Polypeptide and immune modulation

• US 9,796,762 B2
• Filed: 04/10/2014
• Issued: 10/24/2017
• Est. Priority Date: 04/10/2013
• Status: Active Grant

• Current Assignee: 4D Pharma Research Limited (4D Pharma PLC), Armistice Capital Master Fund Ltd. (Armistice Capital LLC)
• Original Assignee: 4D Pharma Research Limited (4D Pharma PLC)
• Inventors: Kelly, Denise, Patterson, Angela, Monnais, Edouard, Mulder, Imke
• Primary Examiner(s): GRASER, JENNIFER E
• Application Number:
  US14/249,710
• Publication Number:
  US 20150071957A1
• Time in Patent Office: 1,293 Days
• Field of Search: None
• CPC Class Codes: A23P 10/30 Encapsulation of particles, e.g. foodstuff additives
• CPC Class Codes: A61K 38/164 from bacteria
• CPC Class Codes: A61K 39/02 Bacterial antigens
• CPC Class Codes: A61P 1/00 Drugs for disorders of the alimentary tract or the digestive system
• CPC Class Codes: A61P 1/04 for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
• CPC Class Codes: A61P 1/14 Prodigestives, e.g. acids, enzymes, appetite stimulants, antidyspeptics, tonics, antiflatulents
• CPC Class Codes: A61P 11/02 Nasal agents, e.g. decongestants
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 17/02 for treating wounds, ulcers, burns, scars, keloids, or the like
• CPC Class Codes: A61P 17/06 Antipsoriatics
• CPC Class Codes: A61P 19/00 Drugs for skeletal disorders
• CPC Class Codes: A61P 19/02 for joint disorders, e.g. arthritis, arthrosis
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 3/02 Nutrients, e.g. vitamins, minerals
• CPC Class Codes: A61P 3/04 Anorexiants; Antiobesity agents
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 37/00 Drugs for immunological or allergic disorders
• CPC Class Codes: A61P 37/02 Immunomodulators
• CPC Class Codes: A61P 37/06 Immunosuppressants, e.g. drugs for graft rejection
• CPC Class Codes: A61P 37/08 : Antiallergic agents antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14
• CPC Class Codes: A61P 43/00 : Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07K 14/195 : from bacteria

Abstract

The present invention relates to Roseburia flagellin, and/or a polynucleotide sequence encoding said Roseburia flagellin, and/or a vector comprising said polynucleotide sequence, and/or a host cell, including bacteria, comprising said vector, and/or a host cell, including bacteria, comprising said polynucleotide sequence, for use in modulating the inflammation of a tissue or an organ in a subject.

Claims

1. A method of treating a gastrointestinal inflammatory disorder or an autoimmune disorder, comprising administering to a subject in need thereof a Roseburia flagellin,

wherein said Roseburia flagellin is a FlaA1 polypeptide with a sequence that has at least 95% identity to SEQ ID NO:

2 or a fragment thereof, and

wherein said Roseburia flagellin comprises amino acids 79-117 of SEQ ID NO;

2 and binds to TLR5.

2. The method according to claim 1 wherein the gastrointestinal inflammatory disorder or autoimmune disorder affects an alimentary canal, or a section thereof, of said subject.

3. The method according to claim 1 wherein the gastrointestinal inflammatory disorder or autoimmune disorder affects a mucosal site of said subject, such as an esophagus, stomach, or intestine.

4. The method according to claim 1 wherein the gastrointestinal inflammatory disorder or autoimmune disorder affects an intestine.

5. The method according to claim 1 wherein the subject is treated for an autoimmune disorder, wherein the autoimmune disorder is neutropenia.

6. The method according to claim 1 wherein said Roseburia flagellin comprises the polypeptide of SEQ ID NO:

2 or a fragment thereof.

7. The method according to claim 1 wherein the Roseburia flagellin is a truncated FlaA1 polypeptide, and wherein said truncated FlaA1 polypeptide binds to TLR5 when administered to the subject.

8. The method according to claim 7 wherein the subject is administered the truncated FlaA1 polypeptide, wherein the truncated FlaA1 polypeptide comprises at least 40 amino acids of a polypeptide of SEQ ID NO:

2.

9. The method of claim 1, wherein the subject is treated for a gastrointestinal inflammatory disorder selected from the group consisting of irritable bowel syndrome (IBS), colitis, and inflammatory bowel disorder (IBD).

10. The method of claim 1, wherein the subject is treated for a gastrointestinal inflammatory disorder, wherein the gastrointestinal inflammatory disorder is Crohn'"'"'s disease.

11. The method of claim 1, wherein the subject is treated for an autoimmune disorder selected from the group consisting of ulcerative colitis and pouchitis.

12. The method of claim 1, wherein said FlaA1 polypeptide has at least 97% identity to the polypeptide of SEQ ID NO:

2 or a fragment thereof.

13. The method of claim 1, wherein said FlaA1 polypeptide has at least 98% identity to the polypeptide of SEQ ID NO:

2 or a fragment thereof.

14. The method of claim 1, wherein said FlaA1 polypeptide has at least 99% identity to the polypeptide of SEQ ID NO:

2 or a fragment thereof.

15. The method of claim 7, wherein the subject is administered the truncated FlaA1 polypeptide, and wherein the truncated FlaA1 polypeptide comprises at least 50 amino acids of a polypeptide of SEQ ID NO:

2.

16. The method of claim 7, wherein the subject is administered the truncated FlaA1 polypeptide, and wherein the truncated FlaA1 polypeptide comprises at least 75 amino acids of a polypeptide of SEQ ID NO:

2.

17. The method of claim 7, wherein the subject is administered the truncated FlaA1 polypeptide, and wherein the truncated FlaA1 polypeptide comprises at least 100 amino acids of a polypeptide of SEQ ID NO:

2.

18. The method of claim 7, wherein the subject is administered the truncated FlaA1 polypeptide, and wherein the truncated FlaA1 polypeptide comprises at least 125 amino acids of a polypeptide of SEQ ID NO:

2.

19. The method of claim 7, wherein the subject is administered the truncated FlaA1 polypeptide, and wherein the truncated FlaA1 polypeptide comprises at least 150 amino acids of a polypeptide of SEQ ID NO:

2.

20. The method according to claim 7, wherein the subject is administered the truncated FlaA1 polypeptide, and wherein the truncated FlaA1 polypeptide comprises at least 175 amino acids of a polypeptide of SEQ ID NO:

2.

21. The method of claim 1, wherein the subject is treated for a gastrointestinal inflammatory disorder.

22. The method of claim 1, wherein the subject is treated for an autoimmune disorder.