# US 12,601,002 B2 · Method for predicting and improving treatment response to intestinal microbiome-based cancer immunotherapy and method for screening for candidate prebiotics > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 12,601,002 B2 - Document ID: US12601002B2 - Status: Granted - Kind: B2 - Application number: 18/004,390 - Filed: 2021-06-30 - Published: 2023-07-27 - Granted: 2026-04-14 - Earliest claimed: 2020-07-06 - Assignees: Industry-Academic Cooperation Foundation, Yonsei University - Applicants: Industry-Academic Cooperation Foundation, Yonsei University - Inventors: In Suk Lee; Sang Jun Ha; Chan Yeong Kim; Hye Ryun Kim; Beung Chul Ahn - Web page: https://patentgrep.com/patent/US12601002B2 ## CPC - A61P 37/00: Drugs for immunological or allergic disorders - C12Q 1/025: {for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics (antimicrobial activity C12Q1/18)} - A61P 35/00: Antineoplastic agents - C12Q 1/04: Determining presence or kind of microorganism; Use of selective media for testing antibiotics or bacteriocides; Compositions containing a chemical indicator therefor {(C12Q1/6897 takes precedence)} - C12Q 1/6886: for cancer (immunoassay for cancer G01N33/575) - C12Q 1/689: for bacteria - A61K 35/741: Probiotics (probiotic yeast, e.g. saccharomyces A61K36/06) - C12Q 2600/106: Pharmacogenomics, i.e. genetic variability in individual responses to drugs and drug metabolism - G01N 2800/52: Predicting or monitoring the response to treatment, e.g. for selection of therapy based on assay results in personalised medicine; Prognosis - G01N 2800/7028: Cancer - A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS - C12Q: MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS (immunoassay G01N33/53); COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES - 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) - G01N: INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES (measuring or testing apparatus or processes other than immunoassay, involving enzymes or microorganisms C12M, C12Q) ## Abstract Provided are a method for predicting a treatment response to cancer immunotherapy, the method comprising a step of evaluating, from feces isolated from a patient, the enrichment of a strain of the order TANB77 according to GTDB phylogenetic classification or taxa belonging to the order TANB77, and a step of predicting a treatment response of the patient to cancer immunotherapy on the basis of the enrichment of the order TANB77 or the taxa; a probiotics composition for improving a treatment response; a fecal microbiota transplantation composition; and a method for screening for candidate prebiotics by using same. ## Claims ### Claim 1 A method for generating microbial taxonomic profile data for predicting a treatment response to cancer immunotherapy, comprising: performing metagenomic sequencing on a fecal sample from a patient to generate the microbial taxonomic profile data; wherein the cancer immunotherapy is anti-PD-1 treatment, wherein the microbial taxonomic profile data shows enrichment in the fecal sample from the patient of the order TANB77, phylogenetically distinct from the Clostridium genus, Clostridiales or Clostridia class, according to Genome Taxonomy Database (GTDB) phylogenetic classification or taxa belonging to the order TANB77, or a strain according to the GTDB phylogenetic classification of at least one CAG-269 sp000431335 species, CAG-465 sp000433135 species, CAG-465 sp000433335 species, CAG-269 sp001916055 species, CAG-465 sp000433755 species, CAG-793 sp000433915 species, CAG-492 sp000434015 species, CAG-452 sp000434035 species, CAG-245 sp000434195 species, CAG-492 sp000434335 species, CAG-245 sp000435175 species, CAG-273 sp003507395 species, CAG-269 sp000435535 species, CAG-273 sp000435755 species, CAG-269 sp001916065 species, CAG-269 sp000437215 species, CAG-354 sp001915925 species, CAG-273 sp000437855 species, CAG-269 sp003525075 species, CAG-269 sp000438255 species, CAG-273 sp000438355 species, CAG-269 sp001915995 species, CAG-269 sp001916005 species, CAG-269 sp001916035 species, UBA1234 sp002308995 species, CAG-452 sp002314935 species, CAG-269 sp002372935 species, CAG-793 sp002393975 species, UBA1234 sp002404755 species, UBA7001 sp002449785 species, CAG-492 sp002633185 species, CAG-269 sp003518755 species, CAG-273 sp003534295 species, CAG-269 genus, CAG-492 genus, CAG-793 genus, CAG-452 genus, CAG-245 genus, CAG-273 genus, CAG-354 genus, UBA7001 genus, CAG-465 genus, UBA1234 genus, CAG-508 family, CAG-465 family, or UBA1234 family according to the GTDB phylogenetic classification; wherein the enrichment of the order TANB77 or the taxa, or the at least one strain according to the GTDB phylogenetic classification is a biomarker for predicting the treatment response to the anti-PD-1 treatment, and wherein the fecal sample includes gut microbiota. ### Claim 2 (depends on 1) The method for generating microbial taxonomic profile data for predicting the treatment response to cancer immunotherapy of claim 1, wherein the fecal sample includes feces isolated from the patient before the anti-PD-1 treatment is performed. ### Claim 3 (depends on 1) The method for generating microbial taxonomic profile data for predicting the treatment response to cancer immunotherapy of claim 1, wherein the microbial taxonomic profile data comprises a relative abundance of the order TANB77, the taxa, or the at least one strain according to the GTDB phylogenetic classification in the gut microbiota, and wherein the relative abundance at a predetermined level or higher is a biomarker for a positive treatment response. ### Claim 4 (depends on 3) The method for generating microbial taxonomic profile data for predicting the treatment response to cancer immunotherapy of claim 3, wherein the microbial taxonomic profile data comprises the enrichment of the order TANB77 or the taxa, and wherein the predetermined level of the relative abundance of the order TANB77 or the taxa is 0.01% to 0.5%. ### Claim 5 (depends on 1) The method for generating microbial taxonomic profile data for predicting the treatment response to cancer immunotherapy of claim 1, wherein the microbial taxonomic profile data shows enrichment in the fecal sample from the patient of the order TANB77 or the taxa, and the enrichment of at least one additional strain of Faecalicatena torques species, CAG 269 genus, Dethiosulfovibrio naceae family, Desulfovibrio piger species, CAG-274 family, CAG-508 family, CAG-521 genus, Mailhella genus, UBA3700 family, CAG-273 sp000438355 species, Risungbinella genus, Thermoactinomycetaceae family, Risungbinella massiliensis species, or CAG-245 genus according to the GTDB phylogenetic classification; and wherein the enrichment of the order TANB77 or the taxa, and the at least one additional strain is a biomarker for predicting the treatment response to the anti-PD-1 treatment. ### Claim 6 (depends on 5) The method for generating microbial taxonomic profile data for predicting the treatment response to cancer immunotherapy of claim 5, wherein the enrichment of the order TANB77 or the taxa, and the at least one additional strain at a predetermined level or higher is a biomarker for a positive treatment response. ### Claim 7 (depends on 1) The method for generating microbial taxonomic profile data for predicting the treatment response to cancer immunotherapy of claim 1, wherein the microbial taxonomic profile data shows enrichment in the fecal sample from the patient of at least one additional strain of Intestinibacter bartlettii species, Intestinibacter genus, Morganella morganii species, CAG 103 sp000432375 species, Negativibacillus genus, CAG 83 sp000431575 species, CAG 103 genus, Rs-D84 genus, CAG-873 genus, Collinsella genus, Butyricicoccus genus, Pseudescherichia genus, Yersinia mollaretii species, Campylobacter fetus_A species, Paenibacillus_F sp000411255 species, Paenibacillus_F genus, Pseudescherichia sp002298805 species, UBA1417 genus, CAG-103 genus, Leptotricia wadei species, Pantoea vagans_A species, Kurthia massiliensis species, CAG-103 sp000432375 species, Kurthia genus, Akkermansia genus, Porphyromonas somerae_A species, Ezakiella massiliensis species, Enterococcus_B faecium_B species, Bacteroides A genus, CAG-727 family, Nissabacter archeti species, UBA71 genus, Morganella morganii A species, Nissabacter genus, Yersinia kristensenii species, or Anaerococcus lactolyticus species according to the GTDB phylogenetic classification; and wherein the enrichment of the at least one additional strain is a biomarker for predicting the treatment response to the anti-PD-1 treatment. ### Claim 8 (depends on 7) The method for generating microbial taxonomic profile data for predicting the treatment response to cancer immunotherapy of claim 7, wherein the enrichment of the at least one additional strain at a predetermined level or higher is a biomarker for a negative treatment response. ### Claim 9 (depends on 1) The method for generating microbial taxonomic profile data for predicting the treatment response to cancer immunotherapy of claim 1, wherein the patient is a patient suspected of having at least one disease selected from the group consisting of non-small cell lung cancer, skin melanoma, head and neck cancer, stomach cancer, liver cancer, bone cancer, pancreatic cancer, skin cancer, uterine cancer, ovarian cancer, rectal cancer, colorectal cancer, colon cancer, breast cancer, uterine sarcoma, fallopian tube carcinoma, endometrial carcinoma, cervical carcinoma, vaginal carcinoma, vulvar carcinoma, esophageal cancer, laryngeal cancer, small intestine cancer, thyroid cancer, parathyroid cancer, sarcoma of the soft tissue, urethral cancer, penile cancer, prostate cancer, chronic or acute leukemia, childhood solid tumor, differentiated lymphoma, bladder cancer, kidney cancer, renal cell carcinoma, renal pelvic carcinoma, primary central nervous system lymphoma, spinal cord tumor, brainstem glioma, and pituitary adenoma. ### Claim 10 A method for generating microbial taxonomic profile data for predicting a treatment response to cancer immunotherapy comprising: performing metagenomic sequencing on a fecal sample from a patient to generate the microbial taxonomic profile data; wherein the cancer immunotherapy is anti-PD-1 treatment, wherein the microbial taxonomic profile data shows enrichment in the fecal sample from the patient of a strain according to NCBI (National Center for Biotechnology Information) phylogenetic classification of at least one of phylogenetic classification IDs: 1262796, 1262847, 1262772, 1262800, 1262811, 1262840, 1262822, 1262810, 1262839, 1262813, 1262784, 1262841, 1262823, 1262815, 1262812, 1262807, 1262799, 1262820, 1262788, 1262801, 1262789, 1896989, 1896977, 1896978, 1896979, 1896980, 1896981, 1896986, 1950810, 1950830, 1950862, 1950880, 1950887, 1950920, 1958817, or 1506 according to the NCBI phylogenetic classification; and wherein the enrichment of the at least one strain according to the NCBI phylogenetic classification is a biomarker for predicting the treatment response to the anti-PD-1 treatment. ### Claim 11 (depends on 10) The method for generating microbial taxonomic profile data for predicting the treatment response to cancer immunotherapy of claim 10, wherein the microbial taxonomic profile data shows enrichment in the fecal sample from the patient of at least one additional strain of Faecalicatena torques species, CAG 269 genus, Dethiosulfovibrio naceae family, Desulfovibrio piger species, CAG-274 family, CAG-508 family, CAG-521 genus, Mailhella genus, UBA3700 family, CAG-273 sp000438355 species, Risungbinella genus, Thermoactinomycetaceae family, Risungbinella massiliensis species, or CAG-245 genus according to GTDB phylogenetic classification; and wherein the enrichment of the strain according to the NCBI phylogenetic classification and the enrichment of the at least one additional strain are a biomarker for predicting the treatment response to the anti-PD-1 treatment. ### Claim 12 (depends on 10) The method for generating microbial taxonomic profile data for predicting the treatment response to cancer immunotherapy of claim 10, wherein the microbial taxonomic profile data shows enrichment in the fecal sample from the patient of at least one additional strain of Intestinibacter bartlettii species, Intestinibacter genus, Morganella morganii species, CAG 103 sp000432375 species, Negativibacillus genus, CAG 83 sp000431575 species, CAG 103 genus, Rs-D84 genus, CAG-873 genus, Collinsella genus, Butyricicoccus genus, Pseudescherichia genus, Yersinia mollaretii species, Campylobacter fetus_A species, Paenibacillus_F sp000411255 species, Paenibacillus_F genus, Pseudescherichia sp002298805 species, UBA1417 genus, CAG-103 genus, Leptotricia wadei species, Pantoea vagans_A species, Kurthia massiliensis species, CAG-103 sp000432375 species, Kurthia genus, Akkermansia genus, Porphyromonas somerae_A species, Ezakiella massiliensis species, Enterococcus_B faecium_B species, Bacteroides A genus, CAG-727 family, Nissabacter archeti species, UBA71 genus, Morganella morganii A species, Nissabacter genus, Yersinia kristensenii species, or Anaerococcus lactolyticus species according to GTDB phylogenetic classification; and wherein the enrichment of the at least one additional strain is a biomarker for predicting the treatment response to the anti-PD-1 treatment. ### Claim 13 A method for screening candidate prebiotics comprising: performing metagenomic sequencing on a fecal sample from a patient to generate microbial taxonomic profile data, wherein the patient has not received the candidate prebiotics; wherein the microbial taxonomic profile data shows enrichment in the fecal sample from the patient of the order TANB77 according to GTDB phylogenetic classification or taxa belonging to the order TANB77, or a strain according to GTDB phylogenetic classification of at least one of CAG-269 sp000431335 species, CAG-465 sp000433135 species, CAG-465 sp000433335 species, CAG-269 sp001916055 species, CAG-465 sp000433755 species, CAG-793 sp000433915 species, CAG-492 sp000434015 species, CAG-452 sp000434035 species, CAG-245 sp000434195 species, CAG-492 sp000434335 species, CAG-245 sp000435175 species, CAG-273 sp003507395 species, CAG-269 sp000435535 species, CAG-273 sp000435755 species, CAG-269 sp001916065 species, CAG-269 sp000437215 species, CAG-354 sp001915925 species, CAG-273 sp000437855 species, CAG-269 sp003525075 species, CAG-269 sp000438255 species, CAG-273 sp000438355 species, CAG-269 sp001915995 species, CAG-269 sp001916005 species, CAG-269 sp001916035 species, UBA1234 sp002308995 species, CAG-452 sp002314935 species, CAG-269 sp002372935 species, CAG-793 sp002393975 species, UBA1234 sp002404755 species, UBA7001 sp002449785 species, CAG-492 sp002633185 species, CAG-269 sp003518755 species, CAG-273 sp003534295 species, CAG-269 genus, CAG-492 genus, CAG-793 genus, CAG-452 genus, CAG-245 genus, CAG-273 genus, CAG-354 genus, UBA7001 genus, CAG-465 genus, UBA1234 genus, CAG-508 family, CAG-465 family, or UBA1234 family according to the GTDB phylogenetic classification, before administering the candidate prebiotics; administering the candidate prebiotics; and performing an additional metagenomic sequencing on a fecal sample from the patient to generate microbial taxonomic profile data after the administering of the candidate prebiotics; wherein the microbial taxonomic profile data shows differences in enrichment in the fecal sample from the patient of the order TANB77 or the taxa, or the at least one strain according to the GTDB phylogenetic classification before administering the candidate prebiotics with the enrichment of the order TANB77 or the taxa, or the at least one strain according to the GTDB phylogenetic classification after the administering of the candidate prebiotics; and wherein the candidate prebiotic increases the enrichment after the administration relative to before the administration.