Liquid formulations N-terminal serine of pegylated growth hormone
Pharmaceutical compositions comprising pegylated growth hormone at pH 7 or below are provided.
1. A pharmaceutical composition comprising a pegylated growth hormone and at least one pharmaceutically acceptable excipient, wherein said pegylated growth hormone comprises a growth hormone and a PEG, wherein said growth hormone and said PEG is connected via an oxime bond, and optionally via a linker, wherein said composition does not comprise any substantial amount of carbonate and said composition has a pH from 5 to 7, wherein the PEG moiety is attached to the growth hormone at a serine in the N-terminal of said growth hormone and wherein the composition comprises:
Histidine:
0.002 to 0.34 mg per mg of
pegylated growth hormone
Poloxamer 188:
1 to 4
mg/ml
Mannitol:
10 to 30
mg/ml
Phenol:
1 to 5
mg/ml
pegylated growth hormone:
1 to 200
mg/ml
pH:
5-7.
2. The composition according to claim 1 comprising
Histidine:
0.0085 mg per mg of
pegylated growth hormone
Poloxamer 188:
1.5
mg/ml
Mannitol:
20
mg/ml
Phenol:
5
mg/ml
pegylated growth hormone:
1 to 200
mg/ml
pH:
6.1.
3. A pharmaceutical composition comprising a pegylated growth hormone and at least one pharmaceutically acceptable excipient, wherein said pegylated growth hormone comprises a growth hormone and a PEG, wherein said growth hormone and said PEG is connected via an oxime bond, and optionally via a linker, wherein said composition does not comprise any substantial amount of carbonate and said composition has a pH from 5 to 7, wherein the PEG moiety is attached to the growth hormone at a serine in the N-terminal of said growth hormone and wherein the composition comprises:
Glycin:
2 to 7
mg/ml
Mannitol:
10 to 30
mg/ml
Total PO 4 3− :
2 to 20
mM
Phenol:
1 to 5
mg/ml
pegylated growth hormone:
1 to 200
mg/ml
pH:
5-7
4. The composition according to claim 3 comprising
Glycin:
2.2
mg/ml
Mannitol:
11
mg/ml
Total PO 4 3− :
4.5
mM
Phenol:
5
mg/ml
pegylated growth hormone:
1 to 200
mg/ml
pH:
5-7