Pharmaceutical composition
The present invention relates to pharmaceutical compositions comprising an antibody or a fragment thereof suitable for freeze-drying (i.e. lyophilizing). The pharmaceutical compositions, which comprise an antibody or an antigen-binding fragment thereof; from 1% to 20% w/v sucrose; an amino acid or a mixture of amino acids; and surfactant, are provided as pharmaceutical compositions for freeze-drying; as freeze-dried (i.e. lyophilized) compositions which can be reconstituted into a solvent at the time of use or as reconstituted liquid formulations ready for administration.
1. A pharmaceutical composition comprising:
a. an antibody or an antigen-binding fragment thereof comprising a light variable region as defined in SEQ ID NO: 7 and a heavy variable region as defined in SEQ ID NO: 8 and having a concentration of from 80 to 200 mg/mL;
b. from 7% to 13% w/v sucrose;
c. a mixture of 10 mM to 50 mM histidine and 180 mM proline;
d. 0.01% to 1.0% surfactant; and
e. a pH of from 4.0 to 7.5.
2. The pharmaceutical composition according to claim 1 , wherein the antibody or antigen-binding fragment thereof is at a concentration of from 80 to 140 mg/mL.
3. The pharmaceutical composition according to claim 1 , wherein the composition comprises from 7% to 10% w/v sucrose.
4. The pharmaceutical composition according to claim 1 , wherein the composition comprises 0.01 to 0.5% w/v of the surfactant.
5. The pharmaceutical composition according to claim 4 , wherein the surfactant is polysorbate 80.
6. The pharmaceutical composition according to claim 1 , wherein the antibody is a human or humanised antibody.
7. The pharmaceutical composition according to claim 1 , wherein the composition comprises from 80 mg/mL to 140 mg/mL of antibody or antigen-binding fragment thereof, 30 mM histidine, from 180 mM proline, 7% w/v sucrose, 0.03% w/v polysorbate 80, at pH 5.6.
8. The pharmaceutical composition according to claim 1 , wherein the composition further comprises mannitol and/or arginine and/or glycine.
9. A freeze-dried formulation comprising an antibody or an antigen-binding fragment thereof, sucrose, an amino acid or a mixture of histidine and proline, and optionally a surfactant, wherein the formulation comprises from 20% to 40% w/w sucrose, wherein the antibody or antigen-binding fragment thereof comprises a light variable region as defined in SEQ ID NO: 7 and a heavy variable region as defined in SEQ ID NO: 8 and wherein the antibody or antigen-binding fragment thereof had, before freeze-drying, a concentration of 80 to 200 mg/mL, 10 mM to 50 mM of the histidine, 180 mM of the proline; and if present 0.01% to 1.0% w/v of the surfactant.
10. A liquid pharmaceutical formulation comprising the freeze-dried formulation of claim 9 and a solvent.
11. A container comprising the freeze-dried formulation of claim 9 or a liquid pharmaceutical formulation comprising the freeze-dried formulation.
12. The freeze-dried formulation according to claim 9 , wherein said formulation comprises about 50.8% w/w of the antibody or antigen-binding fragment thereof, about 35.5% w/w sucrose, about 3.0% w/w histidine, about 10.5% w/w proline and 0.2% w/w polysorbate 80.