginine;
wherein the pH of the formulation is at or below the lower of about pH 6.0 and the pI of the binding agent.
4. The formulation of claim 3 , wherein the formulation is a liquid formulation.
5. The formulation of claim 3 , wherein the formulation is a lyophilized formulation.
6. The formulation of claim 3 , wherein 5% or less of the binding agent in the formulation forms aggregates.
7. The formulation of claim 3 , wherein a monomer of the antibody has a purity of about 90%.
8. The formulation of claim 3 , wherein the antibody has a biological activity of at least about 90% of the biological activity exhibited at the time the formulation was prepared, as determined in an antigen binding assay.
9. The formulation of claim 3 , wherein the humanized IgG4 anti-CXCR5 (C-X-C chemokine receptor type 5) antibody is present in an amount of from about 5 to about 25 mg/mL, from about 26 to about 50 mg/mL, from about 51 to about 75 mg/mL, from about 76 to about 100 mg/mL, from about 101 to about 125 mg/mL, from about 126 to about 150 mg/mL, from about 151 to about 175 mg/mL, from about 176 to about 200 mg/mL, from about 201 mg/mL to about 225 mg/mL, from about 226 mg/mL to about 250 mg/mL, or from about 251 to about 280 mg/mL.
10. A kit comprising a container comprising: 1) the formulation of claim 3 , and 2) a label or instructions for the administration and use of the formulation.
11. A pre-filled device or pre-filled container comprising the formulation of claim 3 .
12. The pre-filled device of claim 11 , wherein the pre-filled device comprises a pre-filled syringe or a pre-filled autoinjector.
13. The pre-filled container of claim 11 , wherein the pre-filled container comprises a sealed ampoule, a vial, a bottle, a test tube, a cartouche, or a sachet.