Lyophilized therapeutic peptibody formulations
The present invention provides long-term stable formulations of a lyophilized therapeutic peptibody and methods for making a lyophilized composition comprising a therapeutic peptibody.
1. A stable lyophilized therapeutic peptibody composition comprising a buffer, a bulking agent, a stabilizing agent, and a surfactant wherein;
said buffer is 10 mM histidine;
the pH is 5.0;
said bulking agent is 4% w/v mannitol;
said stabilizing agent is 2% w/v sucrose;
said surfactant is 0.004% w/v polysorbate-20; and
said therapeutic peptibody is a dimer that comprises a structure of the formula
F 1 -(L 1 ) e -P 1 (L 2 ) f -P 2
wherein:
F 1 is an Fc domain, wherein the Fc domain is attached at the N-terminus of -L 1 -P 1 -L 2 -P 2 ;
P 1 and P 2 are each independently selected from Table 6;
L 1 and L 2 are each independently linkers; and
e and f are each independently 0 or 1.
2. The composition of claim 1 wherein P 1 and P 2 have the same amino acid sequence.
3. The composition of claim 1 wherein the Fc domain is set out in SEQ ID NO: 1.
4. The composition of claim 1 wherein the therapeutic peptibody concentration is between about 0.25 mg/mL and 250 mg/mL.
5. The composition of claim 1 wherein the therapeutic peptibody concentration is 0.5 mg/mL.
6. A kit for preparing an aqueous pharmaceutical composition comprising a first container having a stable lyophilized therapeutic peptibody composition of claim 1 , and a second container having a physiologically acceptable solvent for the lyophilized composition.
7. The composition of claim 1 , wherein the Fc domain is SEQ ID NO: 1 and wherein the peptibody comprises SEQ ID NO: 1017.
8. The composition of claim 7 , wherein methionine is at the N-terminus of the peptibody, SEQ ID NO: 1 is at the C-terminus of said methionine and SEQ ID NO: 1017 is at the C-terminus of the peptibody.