Porcine G-CSF variants and their uses
The present invention relates to variants of porcine granulocyte colony stimulating factor (pG-CSF). The pG-CSF variants are useful in treating preventing or reducing the incidence of bacterial infections in swine. Methods of treating swine are disclosed.
1. A porcine granulocyte colony stimulating factor (pG-CSF) variant consisting of a sequence of:
X 1 PLSPASSLPQSFLLKX 2 LEQVRKIQADGAELQERLCATHKLC(pAF)PQELVLLGHSLGL PQASLSSCSSQALQLTGCLNQLHGGLVLYQGLLQALAGISPELAPALDILQLDVTDLATN IWLQX 3 EDLRX 3 APASLPTQGTVPTFTSAFQRRAGGVLVVSQLQSFLELAYRVLRYLAEP (SEQ ID NO: 13);
wherein X 1 is selected from the group of methionine alanine, norleucine alanine, alanine only, and no amino acids;
wherein X 2 is cysteine or serine;
wherein X 3 is methionine or norleucine; and
wherein a para-acetyl phenylalanine (pAF) synthetic amino acid present at position 43 is covalently attached to a poly(ethylene glycol) (PEG).
2. The pG-CSF variant of claim 1 , wherein the PEG has a molecular weight of about 20 kD to about 50 kD.
3. The pG-CSF variant of claim 1 , wherein the PEG has a molecular weight of about 30 kD.
4. The pG-CSF variant of claim 1 , wherein the PEG is linear.
5. The pG-CSF variant of claim 1 , wherein a para-acetyl phenylalanine (pAF) synthetic amino acid present at position 43 is covalently attached to a 30 kD linear PEG.
6. A pharmaceutical composition comprising the pG-CSF variant of claim 1 , and at least one pharmaceutically acceptable carrier, diluent, or excipient.
7. A method for treating MMA syndrome in a porcine comprising administering a therapeutically effective amount of the pGCSF variant of claim 1 to the porcine in need thereof.
8. The method of claim 7 , wherein the MMA syndrome comprises symptoms of mastitis, metritis and/or agalactia.
9. The method of claim 7 , wherein the porcine is a periparturient sow.
10. The method of claim 7 , wherein the therapeutically effective amount of pG-CSF is about 10-100 μg/kg animal weight.
11. The method of claim 7 , wherein the therapeutically effective amount of pG-CSF is about 30-50 μg/kg animal weight.
12. The method of claim 7 , wherein the administering occurs at least once within 7 days prior to farrowing.
13. The method of claim 7 , wherein the administering occurs at farrowing.
14. The method of claim 12 , further comprising a second administration no later than 14 days after farrowing.
15. A method for increasing blood neutrophils in a porcine comprising administering a therapeutically effective amount of the pG-CSF variant of claim 1 to the porcine.
16. The method of claim 15 , wherein the therapeutically effective amount of pGCSF is about 10-100 μg/kg animal weight.
17. The method of claim 15 , wherein the administering occurs at least once within 7 days prior to farrowing.
18. The method of claim 15 , wherein the administering occurs at farrowing.
19. The method of claim 17 , further comprising a second administration no later than 14 days after farrowing.
20. A method for stimulating innate immune response by increasing blood neutrophils in a porcine comprising administering a therapeutically effective amount of the pG-CSF variant of claim 1 to the porcine in need thereof.