Antimicrobial agents
Inventors
Lavigne, Rob • Miller, Stefan • Briers, Yves • Volckaert, Guido • Walmagh, Maarten
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Assignees
Member
Lysando AGLysando AG is a biopharmaceutical company specialized in antimicrobial protein technologies for combating pathogenic bacteria, particularly resistant and persistent strains. With a core focus on addressing antimicrobial resistance while preserving the human microbiome, the company develops protein-based therapeutic platforms for wound care, dermatology, and broader bacterial infection control. Lysando's solutions aim for effective pathogen management with low risk of resistance development, supporting sustainability and patient-centered healthcare outcomes.
Lysando AG is a biopharmaceutical company specialized in antimicrobial protein technologies for combating pathogenic bacteria, particularly resistant and persistent strains. With a core focus on addressing antimicrobial resistance while preserving the human microbiome, the company develops protein-based therapeutic platforms for wound care, dermatology, and broader bacterial infection control. Lysando's solutions aim for effective pathogen management with low risk of resistance development, supporting sustainability and patient-centered healthcare outcomes.
Publication Number
US-8906365-B2
Publication Date
2014-12-09
Expiration Date
Abstract
The application relates to antimicrobial agents against Gram-negative bacteria, in particular to fusion proteins composed of an enzyme having the activity of degrading the cell wall of Gram-negative bacteria and a peptide stretch fused to the enzyme at the N- or C-terminus, as well as pharmaceutical compositions thereof. Moreover, it relates to nucleic acid molecules encoding such a fusion protein, vectors carrying the nucleic acid molecules and host cells transformed with either the nucleic acid molecules or the vectors. In addition, it relates to such a fusion protein for use as a medicament, in particular for the treatment or prevention of Gram-negative bacterial infections, as diagnostic means or as cosmetic substance. The application also relates to the treatment or prevention of Gram-negative bacterial contamination of foodstuff, of food processing equipment, of food processing plants, of surfaces coming into contact with foodstuff, of medical devices, of surfaces in hospitals and surgeries.
Core Innovation
The invention relates to antimicrobial fusion proteins directed against Gram-negative bacteria. The fusion protein comprises an endolysin having Gram-negative bacteria cell wall degrading activity and an amphipathic peptide segment fused to the endolysin at the N- or C-terminus or at both termini. The amphipathic peptide segment comprises SMAP-29 having the sequence of SEQ ID NO: 11.
The disclosed approach uses modular endolysin/autolysin/bacteriocin components fused with an amphipathic or other permeabilizing peptide segment. The peptide segments include SMAP-29 (SEQ ID NO:11) and additional AMP/Sushi/defensin/hydrophobic peptides, and the fusion design may include N- and/or C-terminal fusion at the endolysin, including endolysins such as gp144/gp188, KZ144, STM0016, and N4gp61.
The fusion proteins are described as improving outer-membrane penetration and antibacterial activity compared with unmodified enzymes. The document reports effects on outer-membrane penetration and antibacterial activity for peptide-fused endolysins versus unmodified endolysins, including inhibition/inactivation and log inactivation against Gram-negative strains such as Pseudomonas aeruginosa. The document also describes nucleic acid encoding and composition/medicament uses for treatment or prevention of Gram-negative infections, as well as disinfection/sanitization of surfaces and devices.
Claims Coverage
The claims coverage identifies one independent fusion-protein claim with dependent claim variations, centered on an endolysin fused to an amphipathic peptide segment comprising SMAP-29. Additional claim features specify the fusion termini, endolysin source or sequence, optional terminal tags or additional protein, and use claims for treatment and disinfection.
N- or C-terminal endolysin–SMAP-29 amphipathic fusion
A fusion protein comprising an endolysin having Gram-negative bacteria cell wall degrading activity and an amphipathic peptide segment fused to the endolysin at the N- or C-terminus or at both termini, wherein the amphipathic peptide segment comprises SMAP-29 having the sequence of SEQ ID NO: 11.
SMAP-29 endolysin fusion for treating Gram-negative bacterial infection
The fusion protein defined in the N- or C-terminal endolysin–SMAP-29 amphipathic fusion for treating Gram-negative bacterial infection.
SMAP-29 endolysin fusion for disinfecting surfaces or preventing contamination
The fusion protein defined in the N- or C-terminal endolysin–SMAP-29 amphipathic fusion for disinfecting surfaces or articles or preventing contamination.
Pseudomonas aeruginosa phage endolysin as the Gram-negative cell wall degrading endolysin
The fusion protein defined in the N- or C-terminal endolysin–SMAP-29 amphipathic fusion wherein the endolysin is an endolysin from Pseudomonas aeruginosa phages ΦKZ or EL.
Endolysin defined by amino acid sequence corresponding to listed SEQ IDs
The fusion protein defined in the N- or C-terminal endolysin–SMAP-29 amphipathic fusion wherein the endolysin has an amino acid sequence corresponding to one of the listed SEQ ID NOs.
Optional terminal tag or additional protein
The fusion protein defined in the N- or C-terminal endolysin–SMAP-29 amphipathic fusion including a tag or an additional protein attached to the C-terminus and/or the N-terminus.
Overall, the claims coverage is centered on a fusion protein architecture that links a Gram-negative cell wall degrading endolysin to an amphipathic peptide segment comprising SMAP-29 (SEQ ID NO:11), with defined options for fusion placement, endolysin source or sequence, and optional terminal tagging. The dependent claim set further specifies use for treating Gram-negative bacterial infection and for disinfecting surfaces or articles or preventing contamination.
Stated Advantages
Improved outer-membrane penetration and improved antibacterial activity for peptide-fused endolysins versus unmodified enzymes.
Documented Applications
Treatment or prevention of Gram-negative infections.
Disinfection and sanitization of surfaces and devices by contacting the surface or article with the fusion protein.
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