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Patent No.: US 7.514,085 B2 3. 38. an Al Primary Examiner Christopher Tate

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US007514085B2 (12) United States Patent (10) Patent No.: US 7.514,085 B2 Kristiansen (45) Date of Patent: Apr. 7, 2009 (54) IMMUNE MODULATING COMPOUNDS 6,020,324. A 2/2000 Jamas et al. FROM FUNG 6,046,323. A 4/2000 Park 6,084,092 A 7/2000 WakShullet al. (75) Inventor: Bjorn Kristiansen, Frederikstad (NO) 6,090,615 A 7/2000 Nagaoka 6,090,938 A 7/2000 WakShullet al. rsr rr 6,110,892. A 8, 2000 Barbier et al. (73) Assignee: MediMush A/S, Horsholm (DK) 6,117,850 A 9, 2000 Patchen et al. c - r - 6,120,772 A 9, 2000 to (*) Notice: Subject to any disclaimer, the term of this 6,143,731 A 11/2000 Jamas et al. patent is extended or adjusted under 35 6.294,321 B1 9, 2001 WalkShullet al. U.S.C. 154(b) by 325 days. 6,297.363 B1 * 10/2001 Kubo et al. ................ 536,174 6,369,216 B1 4/2002 Patchen et al. (21) Appl. No.: 10/892,393 64 13,715 B2 7/2002 Wakshull et al. 6,440,448 B1 8/2002 Intelisano (22) Filed: Jul. 16, 2004 6,630,310 B1 10/2003 Wakshull et al. 6,692,739 B1 2/2004 Patti et al. (65) Prior Publication Data 6,702.999 B2 * 3/2004 Lawlor ........................ 424/48 7,022,685 B2 4/2006 Patchen et al. US 2006/0013825 A1 Jan. 19, 2006 2001/0051717 A1 12/2001 Wakshu11 et al. 2002fO164317 A1 11, 2002 GorSek (51) Int. Cl. 2002fO164773 A1 11, 2002 Wasser A6 IK 36/06 (2006.01) 2003/0208796 A1 1 1/2003 Song et al. A6 IK 36/09 (2006.01) 2005.0002962 A1 1/2005 Pasco et al. (52) U.S. Cl. ................................................. 424/195.15 2005, OO69989 A1 3, 2005 Kim et al. (58) Field of Classification Search ....................... None 2005/0130273 Al 6 2005 Versali See application file for complete search history. 2005. O158258 A1 7, 2005 Fisher 2005, 0163800 A1 7/2005 Kristiansen (56) References Cited 2005/0238654 A1 10, 2005 Takeda 2005.0245480 A1 11/2005 Ostroffet al. U.S. PATENT DOCUMENTS 2006, OO13825 A1 1/2006 Kristiansen 3,943,247 A 3, 1976 Komatsu 2006, O159698 A1 7/2006 Murata et al. 3,987,166 A 10, 1976 Komatsu 2007/004.1994 A1 2, 2007 McDowell 4,163,780 A 8, 1979 Ishida et al. 2007/O104728 A1 5/2007 Rangel et al. 4, 174,388 A 11, 1979 McAleer et al. 2007/0172934 A1 7/2007 Muller et al. 4,207,312 A 6/1980 Fujii et al. 2007/0178118 A1 8, 2007 Goino 4,247,541 A 1/1981 Ishida et al. 2008, OO63650 A1 3, 2008 Yan 4454,289 A 6/1984 Nakajima et al. 4,461,760 A 7, 1984 Sugano (Continued) 4,617,379 A 10, 1986 Dobkin et al. 4,769,363 A 9/1988 Misaki et al. FOREIGN PATENT DOCUMENTS 4,851,395 A 7, 1989 Ueno et al. 4,962,094. A 10, 1990 Jamas et al. CN 1082551 2, 1994 5,032,401 A 7, 1991 Jamas et al. 5,223,491 A 6, 1993 Donzis 5,283.239 A 2/1994 Koga et al. (Continued) 5,322,841 A 6, 1994 Jamas et al. OTHER PUBLICATIONS 5,397,773. A 3, 1995 Donzis 5.488,040 A 1/1996 Jamas et al. Zhang, L., et al. “Correlation between antitumor activity, molecular 5,504,079 A 4, 1996 Jamas et al. weight, and conformation of lentinan' Carbohydrate Research, 340, 5,519,009 A 5, 1996 Donzis (2005), 1515-1521. 5,532,223. A 7, 1996 Jamas et al. 5,576,015 A 1 1/1996 Donzis (Continued) 3. 38. an al Primary Examiner Christopher Tate 5,622,940 A 4, 1997 Ostroff Assistant Examiner Deborah A. Davis 5,633,369 A 5, 1997 Jamas et al. (74) Attorney, Agent, or Firm—Davis Wright Tremaine LLP 5,641,761 A 6, 1997 Takahashi 5,663,324 A 9, 1997 James et al. (57) ABSTRACT 5,702,719 A 12/1997 Donzis 5,705,184 A 1/1998 Donzis The present invention relates to compositions comprising 5,741,495 A 4, 1998 Jamas et al. polypeptides and polysaccharides. The compositions are in 5,744, 187 A 4/1998 Gaynor 5,756,318 A 5, 1998 KOsuna general immune modulating. The invention also discloses 5,783,569 A 7, 1998 Jamas et al. methods of producing- these compositions using filamentous 5,811,542 A 9, 1998 Jamas et al. fungi cultivated 1n liquid medium. The compositions are use: 5,817,643 A 10/1998 Jamas et al. ful for example in the treatment of immune compromised 5,849,720 A 12/1998 Jamas et al. conditions. 5,934,012 A 8, 1999 Holtz et al. 5.998,173 A * 12/1999 Haynes et al. ................ 435.84 41 Claims, No Drawings US 7,514,085 B2 Page 2 U.S. PATENT DOCUMENTS Zhou Weidong et al., Biological activity of hydrosoluble exopolysac charide (HEP) from Lentinus edodes CL-2 by submerged fermenta 2008. O103112 A1 5/2008 Magee et al. tion, Junwu Xitong, vol. 16, No. 3, 1997, p. 202-207. 2008/01061.14 A1 5/2008 Wheatley Zheng Xueyu et al., Immune function of the extracellular and 2008.0167268 A1 7, 2008 Yan intracellular polysaccharides of Lentinus edodes, Zhongcaoyao, vol. 16, No. 11, 1985, p. 494-497. FOREIGN PATENT DOCUMENTS Budavari. The Merck Index and encyclopedia of chemicals, drugs CN 1269423 11, 2000 and biologicals, 1996 (12th edition), p. 927, right-hand column. CN 1297994 6, 2001 Jong SC and Birmingham J.M. Medicinal Benefits of the Mushroom CN 1314417 9, 2001 Ganoderma, Advances in applied Microbiology, 1992, vol. 37, p. CN 1477130 2, 2004 101-134. CN 1490016 4/2004 S. Aouadiet. al., “Structural analysis and rheological behaviour of an CN 1528335 9, 2004 extracellular polysaccharide from Drechslera spicifera'. Carbohy CN 1765935 3, 2006 drate Polymers, vol. 17 pp. 177-183, 1992. EP O 292 601 11, 1988 Giovanni Giovannozzi Sermanni et. al., “The Production of Exo EP O 298 706 11, 1989 Enzymes by Lentinus Edodes and Pleurotus ostreatus and their use EP O 370 673 5, 1990 for Upgrading Corn Straw'. Bioresource Technology, vol. 48, pp. EP O38.2551 8, 1990 173-178, 1994. EP 11556.23 11, 2001 Byung-KeunYanget. al., “Hypoglycemic Effect of a Lentinus edodes GB 1331513 A 9, 1973 Exo-polymer Produced from a Submerged Mycelial Culture'. JP 56531.01 5, 1981 Biosci. Biotechnol. Biochem., vol. 66:5, pp. 937-942, 2002. JP O1132315 5, 1989 Nora Hatvani, 'Antibacterial effect of the culture fluid of Lentinus JP O6172217 6, 1994 edodes mycelium grown in Submerged liquid culture'. International JP 717307O 7, 1995 Journal of Antimicrobial Agents, vol. 17, pp. 71-74, 2001. JP 63296.662 12/1998 Zhou Weidong et al., “Biological activity of hydrosoluble JP 11080206 3, 1999 exopolysaccharide (HEP) from Lentinus edodes CL-2 by submerged JP 2001-078714 3, 2001 fermentation”. Junwu Xiong, vol. 16, No. 3, p. 202-207, 1997. JP 2002060344 2, 2002 Zheng Xueyu et al., “Immune function of the extracellular and JP 20043.00438 3, 2004 intracellular polysaccharides of Lentinus edodes'. Zhongcaoyao, KR 470734 2, 2005 vol. 16, No. 11, p. 494-497, 1985. KR 2003097062 2, 2005 Gou et al. Effects of mushroom and herb polysaccharides, as alter SU 1244.179 A T 1986 natives for an antibiotic, on growth performance of broilers. British WO 89.12106 12/1989 Poultry Science vol. 45, No. 5, p. 684-694, Oct. 2004. WO WO 89.12106 12/1989 Lobanok et al. Composition and biological activity of Submerged WO WO91,06307 5, 1991 mycelium of the Xylotrophic basidiomycete Lentinus edodes. WO WO96, 15659 5, 1996 Applied Biochemistry and microbiology, vol. 39, No. 1, 2003, p. WO WOOO.32212 6, 2000 60-64 (translated from Priki Biokhi Mikkrobiol Jan.-Feb. 2003, WO WOOO.32213 6, 2000 39(1):69-73). WO WOOO,54795 9, 2000 Van Nevel et al., “The influence of Lentinus edodes (Shiitake WO WOOOf 65029 11, 2000 muhroom) preparations on bacteriological and morphological WO WOO1,27305 4/2001 aspects of the Small intestine in piglets'. Archives of animal WO WOO151070 T 2001 nutrition—archive fur tierernahrung 57(6):399-412, Dec. 2003 WO WOO1? 64057 9, 2001 (abstract). WO WOO1/82935 11, 2001 Kawazoe T. et al., “Influence of an excessive supply of vitamin D-1 WO WO O2/O7708 1, 2002 fortified Shiitake mushroom on laying hens'. Journal of the Japanese WO WO O2/O87603 11, 2002 Society for food and Science technology—Nippon Shokuhin Kagaku WO WO O2/O98440 12/2002 Kaishi 44(4):300-305, 1997 (Abstract). WO O3020944 3, 2003 Gou FC, et al., “Effects of mushroom and herb polysaccharides, as WO WO 03/020944 3, 2003 alternatives for an antibiotic, on the cecal microbial ecosystm in WO WO 03/043440 5, 2003 broiler chickens', Poultry Science 83(2): 175-182 Feb. 2004 WO WO 03/0491.17 A2 6, 2003 (abstract). WO WO 03/080077 10, 2003 Gou et al., “Immunoactive, medicinal properties of mushroom and WO WO 2004/075907 9, 2004 herb polysaccharides and their potential use in chicken diets'. Worlds WO WO 2004f1OO965 11, 2004 poultry science journal 59(4): 427-440 Dec. 2003 (abstract). WO WO 2005/044182 5, 2005 Nikl L et al., “Influence of 7 immunostimulants on the immune WO WO 2006/007848 1, 2006 response of Coho Salmon to Aeromonas-Salmonicida’. Diseases of WO WO 2006,133707 12/2006 Aquatic organisms 12(1):7-12 Dec.
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  • New North American Records for Ascocoryne Turficola (Ascomycota

    New North American Records for Ascocoryne Turficola (Ascomycota

    New North American Records for Ascocoryne turfi cola (Ascomycota: Helotiales) Britt A. Bunyard,1* Zheng Wang,2 David Malloch,3 Stephen Clayden,3 and Andrus Voitk4 Abstract History Ascocoryne turfi cola (Boud.) Korf, one of the rarest fungi in Eu rope, The organism was first described by Boudier (1905) and was is reported from North America. This interesting as comycete was possibly not found again until it was collected in 1935 by Jules collected in 2007 from boggy localities in eastern and west ern Favre (Favre, 1948). Favre described five collections he had made Newfoundland. Morphological descriptions and ecological notes between 1935 and 1944 in the same Jura Mountains explored by for this mysterious fungus, as well as its placement within the Boudier. Four of these resembled Boudier’s C. turfi cola, while one Helotiales, are discussed. collection differed somewhat; this he accepted as natural variation within the general spectrum of a species. KEY WORDS: Ascomycetes, Coryne, mushrooms, New found land Groves and Wilson (1967) reviewed the genus Coryne and fungi, Sarcoleotia concluded that the generic name was typified by an asexual form (an anamorph or “imperfect state”) and was there fore not avail able Introduction for sexually reproducing (“perfect”) fungi like C. turfi cola. For the This communication reports the occurrence of Ascocoryne turfi - sexual forms of fungi described in the genus Coryne, they pro posed cola (Boud.) Korf in three disparate areas of Newfoundland over a new genus, Ascocoryne, to which they trans ferred Coryne sar coides one season. Ascocoryne turfi cola is an uncommon fungus, recorded as the type species (Groves and Wilson, 1967).

  • Fungi – Macrofungi

    Fungi – Macrofungi Morphology Taxonomy Microhabitat Within the fungus kingdom, macrofungi are a group that form Macrofungi, taxonomically belonging to the subkingdom Dikarya, Macrofungi are found in most terrestrial habitats, from woodlands visible, often coloured, cup- or cap-like structures (scientifically are classified into two main phyla: Ascomycota and Basidiomycota. to grasslands, but they are probably most diverse in forests. known as ‘fruiting bodies’ or ‘sporophores’) that emerge from the The Ascomycota, the largest group of macrofungi with more They need the right climatic conditions to form fruiting bodies; in soil. These fruiting bodies are where the spores are formed. The than 64 000 described species, are usually characterised by a particular, moisture to allow their spores to develop. Depending spores are small (1 - 100 µm), usually single-celled, reproductive cup-like or disc-like fruiting body (technically known as ascoma), on their functions, they can be defined as saprotrophic, parasitic structures able to tolerate unfavourable growing conditions (e.g. where spores are formed within a typical structure, named the or mycorrhizal. The saprotrophic species play a key role in the drought). Below the fruiting bodies, each fungus has a mass of ‘ascus’. The Basidiomycota (more than 31 000 described species) degradation of decaying organic matter (i.e. soil, leaf litter hyphae, the typical branching thread-like filaments produced mostly have a fruiting body (called basidioma) with an umbrella- and dead wood). The parasitic (see box on page 33) fungi are by most fungi. The mycelium is made up of the mass of these shaped cap (known as pileus) borne on a stalk (known as a stipe) responsible for several diseases in plants (see box, next page), hyphae and is responsible for its growth.