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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-10329550-B2
Publication Date
2019-06-25
Expiration Date
Abstract
The present invention relates to polypeptides comprising an amino sequence selected from the group consisting of: SEQ ID NO: 1, and fragments and derivatives of these. The invention also relates to the corresponding nucleic acids vectors, host cells and compositions. The present inventions also relates to the use of said polypeptides, nucleic acids, vectors, host cells and compositions in a method for treatment of the human or animal body by surgery or therapy or in diagnostic methods practiced on the human or animal body, in particular for the treatment or prevention of Gram-negative bacterial infections. The polypeptides, nucleic acids, vectors, host cells and compositions according to the invention may also be used as an antimicrobial in food or feed, or in cosmetics, as disinfecting agent or in the environmental field.
Core Innovation
The invention relates to an antimicrobial polypeptide comprising an amino sequence selected from SEQ ID NO: 1, and a fragment thereof that is at most 20 amino acids shorter than SEQ ID NO: 1. The polypeptide further comprises at least one heterologous amino acid sequence selected from amphipathic peptide, cationic peptide, polycationic peptide, hydrophobic peptide, or naturally-occurring antimicrobial peptide. This polypeptide design builds endolysin-based activity around an enzymatic domain while adding heterologous peptide sequences.
The background problem addressed is that Gram-negative outer membranes shield endolysins, and that the outer membrane and lipopolysaccharide (LPS) interfere with endolysin activity. The invention provides a polypeptide framework intended to disrupt the outer membrane/LPS barrier in order to enable activity against Gram-negative pathogens. The described polypeptides include active N/C-terminally truncated fragments derived from SEQ ID NO: 92.
In embodiments described, the polypeptide comprises optional added heterologous peptide stretches, including amphipathic, cationic/polycationic, and hydrophobic peptide classes, and optionally naturally occurring antimicrobial peptides such as sushi peptides or defensins. Documented experimental examples include muralytic assays demonstrating enzymatic activity for multiple SEQ ID NO: 92 fragments on Gram-negative bacteria including E. coli and Salmonella, and comparative activity versus prior endolysins. Additional examples described include MIC results for fusion proteins combining SEQ ID NO: 92 with various peptide sequences across multiple Gram-negative bacteria strains.
Claims Coverage
The independent claim covers a polypeptide with an amino sequence selected from SEQ ID NO: 1 or a fragment no more than 20 amino acids shorter than SEQ ID NO: 1, and further including at least one heterologous peptide sequence selected from defined amphipathic/cationic/polycationic/hydrophobic/naturally-occurring antimicrobial peptide classes. The claim set includes multiple dependent claims that narrow fragment selection and specify particular heterologous peptide sequences and functional activity against Gram-negative peptidoglycan, as well as broader coverage to nucleic acids, vectors, host cells, and compositions.
Polypeptide selected from SEQ ID NO: 1 or a fragment thereof with heterologous peptide sequence
A polypeptide comprising an amino sequence selected from SEQ ID NO: 1 and a fragment of SEQ ID NO: 1 that is at most 20 amino acids shorter than SEQ ID NO: 1, wherein the polypeptide further comprises at least one heterologous amino acid sequence selected from amphipathic peptide, cationic peptide, polycationic peptide, hydrophobic peptide, or naturally-occurring antimicrobial peptide.
Polypeptide that degrades Gram-negative peptidoglycan
A polypeptide wherein the specified activity is degrading peptidoglycan in Gram-negative bacteria.
The claimed subject matter is centered on SEQ ID NO: 1 (or short fragments thereof) combined with at least one heterologous amphipathic/cationic/polycationic/hydrophobic/naturally-occurring antimicrobial peptide sequence, and is further constrained in dependent claims to peptidoglycan degradation in Gram-negative bacteria.
Stated Advantages
Enables activity against Gram-negative pathogens by disrupting the outer membrane/LPS barrier.
Provides antimicrobial endolysin polypeptides with enzymatic activity for multiple SEQ ID NO: 92 fragments.
Supports fusion protein designs that show activity results including MIC against multiple Gram-negative bacteria strains.
Documented Applications
Therapeutic use, as covered by embodiments described as therapeutic.
Diagnostic use, as covered by embodiments described as diagnostic.
Disinfecting/sanitizing use, as covered by embodiments described as disinfecting/sanitizing.
Environmental/food/feed/cosmetic uses, as covered by embodiments described for environmental and food/feed/cosmetic contexts.
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