Porcine G-CSF variants and their uses
Inventors
CANNING, Peter Connor • KNUDSEN, Nickolas • RASHID, MD HARUNUR
Assignees
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Publication Number
US-12286462-B2
Publication Date
2025-04-29
Expiration Date
Abstract
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.
Core Innovation
The invention relates to porcine granulocyte colony stimulating factor (pG-CSF) variants in which a para-acetyl phenylalanine (pAF) synthetic amino acid is covalently attached to poly(ethylene glycol) (PEG) at position 43. The variants include an amino acid sequence defined by specific position-based substitutions, with X1, X2, and X3 selected from recited groups, and with pAF present at position 43 as the site of the PEG covalent attachment.
The problem addressed is bacterial infections in swine, particularly periparturient sow mastitis/metritis/agalactia (MMA) syndrome. The disclosure links the therapeutic concept to increasing neutrophils and to prolonging pharmacokinetics (PK) through PEG modification, and frames the objective as reducing MMA incidence and improving piglet survival in the relevant production context.
The document provides experimental examples including generation of pG-CSF/pAF PEGylated constructs using an expanded genetic code system for pAF incorporation. In vitro results are reported using M-NSF-60 cells, along with EC50 observations, and in vivo results are reported with PK and complete blood count (CBC) measurements and neutrophil observations. Additional sow studies under hygienic-challenge conditions report increased blood neutrophils after intramuscular (IM) dosing and a reduction in MMA incidence, with piglet survival trends described as part of the outcomes.
Claims Coverage
The document includes one independent claim that defines pG-CSF variant structure and covalent pAF-PEG attachment at position 43, and the claim set refines this through additional limitations focused on PEG selection and disease/administration context. The independent claim includes two main inventive aspects: a specific pG-CSF sequence architecture with position-specific substitutions, and covalent attachment of pAF at position 43 to PEG.
pG-CSF variant with covalently attached pAF at position 43 to PEG
A porcine granulocyte colony stimulating factor (pG-CSF) variant comprising a defined amino acid sequence with specified selections for X1, X2, and X3, wherein a para-acetyl phenylalanine (pAF) synthetic amino acid present at position 43 is covalently attached to a poly(ethylene glycol) (PEG).
Across the claim set, the inventive coverage centers on a pG-CSF variant defined by a specific sequence framework with position-specific substitutions, together with covalent PEG attachment using pAF at position 43. Dependent claims further narrow PEG characteristics and ground the use in porcine MMA syndrome and related outcome-oriented effects described for the claimed formulations.
Stated Advantages
Increases blood neutrophils after intramuscular (IM) dosing in sow studies.
Reduces MMA incidence under hygienic-challenge conditions.
A piglet survival improvement trend is described in the sow study context.
Documented Applications
Treating or preventing bacterial infections in swine, including periparturient sow mastitis/metritis/agalactia (MMA) syndrome.
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