Selectively altering microbiota for immune modulation

Patent metadata

Field	Value
Publication number	US-2018326057-A1
Application number	US-201816041595-A
Country	US
Kind code	A1
Filing date	Jul 20, 2018
Priority date	Jun 5, 2016
Publication date	Nov 15, 2018
Grant date	—

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.

First claim

1 . A method for modulating a therapy of a disease or condition in a human or animal patient, the method comprising altering 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 PD-1 inhibitor or a PD-L1 inhibitor.

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 method comprises increasing the relative proportion of the sub-population of the gram positive bacteria in the microbiota of the patient

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

10 . The method of claim 8 , wherein the gram positive bacteria comprise Clostridium.

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

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

13 . The method of claim 11 , wherein the bacterial transplant comprises Clostridium.

14 . The method of claim 8 , wherein the method comprises selectively killing or reducing growth of a bacterial or archael sub-population in the microbiota using a guided nuclease.

15 . The method of claim 14 , wherein the guided nuclease is a Cas, TALEN, meganuclease or zinc finger nuclease.

16 . The method of claim 15 , 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.

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

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

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

20 . The method of claim 19 , wherein the cancer is melanoma, renal cell carcinoma, lung cancer, bladder carcinoma, CNS tumor or Hodgkin's disease.

Assignees

• Snipr Tech Ltd

Inventors

• Clube Jasper
• Sommer Morten
• Grøndahl Christian
• Vazquez-Uribe Ruben
• Van Der Helm Eric

Classifications

• A61P37/00

  Drugs for immunological or allergic disorders · CPC title

• A61K31/7105 Primary

  Natural ribonucleic acids, i.e. containing only riboses attached to adenine, guanine, cytosine or uracil and having 3'-5' phosphodiester links · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• A61K2039/505

  comprising antibodies · CPC title

• A61K39/3955 Primary

  against proteinaceous materials, e.g. enzymes, hormones, lymphokines · CPC title