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Compositions and methods for treating or preventing intestinal paracellular permeability

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  • Publication Date:
    June 25, 2024
  • معلومة اضافية
    • Patent Number:
      12016,889
    • Appl. No:
      16/971741
    • Application Filed:
      February 25, 2019
    • نبذة مختصرة :
      The present invention provides methods and compositions for maintaining and improving the integrity of gastrointestinal epithelial tight junctions, thereby helping to maintain healthy paracellular permeability of the GI epithelium. The present invention provides methods and compositions for the treatment or prevention of various conditions that are associated with gastrointestinal paracellular permeability, including various autoimmune conditions, inflammatory liver diseases, as well as inflammatory conditions of the large or small intestines.
    • Inventors:
      9 Meters Biopharma, Inc. (Raleigh, NC, US)
    • Assignees:
      9 Meters Biopharma, Inc. (Raleigh, NC, US)
    • Claim:
      1. A microorganism comprising a polynucleotide encoding a peptide that consists of the amino acid sequence of larazotide (SEQ ID NO: 1), the polynucleotide further comprising a promoter controlling expression of the peptide, wherein the microorganism is a species or strain naturally present in the duodenum and/or jejunum.
    • Claim:
      2. The microorganism of claim 1 , wherein the microorganism is a probiotic species.
    • Claim:
      3. The microorganism of claim 1 , wherein the microorganism is of the genus Saccharomyces, Lactobacillus, Clostridium, Streptococcus, Bifidobacterium, Enterococcus, Corynebacterium , or Candida.
    • Claim:
      4. The microorganism of claim 3 , wherein the microorganism is a species selected from Saccharomyces boulardii, Lactobacillus rhamnosus, Lactobacillus plantarum, Clostridium butyricum , non-toxigenic Clostridium difficile, Lactobacillus casei, Lactobacillus acidophilus, Lactobacillus bulgaricus, Streptococcus thermophilus, Bifidobacterium bifidum, Bifidobacterium longum, Bifidobacterium lactis, Bifidobacterium infantis, Bifidobacterium breve, Candida albicans , and Streptococcus salivarius.
    • Claim:
      5. The microorganism of claim 1 , wherein the microorganism is a commensal microorganism.
    • Claim:
      6. The microorganism of claim 1 , wherein the polynucleotide further encodes a secretory signal at the N-terminus of the peptide.
    • Claim:
      7. A bacteriophage comprising a polynucleotide encoding a peptide that consists of the amino acid sequence of larazotide (SEQ ID NO: 1), the polynucleotide further comprising a promoter controlling expression of the peptide in a host bacteria, wherein the bacteriophage infects a host bacteria naturally present in the duodenum and/or jejunum.
    • Claim:
      8. The bacteriophage of claim 7 , wherein the host bacteria is of the genus Lactobacillus, Clostridium, Streptococcus, Bifidobacterium, Enterococcus , or Corynebacterium.
    • Claim:
      9. The bacteriophage of claim 8 , wherein the host bacteria is a species selected from Lactobacillus rhamnosus, Lactobacillus plantarum, Clostridium butyricum , non-toxigenic Clostridium difficile, Lactobacillus casei, Lactobacillus acidophilus, Lactobacillus bulgaricus, Streptococcus thermophilus, Bifidobacterium bifidum, Bifidobacterium longum, Bifidobacterium lactis, Bifidobacterium infantis, Bifidobacterium breve , and Streptococcus salivarius.
    • Claim:
      10. The bacteriophage of claim 7 , wherein the host bacteria is a commensal microorganism.
    • Claim:
      11. The bacteriophage of claim 7 , wherein the polynucleotide further encodes a secretory signal at the N-terminus of the peptide.
    • Claim:
      12. The bacteriophage of claim 7 , wherein the bacteriophage is lytic or lysogenic.
    • Claim:
      13. The bacteriophage of claim 7 , wherein the bacteriophage is of the order Caudovirales, Siphoviridae, Myoviridae, or Podoviridae.
    • Patent References Cited:
      20150164978 June 2015 Paterson et al.
      20160022760 January 2016 Perrow et al.
      20160052996 February 2016 Grimm
      2017109087 June 2017
      2017123610 July 2017





    • Other References:
      Kelesidis et al., Therapeutic Advances in Gastroenterology, 2012; 5(2):111-125 (Year: 2012). cited by examiner
      Vessler et al., Microbiology and Molecular Biology Reviews, 2011; 75(3):423-433 (Year: 2011). cited by examiner
      Filloux, Journal of Bacteriology, 2010; 192(15):3847-3849 (Year: 2010). cited by examiner
      Steward Technology Networks Immunology and Microbiology, 2018; https://www.technologynetworks.com/immunology/articles/lytic-vs-lysogenic-understanding-bacteriophage-life-cycles-308094 (Year: 2018). cited by examiner
      Klein et al., Proc. Natl. Acad. Sci. USA, 1996; 93:7108-7113 (Year: 1996). cited by examiner
      International Search Report and Written Opinion for International Application No. PCT/US2019/019348 , dated May 8, 2019, 14 pages. cited by applicant
    • Assistant Examiner:
      Jackson-Tongue, Lakia J
    • Primary Examiner:
      Gangle, Brian
    • Attorney, Agent or Firm:
      Morgan, Lewis & Bockius LLP
    • الرقم المعرف:
      edspgr.12016889