| EP3146065 - METHODS AND COMPOSITIONS FOR REDUCING CLOSTRIDIUM DIFFICILE INFECTION [Right-click to bookmark this link] | Status | No opposition filed within time limit Status updated on 19.09.2025 Database last updated on 01.04.2026 | |
| Former | The patent has been granted Status updated on 11.10.2024 | ||
| Former | Grant of patent is intended Status updated on 09.06.2024 | ||
| Former | Examination is in progress Status updated on 07.02.2019 | ||
| Former | Request for examination was made Status updated on 24.02.2017 | ||
| Former | The international publication has been made Status updated on 16.12.2016 | Most recent event Tooltip | 06.02.2026 | Lapse of the patent in a contracting state New state(s): MC | published on 11.03.2026 [2026/11] | Applicant(s) | For all designated states Memorial Sloan Kettering Cancer Center 1275 York Avenue New York, NY 10065 / US | [2017/13] | Inventor(s) | 01 /
PAMER, Eric, G. 84 Fair Street Guilford, CT 06437-26117 / US | 02 /
BUFFIE, Charlie 1230 York Avenue Box 14 New York, NY 10065 / US | 03 /
MCKENNEY, Peter 504 E8 1st St Apt 1E New York, NY 10028 / US | [2017/18] |
| Former [2017/13] | 01 /
PAMER, Eric, G. 84 Fair Street Guilford, CT 06437-26117 / US | ||
| 02 /
BUFFIE, Charlie 1230 York Avenue Box 14 New York, NY 10065 / US | |||
| 03 /
MCKENNEY, Peter 75 West Street Apt. 5E New York, NY 10006 / US | Representative(s) | Barker Brettell LLP 100 Hagley Road Edgbaston Birmingham B16 8QQ / GB | [2024/46] |
| Former [2017/13] | Atkinson, Jennifer Barker Brettell LLP 100 Hagley Road Edgbaston Birmingham B16 8QQ / GB | Application number, filing date | 15796000.6 | 19.05.2015 | [2017/13] | WO2015US31627 | Priority number, date | US201462000308P | 19.05.2014 Original published format: US 201462000308 P | [2017/13] | Filing language | EN | Procedural language | EN | Publication | Type: | A1 Application with search report | No.: | WO2015179437 | Date: | 26.11.2015 | Language: | EN | [2015/47] | Type: | A1 Application with search report | No.: | EP3146065 | Date: | 29.03.2017 | Language: | EN | The application published by WIPO in one of the EPO official languages on 26.11.2015 takes the place of the publication of the European patent application. | [2017/13] | Type: | B1 Patent specification | No.: | EP3146065 | Date: | 13.11.2024 | Language: | EN | [2024/46] | Search report(s) | International search report - published on: | US | 26.11.2015 | (Supplementary) European search report - dispatched on: | EP | 13.04.2018 | Classification | IPC: | C12Q1/26, A61K35/74 | [2017/13] | CPC: |
A61K35/74 (EP,US);
A61K31/545 (EP);
A61K35/741 (EP);
A61K35/742 (EP);
A61K38/443 (EP,US);
A61K45/06 (EP,US);
A61P31/00 (EP);
C12N9/0006 (EP,US);
C12Q1/26 (EP,US);
C12Y101/01159 (EP,US)
(-)
| Designated contracting states | AL, AT, BE, BG, CH, CY, CZ, DE, DK, EE, ES, FI, FR, GB, GR, HR, HU, IE, IS, IT, LI, LT, LU, LV, MC, MK, MT, NL, NO, PL, PT, RO, RS, SE, SI, SK, SM, TR [2017/13] | Extension states | BA | Not yet paid | ME | Not yet paid | Validation states | MA | Not yet paid | Title | German: | VERFAHREN UND ZUSAMMENSETZUNGEN ZUR VERRINGERUNG VON CLOSTRIDIUM-DIFFICILE-INFEKTIONEN | [2017/13] | English: | METHODS AND COMPOSITIONS FOR REDUCING CLOSTRIDIUM DIFFICILE INFECTION | [2017/13] | French: | PROCÉDÉS ET COMPOSITIONS POUR RÉDUIRE UNE INFECTION PAR CLOSTRIDIUM DIFFICILE | [2017/13] | Entry into regional phase | 16.12.2016 | National basic fee paid | 16.12.2016 | Search fee paid | 16.12.2016 | Designation fee(s) paid | 16.12.2016 | Examination fee paid | Examination procedure | 16.12.2016 | Examination requested [2017/13] | 16.12.2016 | Date on which the examining division has become responsible | 13.11.2018 | Amendment by applicant (claims and/or description) | 11.02.2019 | Despatch of a communication from the examining division (Time limit: M06) | 21.08.2019 | Reply to a communication from the examining division | 26.02.2020 | Despatch of a communication from the examining division (Time limit: M06) | 10.09.2020 | Reply to a communication from the examining division | 26.02.2021 | Despatch of a communication from the examining division (Time limit: M04) | 08.07.2021 | Reply to a communication from the examining division | 10.06.2024 | Communication of intention to grant the patent | 03.10.2024 | Fee for grant paid | 03.10.2024 | Fee for publishing/printing paid | 03.10.2024 | Receipt of the translation of the claim(s) | Divisional application(s) | EP24212532.6 / EP4527400 | EP25222653.5 / EP4684833 | Opposition(s) | 14.08.2025 | No opposition filed within time limit [2025/43] | Request for further processing for: | The application is deemed to be withdrawn due to failure to reply to the examination report | 10.09.2020 | Request for further processing filed | 10.09.2020 | Full payment received (date of receipt of payment) Request granted | 21.09.2020 | Decision despatched | Fees paid | Renewal fee | 10.05.2017 | Renewal fee patent year 03 | 11.05.2018 | Renewal fee patent year 04 | 15.05.2019 | Renewal fee patent year 05 | 31.03.2020 | Renewal fee patent year 06 | 12.05.2021 | Renewal fee patent year 07 | 18.03.2022 | Renewal fee patent year 08 | 14.03.2023 | Renewal fee patent year 09 | 13.03.2024 | Renewal fee patent year 10 |
| Opt-out from the exclusive Tooltip competence of the Unified Patent Court | See the Register of the Unified Patent Court for opt-out data | ||
| Responsibility for the accuracy, completeness or quality of the data displayed under the link provided lies entirely with the Unified Patent Court. | Lapses during opposition Tooltip | BG | 13.11.2024 | CZ | 13.11.2024 | EE | 13.11.2024 | HR | 13.11.2024 | LV | 13.11.2024 | MC | 13.11.2024 | PL | 13.11.2024 | RO | 13.11.2024 | SK | 13.11.2024 | SM | 13.11.2024 | RS | 13.02.2025 | GR | 14.02.2025 | IS | 13.03.2025 | LU | 19.05.2025 | [2026/11] |
| Former [2026/08] | BG | 13.11.2024 | |
| CZ | 13.11.2024 | ||
| EE | 13.11.2024 | ||
| HR | 13.11.2024 | ||
| LV | 13.11.2024 | ||
| PL | 13.11.2024 | ||
| RO | 13.11.2024 | ||
| SK | 13.11.2024 | ||
| SM | 13.11.2024 | ||
| RS | 13.02.2025 | ||
| GR | 14.02.2025 | ||
| IS | 13.03.2025 | ||
| LU | 19.05.2025 | ||
| Former [2025/36] | BG | 13.11.2024 | |
| CZ | 13.11.2024 | ||
| EE | 13.11.2024 | ||
| HR | 13.11.2024 | ||
| LV | 13.11.2024 | ||
| PL | 13.11.2024 | ||
| RO | 13.11.2024 | ||
| SK | 13.11.2024 | ||
| SM | 13.11.2024 | ||
| RS | 13.02.2025 | ||
| GR | 14.02.2025 | ||
| IS | 13.03.2025 | ||
| Former [2025/35] | BG | 13.11.2024 | |
| EE | 13.11.2024 | ||
| HR | 13.11.2024 | ||
| LV | 13.11.2024 | ||
| PL | 13.11.2024 | ||
| RO | 13.11.2024 | ||
| SM | 13.11.2024 | ||
| RS | 13.02.2025 | ||
| GR | 14.02.2025 | ||
| IS | 13.03.2025 | ||
| Former [2025/32] | BG | 13.11.2024 | |
| HR | 13.11.2024 | ||
| LV | 13.11.2024 | ||
| PL | 13.11.2024 | ||
| SM | 13.11.2024 | ||
| RS | 13.02.2025 | ||
| GR | 14.02.2025 | ||
| IS | 13.03.2025 | ||
| Former [2025/23] | BG | 13.11.2024 | |
| HR | 13.11.2024 | ||
| LV | 13.11.2024 | ||
| PL | 13.11.2024 | ||
| RS | 13.02.2025 | ||
| GR | 14.02.2025 | ||
| IS | 13.03.2025 | ||
| Former [2025/22] | BG | 13.11.2024 | |
| HR | 13.11.2024 | ||
| LV | 13.11.2024 | ||
| GR | 14.02.2025 | ||
| IS | 13.03.2025 | ||
| Former [2025/21] | BG | 13.11.2024 | |
| HR | 13.11.2024 | ||
| IS | 13.03.2025 | Documents cited: | Search | [Y] WO2013053836 (QUANTUM PHARMACEUTICALS SA et al.) [Y] 1-4,11,14,15 * page 9, lines 19-20; claims 1-13,21 * | [XPI] CHARLIE G. BUFFIE ET AL: "Precision microbiome reconstitution restores bile acid mediated resistance to Clostridium difficile", NATURE, vol. 517, no. 7533, 22 October 2014 (2014-10-22), pages 205 - 208, XP055363406, ISSN: 0028-0836, DOI: 10.1038/nature13828 [XP] 1-4,14,15 * the whole document * [I] 11 DOI: http://dx.doi.org/10.1038/nature13828 | [Y] C. UBEDA ET AL: "Intestinal Microbiota Containing Barnesiella Species Cures Vancomycin-Resistant Enterococcus faecium Colonization", INFECTION AND IMMUNITY, vol. 81, no. 3, 1 March 2013 (2013-03-01), pages 965 - 973, XP055386852, ISSN: 0019-9567, DOI: 10.1128/IAI.01197-12 [Y] 1-4,11,14,15 * the whole document * DOI: http://dx.doi.org/10.1128/IAI.01197-12 | [Y] ROBERT A. BRITTON ET AL: "Role of the Intestinal Microbiota in Resistance to Colonization by Clostridium difficile", GASTROENTEROLOGY, vol. 146, no. 6, 1 May 2014 (2014-05-01), US, pages 1547 - 1553, XP055436453, ISSN: 0016-5085, DOI: 10.1053/j.gastro.2014.01.059 [Y] 1-4,11,14,15 * the whole document * DOI: http://dx.doi.org/10.1053/j.gastro.2014.01.059 | International search | [XY] WO2013080561 (UNIV TOKYO et al.) [X] 7 * , paragraphs [0050], [0066] *[Y] 8 | [XY] US2011280847 (SORG JOSEPH et al.) [X] 14, 15 * , paragraphs [0040]-[0042], [0044], [0050], [0071], [0072], [0124], [0125], [0165]-[0167] *[Y] 9/1, 9/4-9/6, 10/9/1, 10/9/4-10/9/6, 11/9/1, 11/9/4-11/9/6, 27, 34, 43/1, 43/4-43/6, 44/1, 44/4-44/6, 45/1, 45/4-45/6, 46/1, 46/4-46/6, 47/1, 47/4-47/6, 48/1, 48/4-48/6 | [Y] US7326551 (MAUPIN-FURLOW JULIE A et al.) [Y] 5, 9/1, 9/4-9/6, 10/9/1, 10/9/4-10/9/6, 11/9/1, 11/9/4-11/9/6, 43/1, 43/4-43/6, 44/1, 44/4-44/6, 45/1, 45/4-45/6, 46/1, 46/4-46/6, 47/1, 47/4-47/6, 48/1, 48/4-48/6 * , column 5, lines 10-17 * | [Y] WO2013171515 (GENOME RES LTD et al.) [Y] 8 * , abstract, page 9 * | [Y] WO2012142605 (SAMARITAN HEALTH SERVICES et al.) [Y] 8 * , abstract, pages 3, 4 * | [XY] RIDLON, JM., ENZYMOLOGY AND MOLECULAR BIOLOGY OF BILE ACID 7-ALPHA- AND 7-BETA- DEHYDROXYLATION BY THE INTESTINAL BACTERIA CLOSTRIDIUM SCINDENS AND CLOSTRIDIUM HYLEMONAE. VCU THESES AND DISSERTATIONS, 2008, pages 2, 6, 26, 74, 75, 79, 98, XP055360846 [X] 1, 2, 4, 6 * ; figure 7. *[Y] 9/1, 9/4-9/6, 10/9/1, 10/9/4-10/9/6, 11/9/1, 11/9/4-11/9/6, 28, 43/1, 43/4-43/6, 44/1, 44/4-44/6, 45/1, 45/4-45/6, 46/1, 46/4-46/6, 47/1, 47/4-47/6, 48/1, 48/4-48/6 | [Y] GIEL, JL ET AL.: "Metabolism Of Bile Salts In Mice Influences Spore Germination in Clostridium difficile.", PLOS ONE, vol. 5, no. 1, pages 2. 4. 6, XP055056664 [Y] 28, 33 * figures 4. 5A. * DOI: http://dx.doi.org/10.1371/journal.pone.0008740 | [Y] MANGES, AR ET AL.: "Comparative Metagenomic Study Of Alterations To The Intestinal Microbiota And Risk Of Nosocomial Clostridum difficil-Associated Disease.", JOURNAL OF INFECTIOUS DISEASES, vol. 202, 2010, pages 2, 3, 5, XP055238579 [Y] 27, 34 * DOI: 0.1086/657319. * DOI: http://dx.doi.org/10.1086/657319 | [Y] KRISHNA, SG ET AL.: "Risk Factors, Preemptive Therapy, And Antiperistaltic Agents For Clostridium difficile Infection In Cancer Patients.", TRANSPL INFECT DIS., vol. 15, 22 January 2013 (2013-01-22), pages 495, XP055238581 [Y] 27, 34 * . DOI: 10.1111/tid.12112. * DOI: http://dx.doi.org/10.1111/tid.12112 | [Y] OTT,.SJ ET AL.: "Quantification of Intestinal Bacterial Populations by Real-Time PCR with a Universal Primer Set and Minor Groove Binder Probes: a Global Approach to the Enteric Flora.", JOURNAL OF CLINICAL MICROBIOLOGY, June 2004 (2004-06-01), XP002428203 [Y] 33 * ; abstract, figure 4, DOI: 10.1128/JCM.42.6.2566-2572.2004 * DOI: http://dx.doi.org/10.1128/JCM.42.6.2566-2572.2004 | [Y] KANG, D ET AL.: "Clostridium scindens baiCD and baiH genes encode stereospecific 7alpha/7beta-hydroxy-3-oxo-DELTA4-cholenoic acid oxidoreductases.", BIOCHIM BIOPHYS ACTA, vol. 1781, 2008, XP022459144 [Y] 2 * ; abstract * DOI: http://dx.doi.org/10.1016/j.bbalip.2007.10.008 | [Y] WELLS, JE ET AL.: "Development and application of a polymerase chain reaction assay for the detection and enumeration of bile acid 7a-dehydroxylating bacteria in human feces.", CLINICA CHIMICA ACTA., vol. 331, 2003, XP055360854 [Y] 2 * ; abstract, doi:10.1016/S0009-8981(03)00115-3 * DOI: http://dx.doi.org/10.1016/S0009-8981(03)00115-3 | by applicant | WO9408598 | TURNBAUGH, P. J.HAMADY, M.YATSUNENKO, T.CANTAREL, B. L. ET AL.: "A core gut microbiome in obese and lean twins", NATURE, vol. 457, 2009, pages 480 - 484, XP055006664, DOI: 10.1038/nature07540 [Y] 8 DOI: http://dx.doi.org/10.1038/nature07540 | KOETH, R. A.WANG, Z.LEVISON, B. S.BUFFA, J. A. ET AL.: "Intestinal microbiota metabolism of 1-carnitine, a nutrient in red meat, promotes atherosclerosis", NAT MED, 2013 [Y] 9/1, 9/4-9/6, 10/9/1, 10/9/4-10/9/6, 11/9/1, 11/9/4-11/9/6, 27, 34, 43/1, 43/4-43/6, 44/1, 44/4-44/6, 45/1, 45/4-45/6, 46/1, 46/4-46/6, 47/1, 47/4-47/6, 48/1, 48/4-48/6 | RAKOFF-NAHOUM, S.PAGLINO, J.ESLAMI-VARZANEH, F.EDBERG, S.MEDZHITOV, R.: "Recognition of commensal microflora by toll-like receptors is required for intestinal homeostasis", CELL, vol. 118, 2004, pages 229 - 241, XP008166084, DOI: 10.1016/j.cell.2004.07.002 DOI: http://dx.doi.org/10.1016/j.cell.2004.07.002 | IVANOV, I. I.ATARASHI, K.MANEL, N.BRODIE, E. L. ET AL.: "Induction of intestinal Thl7 cells by segmented filamentous bacteria", CELL, vol. 139, 2009, pages 485 - 498, XP055005112, DOI: 10.1016/j.cell.2009.09.033 [Y] 28, 33 * figures 4. 5A. * DOI: http://dx.doi.org/10.1016/j.cell.2009.09.033 | CHUNG, H.PAMP, S. J.HILL, J. A.SURANA, N. K. ET AL.: "Gut immune maturation depends on colonization with a host-specific microbiota", CELL, vol. 149, 2012, pages 1578 - 1593, XP028497257, DOI: 10.1016/j.cell.2012.04.037 DOI: http://dx.doi.org/10.1016/j.cell.2012.04.037 | DIEHL, G. E.LONGMAN, R. S.ZHANG, J. X.BREART, B. ET AL.: "Microbiota restricts trafficking of bacteria to mesenteric lymph nodes by CX(3)CR1(hi) cells", NATURE, vol. 494, 2013, pages 116 - 120, XP037227940, DOI: 10.1038/nature11809 DOI: http://dx.doi.org/10.1038/nature11809 | DUAN, J.CHUNG, H.TROY, E.KASPER, D. L.: "Microbial colonization drives expansion of IL-1 receptor 1-expressing and IL-17-producing gamma/delta T cells", CELL HOST MICROBE, vol. 7, 2010, pages 140 - 150 [Y] 27, 34 * DOI: 0.1086/657319. * | FARACHE, J.KOREN, I.MILO, I.GUREVICH, I. ET AL.: "Luminal Bacteria Recruit CD103(+) Dendritic Cells into the Intestinal Epithelium to Sample Bacterial Antigens for Presentation", IMMUNITY, vol. 38, 2013, pages 581 - 595 [Y] 27, 34 * . DOI: 10.1111/tid.12112. * | OLSZAK, T.AN, D.ZEISSIG, S.VERA, M. P. ET AL.: "Microbial exposure during early life has persistent effects on natural killer T cell function", SCIENCE, vol. 336, 2012, pages 1553 - 1556 [Y] 33 * ; abstract, figure 4, DOI: 10.1128/JCM.42.6.2566-2572.2004 * | WINGENDER, G.STEPNIAK, D.KREBS, P.LIN, L. ET AL.: "Intestinal microbes affect phenotypes and functions of invariant natural killer T cells in mice", GASTROENTEROLOGY, vol. 143, 2012, pages 418 - 428, XP028449325, DOI: 10.1053/j.gastro.2012.04.017 [Y] 2 * ; abstract * DOI: http://dx.doi.org/10.1053/j.gastro.2012.04.017 | HILL, D. A.SIRACUSA, M. C.ABT, M. C.KIM, B. S. ET AL.: "Commensal bacteria-derived signals regulate basophil hematopoiesis and allergic inflammation", NAT MED, vol. 18, 2012, pages 538 - 546 [Y] 2 * ; abstract, doi:10.1016/S0009-8981(03)00115-3 * | LATHROP, S. K.BLOOM, S. M.RAO, S. M.NUTSCH, K. ET AL.: "Peripheral education of the immune system by colonic commensal microbiota", NATURE, vol. 478, 2011, pages 250 - 254 | MACPHERSON, A. J.UHR, T.: "Induction of protective IgA by intestinal dendritic cells carrying commensal bacteria", SCIENCE, vol. 303, 2004, pages 1662 - 1665, XP055046628, DOI: 10.1126/science.1091334 DOI: http://dx.doi.org/10.1126/science.1091334 | BASLER, M.HO, B. T.MEKALANOS, J. J.: "Tit-for-tat: type VI secretion system counterattack during bacterial cell-cell interactions", CELL, vol. 152, 2013, pages 884 - 894, XP028979909, DOI: 10.1016/j.cell.2013.01.042 DOI: http://dx.doi.org/10.1016/j.cell.2013.01.042 | BASLER, M.PILHOFER, M.HENDERSON, G. P.JENSEN, G. J.MEKALANOS, J. J.: "Type VI secretion requires a dynamic contractile phage tail-like structure", NATURE, vol. 483, 2012, pages 182 - 186 | REA, PROC NATL ACAD SCI USA, vol. 108, no. 1, 2011, pages 4639 - 4644 | REA, PROC NATL ACAD SCI USA, vol. 107, 2010, pages 9352 - 9357 | ABT, M. C.OSBORNE, L. C.MONTICELLI, L. A.DOERING, T. A. ET AL.: "Commensal bacteria calibrate the activation threshold of innate antiviral immunity", IMMUNITY, vol. 37, 2012, pages 158 - 170, XP055808532, DOI: 10.1016/j.immuni.2012.04.011 DOI: http://dx.doi.org/10.1016/j.immuni.2012.04.011 | "GenBank", Database accession no. ABFY 02000000 | MCAULIFFE ET AL., APPL ENVIRON MICROBIOL., vol. 71, no. 8, August 2005 (2005-08-01), pages 4925 - 9 | BEGLEY ET AL., APPL ENVIRON MICROBIOL., vol. 72, no. 3, March 2006 (2006-03-01), pages 1729 - 38 | ATTA, WORLD J GASTROENTEROL., vol. 16, no. 32, 28 August 2010 (2010-08-28), pages 4019 - 4030 | KRONKREPPEL, CURR GENE THER, vol. 12, no. 5, 2012, pages 362 - 73 | YI ET AL., CURR GENE THER, vol. 11, no. 3, 2011, pages 218 - 28 | GOLDSPIEL ET AL., CLINICAL PHARMACY, vol. 12, 1993, pages 488 - 505 | WUWU, BIOTHERAPY, vol. 3, 1991, pages 87 - 95 | TOLSTOSHEV, ANN. REV. PHARMACOL. TOXICOL., vol. 32, 1993, pages 573 - 596 | MULLIGAN, SCIENCE, vol. 260, 1993, pages 926 - 932 | MORGANANDERSON, ANN. REV. BIOCHEM., vol. 62, 1993, pages 191 - 217 | MAY, TIBTECH, vol. 11, no. 5, 1993, pages 155 - 215 | COHEN ET AL., METH. ENZYMOL., vol. 217, 1993, pages 618 - 644 | KRIEGLER: "A Laboratory Manual", 1990, STOCKTON PRESS, article "Gene Transfer and Expression" | CLINE, PHARMAC. THER., vol. 29, 1985, pages 69 - 92m | PORADAPORADA, J. GENET SYNDR GENE THER., vol. 25, 2012, pages 1 | STEMPLEANDERSON, CELL, vol. 71, 1992, pages 973 - 985 | RHEINWALD, METH. CELL BIO., vol. 21A, 1980, pages 229 | PITTELKOWSCOTT, MAYO CLINIC PROC., vol. 61, 1986, pages 771 | MORRIS ET AL.: "Clostridium scindens sp. nov., a Human Intestinal Bacterium with Desmolytic Activity on Corticoids", INT J SYST BACTERIOL, vol. 35, October 1985 (1985-10-01), pages 478 - 481 | KRAFFT ET AL.: "Purification and characterization of a novel form of 20 alpha-hydroxysteroid dehydrogenase from Clostridium scindens", J. BACTERIOL., vol. 171, June 1989 (1989-06-01), pages 2925 - 2932 | BUFFIEPAMER: "Microbiota-mediated colonization resistance against intestinal pathogens", NATURE REVIEWS IMMUNOLOGY, vol. 13, 2013, pages 790 - 801 | RIDLON JMHYLEMON PB: "Identification and characterization of two bile-acid coenzyme A transferases from Clostridium scindens, a bile acid 7a-dehydroxylating intestinal bacterium", J. LIPID RES., vol. 53, 2012, pages 66 - 76 | RIDLON, J. M.KANG, D. J.HYLEMON, P. B.: "Bile salt biotransformations by human intestinal bacteria", J LIPID RES, vol. 47, 2006, pages 241 - 259 | "Remington's Pharmaceutical Sciences", 1980, MACK | ZAR FABAKKANAGARI SR ET AL.: "A comparison of vancomycin and metronidazole for the treatment of Clostridium difficile-associated diarrhea, stratified by disease severity", CLIN. INFECT. DIS., vol. 45, 2007, pages 302 - 307, XP055192004, DOI: 10.1086/519265 DOI: http://dx.doi.org/10.1086/519265 | RIDLON JM ET AL.: "Clostridium scindens: a human gut microbe with a high potential to convert glucocorticoids into androgens", J. LIPID RES., vol. 54, 2013, pages 2437 - 2449 | RUPNIK, M.WILCOX, M. H.GERDING, D. N.: "Clostridium difficile infection: new developments in epidemiology and pathogenesis", NAT REV MICROBIOL, vol. 7, 2009, pages 526 - 536, XP009169073, DOI: 10.1038/nrmicro2164 DOI: http://dx.doi.org/10.1038/nrmicro2164 | SURAWICZ, C. M.ALEXANDER, J.: "Treatment of refractory and recurrent Clostridium difficile infection", NAT REV GASTROENTEROL HEPATOL, vol. 8, 2011, pages 330 - 339 | HAND, T. W.DOS SANTOS, L. M.BOULADOUX, N.MOLLOY, M. J. ET AL.: "Acute gastrointestinal infection induces long-lived microbiota-specific T cell responses", SCIENCE, vol. 337, 2012, pages 1553 - 1556 | REA, M. C.DOBSON, A.O'SULLIVAN, O.CRISPIE, F. ET AL.: "Effect of broad- and narrow-spectrum antimicrobials on Clostridium difficile and microbial diversity in a model of the distal colon", PROC NATL ACAD SCI U S A, vol. 108, no. 1, 2011, pages 4639 - 4644 | REA, M. C.SIT, C. S.CLAYTON, E.O'CONNOR, P. M. ET AL.: "Thuricin CD, a posttranslationally modified bacteriocin with a narrow spectrum of activity against Clostridium difficile", PROC NATL ACAD SCI U S A, vol. 107, 2010, pages 9352 - 9357 | HUSE, S. M.DETHLEFSEN, L.HUBER, J. A.MARK WELCH, D. ET AL.: "Exploring microbial diversity and taxonomy using SSU rRNA hypervariable tag sequencing", PLOS GENET, vol. 4, 2008, pages e1000255 | DETHLEFSEN, L.RELMAN, D. A.: "Incomplete recovery and individualized responses of the human distal gut microbiota to repeated antibiotic perturbation", PROC NATL ACAD SCI U S A, vol. 108, no. 1, 2011, pages 4554 - 4561 | BUFFIE, C. G.JARCHUM, I.EQUINDA, M.LIPUMA, L. ET AL.: "Profound alterations of intestinal microbiota following a single dose of clindamycin results in sustained susceptibility to Clostridium difficile-induced colitis", INFECT IMMUN, vol. 80, 2012, pages 62 - 73 | BRANDL, K.PLITAS, G.MIHU, C. N.UBEDA, C. ET AL.: "Vancomycin-resistant enterococci exploit antibiotic-induced innate immune deficits", NATURE, vol. 455, 2008, pages 804 - 807 | UBEDA, C.TAUR, Y.JENQ, R. R.EQUINDA, M. J. ET AL.: "Vancomycin-resistant Enterococcus domination of intestinal microbiota is enabled by antibiotic treatment in mice and precedes bloodstream invasion in humans", J CLIN INVEST, vol. 120, 2010, pages 4332 - 4341, XP055386855, DOI: 10.1172/JCI43918 DOI: http://dx.doi.org/10.1172/JCI43918 | FERREIRA, R. B.GILL, N.WILLING, B. P.ANTUNES, L. C. ET AL.: "The intestinal microbiota plays a role in Salmonella-induced colitis independent of pathogen colonization", PLOS ONE, vol. 6, 2011, pages e20338 | KYNE, L.HAMEL, M. B.POLAVARAM, R.KELLY, C. P.: "Health care costs and mortality associated with nosocomial diarrhea due to Clostridium difficile", CLIN INFECT DIS, vol. 34, 2002, pages 346 - 353 | ZILBERBERG, M. D.SHORR, A. F.KOLLEF, M. H.: "Increase in adult Clostridium difficile-related hospitalizations and case-fatality rate, United States, 2000-2005", EMERG INFECT DIS, vol. 14, 2008, pages 929 - 931 | MARSH, J. W.ARORA, R.SCHLACKMAN, J. L.SHUTT, K. A. ET AL.: "Association of relapse of Clostridium difficile disease with BI/NAP1/027", J CLIN MICROBIOL, vol. 50, 2012, pages 4078 - 4082 | BAKKEN, J. S.BORODY, T.BRANDT, L. J.BRILL, J. V. ET AL.: "Treating Clostridium difficile infection with fecal microbiota transplantation", CLIN GASTROENTEROL HEPATOL, vol. 9, 2011, pages 1044 - 1049, XP009155259, DOI: 10.1016/j.cgh.2011.08.014 DOI: http://dx.doi.org/10.1016/j.cgh.2011.08.014 | VAN NOOD, E.VRIEZE, A.NIEUWDORP, M.FUENTES, S. ET AL.: "Duodenal infusion of donor feces for recurrent Clostridium difficile", N ENGL J MED, vol. 368, 2013, pages 407 - 415, XP055095085, DOI: 10.1056/NEJMoa1205037 DOI: http://dx.doi.org/10.1056/NEJMoa1205037 | PAMER, E. G.: "Fecal microbiota transplantation: effectiveness, complexities, and lingering concerns", MUCOSAL IMMUNOL, vol. 7, 2014, pages 210 - 214, XP055719149, DOI: 10.1038/mi.2013.117 DOI: http://dx.doi.org/10.1038/mi.2013.117 | REEVES, A. E.THERIOT, C. M.BERGIN, I. L.HUFFNAGLE, G. B. ET AL.: "The interplay between microbiome dynamics and pathogen dynamics in a murine model of Clostridium difficile Infection", GUT MICROBES, vol. 2, 2011, pages 145 - 158 | LAWLEY, T. D.CLARE, S.WALKER, A. W.STARES, M. D. ET AL.: "Targeted restoration of the intestinal microbiota with a simple, defined bacteriotherapy resolves relapsing Clostridium difficile disease in mice", PLOS PATHOG, vol. 8, 2012, pages e1002995, XP055077330, DOI: 10.1371/journal.ppat.1002995 DOI: http://dx.doi.org/10.1371/journal.ppat.1002995 | PETROF, E. O.GLOOR, G. B.VANNER, S. J.WEESE, S. J. ET AL.: "Stool substitute transplant therapy for the eradication of Clostridium difficile infection: 'RePOOPulating' the gut", MICROBIOME, vol. 1, 2013, pages 3, XP021138289, DOI: 10.1186/2049-2618-1-3 DOI: http://dx.doi.org/10.1186/2049-2618-1-3 | HAMILTON, M. J.WEINGARDEN, A. R.UNNO, T.KHORUTS, A.SADOWSKY, M. J.: "High-throughput DNA sequence analysis reveals stable engraftment of gut microbiota following transplantation of previously frozen fecal bacteria", GUT MICROBES, vol. 4, 2013, pages 125 - 135 | CHANG, J. Y.ANTONOPOULOS, D. A.KALRA, A.TONELLI, A. ET AL.: "Decreased diversity of the fecal Microbiome in recurrent Clostridium difficile-associated diarrhea", J INFECT DIS, vol. 197, 2008, pages 435 - 438 | LOZUPONE, C.KNIGHT, R.: "UniFrac: a new phylogenetic method for comparing microbial communities", APPL ENVIRON MICROBIOL, vol. 71, 2005, pages 8228 - 8235 | TAUR, Y.XAVIER, J. B.LIPUMA, L.UBEDA, C. ET AL.: "Intestinal domination and the risk of bacteremia in patients undergoing allogeneic hematopoietic stem cell transplantation", CLIN INFECT DIS, vol. 55, 2012, pages 905 - 914, XP055297806, DOI: 10.1093/cid/cis580 DOI: http://dx.doi.org/10.1093/cid/cis580 | KINNEBREW, M. A.LEE, Y. J.JENQ, R. R.LIPUMA, L. ET AL.: "Early Clostridium difficile Infection during Allogeneic Hematopoietic Stem Cell Transplantation", PLOS ONE, vol. 9, 2014, pages e90158 | STEIN, R. R.BUCCI, V.TOUSSAINT, N. C.BUFFIE, C. G. ET AL.: "Ecological modeling from time-series inference: insight into dynamics and stability of intestinal microbiota", PLOS COMPUTBIOL, vol. 9, 2013, pages e1003388 | CHEN, X.KATCHAR, K.GOLDSMITH, J. D.NANTHAKUMAR, N. ET AL.: "A mouse model of Clostridium difficile-associated disease", GASTROENTEROLOGY, vol. 135, 2008, pages 1984 - 1992, XP026147662, DOI: 10.1053/j.gastro.2008.09.002 DOI: http://dx.doi.org/10.1053/j.gastro.2008.09.002 | SORG, J. A.SONENSHEIN, A. L.: "Bile salts and glycine as cogerminants for Clostridium difficile spores", J BACTERIOL, vol. 190, 2008, pages 2505 - 2512, XP002636062, DOI: 10.1128/JB.01765-07 DOI: http://dx.doi.org/10.1128/JB.01765-07 | DE AGUIAR VALLIM, T. Q.TARLING, E. J.EDWARDS, P. A.: "Pleiotropic roles of bile acids in metabolism", CELL METAB, vol. 17, 2013, pages 657 - 669 | KANG, D. J.RIDLON, J. M.MOORE, D. R.BARNES, S.HYLEMON, P. B.: "Clostridium scindens baiCD and baiH genes encode stereo-specific 7alpha/7beta-hydroxy-3-oxo-delta4-cholenoic acid oxidoreductases", BIOCHIM BIOPHYS ACTA, vol. 1781, 2008, pages 16 - 25, XP022459144, DOI: 10.1016/j.bbalip.2007.10.008 DOI: http://dx.doi.org/10.1016/j.bbalip.2007.10.008 | LANGILLE, M. G.ZANEVELD, J.CAPORASO, J. G.MCDONALD, D. ET AL.: "Predictive functional profiling of microbial communities using 16S rRNA marker gene sequences", NAT BIOTECHNOL, vol. 31, 2013, pages 814 - 821, XP055328402, DOI: 10.1038/nbt.2676 DOI: http://dx.doi.org/10.1038/nbt.2676 | WELLS, J. E.WILLIAMS, K. B.WHITEHEAD, T. R.HEUMAN, D. M.HYLEMON, P. B.: "Development and application of a polymerase chain reaction assay for the detection and enumeration of bile acid 7a-dehydroxylating bacteria in human feces", CLINICA CHIMICA ACTA, vol. 331, 2003, pages 127 - 134, XP055360854, DOI: 10.1016/S0009-8981(03)00115-3 DOI: http://dx.doi.org/10.1016/S0009-8981(03)00115-3 | BARRASA, J. I.OLMO, N.LIZARBE, M. A.TURNAY, J.: "Bile acids in the colon, from healthy to cytotoxic molecules", TOXICOL IN VITRO, vol. 27, 2013, pages 964 - 977 | KITAHARA, M.TAKAMINE, F.IMAMURA, T.BENNO, Y.: "Assignment of Eubacterium sp. VPI 12708 and related strains with high bile acid 7alpha-dehydroxylating activity to Clostridium scindens and proposal of Clostridium hylemonae sp. nov., isolated from human faeces", INT J SYST EVOL MICROBIOL, vol. 50, 2000, pages 971 - 978 | WELLS, . E.HYLEMON, . B.: "Identification and Characterization of a Bile Acid 7alpha - Dehydroxylation Operon in Clostridium sp. Strain TO-931, a Highly Active 7alpha - Dehydroxylating Strain Isolated from Human Feces", APPLIED AND ENVIRONMENTAL MICROBIOLOGY, vol. 66, 2000, pages 1107 - 1113 | COLLINS, M. D.LAWSON, P. A.WILLEMS, A.CORDOBA, J. J. ET AL.: "The phylogeny of the genus Clostridium: proposal of five new genera and eleven new species combinations", INT J SYST BACTERIOL, vol. 44, 1994, pages 812 - 826, XP055107539, DOI: 10.1099/00207713-44-4-812 DOI: http://dx.doi.org/10.1099/00207713-44-4-812 | LIU, C.FINEGOLD, S. M.SONG, Y.LAWSON, P. A.: "Reclassification of Clostridium coccoides, Ruminococcus hansenii, Ruminococcus hydrogenotrophicus, Ruminococcus luti, Ruminococcus productus and Ruminococcus schinkii as Blautia coccoides gen. nov. , comb. nov. , Blautia hansenii comb. nov. , Blautia hydrogenotrophica comb. nov. , Blautia luti comb.", INT J SYST EVOL MICROBIOL, vol. 58, 2008, pages 1896 - 1902, XP055005236, DOI: 10.1099/ijs.0.65208-0 DOI: http://dx.doi.org/10.1099/ijs.0.65208-0 | CARLIER, J. P.BEDORA-FAURE, M.K'OUAS, G.ALAUZET, C.MORY, F. ET AL.: "Proposal to unify Clostridium orbiscindens Winter et al. 1991 and Eubacterium plautii (Seguin 1928) Hofstad and Aasjord 1982, with description of Flavonifractor plautii gen. nov., comb. nov., and reassignment of Bacteroides capillosus to Pseudoflavonifractor capillosus gen. nov., comb. nov.", INT J SYST EVOL MICROBIOL, vol. 60, 2010, pages 585 - 590, XP055709216, DOI: 10.1099/ijs.0.016725-0 DOI: http://dx.doi.org/10.1099/ijs.0.016725-0 | YUTIN, N.GALPERIN, M. Y.: "A genomic update on clostridial phylogeny: Gram-negative spore formers and other misplaced clostridia", ENVIRON MICROBIOL, vol. 15, 2013, pages 2631 - 2641 | THERIOT, C. M.KOENIGSKNECHT, M. J.CARLSON, P. E.HATTON, G. E. ET AL.: "Antibiotic-induced shifts in the mouse gut microbiome and metabolome increase susceptibility to Clostridium difficile infection", NATURE COMMUNICATIONS, vol. 5, 2014, XP055371377, DOI: 10.1038/ncomms4114 DOI: http://dx.doi.org/10.1038/ncomms4114 | WEINGARDEN, A. R.CHEN, C.BOBR, A.YAO, D. ET AL.: "Microbiota transplantation restores normal fecal bile acid composition in recurrent Clostridium difficile infection", AM J PHYSIOL GASTROINTEST LIVER PHYSIOL, vol. 306, 2014, pages G310 - G319, XP055425865, DOI: 10.1152/ajpgi.00282.2013 DOI: http://dx.doi.org/10.1152/ajpgi.00282.2013 | LOUIE, T. J.PEPPE, J.WATT, C. K.JOHNSON, D. ET AL.: "Tolevamer, a novel nonantibiotic polymer, compared with vancomycin in the treatment of mild to moderately severe Clostridium difficile-associated diarrhea", CLIN INFECT DIS, vol. 43, 2006, pages 411 - 420, XP008152137, DOI: 10.1086/506349 DOI: http://dx.doi.org/10.1086/506349 | GIEL, J. L.SORG, J. A.SONENSHEIN, A. L.ZHU, J.: "Metabolism of bile salts in mice influences spore germination in Clostridium difficile", PLOS ONE, vol. 5, 2010, pages e8740, XP055056664, DOI: 10.1371/journal.pone.0008740 DOI: http://dx.doi.org/10.1371/journal.pone.0008740 | SORG, J. A.SONENSHEIN, A. L.: "Chenodeoxycholate is an inhibitor of Clostridium difficile spore germination", J BACTERIOL, vol. 191, 2009, pages 1115 - 1117, XP055027727, DOI: 10.1128/JB.01260-08 DOI: http://dx.doi.org/10.1128/JB.01260-08 | OUT, C.GROEN, A. K.BRUFAU, G.: "Bile acid sequestrants: more than simple resins", CURR OPIN LIPIDOL, vol. 23, 2012, pages 43 - 55 | BERNSTEIN, H.BERNSTEIN, C.PAYNE, C. M.DVORAKOVA, K.GAREWAL, H.: "Bile acids as carcinogens in human gastrointestinal cancers", MUTAT RES, vol. 589, 2005, pages 47 - 65, XP086368520, DOI: 10.1016/j.mrrev.2004.08.001 DOI: http://dx.doi.org/10.1016/j.mrrev.2004.08.001 | EDGAR, R. C.HAAS, B. J.CLEMENTE, J. C.QUINCE, C.KNIGHT, R.: "UCHIME improves sensitivity and speed of chimera detection", BIOINFORMATICS, vol. 27, 2011, pages 2194 - 2200, XP055534113, DOI: 10.1093/bioinformatics/btr381 DOI: http://dx.doi.org/10.1093/bioinformatics/btr381 | SCHLOSS, P. D.WESTCOTT, S. L.RYABIN, T.HALL, J. R. ET AL.: "Introducing mothur: open-source, platform-independent, community-supported software for describing and comparing microbial communities", APPL ENVIRON MICROBIOL, vol. 75, 2009, pages 7537 - 7541, XP055154024, DOI: 10.1128/AEM.01541-09 DOI: http://dx.doi.org/10.1128/AEM.01541-09 | "Human Microbiome Project Consortium Structure, function and diversity of the healthy human microbiome", NATURE, vol. 486, 2012, pages 207 - 214 | CAPORASO, J. G.LAUBER, C. L.WALTERS, W. A.BERG-LYONS, D. ET AL.: "Ultra-high-throughput microbial community analysis on the Illumina HiSeq and MiSeq platforms", ISME J, vol. 6, 2012, pages 1621 - 1624, XP055341618, DOI: 10.1038/ismej.2012.8 DOI: http://dx.doi.org/10.1038/ismej.2012.8 | UBEDA, C.BUCCI, V.CABALLERO, S.DJUKOVIC, A. ET AL.: "Intestinal microbiota containing Barnesiella cures vancomycin-resistant Enterococcus faecium colonization", INFECT IMMUN, vol. 81, 2013, pages 965 - 973, XP055386852, DOI: 10.1128/IAI.01197-12 DOI: http://dx.doi.org/10.1128/IAI.01197-12 | SHENEMAN, L.EVANS, J.FOSTER, J. A.: "Clearcut: a fast implementation of relaxed neighbor joining", BIOINFORMATICS, vol. 22, 2006, pages 2823 - 2824 | JG CAPORASOJ KUCZYNSKIJ STOMBAUGHK BITTINGERFD BUSHMANEK COSTELLON FIERERAG PENAJK GOODRICHJI GORDON: "QIIME allows analysis of high-throughput community sequencing data", NAT METHODS, vol. 7, no. 5, May 2010 (2010-05-01), pages 335 - 6 | HALL, B. G.: "Building phylogenetic trees from molecular data with MEGA", MOL BIOL EVOL, vol. 30, 2013, pages 1229 - 1235 | ZHAO, Y.TANG, H.YE, Y: "RAPSearch2: a fast and memory-efficient protein similarity search tool for next-generation sequencing data", BIOINFORMATICS, vol. 28, 2012, pages 125 - 126 | COHEN, J., ROUTLEDGE, vol. Statistical power analysis for the behavioral scie, 1988 | STEIN, R. R.BUCCI, V.TOUSSAINT, N. C.BUFFIE, C. G. ET AL.: "Ecological modeling from time-series inference: insight into dynamics and stability of intestinal microbiota", PLOS COMPUT BIOL, vol. 9, 2013, pages e1003388 | BARTLETT JGCHANG TWGURWITH M ET AL.: "Antibiotic-associated psudomembranous colitis due to toxin-producing clostridia", N. ENGL. J. MED., vol. 298, 1978, pages 531 - 534 | CHEN XLAMONT JT: "Overview of Clostridium difficile infection: implications for China", GASTROENTEROLOGY REPORT, vol. 1, 2013, pages 153 - 158 | RIDLON JM ET AL.: "Bile salt biotransformations by Human Intestinal bacteria", J. LIPID RES., vol. 47, 2006, pages 241 - 259 |