# US 10,765,740 B2 · Selectively altering microbiota for immune modulation > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 10,765,740 B2 - Document ID: US10765740B2 - Status: Granted - Kind: B2 - Application number: 16/593,825 - Filed: 2019-10-04 - Published: 2020-01-30 - Granted: 2020-09-08 - Earliest claimed: 2016-06-05 - Assignees: SNIPR Technologies Limited - Applicants: SNIPR Technologies Limited - Inventors: Jasper Clube - Web page: https://patentgrep.com/patent/US10765740B2 ## CPC - A61K 39/3955: {against proteinaceous materials, e.g. enzymes, hormones, lymphokines} - A61K 31/7105: Natural ribonucleic acids, i.e. containing only riboses attached to adenine, guanine, cytosine or uracil and having 3'-5' phosphodiester links - 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) - 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) - A61K 35/74: Bacteria (therapeutic use of a bacterial protein A61K38/00) - A61P 35/00: Antineoplastic agents - A61P 37/00: Drugs for immunological or allergic disorders - A61K 39/0011: {Cancer antigens} - A61K 2039/505: {comprising antibodies} - C12N 2320/30: Special therapeutic applications - C12N 2320/50: Methods for regulating/modulating their activity - A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D) - A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS - C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00) ## 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 ### Claim 1 A method for treating an infectious disease in a human patient, wherein the method comprises (a) exposing a microbiota in the patient to a guided nuclease to selectively target the genome of cells of a first species in the microbiota using the guided nuclease, wherein the first species is a bacterial or archaeal species; and simultaneously or sequentially administering to the patient an effective amount of an immunotherapy; and (b) allowing the guided nuclease to cut one or more target nucleotide sequences comprised by first cells of a first strain of the first species, thereby killing the first cells or reducing the growth thereof, whereby the proportion of the first cells comprised by the microbiota is reduced; wherein (c) the selective targeting avoids targeting second cells comprised by the microbiota, wherein the second cells are of a different strain or a different species from the first cells, wherein the second cells are probiotic, commensal or symbiotic with humans; and (d) the reducing of the proportion of the first cells modulates immune cells in the patient, whereby the efficacy of the immunotherapy is enhanced for treatment of the infectious disease in the patient. ### Claim 2 (depends on 1) The method of claim 1, wherein the infectious disease is selected from the group consisting of malaria, Human Immunodeficiency Virus (HIV) infection, tuberculosis infection, cholera, Salmonella typhimurium infection, Clostridium difficile infection, Bordetella pertussis infection or chlamydia infection. ### Claim 3 (depends on 1) The method of claim 1, wherein the infectious disease is a viral infection or mediated by a viral infection. ### Claim 4 (depends on 1) The method of claim 1, wherein the immunotherapy is a vaccine therapy. ### Claim 5 (depends on 4) The method of claim 4, wherein the immunotherapy is a bacterial vaccine. ### Claim 6 (depends on 4) The method of claim 4, wherein the immunotherapy is a viral vaccine. ### Claim 7 (depends on 4) The method of claim 4, wherein the immunotherapy is a cancer vaccine. ### Claim 8 (depends on 3) The method of claim 3, wherein the immunotherapy is an anti-retroviral therapy. ### Claim 9 (depends on 8) The method of claim 8, wherein the immunotherapy is an HIV vaccine therapy. ### Claim 10 (depends on 1) The method of claim 1, wherein the growth of the first cells is inhibited by at least 1000 times compared to the growth inhibition of the second cells 24 hours after exposing the first and second cells to the guided nuclease in an in vitro assay. ### Claim 11 (depends on 1) The method of claim 1, wherein and the immune cells comprise cells selected from CD8+ cells, tumor infiltrating lymphocytes (TILs), CD4+ cells, Treg cells and memory cells. ### Claim 12 (depends on 1) The method of claim 1, wherein the first species is a gram negative bacterial species. ### Claim 13 (depends on 1) The method of claim 1, wherein the immune cells are upregulated or expanded in the patient. ### Claim 14 (depends on 1) The method of claim 1, wherein the immune cells comprise memory cells selected from the group consisting of central memory T-cells (TCM), effector memory T-cells (TEM), stem cell memory cells (TSCM), and memory effector T-cells (Teff). ### Claim 15 (depends on 1) The method of claim 1, wherein the immune cells comprise memory cells selected from the group consisting of CD45RO+CD62L+ and CD25+CD45RA− CD45RO+CD127+ cells. ### Claim 16 (depends on 1) The method of claim 1, wherein the microbiota is a gut microbiota of the patient. ### Claim 17 (depends on 1) The method of claim 1, wherein the immune cells comprise administered cells via adoptive cell therapy. ### Claim 18 (depends on 1) The method of claim 1, wherein the guided nuclease is a Cas, Transcription activator-like effector nuclease (TALEN), meganuclease or zinc finger nuclease. ### Claim 19 (depends on 1) The method of claim 1, wherein the efficacy of the immunotherapy is enhanced by upregulating TH17 cells in the patient. ### Claim 20 (depends on 19) The method of claim 19, wherein the TH17 cells are endogenous cells of the patient. ### Claim 21 (depends on 1) The method of claim 1, wherein the second cells have a 16s ribosomal RNA-encoding DNA sequence that is at least 80% identical to a 16s ribosomal RNA-encoding DNA sequence of the first cells. ### Claim 22 (depends on 1) The method of claim 1, wherein the first cells and the second cells are comprised by a gut microbiota, skin microbiota, oral cavity microbiota, throat microbiota, hair microbiota, armpit microbiota, vaginal microbiota, rectal microbiota, anal microbiota, ocular microbiota, nasal microbiota, tongue microbiota, lung microbiota, liver microbiota, kidney microbiota, genital microbiota, penile microbiota, scrotal microbiota, mammary gland microbiota, ear microbiota, urethra microbiota, labial microbiota, organ microbiota or dental microbiota.