Liquid formulation comprising GM-CSF neutralizing compound
The present invention relates to aqueous formulations comprising a compound neutralizing GM-CSF in concentrations of at least 20 mg/ml, a tonicity modifier, a buffer and one or more of surfactants, amino acids, antioxidants and/or chelators, wherein the composition is stable. The ingredients of the formulation preferably provide stability to the compound neutralizing GM-CSF in view of long-term storage. In a preferred aspect, the formulation is for use in therapy, preferably for use in the treatment of inflammatory and autoimmune disorders, preferably including allergic and psoriatic disorders, as well as arthritic and asthmatic disorders.
1. An aqueous composition comprising
i) an antibody or functional fragment thereof binding to GM-CSF, wherein the antibody or functional fragment is a human monoclonal antibody or functional fragment thereof which comprises in its light chain variable region an amino acid sequence as set forth in any of SEQ ID NOs: 19, 54 and 55 and in its heavy chain variable region an amino acid sequence as set forth in any of SEQ ID NOs: 20-33, 52 and 53 in a concentration of at least about 50 mg/ml and less than about 200 mg/ml,
ii) a tonicity modifier, which is sorbitol in a concentration from about 3% to about 7% (w/v),
iii) a buffer, which is a histidine buffer in a concentration from about 20 mM to about 40 mM, and
iv) a surfactant, which is polysorbate 80 in a concentration from about 0.001% to about 1% (w/v), wherein the pH is between about 5 and about 7, and wherein the composition is stable for up to 6 months at about 2-8° C. or at least 28 days at room temperature.
2. The composition according to claim 1 , which further comprises an antioxidant.
3. The composition according to claim 1 , wherein the polysorbate 80 amount is above the critical aggregation concentration (CAC).
4. The composition according to claim 1 , wherein the polysorbate 80 concentration is from about 0.01% (w/v) to about 0.08% (w/v).
5. The composition according to claim 1 , wherein the polysorbate 80 to protein ratio is from about 0.3:1 to about 0.6:1.
6. The composition according to claim 1 , which comprises
i) about 50 mg/ml to about 180 mg/ml of the antibody or functional fragment thereof binding to GM-CSF,
ii) about 5% (w/v) sorbitol,
iii) about 30 mM L-histidine, and
iv) from about 0.01% (w/v) to about 0.08% (w/v) polysorbate 80, wherein the composition has a pH of about 5.8.
7. The composition according to claim 1 , which comprises about 80 mg/ml or 150 mg/ml of the human monoclonal antibody or functional fragment thereof binding to GM-CSF.
8. The composition of claim 1 , wherein said antibody or functional fragment thereof comprises a light chain amino acid sequence as set out in SEQ ID NO: 34 and a heavy chain amino acid sequence as set out in SEQ ID NO: 35.
9. A method of treating inflammatory and autoimmune disorders by administering an aqueous composition according to claim 1 .
10. The method of claim 9 , wherein the disorders are selected from allergic, psoriatic, arthritic and asthmatic disorders.
11. The aqueous composition of claim 1 which is stable for up to 3 months at about 2-8° C.