Granted Patent
B2
US 12,409,196 · App. 17/371,692 · Granted Sep 9, 2025
Composition for inducing proliferation or accumulation of regulatory T cells
Inventors:
Kenya Honda (Tokyo, JP); Koji Atarashi (Tokyo, JP); Kikuji Itoh (Tokyo, JP); Takeshi Tanoue (Tokyo, JP)
Assignee:
The University of Tokyo
A61K35/742A01K67/0275A61K9/0053A61K9/48A61K35/74A61K39/0008A61K39/08A61K39/39A61K45/00A61K45/06C12Q1/689G01N33/505A01K2267/0325A61K35/00A61K2039/52A61K2039/542A61K2039/55594A61K2039/57C12Q2600/158G01N2333/33G01N2500/10
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Abstract
It was found that bacteria belonging to the genus Clostridium induce accumulation of regulatory T cells (Treg cells) in the colon. Moreover, the present inventors found that regulatory T cells (Treg cells) induced by from these bacteria suppressed proliferation of effector T-cells. From these findings, the present inventors found that the use of bacteria belonging to the genus Clostridium or a physiologically active substance derived therefrom made it possible to induce proliferation or accumulation of regulatory T cells (Treg cells), and further to suppress immune functions.
Claims (20)
1. A pharmaceutical composition, comprising six or more live bacterial strains belonging to Clostridium clusters IV and/or XIVa, wherein the six or more bacterial strains induce proliferation and/or accumulation of regulatory T cells, wherein at least one of the bacterial strains is a human commensal bacterial strain, and wherein the pharmaceutical composition is formulated for delivery to the intestine.
2. The pharmaceutical composition of claim 1 , wherein the pharmaceutical composition comprises seven or more bacterial strains.
3. The pharmaceutical composition of claim 1 , wherein the pharmaceutical composition comprises eight or more bacterial strains.
4. The pharmaceutical composition of claim 1 , wherein the pharmaceutical composition comprises nine or more bacterial strains.
5. The pharmaceutical composition of claim 1 , wherein the pharmaceutical composition comprises ten or more bacterial strains.
6. The pharmaceutical composition of claim 1 , wherein the pharmaceutical composition comprises eleven or more bacterial strains.
7. The pharmaceutical composition of claim 1 , wherein the pharmaceutical composition comprises twelve or more bacterial strains.
8. The pharmaceutical composition of claim 1 , wherein the pharmaceutical composition comprises thirteen or more bacterial strains.
9. The pharmaceutical composition of claim 1 , wherein the pharmaceutical composition comprises fourteen or more bacterial strains.
10. The pharmaceutical composition of claim 1 , wherein the pharmaceutical composition comprises fifteen or more bacterial strains.
11. The pharmaceutical composition of claim 1 , wherein the pharmaceutical composition further comprises one or more bacterial strains belonging to a Clostridium cluster other than Clostridium cluster IV or cluster XIVa.
12. The pharmaceutical composition of claim 1 , wherein the pharmaceutical composition is formulated for oral administration.
13. The pharmaceutical composition of claim 1 , wherein the pharmaceutical composition further comprises a pharmacologically acceptable excipient.
14. The pharmaceutical composition of claim 1 , wherein the pharmaceutical composition is in the form of a capsule.
15. The pharmaceutical composition of claim 1 , wherein the pharmaceutical composition further comprises a pH sensitive composition comprising one or more enteric polymers.
16. A method of treating a human subject having an infectious disease, an autoimmune disease or an allergic disease, the method comprising administering the pharmaceutical composition of claim 1 .
17. The method of claim 16 , wherein the human subject has an autoimmune disease.
18. The method of claim 16 , wherein the autoimmune disease is organ transplant rejection, inflammatory bowel disease (IBD), ulcerative colitis, Crohn's disease, sprue, rheumatoid arthritis, Type 1 diabetes, graft versus host disease, or multiple sclerosis.
19. The method of claim 16 , wherein the subject has an infectious disease, and wherein the infectious disease is Clostridium difficile infection.
20. The method of claim 16 , wherein the subject has an allergic disease, optionally wherein the allergic disease is food allergy.
Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded Apr 6, 2023
From: HONDA, KENYA; ATARASHI, KOJI; ITOH, KIKUJI; TANOUE, TAKESHI
To: THE UNIVERSITY OF TOKYO
Reel/Frame 063242/0285 →
Priority Claims (2)
JP 2010-129134
· Jun 4, 2010
· national
WO PCT/JP2010/071746
· Dec 3, 2010
· international
Continuity (10)
Continuation
13701467
References Cited (400)
US 4576936A
· MacDonald
· 1986
[cited by applicant]
US 5599795A
· McCann et al.
· 1997
[cited by applicant]
US 5700787A
· Tzianabos et al.
· 1997
[cited by applicant]
US 5922352A
· Chen et al.
· 1999
[cited by applicant]
US 6348452B1
· Brown et al.
· 2002
[cited by applicant]
US 6551632B2
· Borody
· 2003
[cited by applicant]
US 6635260B1
· Gerding
· 2003
[cited by applicant]
US 6645530B1
· Borody
· 2003
[cited by applicant]
US 7629330B2
· Wang et al.
· 2009
[cited by applicant]
US 7749494B2
· Renaud et al.
· 2010
[cited by applicant]
US 8460648B2
· Borody
· 2013
[cited by applicant]
US 8586029B2
· Kasper et al.
· 2013
[cited by applicant]
US 8906668B2
· Henn et al.
· 2014
[cited by applicant]
US 9011834B1
· McKenzie et al.
· 2015
[cited by applicant]
US 9028841B2
· Henn et al.
· 2015
[cited by applicant]
US 9040036B2
· Borody
· 2015
[cited by applicant]
US 9050358B2
· Borody
· 2015
[cited by applicant]
US 9180147B2
· McKenzie et al.
· 2015
[cited by applicant]
US 9320763B2
· Borody
· 2016
[cited by applicant]
US 9328324B2
· Mitragotri et al.
· 2016
[cited by applicant]
US 9408872B2
· Borody
· 2016
[cited by applicant]
US 9415079B2
· Honda et al.
· 2016
[cited by applicant]
US 9421230B2
· Honda et al.
· 2016
[cited by applicant]
US 9433652B2
· Honda et al.
· 2016
[cited by applicant]
US 9446080B2
· McKenzie et al.
· 2016
[cited by applicant]
US 9468658B2
· Borody
· 2016
[cited by applicant]
US 9533014B2
· Henn et al.
· 2017
[cited by applicant]
US 9585921B2
· McKenzie et al.
· 2017
[cited by applicant]
US 9603878B2
· Berry et al.
· 2017
[cited by applicant]
US 9610307B2
· Berry et al.
· 2017
[cited by applicant]
US 9642281B1
· Chen
· 2017
[cited by applicant]
US 9642881B2
· Honda et al.
· 2017
[cited by applicant]
US 9642882B2
· Honda et al.
· 2017
[cited by applicant]
US 9649345B2
· Honda et al.
· 2017
[cited by applicant]
US 9662381B2
· Honda et al.
· 2017
[cited by applicant]
US 9764019B2
· Honda et al.
· 2017
[cited by applicant]
US 9801933B2
· Honda et al.
· 2017
[cited by applicant]
US 9808519B2
· Honda et al.
· 2017
[cited by applicant]
US 9827276B2
· Honda et al.
· 2017
[cited by applicant]
US 9833483B2
· Honda et al.
· 2017
[cited by applicant]
US 9848853B2
· Mitragotri et al.
· 2017
[cited by applicant]
US 9855303B2
· McKenzie et al.
· 2018
[cited by applicant]
US 9962414B2
· Borody
· 2018
[cited by applicant]
US 9987311B2
· Mulder et al.
· 2018
[cited by applicant]
US 9987312B2
· Miyamoto et al.
· 2018
[cited by applicant]
US 9999641B2
· Schneider et al.
· 2018
[cited by applicant]
US 20030113306A1
· Collins et al.
· 2003
[cited by applicant]
US 20040170617A1
· Finegold
· 2004
[cited by applicant]
US 20040219160A1
· Tzianabos et al.
· 2004
[cited by applicant]
US 20060067924A1
· Lee et al.
· 2006
[cited by applicant]
US 20060240482A1
· Kwok et al.
· 2006
[cited by applicant]
US 20070258953A1
· Duncan et al.
· 2007
[cited by applicant]
US 20080311080A1
· Collins et al.
· 2008
[cited by applicant]
US 20090124573A1
· Mazmanian et al.
· 2009
[cited by applicant]
US 20100119488A1
· Huber-Haag et al.
· 2010
[cited by applicant]
US 20100275282A1
· Round et al.
· 2010
[cited by applicant]
US 20110009360A1
· Kasper et al.
· 2011
[cited by applicant]
US 20120020941A1
· Wacklin et al.
· 2012
[cited by applicant]
US 20120276149A1
· Littman et al.
· 2012
[cited by applicant]
US 20130149339A1
· Honda et al.
· 2013
[cited by applicant]
US 20140171339A1
· Keku et al.
· 2014
[cited by applicant]
US 20140363397A1
· Allen-Vercoe et al.
· 2014
[cited by applicant]
US 20150224152A1
· Littman et al.
· 2015
[cited by applicant]
US 20150297642A1
· Borody
· 2015
[cited by applicant]
US 20150320805A9
· Honda et al.
· 2015
[cited by applicant]
US 20160040215A1
· Henn et al.
· 2016
[cited by applicant]
US 20160235792A1
· Berry et al.
· 2016
[cited by applicant]
US 20160271188A1
· Berry et al.
· 2016
[cited by applicant]
US 20170165302A1
· Henn et al.
· 2017
[cited by applicant]
US 20170290889A1
· Loke et al.
· 2017
[cited by applicant]
US 20180015130A1
· Berry et al.
· 2018
[cited by applicant]
US 20180169153A1
· Berry et al.
· 2018
[cited by applicant]
US 20190134179A1
· Honda et al.
· 2019
[cited by applicant]
US 20240173365A1
· Crossette et al.
· 2024
[cited by applicant]
US 20240307463A1
· Honda et al.
· 2024
[cited by applicant]
AU 2001276160B2
· 2007
[cited by applicant]
CA 2850000A1
· 2013
[cited by applicant]
CN 101310730A
· 2008
[cited by applicant]
CN 101496819A
· 2009
[cited by applicant]
CN 103079582A
· 2013
[cited by applicant]
DE 102006062250A1
· 2008
[cited by applicant]
EP 1749538A1
· 2007
[cited by applicant]
EP 1955706A1
· 2008
[cited by applicant]
EP 2823822A1
· 2015
[cited by applicant]
EP 3539548B1
· 2020
[cited by applicant]
JP 2001112485A
· 2001
[cited by applicant]
JP 2005124495A
· 2005
[cited by applicant]
JP 2009084215A
· 2009
[cited by applicant]
JP 2010129134A
· 2010
[cited by applicant]
JP 5592958B2
· 2014
[cited by applicant]
JP 2017213526A
· 2017
[cited by applicant]
JP 6492151B2
· 2019
[cited by applicant]
KR 100913405B1
· 2009
[cited by applicant]
WO WO2002007741A1
· 2002
[cited by applicant]
WO WO2004085628A1
· 2004
[cited by applicant]
WO WO2009050486A2
· 2009
[cited by applicant]
WO WO2009149149A1
· 2009
[cited by applicant]
WO 2010103119A1
· 2010
[cited by applicant]
WO WO2011005756A1
· 2011
[cited by applicant]
WO WO2011022542A2
· 2011
[cited by applicant]
WO WO2011022660A1
· 2011
[cited by applicant]
WO WO2011027990A2
· 2011
[cited by applicant]
WO WO2011151941A1
· 2011
[cited by applicant]
WO WO2011152566A2
· 2011
[cited by applicant]
WO WO2012013861A2
· 2012
[cited by applicant]
WO WO2012062951A1
· 2012
[cited by applicant]
WO WO2013080561A1
· 2013
[cited by applicant]
WO WO2015156419A1
· 2015
[cited by applicant]
WO WO2016086205A2
· 2016
[cited by applicant]
WO WO2016194427A1
· 2016
[cited by applicant]
WO WO2017160944A2
· 2017
[cited by applicant]
WO WO2018084172A1
· 2018
[cited by applicant]
WO WO2019032572A1
· 2019
[cited by applicant]
WO WO2019118515A2
· 2019
[cited by applicant]
WO WO2019156234A1
· 2019
[cited by applicant]
WO WO2020037271A1
· 2020
[cited by applicant]
WO WO2020234746A1
· 2020
[cited by applicant]
[No Author Listed], Japanese Journal of Bacteriology. 2008;63(1): 166, 3-E-27/P43.
[cited by applicant]
[No Author Listed], Poster Presentation Schedule 14th International Congress of Immunology. Aug. 25, 2010. Kyoto, Japan.
[cited by applicant]
[No Author Listed], Ruminococcus. Microbe Wiki. Aug. 2010. Last accessed at https://microbewiki.kenyon.edu/index.php/Ruminococcus on Apr. 19, 2016.
[cited by applicant]
[No Author Listed], Screenshot—pre-conference itinerary tool for the XIVth International Congress of Immunology held in Kobe on Aug. 2010 as “D98” in EP Opposition 2575835.
[cited by applicant]
[No Author Listed], Summary table of best hits for all SEQ ID NOs. in non-patent databases. Cited in Opposition to EP 2875828 on Jan. 18, 2021.
[cited by applicant]
[No Author Listed], There are more than 100 Autoimmune Disease. Autoimmune Disease List excerpt. Retrieved from www.aarda.org/diseaselist/. Accessed on Jul. 17, 2017. 1 page.
[cited by applicant]
Aas et al., Recurrent Clostridium difficile colitis: case series involving 18 patients treated with donor stool administered via a nasogastric tube. Clin Infect Dis. Mar. 1, 2003;36(5):580-5. Epub Feb. 14, 2003.
[cited by applicant]
Abbas et al., Regulatory T cells: recommendations to simplify the nomenclature. Nat Immunol. Apr. 2013;14(4):307-8. doi: 10.1038/ni.2554.
[cited by applicant]
Abraham et al., Molecular mechanisms of IL-2 gene regulation following costimulation through LFA-1. J Immunol. Nov. 1, 2001;167(9):5193-201.
[cited by applicant]
Abrams, Open-Label, Uncontrolled Trial of Bowel Sterilization and Repopulation With Normal Bowel Flora for Treatment of Inflammatory Bowel Disease. Current Therapeutic Research. Dec. 1997;58(12):1001-1012.
[cited by applicant]
Andoh et al., Terminal restriction fragment polymorphism analyses of fecal microbiota in five siblings including two with ulcerative colitis. Clin J Gastroenterol. Oct. 2009;2(5):343-345. doi:10.1007/s12328-009-0106-8. …
[cited by applicant]
Andoh et al., Faecal microbiota profile of Crohn's disease determined by terminal restriction fragment length polymorphism analysis. Aliment Pharmacol Ther. Jan. 2009;29(1):75-82. doi: 10.1111/j.1365-2036.2008.03860.x. …
[cited by applicant]
Arpaia et al., A Distinct Function of Regulatory T Cells in Tissue Protection. Cell. Aug. 27, 2015;162(5):1078-89. doi: 10.1016/j.cell.2015.08.021. Supplemental Information.
[cited by applicant]
Atarashi et al., ATP drives lamina propria T(H)17 cell differentiation. Nature. Oct. 9, 2008;455(7214):808-12. doi: 10.1038/nature07240. Epub Aug. 20, 2008.
[cited by applicant]
Atarashi et al., Induction of Colonic Regulatory T Cells by Indigenous
[cited by applicant]
Atarashi et al., Induction of Colonic Regulatory T Cells by Indigenous
[cited by applicant]
Atarashi et al., Microbiota in autoimmunity and tolerance. Curr Opin; Immunol. Dec. 2011;23(6):761-8. doi: 10.1016/j.coi.2011.11.002. Epub Nov. 22, 2011.
[cited by applicant]
Atarashi et al., Microbiotal influence on T cell subset development. Seminars in Immunology. Apr. 04, 2011;23(2):146-153.
[cited by applicant]
Atarashi et al., Regulation of colonic regulatory T cells by
[cited by applicant]
Atarashi et al., Regulation of colonic regulatory T cells by
[cited by applicant]
Atarashi et al., Treg induction by a rationally selected mixture of Clostridia strains from the human microbiota. Nature. Aug. 8, 2013;500(7461):232-6. doi: 10.1038/nature12331. Epub Jul. 10, 2013.
[cited by applicant]
Autoimmune Disease List. American Autoimmune Related Diseases Association. 2017.
[cited by applicant]
Bag et al., Complete Genome Sequence of
[cited by applicant]
Bakken, Fecal bacteriotherapy for recurrent Clostridium difficile infection. Anaerobe. Dec. 2009;15(6):285-9. doi: 10.1016/j.anaerobe.2009.09.007. Epub Sep. 22, 2009.
[cited by applicant]
Barnes et al., Regulatory T cells reinforce intestinal homeostasis. Immunity. Sep. 18, 2009;31(3):401-11. doi: 10.1016/j.immuni.2009.08.011.
[cited by applicant]
Bassaganya-Riera et al., Punicic acid modulates mucosal immune responses and prevents gut inflammation through PPAR gamma and delta-dependent mechanisms. Faseb J. 2010; 24 (Meeting Abstract Supplement). Abstract.
[cited by applicant]
Bassaganya-Riera et al., Soluble fibers and resistant starch ameliorate disease activity in an experimental model of inflammatory bowel disease. Faseb J. 2010; 24 (Meeting Abstract Supplement). Abstract.
[cited by applicant]
Belkaid et al., Natural regulatory T cells in infectious disease. Nat Immunol. Apr. 2005;6(4):353-60.
[cited by applicant]
Bergey et al., (2009). Bergey's manual of systematic bacteriology: vol. 3. New York: Springer. 795, 814-815 and 820. (17 pages).
[cited by applicant]
Biddle et al., The complete genome sequence of Clostridium indolis DSM 755(T.). Stand Genomic Sci. Mar. 18, 2014;9(3):1089-104. doi: 10.4056/sigs.5281010.
[cited by applicant]
Borody et al., Treatment of ulcerative colitis using fecal bacteriotherapy. J Clin Gastroenterol. Jul. 2003;37(1):42-7.
[cited by applicant]
Bouskra et al., Lymphoid tissue genesis induced by commensals through NOD1 regulates intestinal homeostasis. Nature. Nov. 27, 2008;456(7221):507-10. doi: 10.1038/nature07450. Epub Nov. 5, 2008.
[cited by applicant]
Braat et al., A phase I trial with transgenic bacteria expressing interleukin-10 in Crohn's disease. Clin Gastroenterol Hepatol. Jun. 2006;4(6):754-9. doi: 10.1016/j.cgh.2006.03.028. Epub May 22, 2006.
[cited by applicant]
Brief Communication issued in EP Patent 3178483, dated Oct. 29, 2021, transmitting Letter from Opponent 2 in response to Proprietor's Response to notices of opposition. 11 pages.
[cited by applicant]
Browne et al., Culturing of ‘unculturable’ human microbiota reveals novel taxa and extensive sporulation. Nature. May 4, 2016. doi: 10.1038/nature17645.
[cited by applicant]
Bueche et al., Quantification of endospore-forming firmicutes by quantitative PCR with the functional gene spo0A. Appl Environ Microbiol. Sep. 2013;79(17):5302-12. doi: 10.1128/AEM.01376-13. Epub Jun. 28, 2013.
[cited by applicant]
Cai Miaoying et al, Names of Bacteria. The 2nd edition, Science Press, 1996-06, p. 179.
[cited by applicant]
Carvalho et al., Crohn's disease-associated
[cited by applicant]
Cato et al.,
[cited by applicant]
Cebra, Influences of microbiota on intestinal immune system development. Am J Clin Nutr. May 1999;69(5):1046S-1051S.
[cited by applicant]
Chandrasekaran et al., Clostridium difficile Toxin B blocks effector T cells proliferation by inhibiting PLD signaling. J. Immunol. Apr. 2010; 184(1): 49.19. Abstract.
[cited by applicant]
Clavel et al., Survival of Bacillus cereus spores and vegetative cells in acid media simulating human stomach. J Appl Microbiol. 2004;97(1):214-9.
[cited by applicant]
Collins et al., The phylogeny of the genus
[cited by applicant]
Communication of a Notice of Opposition for Application No. EP 12854485.5 (EP2785828), mailed Jan. 18, 2021.
[cited by applicant]
Curotto De Lafaille et al., Natural and adaptive foxp3+ regulatory T cells: more of the same or a division of labor? Immunity. May 2009;30(5):626-35. doi: 10.1016/j.immuni.2009.05.002.
[cited by applicant]
Declaration by Asuncion Martinez, PhD. Issued in the matter of EP 2575835 B1 and the opposition thereto by Seres Therapeutics, Inc. May 17, 2018. 15 pages.
[cited by applicant]
Declaration by Main Vuliè, Ph.D. Concerning European Patent 2575835. Dec. 17, 2018.
[cited by applicant]
Declaration of Alexander Rudensky, Ph.D. Concerning European Patent 2575835. Dec. 16, 2018.
[cited by applicant]
Declaration of Dr. James Dooley regarding abstracts of the XIVth International Congress of Immunology in Kobe in Aug. 2010, cited in EP Opposition 2575835.
[cited by applicant]
Declaration of Geraint James of Patent Seekers, dated Jan. 8, 2021. Concerning European Patent 2785828.
[cited by applicant]
Declaration of Joseph Sorg, Ph.D. Concerning European Patent 2575835. Dec. 16, 2018.
[cited by applicant]
Dewhirst et al., Phylogeny of the defined murine microbiota: altered Schaedler flora. Appl Environ Microbiol. Aug. 1999;65(8):3287-92.
[cited by applicant]
Di Giacinto et al., Probiotics ameliorate recurrent Th1-mediated murine colitis by inducing IL-10 and IL-10-dependent TGF-beta-bearing regulatory cells. J Immunol. Mar. 15, 2005;174(6):3237-46.
[cited by applicant]
Eeckhaut et al. The anaerobic butyrate-producing strain Butyricicoccus pullicaecorum decreases colonic inflammation and ulceration in a TNBS-induced colitis rat model. In, 5th Probiotics, Prebiotics and New Foods Congre…
[cited by applicant]
Eiseman B et al.; Fecal Enema as an Adjunct in the Treatment of Pseudomembranous Enterocolitis; Surgery vol. 44 No. 5; Nov. 1958.
[cited by applicant]
Ellis et al., Molecular characterization of stool microbiota in HIV-infected subjects by panbacterial and order-level 16S ribosomal DNA (rDNA) quantification and correlations with immune activation. J Acquir Immune Defi…
[cited by applicant]
European Office Action for Application No. 11 728 077.6. dated Sep. 18, 2015.
[cited by applicant]
Favier et al., Development of bacterial and bifidobacterial communities in feces of newborn babies. Anaerobe. Oct. 2003;9(5):219-29.
[cited by applicant]
Foditsch et al., Isolation and characterization of Faecalibacterium prausnitzii from calves and piglets. PLoS One. Dec. 31, 2014;9(12):e116465. doi: 10.1371/journal.pone.0116465. eCollection 2014.
[cited by applicant]
Foligne et al., A key role of dendritic cells in probiotic functionality. PLoS One. Mar. 21, 2007;2(3):e313.
[cited by applicant]
Foligne et al., Correlation between in vitro and in vivo immunomodulatory properties of lactic acid bacteria. World J Gastroenterol. Jan. 14, 2007;13(2):236-43.
[cited by applicant]
Fontenot et al., Regulatory T Cell Lineage Specification by the Forkhead Transcription Factor Foxp3. Immunity. Mar. 2005;22(3):329-41.
[cited by applicant]
Frank et al., Molecular-phylogenetic characterization of microbial community imbalances in human inflammatory bowel diseases. Proc Natl Acad Sci U S A. Aug. 21, 2007;104(34):13780-5. Epub Aug. 15, 2007.
[cited by applicant]
Furusawa et al., Commensal microbe-derived butyrate induces the differentiation of colonic regulatory T cells. Nature. Dec. 19, 2013;504(7480):446-50. doi: 10.1038/nature12721. Epub Nov. 13, 2013. Erratum in: Nature. Fe…
[cited by applicant]
Gaboriau-Routhiau et al., The key role of segmented filamentous bacteria in the coordinated maturation of gut helper T cell responses. Immunity. Oct. 16, 2009;31(4):677-89. doi: 10.1016/j.immuni.2009.08.020.
[cited by applicant]
Garrett et al., Communicable ulcerative colitis induced by T-bet deficiency in the innate immune system. Cell. Oct. 5, 2007;131(1):33-45.
[cited by applicant]
Geuking et al., Intestinal bacterial colonization induces mutualistic regulatory T cell responses. Immunity. May 27, 2011;34(5):794-806. doi: 10.1016/j.immuni.2011.03.021. Epub. May 19, 2011.
[cited by applicant]
Grehan et al., Durable alteration of the colonic microbiota by the administration of donor fecal flora. J Clin Gastroenterol. Sep. 2010;44(8):551-61. doi: 10.1097/MCG.0b013e3181e5d06b.
[cited by applicant]
Hart et al., Modulation of human dendritic cell phenotype and function by probiotic bacteria. Gut. Nov. 2004;53(11):1602-9.
[cited by applicant]
Hata et al., Blood group B degrading activity of Ruminococcus gnavus alpha-galactosidase. Artif Cells Blood Substit Immobil Biotechnol. May 2004;32(2):263-74.
[cited by applicant]
Hattori et al., Bunchi Shokakibyo, 2011, 8/2:116-121, abstract only (Year: 2011).
[cited by applicant]
Hattori et al., Bunshi Shokakibyo, 2012, 9/2:130-137, abstract only (Year: 2012).
[cited by applicant]
Hattori et al., Kagaku Ryoho no Ryoiki, 2011, 27/9:1989-1997, abstract only (Year: 2011).
[cited by applicant]
Hattori et al., Rinsho Kensa, 55/2:135-141, abstract only (Year: 2011).
[cited by applicant]
Hayashi et al., Fecal microbial diversity in a strict vegetarian as determined by molecular analysis and cultivation. Microbiol Immunol. 2002;46(12):819-31.
[cited by applicant]
Hayashi et al., Phylogenetic analysis of the human gut microbiota using 16S rDNA clone libraries and strictly anaerobic culture-based methods. Microbiol Immunol. 2002;46(8):535-48.
[cited by applicant]
Hazenberg et al., Effects of the human intestinal flora on germ-free mice. J Appl Bacteriol. Feb. 1981;50(1):95-106.
[cited by applicant]
Honda et al. Immune regulation by intestinal microflora. Presentation, Dec. 4, 2009. 28 pages.
[cited by applicant]
Honda et al., Regulation of T Cell Responses by Intestinal Commensal Bacteria. J Intestinal Microbiol. 2011;25(2):103-104.
[cited by applicant]
Hsu et al., IL-10 Potentiates Differentiation of Human Induced Regulatory T Cells via STAT3 and Foxol. J Immunol. Oct. 15, 2015;195(8):3665-74. doi: 10.4049/jimmunol.1402898. Epub. Sep. 11, 2015.
[cited by applicant]
ICI Wrap-Up Report. 14th International Congress of Immunology. Aug. 22-27, 2010.
[cited by applicant]
Iizuka et al., Novel evidence suggesting Clostridium difficile is present in human gut microbiota more frequently than previously suspected. Microbiol Immunol. 2004;48(11):889-92.
[cited by applicant]
International Statistical Classification of Diseases and Related Health Problems 10th Revision. WHO (ICD-10). 2016. Chapter 1. Certain infectious and parasitic diseases (A00-B99).
[cited by applicant]
Itoh et al., Characterization of clostridia isolated from faeces of limited flora mice and their effect on caecal size when associated with germ-free mice. Lab Anim Apr. 1985;19(2):111-8.
[cited by applicant]
Itoh et al., Colonization resistance against Pseudomonas aeruginosa in gnotobiotic mice. Lab Anim. Jul. 1986;20(3):197-201.
[cited by applicant]
Itoh et al., Intestinal bacteria antagonistic to Clostridium difficile in mice. Lab Anim. Jan. 1987;21(1):20-5.
[cited by applicant]
Itoh et al., Production of gnotobiotic mice with normal physiological functions. I. Selection of useful bacteria from feces of conventional mice. Z Versuchstierkd. 1980;22(3):173-8.
[cited by applicant]
Ivanov et al., Induction of intestinal Th17 cells by segmented filamentous bacteria. Cell. Oct. 30, 2009;139(3):485-98. doi: 10.1016/j.cell.2009.09.033.
[cited by applicant]
Ivanov et al., Specific microbiota direct the differentiation of IL-17-producing T-helper cells in the mucosa of the small intestine. Cell Host Microbe. Oct. 16, 2008;4(4):337-49. doi: 10.1016/j.chom.2008.09.009.
[cited by applicant]
Janeway et al., Autoimmune responses are directed against self antigens. Immunobiology: The Immune System in Health and Disease. 5th edition. 2001. New York: Garland Science.
[cited by applicant]
Janeway et al., Immunobiology: The Immune System in Health and Disease. 6th edition. 2005. Chapter 10. 414. Figure 10.4.
[cited by applicant]
Jarry et al., Mucosal IL-10 and TGF-beta play crucial roles in preventing LPS-driven,; IFN-gamma-mediated epithelial damage in human colon explants. J Clin Invest. Mar. 2008;118(3):1132-42.
[cited by applicant]
Jawetz et al., Spore-forming gram-positive bacilli:
[cited by applicant]
Jawhara et al.,
[cited by applicant]
Jordan et al., Thymic selection of CD4+CD25+ regulatory T cells induced by an agonist self-peptide. Nat Immunol. Apr. 2001;2(4):301-6.
[cited by applicant]
Kakihana et al., Fecal microbiota transplantation for patients with steroid-resistant acute graft-versus-host disease of the gut. Blood. Oct. 20, 2016;128(16):2083-2088. doi: 10.1182/blood-2016-05-717652. Epub Jul. 26, …
[cited by applicant]
Kamanaka et al., Expression of interleukin-10 in intestinal lymphocytes detected by an interleukin-10 reporter knockin tiger mouse. Immunity. Dec. 2006;25(6):941-52. Epub Nov. 2006.
[cited by applicant]
Karimi et al., Lactobacillus reuteri-induced regulatory T cells protect against an allergic airway response in mice. Am J Respir Crit Care Med. Feb. 1, 2009;179(3):186-93. doi: 10.1164/rccm.200806-9510C. Epub Nov. 21, 2…
[cited by applicant]
Kelly et al., Commensal gut bacteria: mechanisms of immune modulation. Trends Immunol. Jun. 2005;26(6):326-33.
[cited by applicant]
Keynan et al., The role of regulatory T cells in chronic and acute viral infections. Clin Infect Dis. Apr. 1, 2008;46(7):1046-52. doi: 10.1086/529379.
[cited by applicant]
Khoruts et al., Changes in the composition of the human fecal microbiome after bacteriotherapy for recurrent Clostridium difficile-associated diarrhea. J Clin Gastroenterol. May-Jun. 2010;44(5):354-60. doi: 10.1097/MCG.…
[cited by applicant]
Kita, Intestinal colonization and transmission of Clostridium difficile among students as a community. J Antibact Antifung Agents. 2004;32(3):105-113.
[cited by applicant]
Krogius-Kurikka et al., Sequence analysis of percent G+C fraction libraries of human faecal bacterial DNA reveals a high number of Actinobacteria. BMC Microbiol. Apr. 8, 2009;9:68. doi: 10.1186/1471-2180-9-68.
[cited by applicant]
Kumar et al., Probiotic administration alters the gut flora and attenuates colitis in mice administered dextran sodium sulfate. J. Gastroenterology and Hepatology. Dec. 2008;23(12):1834-9. Epub Nov. 28, 2008. https://do…
[cited by applicant]
Kuswanto et al., Poor Repair of Skeletal Muscle in Aging Mice Reflects a Defect in Local, Interleukin-33-Dependent Accumulation of Regulatory T Cells. Immunity. Feb. 16, 2016;44(2):355-67. doi: 10.1016/j.immuni.2016.01.…
[cited by applicant]
Kwon et al., Generation of regulatory dendritic cells and CD4+Foxp3+ T cells by probiotics administration suppresses immune disorders. Proc Natl Acad Sci U S A. Feb. 2, 2010;107(5):2159-64. doi: 10.1073/pnas.0904055107.…
[cited by applicant]
Lafaille et al., High Incidence of Spontaneous Autoimmune Encephalomyelitis in Immunodeficient Anti-Myelin Basic Protein T cell Receptor Transgenic Mice. Cell. Aug. 12, 1994;78(3):399-408.
[cited by applicant]
Latvala et al., Potentially probiotic bacteria induce efficient maturation but differential cytokine production in human monocyte-derived dendritic cells. World J Gastroenterol. Sep. 28, 2008;14(36):5570-83; discussion …
[cited by applicant]
Lau et al., Bacteraemia caused by Anaerotruncus colihominis and emended description of the species. J Clin Pathol. Jul. 2006;59(7):748-52. Epub Feb. 7, 2006.
[cited by applicant]
Lawley et al., Targeted restoration of the intestinal microbiota with a simple, defined bacteriotherapy resolves relapsing Clostridium difficile disease in mice. PLoS Pathog. 2012;8(10):e1002995. doi: 10.1371/journal.pp…
[cited by applicant]
Lawson et al.,
[cited by applicant]
Lawson, Anaerotruncus. Bergey's Manual of Systematics of Archaea and Bacteria. Sep. 2015 14;1-4.
[cited by applicant]
Leber et al., Systems Modeling of Interactions between Mucosal Immunity and the Gut Microbiome during
[cited by applicant]
Levine et al., Continuous requirement for the TCR in regulatory T cell function. Nat Immunol. Nov. 2014;15(11):1070-8. doi: 10.1038/ni.3004. Epub Sep. 28, 2014.
[cited by applicant]
Levine et al., Suppression of lethal autoimmunity by regulatory T cells with a single TCR specificity. J Exp Med. Mar. 6, 2017;214(3):609-622. doi: 10.1084/jem.20161318. Epub Jan. 27, 2017.
[cited by applicant]
Li et al., Effect of oral feeding with Clostridium leptum on regulatory T-cell responses and allergic airway inflammation in mice. Ann Allergy Asthma Immunol. Sep. 2012;109(3):201-7. doi: 10.1016/j.anai.2012.06.017. Epu…
[cited by applicant]
Li et al., IL-10 and its related cytokines for treatment of inflammatory bowel disease. World J Gastroenterol. Mar. 1, 2004;10(5):620-5. doi: 10.3748/wjg.v10.i5.620.
[cited by applicant]
Li et al., Symbiotic gut microbes modulate human metabolic phenotypes. Proc Natl Acad Sci U S A. Feb. 12, 2008;105(6):2117-22. doi: 10.1073/pnas.0712038105.
[cited by applicant]
Liu et al., Reclassification of
[cited by applicant]
Livingston et al., Gut commensal Lactobacillus reuteri 100-23 stimulates an immunoregulatory response. Immunol Cell Biol. Jan. 2010;88(1):99-102. doi: 10.1038/icb.2009.71. Epub Sep. 29, 2009.
[cited by applicant]
Lopetuso et al., Commensal Clostridia:leading players in the maintenance of gut homeostasis. Gut Pathog. Aug. 13, 2013;5(1):23. doi: 10.1186/1757-4749-5-23.
[cited by applicant]
Louis et al., Diversity, metabolism and microbial ecology of butyrate-producing bacteria from the human large intestine. FEMS Microbiol Lett. May 2009;294(1):1-8. doi: 10.1111/j.15746968.2009.01514.x. Epub Feb. 13, 2009.
[cited by applicant]
Lu et al., Molecular orchestration of differentiation and function of regulatory T cells. Genes Dev. Jun. 1, 2009;23(11):1270-82. doi:10.1101/gad.1791009.
[cited by applicant]
Lupp et al., Host-mediated inflammation disrupts the intestinal microbiota and promotes the overgrowth of Enterobacteriaceae. Cell Host Microbe. Aug. 16, 2007;2(2):119-29. doi: 10.1016/j.chom.2007.06.010.
[cited by applicant]
MacPherson et al., Interactions between commensal intestinal bacteria and the immune system. Nat Rev Immunol. Jun. 2004;4(6):478-85.
[cited by applicant]
Maizels et al., Regulatory T cells in infection. Adv Immunol. 2011;112:73-136. doi: 10.1016/B978-0-12-387827-4.00003-6.
[cited by applicant]
Mandalari et al., in vitro evaluation of the prebiotic properties of almond skins (
[cited by applicant]
Mangin et al., Molecular inventory of faecal microflora in patients with Crohn's disease. FEMS Microbiol Ecol. Oct. 1, 2004;50(1):25-36. doi: 10.1016/j.femsec.2004.05.005.
[cited by applicant]
MartíN et al., The commensal bacterium Faecalibacterium prausnitzii is protective in DNBS-induced chronic moderate and severe colitis models. Inflamm Bowel Dis. Mar. 2014;20(3):417-30. doi: 10.1097/01.MIB.0000440815.766…
[cited by applicant]
Maslowski et al., Regulation of inflammatory responses by gut microbiota and chemoattractant receptor GPR43. Nature. Oct. 29, 2009;461(7268):1282-6. doi: 10.1038/nature08530.
[cited by applicant]
Maynard et al., Regulatory T cells expressing interleukin 10 develop from Foxp3+ and Foxp3-precursor cells in the absence of interleukin 10. Nat Immunol. Sep. 2007;8(9):931-41. Epub Aug. 12, 2007.
[cited by applicant]
Mazmanian et al., A microbial symbiosis factor prevents intestinal inflammatory disease. Nature. May 29, 2008;453(7195):620-5. doi:10.1038/nature07008.
[cited by applicant]
Mazmanian, Gut immune balance is as easy as S-F-B. Immunity. Oct. 16, 2009;31(4):536-8. doi: 10.1016/j.immuni.2009.09.005.
[cited by applicant]
Miquel et al., Faecalibacterium prausnitzii and human intestinal health. Curr Opin Microbiol. Jun. 2013;16(3):255-61. doi:10.1016/j.mib.2013.06.003. Epub Jul. 3, 2013. Review.
[cited by applicant]
Miyake et al., Dysbiosis in the Gut Microbiota of Patients with Multiple Sclerosis, with a Striking Depletion of Species Belonging to Clostridia XIVa and IV Clusters. PLoS One. Sep. 14, 2015;10(9):e0137429. doi: 10.1371…
[cited by applicant]
Momose et al., 16S rRNA gene sequence-based analysis of clostridia related to conversion of germfree mice to the normal state. J Appl Microbiol. Dec. 1, 2009;107(6):2088-97. doi:10.1111/j.1365-2672.2009.04431.x. Epub Ju…
[cited by applicant]
Murai et al., Interleukin 10 acts on regulatory T cells to maintain expression of the transcription factor Foxp3 and suppressive function in mice with colitis. Nat Immunol. Nov. 2009; 10(11):1178-84. doi: 10.1038/ni.179…
[cited by applicant]
Narushima et al., Characterization of the 17 strains of regulatory T cell-inducing human-derived Clostridia. Gut Microbes. May-Jun. 2014;5(3):333-9. doi: 10.4161/gmic.28572. Epub Mar. 18, 2014.
[cited by applicant]
Office Action for Japanese application No. 2017-049543.
[cited by applicant]
O'Garra et al., IL-10-producing and naturally occurring CD4+ Tregs: limiting collateral damage. J Clin Invest. Nov. 2004; 114(10):1372-8.
[cited by applicant]
Okada et al., Effects of fecal microorganisms and their chloroform-resistant variants derived from mice, rats, and humans on immunological and physiological characteristics of the intestines of ex-germfree mice. Infect …
[cited by applicant]
O'Mahony et al., Commensal-induced regulatory T cells mediate protection against pathogen-stimulated NF-kappaB activation. PLoS Pathog. Aug. 1, 2008;4(8):e1000112. doi: 10.1371/journal.ppat.1000112.
[cited by applicant]
Opposition against EP Patent 2 575 835 B1 dated Apr. 25, 2017. 35 pages. Seres Therapeutics.
[cited by applicant]
Opposition against EP Patent 2 575 835 B1 dated Jul. 18, 2017. 23 pages. Strawman Limited.
[cited by applicant]
Opposition against EP Patent 2 575 835 B1 dated Jul. 18, 2017. 4 pages. Mr. Lars Manke.
[cited by applicant]
Opposition against EP Patent 2 575 835 B1 dated Jul. 19, 2017. 20 pages. Dr. Martin Grund.
[cited by applicant]
Opposition against EP Patent 2 575 835 B1 dated Jul. 19, 2017. 27 pages. Müller Fottner Steineke Part mbB.
[cited by applicant]
Opposition against EP Patent 2 575 835 B1. Seres Therapeutics, Inc. Annexure; dated May 25, 2018.
[cited by applicant]
Opposition against EP Patent 2 575 835 B1. Summary of File History for Information; dated Jun. 7, 2018.
[cited by applicant]
Opposition against EP Patent No. 2 575 835 B1 dated Jul. 19, 2017. 37 pages. Nestec S.A.
[cited by applicant]
Opposition against European Patent No. 2575835/The University of Tokyo dated Dec. 18, 2018. Muller Fottner Steinecke.
[cited by applicant]
Opposition to European Patent No. 2575835 dated Dec. 18, 2018. Mathys & Squire.
[cited by applicant]
Panduro et al., Tissue Tregs. Annu Rev Immunol. May 20, 2016;34:609-33. doi: 10.1146/annurev-immunol-032712-095948. Author manuscript.
[cited by applicant]
Paredes-Sabja et al., Clostridium difficile spore biology:sporulation, germination, and spore structural proteins. Trends Microbiol. Jul. 2014;22(7):406-16. doi: 10.1016/j.tim.2014.04.003. Epub May 7, 2014.
[cited by applicant]
Povoleri et al., Human retinoic acid-regulated CD161+ regulatory T cells support wound repair in intestinal mucosa. Nat Immunol. Dec. 2018; 19(12):1403-1414. doi: 10.1038/s41590-018-0230-z. Epub Nov. 5, 2018.
[cited by applicant]
Pre-Hearing Submission Opponent 5 for EP Patent 2575835. Dec. 18, 2018.
[cited by applicant]
Qin et al., A human gut microbial gene catalogue established by metagenomic sequencing. Nature. Mar. 4, 2010;464(7285):59-65. doi: 10.1038/nature08821.
[cited by applicant]
Qiu et al., C. Faecalibacterium prausnitzii upregulates regulatory T cells and anti-inflammatory cytokines in treating TNBS-induced colitis. J Crohns Colitis. Dec. 1, 2013;7(11):e558-68. doi: 10.1016/j.crohns.2013.04.00…
[cited by applicant]
Rautava, Potential uses of probiotics in the neonate. Semin Fetal Neonatal Med. Feb. 2007;12(1):45-53. Epub Nov. 29, 2006.
[cited by applicant]
Reeck et al., “Homology” in proteins and nucleic acids: a terminology muddle and a way out of it. Cell. Aug. 28, 1987;50(5):667.
[cited by applicant]
Reexamination Decision for Chinese application No. 201180037900.8 dated Mar. 19, 2018.
[cited by applicant]
Rehman et al., Transcriptional activity of the dominant gut mucosal microbiota in chronic inflammatory bowel disease patients. J Med Microbiol. Sep. 2010;59(Pt 9):1114-22. doi: 10.1099/jmm.0.021170-0. Epub Jun. 3, 2010.
[cited by applicant]
Response to European Office Action for Application No. 11 728 077.6. dated Feb. 25, 2014.
[cited by applicant]
Response to European Office Action for Application No. 11 728 077.6. dated Jan. 28, 2015.
[cited by applicant]
Response to European Office Action for Application No. 11 728 077.6. dated Nov. 18, 2015.
[cited by applicant]
Response to the Summons to attend oral proceedings pursuant to Rule 115(1) EPC, dated Jun. 7, 2018. dated Nov. 16, 2018. EP Patent 2575835.
[cited by applicant]
Roberts, CSO Vedanta Biosciences Presentation. 1st Microbiome Drug Development Summit. Jun. 28, 2016.
[cited by applicant]
Rohlke et al., Fecal flora reconstitution for recurrent Clostridium difficile infection: results and methodology. J Clin Gastroenterol. Sep. 2010;44(8):567-70. doi: 10.1097/MCG.0b013e3181dadb10.
[cited by applicant]
Rosero et al., Reclassification of Eubacterium rectale (Prévot et al., 1967) in a new genus
[cited by applicant]
Rossi et al., Faecalibacterium prausnitzii A2-165 has a high capacity to induce IL-10 in human and murine dendritic cells and modulates T cell responses. Sci Rep. Jan. 4, 2016;6:18507. doi:10.1038/srep18507.
[cited by applicant]
Round et al., Inducible Foxp3+ regulatory T-cell development by a commensal bacterium of the intestinal microbiota. Proc Natl Acad Sci U S A. Jul. 6, 2010;107(27):12204-9. doi: 10.1073/pnas.0909122107. Epub Jun. 21, 201…
[cited by applicant]
Round et al., The gut microbiota shapes intestinal immune responses during health and disease. Nat Rev Immunol. May 2009;9(5):313-23. doi:10.1038/nri2515. Review. Erratum in: Nat Rev Immunol. Aug. 2009;9(8):600.
[cited by applicant]
Rubtsov et al., Regulatory T cell-derived interleukin-10 limits inflammation at environmental interfaces. Immunity. Apr. 2008;28(4):546-58. doi: 10.1016/j.immuni.2008.02.017.
[cited by applicant]
Sakaguchi et al., Regulatory T cells and immune tolerance. Cell. May 30, 2008;133(5):775-87. doi: 10.1016/j.cell.2008.05.009.
[cited by applicant]
Salzman et al., Enteric defensins are essential regulators of intestinal microbial ecology. Nat Immunol. Jan. 2010;11(1):76-83. doi: 10.1038/ni.1825. Epub Oct. 22, 2009.
[cited by applicant]
Sanchez et al., The role of natural regulatory T cells in infection. Immunol Res. Apr. 2011;49(1-3):124-34. doi: 10.1007/s12026-010-8176-8.
[cited by applicant]
Sanos et al., RORgammat and commensal microflora are required for the differentiation of mucosal interleukin 22-producing NKp46+ cells. Nat Immunol. Jan. 2009; 10(1):83-91. doi: 10.1038/ni.1684. Epub Nov. 23, 2008.
[cited by applicant]
Sartor, Therapeutic correction of bacterial dysbiosis discovered by molecular techniques. Proc Natl Acad Sci U S A. Oct. 28, 2008;105(43):16413-4. doi:10.1073/pnas.0809363105. Epub Oct. 23, 2008.
[cited by applicant]
Schloss et al., The dynamics of a family's gut microbiota reveal variations on a theme. Microbiome. Jul. 21, 2014;2:25. doi:10.1186/2049-2618-2-25. eCollection 2014.
[cited by applicant]
Schouten et al., Oligosaccharide-induced whey-specific CD25(+) regulatory T-cells are involved in the suppression of cow milk allergy in mice. J Nutr. Apr. 2010; 140(4):835-41. doi: 10.3945/jn.109.116061. Epub Feb. 17, …
[cited by applicant]
Screenshot of https://academic.oup.com/intimm/issue/22/Suppl_1_Pt3 showing the publication of Warren et al. at the Workshop abstract WS64 of XIVth International congress of Immunology held in Kobe in Japan on Aug. 2010.
[cited by applicant]
Segain et al., Butyrate inhibits inflammatory responses through NFkappaB inhibition: implications for Crohn's disease. Gut. Sep. 2000;47(3):397-403.
[cited by applicant]
Sequence listing of WO 2011/152566.
[cited by applicant]
Sghir et al., Quantification of bacterial groups within human fecal flora by oligonucleotide probe hybridization. Appl Environ Microbiol. May 2000;66(5):2263-6.
[cited by applicant]
Shen et al., Molecular profiling of the Clostridium leptum subgroup in human fecal microflora by PCR-denaturing gradient gel electrophoresis and clone library analysis. Appl Environ Microbiol. Aug. 2006;72(8):5232-8.
[cited by applicant]
So et al., Lactobacillus casei potentiates induction of oral tolerance in experimental arthritis. Mol Immunol. Nov. 2008;46(1):172-80. doi: 10.1016/j.molimm.2008.07.038. Epub Sep. 19, 2008.
[cited by applicant]
So et al., Lactobacillus casei suppresses experimental arthritis by down-regulating T helper 1 effector functions. Mol Immunol. May 2008;45(9):2690-9. doi:10.1016/j.molimm.2007.12.010. Epub Feb. 19, 2008.
[cited by applicant]
Sokol et al., Faecalibacterium prausnitzii is an anti-inflammatory commensal bacterium identified by gut microbiota analysis of Crohn disease patients. Proc Natl Acad Sci U S A. Oct. 28, 2008;105(43):16731-6. doi: 10.10…
[cited by applicant]
Sokol et al., Low counts of Faecalibacterium prausnitzii in colitis microbiota. Inflamm Bowel Dis. Aug. 2009;15(8):1183-9. doi: 10.1002/ibd.20903.
[cited by applicant]
Solomon et al., Mortality in patients with Clostridium difficile infection correlates with host pro-inflammatory and humoral immune responses. J Med Microbiol. Sep. 2013;62(Pt 9):1453-60. doi: 10.1099/jmm.0.058479-0. Ep…
[cited by applicant]
Song et al.,
[cited by applicant]
Stackebrandt et al., Phylogenetic basis for a taxonomic dissection of the genus
[cited by applicant]
Steer et al.,
[cited by applicant]
Steidler et al., Treatment of murine colitis by Lactococcus lactis secreting interleukin-10. Science. Aug. 25, 2000;289(5483):1352-5. doi: 10.1126/science.289.5483.1352.
[cited by applicant]
Sydora et al. CD4+CD25+ regulatory T cells have divergent effects on intestinal inflammation in IL-10 gene-deficient mice. Dig Dis Sci. Jun. 2008;53(6):1544-52.
[cited by applicant]
Takaishi et al., Imbalance in intestinal microflora constitution could be involved in the pathogenesis of inflammatory bowel disease. Int J Med Microbiol. Jul. 2008;298(5-6):463-72. Epub Sep. 25, 2007.
[cited by applicant]
Tanoue et al., Immune responses to gut microbiota-commensals and pathogens Gut Microbes. Jul.-Aug. 2010; 1(4): 224-233.
[cited by applicant]
Tanoue et al., Indigenous
[cited by applicant]
Tanoue et al., Regulation of intestinal Th17 and Treg cells by gut microbiota. Inflammation Regeneration. May 2015;35(3):99-105.
[cited by applicant]
Tao et al., Deacetylase inhibition promotes the generation and function of regulatory T cells. Nat Med. Nov. 2007; 13(11):1299-307. Epub Oct. 7, 2007.
[cited by applicant]
Thibault et al., Butyrate utilization by the colonic mucosa in inflammatory bowel diseases: a transport deficiency. Inflamm Bowel Dis. Apr. 2010; 16(4):684-95. doi:10.1002/ibd.21108.
[cited by applicant]
Third Party Observations filed in European Patent Application No. 11728077.6 on Jan. 29, 2016.
[cited by applicant]
Umesaki et al., Differential roles of segmented filamentous bacteria and clostridia in development of the intestinal immune system. Infect Immun. Jul. 1999;67(7):3504-11.
[cited by applicant]
Valcheva et al., Prebiotics Prevent Loss Of Intestinal Biodiversity And Reduce Colitis In Hla-B27 Transgenic Rats. Canadian Digestive Diseases Week. Feb. 2009. Poster Session 2—Immunology and Inflammatory Bowel Disease.…
[cited by applicant]