WO2024256710A3 - Engineered lysin polypeptide constructs active against gram-negative bacteria - Google Patents

Engineered lysin polypeptide constructs active against gram-negative bacteria Download PDF

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Publication number
WO2024256710A3
WO2024256710A3 PCT/EP2024/066700 EP2024066700W WO2024256710A3 WO 2024256710 A3 WO2024256710 A3 WO 2024256710A3 EP 2024066700 W EP2024066700 W EP 2024066700W WO 2024256710 A3 WO2024256710 A3 WO 2024256710A3
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WIPO (PCT)
Prior art keywords
engineered
negative bacteria
lysin
gram
active against
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
PCT/EP2024/066700
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French (fr)
Other versions
WO2024256710A2 (en
Inventor
Raymond Schuch
Xavier Vila Farres
Steven Swift
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Aurobac Therapeutics SAS
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Aurobac Therapeutics SAS
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Publication of WO2024256710A2 publication Critical patent/WO2024256710A2/en
Publication of WO2024256710A3 publication Critical patent/WO2024256710A3/en
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
    • C12N9/14—Hydrolases (3)
    • C12N9/24—Hydrolases (3) acting on glycosyl compounds (3.2)
    • C12N9/2402—Hydrolases (3) acting on glycosyl compounds (3.2) hydrolysing O- and S- glycosyl compounds (3.2.1)
    • C12N9/2462—Lysozyme (3.2.1.17)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/04—Antibacterial agents
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/46—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
    • C07K14/47—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
    • C07K14/4701—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals not used
    • C07K14/4723—Cationic antimicrobial peptides, e.g. defensins
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
    • C12N9/14—Hydrolases (3)
    • C12N9/48—Hydrolases (3) acting on peptide bonds (3.4)
    • C12N9/50—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25)
    • C12N9/503—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25) derived from viruses
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2319/00—Fusion polypeptide
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2319/00—Fusion polypeptide
    • C07K2319/01—Fusion polypeptide containing a localisation/targetting motif
    • C07K2319/035—Fusion polypeptide containing a localisation/targetting motif containing a signal for targeting to the external surface of a cell, e.g. to the outer membrane of Gram negative bacteria, GPI- anchored eukaryote proteins
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12R—INDEXING SCHEME ASSOCIATED WITH SUBCLASSES C12C - C12Q, RELATING TO MICROORGANISMS
    • C12R2001/00—Microorganisms ; Processes using microorganisms
    • C12R2001/01—Bacteria or Actinomycetales ; using bacteria or Actinomycetales
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12R—INDEXING SCHEME ASSOCIATED WITH SUBCLASSES C12C - C12Q, RELATING TO MICROORGANISMS
    • C12R2001/00—Microorganisms ; Processes using microorganisms
    • C12R2001/01—Bacteria or Actinomycetales ; using bacteria or Actinomycetales
    • C12R2001/185—Escherichia
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12R—INDEXING SCHEME ASSOCIATED WITH SUBCLASSES C12C - C12Q, RELATING TO MICROORGANISMS
    • C12R2001/00—Microorganisms ; Processes using microorganisms
    • C12R2001/01—Bacteria or Actinomycetales ; using bacteria or Actinomycetales
    • C12R2001/22—Klebsiella
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12R—INDEXING SCHEME ASSOCIATED WITH SUBCLASSES C12C - C12Q, RELATING TO MICROORGANISMS
    • C12R2001/00—Microorganisms ; Processes using microorganisms
    • C12R2001/01—Bacteria or Actinomycetales ; using bacteria or Actinomycetales
    • C12R2001/38—Pseudomonas
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12R—INDEXING SCHEME ASSOCIATED WITH SUBCLASSES C12C - C12Q, RELATING TO MICROORGANISMS
    • C12R2001/00—Microorganisms ; Processes using microorganisms
    • C12R2001/01—Bacteria or Actinomycetales ; using bacteria or Actinomycetales
    • C12R2001/425—Serratia
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Y—ENZYMES
    • C12Y302/00—Hydrolases acting on glycosyl compounds, i.e. glycosylases (3.2)
    • C12Y302/01—Glycosidases, i.e. enzymes hydrolysing O- and S-glycosyl compounds (3.2.1)
    • C12Y302/01017—Lysozyme (3.2.1.17)

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Genetics & Genomics (AREA)
  • Zoology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Wood Science & Technology (AREA)
  • Engineering & Computer Science (AREA)
  • Biochemistry (AREA)
  • Molecular Biology (AREA)
  • Biomedical Technology (AREA)
  • General Engineering & Computer Science (AREA)
  • Microbiology (AREA)
  • Biotechnology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Virology (AREA)
  • Biophysics (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Communicable Diseases (AREA)
  • Oncology (AREA)
  • Toxicology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

Abstract

The present disclosure is directed to an engineered lysin comprising: (a) a Gram-negative base lysin; and (b) one or more antimicrobial peptide (AMP) and/or cell penetrating peptide (CPP), and optionally an outer membrane binding motif and at least one linker, or an active fragment thereof, or a variant thereof having at least 80% sequence identity. Also disclosed herein are methods of treating a bacterial infection caused by at least one Gram-negative bacteria and methods of killing at least one Gram-negative bacteria, comprising administering the engineered lysin disclosed herein.
PCT/EP2024/066700 2023-06-15 2024-06-14 Engineered lysin polypeptide constructs active against gram-negative bacteria Ceased WO2024256710A2 (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US202363508506P 2023-06-15 2023-06-15
US63/508,506 2023-06-15

Publications (2)

Publication Number Publication Date
WO2024256710A2 WO2024256710A2 (en) 2024-12-19
WO2024256710A3 true WO2024256710A3 (en) 2025-01-16

Family

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PCT/EP2024/066700 Ceased WO2024256710A2 (en) 2023-06-15 2024-06-14 Engineered lysin polypeptide constructs active against gram-negative bacteria

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WO (1) WO2024256710A2 (en)

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2019191633A2 (en) * 2018-03-29 2019-10-03 Contrafect Corporation Lysin-antimicrobial peptide (amp) polypeptide constructs, lysins, isolated polynucleotides encoding same and uses thereof
WO2020046747A1 (en) * 2018-08-23 2020-03-05 Contrafect Corporation Lysin-antimicrobial peptide (amp) polypeptide constructs, lysins, isolated polynucleotides encoding same and uses thereof

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
AU8108587A (en) 1986-10-08 1988-05-06 David Bernstein Method for exposing group a streptococcal antigens and an improved diagnostic test for the identification of group a streptococci
EP1536749A2 (en) 2002-07-08 2005-06-08 Joe S. Wilkins, Jr. Antibacterial formulations
AU2016324307B2 (en) 2015-09-17 2021-10-21 Contrafect Corporation Use of lysin to restore/augment antibacterial activity in the presence of pulmonary surfactant of antibiotics inhibited thereby

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2019191633A2 (en) * 2018-03-29 2019-10-03 Contrafect Corporation Lysin-antimicrobial peptide (amp) polypeptide constructs, lysins, isolated polynucleotides encoding same and uses thereof
WO2020046747A1 (en) * 2018-08-23 2020-03-05 Contrafect Corporation Lysin-antimicrobial peptide (amp) polypeptide constructs, lysins, isolated polynucleotides encoding same and uses thereof

Non-Patent Citations (4)

* Cited by examiner, † Cited by third party
Title
GERSTMANS H. ET AL: "A VersaTile-driven platform for rapid hit-to-lead development of engineered lysins", SCIENCE ADVANCES, vol. 6, no. 23, 3 June 2020 (2020-06-03), US, pages eaaz1136, XP055779045, ISSN: 2375-2548, DOI: 10.1126/sciadv.aaz1136 *
GHOSE CHANDRABALI ET AL: "Gram-Negative Bacterial Lysins", ANTIBIOTICS, vol. 9, no. 2, 11 February 2020 (2020-02-11), pages 74, XP055800842, Retrieved from the Internet <URL:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7168136/pdf/antibiotics-09-00074.pdf> DOI: 10.3390/antibiotics9020074 *
LIM JEONGHYUN ET AL: "Eradication of drug-resistant Acinetobacter baumannii by cell-penetrating peptide fused endolysin", JOURNAL OF MICROBIOLOGY, THE MICROBIOLOGICAL SOCIETY OF KOREA, SEOUL, vol. 60, no. 8, 25 May 2022 (2022-05-25), pages 859 - 866, XP037921945, DOI: 10.1007/S12275-022-2107-Y *
SCHWUDKE DOMINIK ET AL: "Broad-Host-Range Yersinia Phage PY100: Genome Sequence, Proteome Analysis of Virions, and DNA Packaging Strategy", JOURNAL OF BACTERIOLOGY, vol. 190, no. 1, 1 January 2008 (2008-01-01), US, pages 332 - 342, XP093212349, ISSN: 0021-9193, Retrieved from the Internet <URL:https://journals.asm.org/doi/pdf/10.1128/JB.01402-07> DOI: 10.1128/JB.01402-07 *

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Publication number Publication date
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