Selectively altering microbiota for immune modulation

• US 10,300,139 B2
• Filed: 07/20/2018
• Issued: 05/28/2019
• Est. Priority Date: 06/05/2016
• Status: Active Grant

• Current Assignee: Snipr Technologies Limited
• Original Assignee: Snipr Technologies Limited
• Inventors: Clube, Jasper
• Primary Examiner(s): Nickol, Gary B
• Assistant Examiner(s): Jackson-Tongue, Lakia J
• Application Number:
  US16/041,595
• Publication Number:
  US 20180326057A1
• Time in Patent Office: 312 Days
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: A61K 31/7105 Natural ribonucleic acids, i.e. containing only riboses attached to adenine, guanine, cytosine or uracil and having 3'-5' phosphodiester links
• CPC Class Codes: A61K 35/15 Cells of the myeloid line, e.g. granulocytes, basophils, eosinophils, neutrophils, leucocytes, monocytes, macrophages or mast cells; Myeloid precursor cells; Antigen-presenting cells, e.g. dendritic cells presenting a specific antigen A61K39/00; therapeutic combinations of antibodies, or fragments thereof, and blood-derived cells A61K39/00
• CPC Class Codes: A61K 35/17 Lymphocytes; B-cells; T-cells; Natural killer cells; Interferon-activated or cytokine-activated lymphocytes when activated by a specific antigen A61K39/00
• CPC Class Codes: A61K 35/74 Bacteria therapeutic use of a bacterial protein A61K38/00
• CPC Class Codes: A61K 39/0011 Cancer antigens
• CPC Class Codes: A61K 39/3955 against proteinaceous materials, e.g. enzymes, hormones, lymphokines
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 37/00 Drugs for immunological or allergic disorders
• CPC Class Codes: C12N 2320/30 Special therapeutic applications
• CPC Class Codes: C12N 2320/50 Methods for regulating/modulating their activity

Abstract

The invention relates to methods of modulating immune cells in a patient by altering microbiota of the patient. The invention also relates to methods of modulating treatments or therapies in a subject organism by altering microbiota of the subject. The invention also relates to cell populations, systems, arrays, cells, RNA, kits and other means for effecting this. In an example, advantageously selective targeting of a particular species in a human gut microbiota using guided nucleic acid modification is carried out to effect the alteration.

Claims

1. A method for modulating a therapy of a disease or condition in a human or animal patient, the method comprising increasing the relative proportion of a sub-population of gram positive bacteria in a microbiota of the patient, wherein the therapy comprises administration of an effective amount of an immune checkpoint inhibitor to the patient, and wherein the immune checkpoint inhibitor is a Programmed Cell Death Protein 1 (PD-1) inhibitor or a Programmed Death-Ligand 1 (PD-L1) inhibitor, and wherein the method comprises selectively killing or reducing growth of a bacterial or archael sub-population in the microbiota using a guided nuclease.

2. The method of claim 1, wherein the immune checkpoint inhibitor is an antibody.

3. The method of claim 1, wherein the immune checkpoint inhibitor is an anti-PD-1 antibody.

4. The method of claim 3, wherein the immune checkpoint inhibitor is nivolumab, pembrolizumab, or pidilizumab, durvalumab, or atezolizumab.

5. The method of claim 1, wherein the immune checkpoint inhibitor is an anti-PD-L1 antibody.

6. The method of claim 5, wherein the immune checkpoint inhibitor is durvalumab or atezolizumab.

7. The method of claim 1, wherein the microbiota is gut microbiota.

8. The method of claim 1, wherein the gram positive bacteria comprise Ruminococcus.

9. The method of claim 1, wherein the gram positive bacteria comprise Clostridium.

10. The method of claim 1, wherein the method comprises administering a bacterial transplant to the patient.

11. The method of claim 10, wherein the bacterial transplant comprises Ruminococcus.

12. The method of claim 10, wherein the bacterial transplant comprises Clostridium.

13. The method of claim 1, wherein the guided nuclease is a Cas, transcription activator-like effector nuclease (TALEN), meganuclease or zinc finger nuclease.

14. The method of claim 13, wherein the microbiota comprises a mixed population of human gut microbiota bacteria of different species, and wherein the selective killing comprises selectively killing cells of one or more of the different species and sparing cells of the other species.

15. The method of claim 1, wherein the sub-population of gram positive bacteria comprise Ruminococcus.

16. The method of claim 14, wherein the sub-population of gram positive bacteria comprise Clostridium.

17. The method of claim 1, wherein the disease is cancer.

18. The method of claim 17, wherein the cancer is melanoma, renal cell carcinoma, lung cancer, bladder carcinoma, central nervous system (CNS) tumor or Hodgkin'"'"'s disease.