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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-11958890-B2
Publication Date
2024-04-16
Expiration Date
Abstract
The present invention relates to a polypeptide comprising a Gram negative endolysin and a peptide selected from the group consisting of an antimicrobial peptide, an amphipathic peptide, a cationic peptide, a sushi peptide or a defensin, wherein the endolysin in turn is selected from the group consisting of SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9 and sequences having at least 80% sequence identity with SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8 and/or SEQ ID NO:9. The present invention relates also to corresponding nucleic acids, vectors, bacteriophages, host cells, compositions and kits. The present inventions also relates to the use of said polypeptides, nucleic acids, vectors, bacteriophages, host cells, compositions and kits in methods for treatment of the human or animal body by surgery or therapy or in diagnostic methods practiced on the human or animal body. The polypeptides, nucleic acids, vectors, bacteriophages, host cells, compositions and kits according to the invention may also be used as an antimicrobial in, e.g., food or feed, in cosmetics, or as disinfecting agent.
Core Innovation
The invention provides a polypeptide comprising a Gram negative endolysin and a peptide selected from an antimicrobial peptide, an amphipathic peptide, a cationic peptide, a sushi peptide and a defensin. The Gram negative endolysin is selected from SEQ ID NO:7, SEQ ID NO:8, and SEQ ID NO:9.
The polypeptide is characterized as having activity for Gram-negative bacteria, including peptidoglycan degradation and antibacterial activity. The disclosed embodiments emphasize maintaining antibacterial activity under conditions with no added outer membrane permeabilizing substances.
In this context, the polypeptide degrades peptidoglycan of at least one Gram-negative bacterial species without the presence of other outer membrane permeabilizing substances, and has a minimal inhibitory concentration (MIC) against Escherichia coli strain RKI 06-08410 of 20 μg/ml or less in the absence of outer membrane permeabilizing substances.
Claims Coverage
Independent claim coverage centers on a Gram-negative endolysin fused to selected peptide classes, with the endolysin restricted to SEQ ID NO:7, SEQ ID NO:8, or SEQ ID NO:9. The claim set also includes dependent refinements for peptide sequence constraints, activity constraints, and use conditions tied to the absence of other outer membrane permeabilizing substances.
Gram negative endolysin fused to class-selected peptides
A polypeptide comprising a Gram negative endolysin and a peptide selected from the group consisting of an antimicrobial peptide, an amphipathic peptide, a cationic peptide, a sushi peptide and a defensin.
Endolysin limited to SEQ ID NO:7, SEQ ID NO:8, and SEQ ID NO:9
The endolysin is selected from the group consisting of SEQ ID NO:7, SEQ ID NO:8, and SEQ ID NO:9.
Motif-constrained peptide sequence
A polypeptide defined by a peptide sequence motif of length 16–20 amino acids having 40–60% first-group amino acids (K/R/H) under run/row constraints and 40–60% second-group amino acids (A/G/I/L/F/S/T/W/Y/V), with any remaining motif amino acids coming from a third group (N/D/Q/E/M/C).
Enumerated amino-acid sequences SEQ ID NO:114–SEQ ID NO:121
The polypeptide includes an amino acid sequence selected from SEQ ID NO:114 through SEQ ID NO:121.
Peptidoglycan degradation without other permeabilizers
The polypeptide degrades peptidoglycan of at least one Gram-negative bacterial species without the presence of other outer membrane permeabilizing substances.
MIC ≤ 20 μg/ml against E. coli RKI 06-08410 without permeabilizers
The polypeptide has, in the absence of outer membrane permeabilizing substances, a minimal inhibitory concentration (MIC) of 20 μg/ml or less against Escherichia coli strain RKI 06-08410.
Treatment of Gram-negative bacterial infection without added permeabilizers
A method treats a Gram-negative bacterial infection in a subject by administering the polypeptide without adding any further outer membrane permeabilizing substances.
The claim coverage centers on Gram-negative endolysin fusion polypeptides where the endolysin is restricted to SEQ ID NO:7, SEQ ID NO:8, or SEQ ID NO:9, fused to a peptide chosen from antimicrobial, amphipathic, cationic, sushi, or defensin classes. Dependent refinements further constrain peptide sequence motifs and enumerated sequences, and require peptidoglycan activity and low MIC values in the absence of other outer membrane permeabilizing substances.
Stated Advantages
Maintained antibacterial activity under conditions without added outer membrane permeabilizing substances.
Peptidoglycan degradation of at least one Gram-negative bacterial species without the presence of other outer membrane permeabilizing substances.
Low MIC against Escherichia coli strain RKI 06-08410 (20 μg/ml or less) in the absence of outer membrane permeabilizing substances.
Documented Applications
Treatment of a Gram-negative bacterial infection in a subject by administering the polypeptide without adding further outer membrane permeabilizing substances.
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