Modified bovine G-CSF polypeptides and their uses
Modified bovine G-CSF polypeptides and uses thereof are provided.
1. A method of treating mastitis in a non-human animal, said method comprising administering to the animal a therapeutically-effective amount of a bG-CSF polypeptide comprising the sequence of SEQ ID NO: 1, wherein position 133 of SEQ ID NO: 1 is substituted with a non-naturally encoded amino acid,
wherein the non-naturally encoded amino acid is para-acetylphenylalanine, and wherein the non-naturally encoded amino acid is linked to a water soluble polymer comprising a poly(ethylene) glycol moiety having a molecular weight of between about 1 kDa and about 100 kDa, and
wherein said bG-CSF polypeptide is characterized by inducing a maximal absolute neutrophil count (ANC) about 10-fold greater than pre-treatment ANC, as measured about 72 hours after a single sub-cutaneous injection at 40 μg/kg in a healthy bovine steer calf.
2. The method according to claim 1 wherein the animal is a bovine.
3. The method according to claim 2 wherein the bovine is a periparturient bovine.
4. A method of preventing mastitis in a non-human animal comprising administering to the animal a therapeutically-effective amount of a bG-CSF polypeptide comprising the sequence of SEQ ID NO: 1, wherein position 133 of SEQ ID NO: 1 is substituted with a non-naturally encoded amino acid,
wherein the non-naturally encoded amino acid is para-acetylphenylalanine, and
wherein the non-naturally encoded amino acid is linked to a water soluble polymer comprising a poly(ethylene) glycol moiety having a molecular weight of between about 1 kDa and about 100 kDa, and
wherein said bG-CSF polypeptide is characterized by inducing a maximal absolute neutrophil count (ANC) about 10-fold greater than pre-treatment ANC, as measured about 72 hours after a single sub-cutaneous injection at 40 μg/kg in a healthy bovine steer calf.
5. The method according to claim 4 wherein the animal is a bovine.
6. The method according to claim 5 wherein the bovine is a periparturient bovine.