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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-10184120-B2
Publication Date
2019-01-22
Expiration Date
Abstract
The present invention relates to polypeptides comprising an amino acid sequence exhibiting at least about 90% sequence identity with the sequence of SEQ ID NO: 1. Said polypeptides preferably degrade the peptidoglycan of Gram-negative bacteria, in particular of Pseudomonas and/or Campylobacter bacteria. In addition, the present invention relates to nucleic acids encoding such polypeptides, vectors comprising such nucleic acids, and corresponding host cells. Finally, the present invention relates to compositions comprising such polypeptides, nucleic acids, vectors, and/or host cells according to the present invention.
Core Innovation
The invention relates to modified KZ144 endolysin polypeptides defined by the sequence of SEQ ID NO: 1. SEQ ID NO: 1 is characterized by specified variable residues at multiple positions and the polypeptides neither comprise the amino-acid sequence of SEQ ID NO: 2 nor SEQ ID NO: 3 nor SEQ ID NO: 4.
A key defining aspect is that the polypeptide comprises the sequence of SEQ ID NO: 1, while at least one residue selected from X14, X23, and X50 is not C. The sequence variations include permissive and required residue substitutions at those positions, together with stabilizing substitutions at additional residue positions.
The disclosure further covers fusion constructs incorporating an antimicrobial peptide fusion partner, SMAP-29 (SEQ ID NO: 76), and optional tag/HIS-tag. The scope also includes nucleic acids, vectors, host cells, and pharmaceutical compositions associated with the engineered polypeptides.
Claims Coverage
The independent claim set centers on one engineered polypeptide sequence based on SEQ ID NO: 1, with explicit exclusions of complete sequences of SEQ ID NO: 2, SEQ ID NO: 3, and SEQ ID NO: 4, plus a non-cysteine requirement at positions X14, X23, and X50. Six inventive features are identified across the provided claims.
Engineered SEQ ID NO: 1 polypeptide defined by variable residues and sequence exclusions
A polypeptide comprising the sequence of SEQ ID NO: 1 with specified positions being any amino acid as recited, wherein the polypeptide neither comprises the amino acid sequence of SEQ ID NO: 2 nor SEQ ID NO: 3 nor SEQ ID NO: 4.
Non-cysteine requirement at positions X14, X23, and X50
The polypeptide of the engineered SEQ ID NO: 1 definition wherein at least one residue selected from the group consisting of X14, X23 and X50 is not C.
Threshold non-cysteine requirement at least two of X14, X23, and X50
The polypeptide is defined so that at least two residues selected from X14, X23 and X50 are not C.
Peptidoglycan degradation activity against Gram-negative bacteria including Pseudomonas and/or Campylobacter
The polypeptide degrades peptidoglycan of Gram-negative bacteria, specifically Pseudomonas and/or Campylobacter.
Fusion constructs including SMAP-29 (SEQ ID NO: 76) sequence stretch
The polypeptide includes at least one additional amino acid sequence stretch with the amino acid sequence of SMAP-29, SEQ ID NO: 76.
Nucleic acid encoding the engineered polypeptide
A nucleic acid that encodes the polypeptide described for the SEQ ID NO: 1 definition.
Coverage centers on an engineered polypeptide defined by SEQ ID NO: 1 with explicit exclusions of SEQ ID NO: 2, SEQ ID NO: 3, and SEQ ID NO: 4, and a non-cysteine constraint at positions X14, X23, and X50. Dependent features further add quantitative constraints on those positions, peptidoglycan degradation activity against Gram-negative bacteria including Pseudomonas and Campylobacter, and embodiments including an SMAP-29-containing fusion sequence stretch and nucleic acids encoding the defined polypeptide.
Stated Advantages
Improved stability/processing while retaining peptidoglycan-hydrolyzing activity against Gram-negative bacteria.
Increased melting temperature (Tmelt) for engineered variants.
Thermostability/activity after heating is reported for engineered variants.
No loss of activity is described in relation to engineered variants in the disclosed examples.
Documented Applications
Peptidoglycan degradation targeting Gram-negative bacteria, including Pseudomonas aeruginosa (PAO1) and Campylobacter species.
Fusion constructs incorporating an antimicrobial peptide fusion partner, SMAP-29 (SEQ ID NO: 76).
Pharmaceutical composition embodiments associated with the engineered polypeptides.
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