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KR-20260065845-A - Microbiome Restoration Therapy (MRT) Composition and Method of Administration

KR20260065845AKR 20260065845 AKR20260065845 AKR 20260065845AKR-20260065845-A

Abstract

A method of administering a dose of a microbiome restoration therapy composition by colonoscopy is disclosed herein. The method disclosed herein is useful for treating gastrointestinal diseases and/or conditions such as GDI, including recurrent Clostridioides difficile infection (GDI), and other gastrointestinal disorders. The method may result in an improvement in quality of life. The method may alter the composition of the intestinal microbiome and/or intestinal metabolites. The microbiome restoration therapy composition comprises fecal microorganisms derived from a human fecal sample and a fecal microbiome suspension comprising a solution of polyethylene glycol and saline.

Inventors

  • 클라크 브라이언 존
  • 스톡하우젠 마리
  • 블런트 케네스 에프.

Assignees

  • 페링 마이크로바이옴 인크.

Dates

Publication Date
20260511
Application Date
20240830
Priority Date
20230906

Claims (20)

  1. As a method for treating recurrent Clostridioides difficile infection (CDI) in human patients requiring treatment for recurrent CDI, The method includes the step of administering a dose of a microbiome restoration therapy composition to a patient by colonoscopy, wherein the microbiome restoration therapy composition Fecal microorganisms derived from human fecal samples, and Polyethylene glycol and saline solution A method comprising a fecal microbiome suspension containing
  2. As a method for treating gastrointestinal disease or disorder in human patients requiring treatment for gastrointestinal disease or disorder, The method includes the step of administering a dose of a microbiome restoration therapy composition to a patient via rectum or colonoscopy, wherein the microbiome restoration therapy composition Fecal microorganisms derived from human fecal samples, and Polyethylene glycol and saline solution A method comprising a fecal microbiome suspension containing
  3. In paragraph 2, the gastrointestinal disease or disorder is one or more selected from ulcerative colitis and Crohn's disease, and optionally the gastrointestinal disease or disorder is mild to moderate ulcerative colitis.
  4. In paragraph 2, the gastrointestinal disease or disorder is one or more selected from irritable bowel syndrome, hard colon, functional bowel disease (FBD), non-ulcer dyspepsia (NUD), gastroesophageal reflux, inflammatory bowel disease, idiopathic or simple constipation, diverticulopathy, AIDS enteropathy, small intestinal bacterial overgrowth, celiac disease/cuellar disease, colonic polyposis, colonic polyps, chronic idiopathic pseudoobstruction syndrome, chronic intestinal infection by specific pathogens, and viral gastrointestinal disorders.
  5. As a method of treating human patients suffering from cancer, The method includes the step of administering a dose of a microbiome restoration therapy composition to a patient by colonoscopy or rectum, wherein the microbiome restoration therapy composition Fecal microorganisms derived from human fecal samples, and Polyethylene glycol and saline solution A method comprising a fecal microbiome suspension containing
  6. As a method for reducing antimicrobial resistant intestinal colonization in human patients requiring reduction of antimicrobial resistant intestinal colonization, The method includes the step of administering a dose of a microbiome restoration therapy composition to a patient by colonoscopy or rectum, wherein the microbiome restoration therapy composition Fecal microorganisms derived from human fecal samples, and Polyethylene glycol and saline solution A method comprising a fecal microbiome suspension containing
  7. As a method for changing the composition of the gut microbiome in human patients who require a change in the composition of the gut microbiome, The method includes the step of administering a dose of a microbiome restoration therapy composition to a patient by colonoscopy or rectum, wherein the microbiome restoration therapy composition Fecal microorganisms derived from human fecal samples, and Polyethylene glycol and saline solution A method comprising a fecal microbiome suspension containing
  8. As a method for altering the intestinal metabolite composition in human patients requiring alteration of the intestinal metabolite composition, The method includes the step of administering a dose of a microbiome restoration therapy composition to a patient by colonoscopy or rectum, wherein the microbiome restoration therapy composition Fecal microorganisms derived from human fecal samples, and Polyethylene glycol and saline solution A method comprising a fecal microbiome suspension containing
  9. A method according to any one of claims 1 to 8, wherein the volume of the composition comprises about 1 × 10⁸ to about 5 × 10¹⁰ colony-forming units (CFU)/mL of fecal microorganisms.
  10. A method according to any one of claims 1 to 9, wherein the fecal microorganisms include spore-forming microorganisms and non-spore-forming microorganisms.
  11. A method according to any one of claims 1 to 10, wherein the fecal microorganism comprises a microorganism of the Bacteroides species.
  12. A method according to any one of claims 1 to 11, wherein the volume of the composition comprises 1 x 10⁵ CFU/mL or more of Bacteroides .
  13. A method according to any one of claims 1 to 12, wherein the fecal microorganisms are obtained by a process comprising the steps of treating a donor human fecal sample with a solution comprising polyethylene glycol and saline solution, and obtaining a filtrate containing fecal microorganisms.
  14. A method according to any one of claims 1 to 13, wherein the solution comprises 20 g to 50 g of polyethylene glycol per 1 L of saline solution.
  15. A method according to any one of claims 1 to 14, wherein the solution comprises 30 g of polyethylene glycol per 1 L of saline solution.
  16. A method according to any one of claims 1 to 15, wherein the polyethylene glycol comprises polyethylene glycol 3350.
  17. A method according to any one of claims 1 to 16, wherein the saline solution is a 0.9% sodium chloride solution.
  18. A method according to any one of claims 1 to 17, wherein the volume of the composition has a volume of about 150 mL.
  19. A method according to any one of claims 1 to 18, wherein the volume of the composition comprises about 6 grams or less of polyethylene glycol.
  20. A method according to any one of claims 1 to 19, wherein the volume of the composition comprises polyethylene glycol in a saline solution of 5.97 grams or less.

Description

Microbiome Restoration Therapy (MRT) Composition and Method of Administration Cross-reference regarding related applications This application claims the benefit of priority to U.S. Provisional Patent Application No. 63/536,756 filed September 6, 2023, the entire contents of which are incorporated herein by reference. field The present disclosure relates to compositions and methods for administering a microbiome restoration therapy composition by colonoscopy or by rectum. In some embodiments, the method is intended to treat gastrointestinal diseases and/or conditions by administering the microbiome restoration therapy composition by colonoscopy, e.g., to treat CDI, including recurrent Clostridioides difficile infection (CDI). In other embodiments, the method is intended to treat other gastrointestinal diseases or disorders, e.g. ulcerative colitis (UC) and Crohn's disease (CD). In other embodiments, the method is intended to treat cancer. Additionally, methods and uses of the microbiome restoration therapy composition as described herein are disclosed, for example , to achieve antimicrobial resistance (AMR) intestinal decolonization by decolonizing patients possessing antibiotic resistance genes (ARGs) in the gut microbiome, e.g., to reduce the abundance of antimicrobial resistance genes and/or reduce the presence of antimicrobial resistance organisms. Additionally, methods and uses of a microbiome restoration therapy composition as described herein are disclosed for changing the composition of the intestinal microbiome and/or changing the composition of intestinal metabolites. There are over 1,000 different species of bacteria in a healthy gastrointestinal (GI) tract. Clostridia are anaerobic, spore-forming bacteria. Certain species of Clostridia are pathogens and produce toxins that can be harmful to humans. Clostridioides difficile (also known as Clostridium difficile , hereinafter referred to as " C. difficile ") is a species of Clostridium that, when it overgrows in the GI tract, can release toxins that can cause a number of symptoms, including abdominal distension, constipation, diarrhea, inflammation, and abdominal pain, and in certain cases, can lead to death. C. difficile infection (CDI) is a common healthcare-associated infection and is frequently acquired in community settings, such as nursing homes. CDI is a cause of significant morbidity, mortality, and healthcare expenditure. A major complication of CDI is recurrent infection despite the absence of additional risk factors. In recent years, CDI has shown an increase in overall prevalence and disease severity. A study of data from 2017 reported that C. difficile accounted for nearly 500,000 infections in the United States (US). A major complication of CDI is recurrent infection despite the absence of additional risk factors. Although the mature colonic microbiota of healthy adults is generally resistant to C. difficile colonization, the widely accepted model of CDI pathogenesis involves the use of broad-spectrum antimicrobial agents that suppress and destroy the microbial community normally preventing the expansion of C. difficile . Since C. difficile spores are highly resistant to antibiotics, they can germinate into trophozoites after antibiotic treatment is discontinued. If the remaining normal gut microbiota is unable to suppress the infection, C. difficile bacteria proliferate and produce toxins that cause the destruction of colonic epithelial cells, inflammation, and disease symptoms. Conventional treatment for CDI involves the use of antibiotics, which further disrupts the intestinal bacterial flora and limits its recovery after CDI. This reduction in intestinal microbiota diversity following antibiotic treatment can make patients vulnerable to recolonization by C. difficile and lead to recurrent infections (e.g., recurrent CDI/rCDI). Recurrent CDI outbreaks can persist for years and may result in the continued use of antibiotics, a significant decline in quality of life (QoL), repeated hospitalizations, and even death. Therefore, there is a need for more effective treatments for CDI, including recurrent CDI (rCDI). Disruption of the gut microbiome has been believed to affect other gastrointestinal diseases and conditions, as well as other gastrointestinal disorders, such as ulcerative colitis (UC) and Crohn's disease (CD). Additionally, disruption of the gut microbiome has been believed to affect certain cancers. Therefore, there is a need for more effective methods to restore the disrupted gut bacterial flora in the treatment of various diseases and conditions, including gastrointestinal diseases and conditions, and cancer. According to some embodiments, a method of administering a microbiome restoration composition by colonoscopy is provided herein. Such a method is useful for treating gastrointestinal diseases and/or conditions, such as recurrent Clostridioides difficile infection (CDI), other gastrointestinal diseases or disorders, su