POLYPEPTIDE AND IMMUNE MODULATION

• US 20150071957A1
• Filed: 04/10/2014
• Published: 03/12/2015
• 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: GT Biologics Limited (4D Pharma PLC)
• Inventors: Kelly, Denise, Mulder, Imke, Patterson, Angela, Monnais, Edouard
• Granted Patent: US 9,796,762 B2
• Time in Patent Office: Days
• US Class Current: 424/190.1
• 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. 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.

2. The Roseburia flagellin, and/or the polynucleotide sequence, and/or the vector, and/or the host cell, including bacteria, comprising said vector, and/or the host cell, including bacteria, comprising said polynucleotide sequence, for the use according to claim 1 wherein said Roseburia flagellin is selected from the group consisting of:

polypeptides having at least 75% identity to SEQ ID NO 2, SEQ ID NO 4, SEQ ID NO 6, SEQ ID NO 8, SEQ ID NO 10 or SEQ ID NO 12 or variants, homologues, fragments or derivatives thereof and combinations thereof;

and wherein the polynucleotide sequence encoding said Roseburia flagellin is selected from the group consisting of;

polynucleotide sequences encoding a polypeptide having at least 75% identity to SEQ ID NO 2, SEQ ID NO 4, SEQ ID NO 6, SEQ ID NO 8, SEQ ID NO 10 or SEQ ID NO 12 or variants, homologues, fragments or derivatives thereof;

polynucleotide sequences having at least 75% identity to SEQ ID NO 1, SEQ ID NO 3, SEQ ID NO 5, SEQ ID NO 7, SEQ ID NO 9 or SEQ ID NO 11 or variants, homologues, fragments or derivatives thereof;

and combinations thereof.

31. A pharmaceutical composition comprising 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 of claim 1, and a pharmaceutically acceptable excipient, carrier or diluent.

32. The pharmaceutical composition according to claim 31 wherein said Roseburia flagellin, and/or said polynucleotide sequence, and/or said vector, and/or said host cell, including bacteria, comprising said vector, and/or said host cell, including bacteria, comprising said polynucleotide sequence, is encapsulated.

33. A nutritional supplement comprising 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 of claim 1, and a nutritional acceptable excipient, carrier or diluent.

34. The nutritional supplement according to claim 33 wherein said Roseburia flagellin, and/or said polynucleotide sequence, and/or said vector, and/or said host cell, including bacteria, comprising said vector, and/or said host cell, including bacteria, comprising said polynucleotide sequence, is encapsulated.

35. A feedstuff, food product, dietary supplement, or food additive comprising a 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 of claim 1.

36. The feedstuff, food product, dietary supplement, or food additive according to claim 35 wherein said feedstuff, food product, dietary supplement, or food additive is encapsulated.

37. A process for producing a pharmaceutical composition according to claim 31, said process comprising admixing said Roseburia flagellin, and/or said polynucleotide sequence, and/or said vector, and/or said host cell, including bacteria, comprising said vector, and/or said host cell, including bacteria, comprising said polynucleotide sequence, with a pharmaceutically acceptable excipient, carrier or diluent;

optionally said Roseburia flagellin, and/or said polynucleotide sequence, and/or said vector, and/or said host cell, including bacteria, comprising said vector, and/or said host cell, including bacteria, comprising said polynucleotide sequence, is encapsulated.

38. A process for producing a nutritional supplement according to claim 33, said process comprising admixing said Roseburia flagellin, and/or said polynucleotide sequence, and/or said vector, and/or said host cell, including bacteria, comprising said vector, and/or said host cell, including bacteria, comprising said polynucleotide sequence, with a nutritionally acceptable excipient, carrier or diluent;

optionally said Roseburia flagellin, and/or said polynucleotide sequence, and/or said vector, and/or said host cell, including bacteria, comprising said vector, and/or said host cell, including bacteria, comprising said polynucleotide sequence, is encapsulated.

39. A method of modulating the inflammation of a tissue or an organ in a subject, said method comprising administering to the subject a 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 of claim 1, and wherein the inflammation of the tissue or organ in the subject is modulated.

40. A method of modulating the production of T cells in a subject, said method comprising administering a 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 of claim 1, and wherein the production of T cells in the subject is modulated, in particular T regulatory cells.

43. A method of modulating dendritic cells and/or epithelial cells in a subject, said method comprising administering a 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 of claim 1, and wherein dendritic cells and/or epithelial cells in the subject are modulated.

44. A method of regulating the production of IL-10 and/or TGFβ

in a cell or cells of a subject, said method comprising administering a 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 of claim 1, to the subject, and wherein the production of IL-10 and/or TGFβ

in a cell or cells of the subject is regulated.

45. A method of regulating the production of cell surface markers involved in immune responses and antigen recognition such as CD40, I-A/I-E, CD317/BST-2, CD103, CD80, CD86, CD83 and/or Siglec-H and/or the species equivalent in a cell or cells of a subject, said method comprising administering a 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 of claim 1, to the subject, and wherein the production of cell surface markers involved in immune responses and antigen recognition such as CD40, I-A/I-E, CD317/BST-2, CD103, CD80, CD86, CD83 and/or Siglec-H and/or the species equivalent in a cell or cells of the subject is regulated.

46. A method of regulating the expression of one of more Type I IFN genes in a cell or cells of a subject, said method comprising administering a 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 of claim 1, wherein the expression of one of more Type I IFN genes in a cell or cells of the subject is regulated.

47. A method of regulating the expression of one or more pro-inflammatory genes in a cell or cells of a subject, said method comprising administering a Roseburia flagellin, 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 of claim 1, wherein the expression of one or more pro-inflammatory genes in a cell or cells of the subject is regulated.

48. A method of improving intestinal microbiota in a subject, said method comprising administering a 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 of claim 1, and wherein the intestinal microbiota in a subject is improved.

49. A method of regulating appetite in a subject, said method comprising administering a 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 of claim 1, and wherein the appetite in the subject is regulated.

50. A method of regulating the expression of the gene encoding cholecystokinin (Cck) and/or the expression of the gene encoding glucagon (Gcg) in a cell or cells of a subject, said method comprising administering a 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 of claim 1, and wherein the expression of the gene encoding cholecystokinin (Cck) and/or the expression of the gene encoding glucagon (Gcg) in a cell or cells of the subject is regulated.

51. A method of improving alimentary canal health in a subject, said method comprising administering a 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 of claim 1, and wherein alimentary canal health in a subject is improved.

66. A method of restoring immunological tolerance in a subject, said method comprising administering a 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 of claim 1, and wherein the immunological tolerance in a subject is restored.

3-10. -10. (canceled)

11. 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 treating a disorder in a subject, wherein said disorder is an inflammatory disorder and/or an autoimmune disorder.

13. The Roseburia flagellin, and/or the polynucleotide sequence, and/or the vector, and/or the host cell, including bacteria, comprising said vector, and/or the host cell, including bacteria, comprising said polynucleotide sequence, for use according to claim 11 wherein said disorder is selected from the group consisting of rheumatoid arthritis, psoriasis, multiple sclerosis, type I diabetes, coeliac disease, atopic dermatitis, rhinitis, irritable bowel syndrome (IBS), colitis, inflammatory bowel disorder (IBD), ulcerative colitis, pouchitis, Crohn'"'"'s disease, functional dyspepsia, atopic diseases, necrotising enterocolitis, and combinations thereof.

12. (canceled)

14-30. -30. (canceled)

41. A method of regulating the immune system of a subject, said method comprising administering a 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, and wherein the immune system of the subject is regulated.

42. A method of treating a disorder in a subject, said method comprising administering a 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, wherein said disorder is an inflammatory disorder and/or an autoimmune disorder.

52-65. -65. (canceled)

67. (canceled)

68. (canceled)