(12) STANDARD PATENT (11) Application No. AU 2008290737 B2 (19) AUSTRALIAN PATENT OFFICE (54) Title Preventing and/or treating metabolic disorders by modulating the amount of en­ terobacteria (51) International Patent Classification(s) A61K 31/702 (2006.01) A61K 35/76 (2006.01) A61K 31/7088 (2006.01) A61K 36/00 (2006.01) A61K 35/74(2006.01) A61P 3/04 (2006.01) (21) Application No: 2008290737 (22) Date of Filing: 2008.07.25 (87) WIPO No: WO09/024429 (30) Priority Data (31) Number (32) Date (33) Country 07114530.4 2007.08.17 EP (43) Publication Date: 2009.02.26 (44) Accepted Journal Date: 2013.11.14 (71) Applicant(s) Nestec S.A. (72) Inventor(s) Arigoni, Fabrizio;Philippe, David;Mace, Catherine;Darimont, Christian;Chou, Chieh Jason (74) Agent / Attorney Shelston IP, L 21 60 Margaret St, Sydney, NSW, 2000 (56) Related Art WO 2006/129092 A2 (THE UNIVERSITY OF BIRMINGHAM), 07 December 2006. LEY RE, et al, 'Human gut microbes associated with obesity,' Nature, (2006), Vol 444, pp 1022-1023 US 2006/0094672 A1 (PASQALINI et al.), 04 May 2006. US 2005/0239706 A1 (BACKHED et al.), 27 October 2005. WO 2008/116700 A1 (NESTEC S.A.), 02 October 2008 WO 2007/135141 A1 (NESTEC S.A.), 29 November 2007. BACKHEAD F, et al. 'The gut microbiodata as an environmental factor that regulates fat storage,' Proceedings of the National Academy of Sciences of USA (PNAS), (2004) Vol 101 No 44, pp 15718-15723. TURNBAUGH PJ, et al. 'An obesity-associated gut microbiome with increased capacity for energy harvest,' Nature, (2006) Vol 444, pp 1027-1031 (12) INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property Organization International Bureau (10) International Publication Number (43) International Publication Date WO 2009/024429 A3 26 February 2009 (26.02.2009) PCT (51) International Patent Classification: [FR/CH]; Avenue des Mousquines 27, CH-1005 Lau­ A61K31/702 (2006.01) A61K35/76 (2006.01) sanne (CH). A61K31/7088 (2006.01) A61K36/00 (2006.01) (74) Agent: MARQUARDT, Ulf; Avenue Nestle 55, A61K35/74 (2006.01) A61P3/04 (2006.01) CH-1800 Vevey (CH). (21) International Application Number: (81) Designated States (unless otherwise indicated, for every PCT/EP2008/059809 kind of national protection available): AE, AG, AL, AM, (22) International Filing Date: AO, AT, AU, AZ, BA, BB, BG, BH, BR, BW, BY, BZ, 25 July 2008 (25.07.2008) CA, CH, CN, CO, CR, CU, CZ, DE, DK, DM, DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, HN, (25) Filing Language: English HR, HU, ID, IL, IN, IS, JP, KE, KG, KM, KN, KP, KR, (26) Publication Language: English KZ, LA, LC, LK, LR, LS, LT, LU, LY, MA, MD, ME, MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, (30) Priority Data: NZ, OM, PG, PH, PL, PT, RO, RS, RU, SC, SD, SE, SG, 07114530.4 17 August 2007 (17.08.2007) EP SK, SL, SM, ST, SV, SY, TJ, TM, TN, TR, TT, TZ, UA, (71) Applicant (for all designated States except US): UG, US, UZ, VC, VN, ZA, ZM, ZW. NESTEC S.A. [CH/CH]; Avenue Nestle 55, CH-1800 (84) Designated States (unless otherwise indicated, for every Vevey (CH). kind of regional protection available): ARIPO (BW, GH, (72) Inventors; and GM, KE, LS, MW, MZ, NA, SD, SL, SZ, TZ, UG, ZM, (75) Inventors/Applicants (for US only): CHOU, Chieh Ja­ ZW), Eurasian (AM, AZ, BY, KG, KZ, MD, RU, TJ, son [CN/CH]; Avenue des Mousquines 25, CH-1005 TM), European (AT, BE, BG, CH, CY, CZ, DE, DK, EE, Lausanne (CH). PHILIPPE, David [FR/CH]; Avenue ES, FI, FR, GB, GR, HR, HU, IE, IS, IT, LT, LU, LV, MC, MT, NL, NO, PL, PT, RO, SE, SI, SK, TR), OAPI Sainte Luce 11, CH-1003 Lausanne (CH). DARIMONT, (BF, BJ, CF, CG, CI, CM, GA, GN, GQ, GW, ML, MR, Christian [FR/CH]; Avenue Montagibert 20, CH-1005 NE, SN, TD, TG). Lausanne (CH). ARIGONI, Fabrizio [CH/CH]; Rue Maurice 2, CH-1204 Geneve (CH). MACE, Catherine Declarations under Rule 4.17: [Continued on next page] (54) Title: PREVENTING AND/OR TREATING METABOLIC DISORDERS BY MODULATING THE AMOUNT OF EN­ TEROBACTERIA (57) Abstract: The present invention relates to support­ ing weight management, weight loss and/or to the pre­ vention and/or treatment of metabolic disorders. In par­ ticular the present invention relates to preventing and/or treating metabolic disorders by modulating, in particular reducing the amount of proteobacteria and/or deferribac­ teres in the gut. One embodiment of the present inven­ tion relates to the use of a primary composition compris­ ing an agent that reduces the amount of proteobacteria, preferably gamma- proteobacteria, even more preferred enterobacteria; and/or deferribacteres in the gut for the preparation of a composition to treat or prevent metabol­ ic disorders, to support weight loss and/or to support weight management. A3 Days FIG. 2 2009/024429 WO wo 2009/024429 A31 lllllllllllll IIII lllllllllllll — as to applicant's entitlement to apply for and be granted — before the expiration of the time limit for amending the a patent (Rule 4.17(H)) claims and to be republished in the event of receipt of amendments (Rule 48.2(h)) — as to the applicant's entitlement to claim the priority of the earlier application (Rule 4.17(Hi)) (88) Date of publication of the international search report: — of inventorship (Rule 4.17 (iv)) 3 December 2009 Published: — with international search report (Art. 21(3)) WO 2009/024429 PCT/EP2008/059809 Gut flora and weight management The present invention relates to supporting weight management, weight loss and/or to the prevention and/or treatment of metabolic disorders. In particular the present invention relates 5 to preventing and/or treating metabolic disorders by modulating, in particular reducing the amount of proteobacteria and/or deferribacteres in the gut. The prevalence of obesity has grown in an alarming rate in the past 20 years. Based on the latest estimate in 2004, in the US alone, 66.3% of adults are either overweight or obese, and 10 32.2% of adults are classified as obese (Cynthia L. Ogden et al., JAMA 2006 April 5;295:1549-1555). Both genetic and environmental factors have been shown to cause positive energy balance and obesity. Obesity by itself is only a part of problems. Many other chronic diseases such as type 2 diabetes, certain cancers and cardiovascular diseases are common co­ morbidities of obesity. Collectively, all the obesity associated medical issues put a 15 tremendous amounts of pressure on health care systems in many countries. Due to the prevalence of obesity, type 2 diabetes has also become a worldwide health problem. According to an epidemiological study, the projective global prevalence for type 2 diabetic population will reach to 366 million people in 2030 (Sarah Wild et al., Diabetes Care 2004 May;27:1047-1053). Drug treatments for obesity are available but not very effective and with 20 undesirable side-effects. For the treatment of type 2 diabetes,, currently available drugs are capable of managing hyperglycemia of the patients. Still more drugs are under development to improve the safety, efficacy of the medications and convenience to use them by patients. To date, all anti-obesity and anti-diabetic drugs are designed to alter the internal metabolism of patients. Most of these drugs are required to be absorbed and delivered to target organs 25 through blood stream for their efficacy. Safety concerns of such a treatment strategy cannot be ignored. In contrast a novel treatment strategy of obesity and type 2 diabetes focussing on targets outside of human tissues is greatly desirable because the active agents are not required to enter our body, and the safety of the treatments can be improved significantly. 30 Human beings are supcrorganisms with a body composed of millions of human cells while many more bacteria live, e.g., in the colon. It has been estimated that more than 1013 to 1014 bacteria are alive in a healthy human intestine. Intestinal bacteria can be separated into 2 major divisions, firmicutes and bacteriodetes (Steven R. Gill,et al., Science 2006 June 2;312: 1355-1359; Peter J. Tumbaugh, et al., Nature 2006 Dec 21 ;444:1027-131). Together, they -2- 2013 represent at least 90% of total bacterial population in the gut. The presence of the gut Sep bacteria is a part of normal human physiology and is important for the development of gut functions (Hooper LV et al., Science. 2001 Feb 2;291 (5505):881-4; Stappenbeck TS, 24 et al., Proc Natl Acad Sci USA. 2002 Nov 26;99(24): 15451 -5), maturation of the 5 immune system (Mazmanian SK, et al., Cell. 2005 Jul 15; 122(1): 107-18), harvesting energy from dietary carbohydrates (Peter J. Tumbaugh, et al., Nature 2006 Dec 21 ;444:1027-131), harvesting essential vitamins (Backhed F, et al., Science. 2005 Mar 25;307(5717): 1915-20) and metabolizing environmental chemicals in the gut (Nicholson JK, et al., Nat Rev Microbiol. 2005 May;3(5):431-8). Recent studies further suggested 2008290737 10 that gut bacteria may be involved in fat storage (Backhed F, et al., Proc Natl Acad Sci U S A. 2004 Nov 2; 101(44): 15718-23). Any discussion of the prior art throughout the specification should in no way be considered as an admission that such prior art is widely known or forms part of common general knowledge in the field. 15 However, until now it has never been taught or suggested to manipulate the composition of gut bacteria to treat or prevent metabolic disorders.