Polypeptide for use in the protection of oxygen sensitive gram-positive bacteria

Patent metadata

Field	Value
Publication number	US-2024197821-A1
Application number	US-202318495355-A
Country	US
Kind code	A1
Filing date	Oct 26, 2023
Priority date	Jul 13, 2017
Publication date	Jun 20, 2024
Grant date	—

Abstract

The present disclosure concerns a Reg3α polypeptide (also known as Hepatocarcinoma-Intestine-Pancreas/Pancreatitis Associated Protein (HIP/PAP)) for protecting oxygen sensitive gram-positive bacteria, compositions including the polypeptide, and their use. The disclosure shows that increasing concentration of the hReg3α lectin into the gastrointestinal tract (GIT) lumen of hReg3α-transgenic mice induced significant changes in composition of gut microbiota, and dramatically improved host resistance to intestinal inflammation. The Reg3α polypeptide may be used for preventing or treating microbiota-related diseases and/or disorders, including inflammatory bowel disease (IBD), colitis, gastrointestinal infections, irritable bowel syndrome and other gastrointestinal functional diseases, gastrointestinal tract cancer, metabolic syndrome and obesity, diabetes, liver diseases, allergic diseases, neurodegenerative diseases and psychological disorders, and the prevention and treatment methods may also include transferring to said patient fecal microbiota from a human or animal expressing the Reg3α polypeptide.

First claim

What is claimed is:

1 . A pharmaceutical composition comprising a Reg3α polypeptide comprising an amino acid sequence selected from the group consisting of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO:3, and SEQ ID NO: 4 in combination with fecal microbiota from a human or animal that expresses the Reg3α polypeptide and at least one pharmaceutically acceptable excipient.

2 . The pharmaceutical composition according to claim 1 wherein the fecal microbiota is from a human or animal that expresses hReg3α.

3 . The pharmaceutical composition according to claim 1 wherein the composition is in a pharmaceutical form suitable for oral or transmucosal administration.

4 . The pharmaceutical composition according to claim 1 wherein the fecal microbiota is from an animal that is transgenic for the Reg3α polypeptide

5 . The pharmaceutical composition according to claim 1 wherein the fecal microbiota is from a heathy human donor.

6 . A method of treating or preventing a microbiota-related disease and/or disorder selected from the group consisting of inflammatory bowel disease (IBD), colitis, gastrointestinal infections, irritable bowel syndrome, gastrointestinal functional diseases, gastrointestinal tract cancer, metabolic syndrome, obesity, diabetes, liver diseases, allergic diseases, neurodegenerative diseases, psychological disorders, autoimmune disease, cystic fibrosis, atopic dermatitis, neurological disease, autism, anxiety, depression, chronic pain, Alzheimer's disease and Parkinson's disease, said method comprising administering to a patient in need thereof an effective amount of the composition according to claim 1 .

7 . A method for preventing or treating destruction of gut microbiota balance resulting from a cause selected from the group consisting of medication, antibiotics, chemotherapy, radiotherapy, immunotherapy, poor nutrition, eating disorders, illness, aging, and genetics comprising administering to a patient in need thereof an effective amount of the composition of claim 1 .

8 . A method for preventing or treating alterations or changes in composition and/or biodiversity of gut microbiota comprising administering to a patient in need thereof an effective amount of the composition of claim 1 .

9 . A method for upregulating modulators of cell-matrix interactions and mucin O-glycosylation of the intestinal barrier in a host in need thereof, comprising administering to a patient in need thereof an effective amount of the composition of claim 1 , wherein the composition protects oxygen sensitive gram-positive bacteria.

10 . A pharmaceutical composition comprising:
a) a Reg3α polypeptide comprising an amino acid sequence selected from the group consisting of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO:3, and SEQ ID NO: 4; b) fecal microbiota from a human or animal that expresses the Reg3α polypeptide; and c) at least one pharmaceutically acceptable excipient.

11 . The pharmaceutical composition according to claim 10 wherein the fecal microbiota is from a human or animal that expresses hReg3α.

12 . The pharmaceutical composition according to the claim 10 wherein the composition is in a pharmaceutical form suitable for oral or transmucosal administration.

13 . The pharmaceutical composition according to the claim 10 wherein the fecal microbiota is from an animal that is transgenic for the Reg3α polypeptide

14 . The pharmaceutical composition according to claim 10 wherein the fecal microbiota is from a heathy human donor.

15 . A method of treating or preventing a microbiota-related disease and/or disorder selected from the group consisting of inflammatory bowel disease (IBD), colitis, gastrointestinal infections, irritable bowel syndrome, gastrointestinal functional diseases, gastrointestinal tract cancer, metabolic syndrome, obesity, diabetes, liver diseases, allergic diseases, neurodegenerative diseases, psychological disorders, autoimmune disease, cystic fibrosis, atopic dermatitis, neurological disease, autism, anxiety, depression, chronic pain, Alzheimer's disease and Parkinson's disease, said method comprising administering to a patient in need thereof an effective amount of the composition according to claim 10 .

16 . A method for preventing or treating destruction of gut microbiota balance resulting from a cause selected from the group consisting of medication, antibiotics, chemotherapy, radiotherapy, immunotherapy, poor nutrition, eating disorders, illness, aging, and genetics comprising administering to a patient in need thereof an effective amount of the composition of claim 10 .

17 . A method for preventing or treating alterations or changes in composition and/or biodiversity of gut microbiota comprising administering to a patient in need thereof an effective amount of the composition of claim 10 .

18 . A method for upregulating modulators of cell-matrix interactions and mucin O-glycosylation of the intestinal barrier in a host in need thereof, comprising administering to a patient in need thereof an effective amount of the composition of claim 10 , wherein the composition protects oxygen sensitive gram-positive bacteria.

Assignees

• Inst Nat Sante Rech Med
• Hopitaux Paris Assist Publique
• Inst Nat De La Rech Agronomique Inra
• Univ Paris Sud

Inventors

• Dore Joël
• Faivre Jamila
• Moniaux Nicolas
• Brechot Christian
• Darnaud Marion

Classifications

• A61K38/00

  Medicinal preparations containing peptides (peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00) · CPC title

• A61P3/00

  Drugs for disorders of the metabolism (of the blood or the extracellular fluid A61P7/00) · CPC title

• A61P1/00

  Drugs for disorders of the alimentary tract or the digestive system · CPC title

• C07K14/4726 Primary

  Lectins · CPC title

• A23L33/19

  Dairy proteins · CPC title