WO2010120682A1 - Milk oligosaccharide compositions and use thereof in treating infection in animals - Google Patents
Milk oligosaccharide compositions and use thereof in treating infection in animals Download PDFInfo
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- WO2010120682A1 WO2010120682A1 PCT/US2010/030728 US2010030728W WO2010120682A1 WO 2010120682 A1 WO2010120682 A1 WO 2010120682A1 US 2010030728 W US2010030728 W US 2010030728W WO 2010120682 A1 WO2010120682 A1 WO 2010120682A1
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- WO
- WIPO (PCT)
- Prior art keywords
- composition
- oligosaccharide
- sugar unit
- milk
- disialyllacto
- Prior art date
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Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23C—DAIRY PRODUCTS, e.g. MILK, BUTTER OR CHEESE; MILK OR CHEESE SUBSTITUTES; MAKING THEREOF
- A23C9/00—Milk preparations; Milk powder or milk powder preparations
- A23C9/20—Dietetic milk products not covered by groups A23C9/12 - A23C9/18
- A23C9/206—Colostrum; Human milk
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23K—FODDER
- A23K20/00—Accessory food factors for animal feeding-stuffs
- A23K20/10—Organic substances
- A23K20/163—Sugars; Polysaccharides
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23K—FODDER
- A23K50/00—Feeding-stuffs specially adapted for particular animals
- A23K50/10—Feeding-stuffs specially adapted for particular animals for ruminants
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23K—FODDER
- A23K50/00—Feeding-stuffs specially adapted for particular animals
- A23K50/30—Feeding-stuffs specially adapted for particular animals for swines
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23K—FODDER
- A23K50/00—Feeding-stuffs specially adapted for particular animals
- A23K50/40—Feeding-stuffs specially adapted for particular animals for carnivorous animals, e.g. cats or dogs
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23K—FODDER
- A23K50/00—Feeding-stuffs specially adapted for particular animals
- A23K50/50—Feeding-stuffs specially adapted for particular animals for rodents
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23K—FODDER
- A23K50/00—Feeding-stuffs specially adapted for particular animals
- A23K50/70—Feeding-stuffs specially adapted for particular animals for birds
- A23K50/75—Feeding-stuffs specially adapted for particular animals for birds for poultry
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/702—Oligosaccharides, i.e. having three to five saccharide radicals attached to each other by glycosidic linkages
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7028—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/715—Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
Definitions
- the present invention features a food composition for animal o consumption, which includes an animal foodstuff and a milk-derived oligosaccharide or a glycoconjugate containing the oligosaccharide.
- the oligosaccharide preferably derived from human milk, contains a first sugar unit (i.e., a fucose, a galactose, a mannose, or a sialic acid) linked to a second sugar unit (i.e., a galactose, a glucose, a mannose, or an N-acetylglucosamine).
- the first sugar unit is located at a non-reducing end of the 5 oligosaccharide.
- the oligosaccharide is a linear molecule having one non-reducing end and one reducing end. In another example, it is a branched molecule having multiple non-reducing ends and one reducing end.
- the sugar unit at one non-reducing end can be fucose and that at the other non-reducing end can be fucose, galactose, or sialic acid, or alternatively, the sugar unit at o one non-reducing end is sialic acid and that at the other non-reducing end is galactose or sialic acid.
- the sugar unit at the reducing end can be a glucose or an N-acetylglucosamine.
- the composition of this invention contains two or more different milk-derived oligosaccharides as described above.
- all of the oligosaccharides are attached to a backbone molecule (e.g., a lipid, a peptide, or a carbohydrate) to form a glycoconjugate.
- a backbone molecule e.g., a lipid, a peptide, or a carbohydrate
- this invention features a veterinary pharmaceutical composition (i.e., a pharmaceutical composition formulated for animal use) containing any of the above mentioned milk-derived oligosaccharides or glycoconjugates and a pharmaceutically acceptable carrier.
- the present invention features a method for treating infection in an animal that needs the treatment by administering to the animal an effective amount of one or more of the above-described milk-derived oligosaccharides or glycoconjugates.
- the infection to be treated by this method can be caused by a bacterium, a fungus (e.g., yeast), a protozoan, or a virus.
- infectious microbes include, but are not limited to, Campylobacter, Clostridium, Escherichia, Streptococcus, Helicobacter, Mycobacterium, pathogenic Bacteriodes, Vibrio, Candida, Astrovirus, Herpesvirus, Influenza, Norovirus, and Rotavirus.
- animal refers to non-human vertebrates (e.g., mammals, birds, fishes, reptiles, and amphibians), including both young and adult ones. Examples include, but are not limited to, cat, cattle, cow, dog, goat, horse, pig, rabbit, rodent, mink, sheep, chicken, duck, goose, turkey, ostrich, emu, swan, peafoul, pheasant, partridge, and guineafowl.
- the details of one or more examples of the invention are set forth in the description below. Other features or advantages of the present invention will be apparent from the following detailed description of several embodiments, and also from the appended claims.
- Fig. 1 is a chart showing the inhibitory effects of human milk (5 g/L), skim human milk (5 g/L), total proteins from human milk (5 g/L), and oligosaccharides from human milk (HMO, 5 g/L) on Clostridium perfringens growth.
- HMO oligosaccharides from human milk
- a milk-derived oligosaccharide effective in treating infection in an animal.
- a milk-derived oligosaccharide i.e., having at least three sugar units, is either a naturally-occurring oligosaccharide found in milk, a fragment of the naturally-occurring oligosaccharide, or a variant thereof that contains a modified (e.g., a sulfated, acetylated, or phosphorylated) sugar unit.
- This oligosaccharide includes a non-reducing end motif SiS 2 , in which Si is fucose, galactose, mannose, or sialic acid (N-acetyl or N-glycolyl) and S 2 is galactose, glucose, mannose, or N-acetylglucosamine.
- Si is linked to S 2 via an ⁇ or ⁇ glycosidic bond.
- the glycosidic bond between Si and S 2 preferably is an ⁇ l ,2, an ⁇ l ,3, or an ⁇ l ,4 bond.
- the glycosidic bond preferably is an ⁇ 2,3 or an ⁇ 2,6 bond.
- the milk-derived oligosaccharide described herein can be prepared by conventional methods, e.g., synthesized chemically, purified from milk, or produced in a microorganism. See WO2005/055944. Their anti-infection properties can be confirmed by methods also known in the art. See, e.g., WO2005/055944.
- the milk-derived oligosaccharide can be linked to a backbone molecule (e.g., a carbohydrate, a lipid, a nucleic acid, or a peptide) directly or via a linker to form a glycoconjugate.
- a backbone molecule e.g., a carbohydrate, a lipid, a nucleic acid, or a peptide
- glycoconjugate refers to a complex containing a sugar moiety associated with a backbone moiety.
- the sugar and the backbone moieties can be associated via a covalent or noncovalent bond, or via other forms of association, such as entrapment (e.g., of one moiety on or within the other, or of either or both entities on or within a third moiety).
- the glycoconjugate described herein can contain one type of milk-derived oligosaccharide (i.e., one or more copies of a milk-derived oligosaccharide attached to one backbone molecule).
- the glycoconjugate contains multiple types of milk-derived oligosaccharides.
- the milk-derived oligosaccharide e.g., lacto-N-fucopentaose I, 2-fucosyllactose, lacto-N-difucohexaose I, lactodifucotetraose, or an acetylated variant thereof
- the milk-derived oligosaccharide is covalently linked via its reducing end sugar unit to a lipid, a protein, a nucleic acid, or a polysaccharide.
- the reducing end sugar unit is N-acetylglucosamine.
- Peptide backbones suitable for making the glycoconjugate described above include those having multiple glycosylation sites (e.g., asparagine, lysine, serine, or threonine 5 residue) and low allergenic potential. Examples include, but are not limited to, amylase, bile salt-stimulated lipase, casein, folate-binding protein, globulin, gluten, haptocorrin, lactalbumin, lactoferrin, lactoperoxidase, lipoprotein lipase, lysozyme, mucin, ovalbumin, and serum albumin.
- a milk-derived oligosaccharide can be covalently attached to a serine or threonine o residue via an 0-linkage or attached to an asparagine residue via an N-linkage.
- the sugar unit at the reducing end of the oligosaccharide is preferably an acetylated sugar unit, e.g., N-acetylgalactosamine, N-acetylglucosamine, and N-acetylmannosamine.
- An oligosaccharide can be attached to a peptide (e.g., a protein) using standard methods.
- a milk-derived oligosaccharide is linked to a backbone molecule via a linker.
- linkers are described in WO2005/055944.
- the oligosaccharide can be bonded to a linker by an enzymatic reaction, e.g., a glycosyltransferase reaction.
- glycosyltransferases including fucosyltransferases, galactosyltransferases, glucosyltransferases, mannosyltransferases, galactosaminyltransferases, sialyltransferases and N-acetylglucosaminyltransferases, can be used to make the glycoconjugate described herein. More details about these glycosyltransferases can be found in U.S.
- One or more of the above described milk-derived oligosaccharides and/or glycoconjugates can be mixed with an animal foodstuff to form a food composition (which is not naturally occurring) for animal consumption.
- an animal foodstuff used o herein refers to a food product or food supplement for animal consumption, not for human consumption.
- the animal foodstuff is a commercially available animal food, e.g., those provided by Purina Mills.
- the animal food composition which may be free of a milk product or milk by-product, can be in any suitable form, such as a biscuit, a cracker, a gel, a granule, a kibble, a liquid, a nugget, a paste, a pellet, a powder, or a syrup.
- the milk-derived oligosaccharides and/or glycoconjugates described herein can also be mixed with a pharmaceutically acceptable carrier to form a veterinary 5 pharmaceutical composition.
- the pharmaceutical composition further contains one or more additional therapeutic agents, e.g., an analgesic, an antibiotic, an anti-inflammatory agent, or a probiotic.
- An "acceptable carrier" is compatible with the active ingredient(s) of the composition, i.e., the milk-derived oligosaccharide(s) or the glycoconjugate(s), preferably capable of stabilizing the active ingredient(s), and not o deleterious to the animal to be treated.
- Suitable carriers include microcrystalline cellulose, mannitol, glucose, polyvinylpyrrolidone, and starch, or a combination thereof.
- Methods for preparing a veterinary pharmaceutical composition are known in the art. See e.g., US Patent No. 5,958,464.
- a veterinary pharmaceutical composition can be administered buccally, nasally,5 orally, parenterally, rectally, topically, vaginally, or via an implanted reservoir, inhalation spray, or direct infusion into the GI tract or stomach.
- a veterinary pharmaceutical composition for oral administration can be any orally acceptable dosage form including, but not limited to bolus, capsule, dispersion, electuary, emulsion and aqueous suspension, gel, granule, paste, pellet, powder, slurry, solution, syrup, o and tablet.
- An orally administered veterinary composition can include binders, lubricants, inert diluents, lubricating, surface active or dispersing agents, flavoring agents, and humectants.
- carriers which are commonly used include lactose and corn starch.
- Lubricating agents such as magnesium stearate, are also typically added.
- Tablets/capsules may optionally be coated or formulated so as to provide sustained, 5 delayed, or controlled release of the active ingredient therein.
- aqueous suspensions or emulsions are administered orally, the active ingredient can be suspended or dissolved in an oily phase combined with emulsifying or suspending agents.
- a nasal aerosol or inhalation composition can be prepared according to techniques well known in the art of pharmaceutical formulation. o The particular formulation and dosage depends on the animal species; the administration route; the characteristics of the formulation; age/size of the animal; and the nature of the animal's infection, if any. In some cases, the dosage will be at a concentration similar to that found for similar oligosaccharides present in human breast milk.
- Also disclosed herein is a method of using the milk-derived oligosaccharide and the glycoconjugate for treating animal infection, i.e., a detrimental colonization of a microbe in a host animal, resulting in an illness in the animal.
- treating refers to 5 the application or administration of a composition including one or more active agents to an animal, who has infection, a symptom of the infection, or a predisposition toward the infection, with the purpose to cure, heal, alleviate, relieve, alter, remedy, ameliorate, improve, or affect the infection, the symptoms of the infection, or the predisposition toward the infection.
- an effective amount of the milk-derived oligosaccharide or the o glycoconjugate can be administered to an animal that is infected by a pathogenic microbe or at risk for infection via conventional routes.
- An "effective amount” is the amount of each active agent required to confer therapeutic effect on the animal, either alone or in combination with one or more other active agents. Effective amounts vary, as recognized by those skilled in the art, depending on route of administration, excipient usage, and 5 co-usage with other active agents.
- the method of this invention can be used for treating infections caused by various pathogens in various types of animals.
- pathogens include, but are not limited to, Actinobacillus, Adenovirus, Aeromonas, Arenavirus (e.g., Lassa virus), Aspergillus, Astrovirus, Bacillus, pathogenic Bacteriodes, Balantidium, Bovine virus diarrhea-mucosal o disease virus, Bovine viral diarrhea virus 2, Brucella, Caliciviruses (including Vesivirus,
- Lagovirus, and Norovirus e.g Norwalk Virus
- Campylobacter e.g., C. jejuni, C. pylori, C. coli, C. lari, and C. upsaliensis
- Candida Classical Swine Fever Virus
- Chlamydophila Clostridium, Coccidia, Coronavirus, Cryptosporidium, Echoviruses, Eimeria, Enterococcus, Enterovirus, Escherichia (e.g, EHEC, EPEC, ETEC, and STEC strains), Foot-and-mouth 5 disease virus, Francisella, Giardia, Haemophilus (e.g., H. influenzae), Helicobacter,
- Hepatitis virus A and E
- Herpesvirus e.g., Herpes spp.
- Histoplasma Influenza, Leptospira, Listeria, Lymphocytic Choriomeningitis Virus, Microsporidia, Mycobacterium (e.g., M. tuberculosis), Parvovirus, Polyomavirus, Poxvirus, Proteus, Prototheca, Psuedomonas, Reovirus, Rinderpest virus, Rotavirus, Salmonella, Sarcocystis, Shigella, SIV, o Streptococcus (e.g, Group B Streptococcus), Toxoplasma, Vesicular stomatitis virus, Vibrio
- V. cholerae V. cholerae
- Yersinia Yersinia
- Animals that can be treated by the method include cat, dog, marsupial, primate, rabbit, rodent (e.g., chinchilla, gerbil, guinea pig, mouse, and rat), ungulate (for example, bovid (e.g., African Buffalo, bison, cow, goat, ox, sheep, water buffalo, or yak), camelid (e.g., alpaca, camel, and llama), deer, equine (e.g., donkey, horse, and mule), and pig), weasel (e.g., ermine, ferret, mink, and weasel), chicken, dove, duck, finch, goose, guinea fowl, 5 hummingbird, parrot (e.g., cockatiel, cockatoo, lorikeet, lovebird, macaw, parakeet), pheasant (e.g., partridge, phea
- An animal in need of the treatment can be fed on the oligosaccharide/glycoconjugate together with water or its daily food (e.g., fruit, raw meat, hay, or a commercial animal food).
- water or its daily food e.g., fruit, raw meat, hay, or a commercial animal food.
- the oligosaccharide can be mixed with fodder (e.g., alfalfa, barley, corn, grain, grass, hay,5 legume, millet, nut, oat, rice, rye, seaweed, seed, sorghum, soybean, straw, and wheat) and provided during regular feedings.
- fodder e.g., alfalfa, barley, corn, grain, grass, hay,5 legume, millet, nut, oat, rice, rye, seaweed, seed, sorghum, soybean, straw, and wheat
- the animal is fed with the animal food compositions described above or administered with the pharmaceutical composition also described
- the milk-derived o oligosaccharide or glycoconjugate is preferably co-used with a probiotic (i.e., a dietary supplements of a live bacterium or yeast that benefits the animal to be treated) or a prebiotic (i.e., a non-digestible food ingredient that beneficially affects an animal to be treated by selectively stimulating the growth and/or activity of beneficial bacteria in the digestive tract).
- a probiotic i.e., a dietary supplements of a live bacterium or yeast that benefits the animal to be treated
- a prebiotic i.e., a non-digestible food ingredient that beneficially affects an animal to be treated by selectively stimulating the growth and/or activity of beneficial bacteria in the digestive tract.
- a prebiotic i.e., a non-digestible food ingredient that beneficially affects an animal to be treated by selectively stimulating the growth and/or activity of beneficial bacteria in the digestive tract.
- prebiotics are typically oligosaccharides, including fructo
- Anaerobic batch cultures were used to study the effect of human milk oligosaccharides on growth of C. perf ⁇ ngens, a pathogen capable of causing severe infections in farm animals (e.g., cow, pig, horse, poultry such as chicken, ostrich, and emu, sheep, rabbit, goat, hog, cattle, mink), birds, dogs, and cats, etc..
- farm animals e.g., cow, pig, horse, poultry such as chicken, ostrich, and emu, sheep, rabbit, goat, hog, cattle, mink
- C. perf ⁇ ngens cells were cultured in a medium (10 ml) in the presence of (a) whole human milk, (b) skim human milk, (c) total proteins isolated from human milk, or (d) oligosaccharides purified from human milk.
- the oligosaccharides and other milk fractions were prepared following the method described in Newburg et al., Journal of Infectious Diseases 1990; 162: 1075-1080, and Y " olken et al., Journal of ' Clinical Investigation 1992; 90: 1984-1991.
- C. perfringens cells cultured in the same medium without any carbohydrate addition, were used as a blank control.
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Abstract
Description
Claims
Priority Applications (4)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
EP10764968.3A EP2418961B1 (en) | 2009-04-13 | 2010-04-12 | Milk oligosaccharide compositions and use thereof in treating infection in animals |
AU2010236721A AU2010236721B2 (en) | 2009-04-13 | 2010-04-12 | Milk oligosaccharide compositions and use thereof in treating infection in animals |
NZ596099A NZ596099A (en) | 2009-04-13 | 2010-04-12 | Milk oligosaccharide compositions and use thereof in treating infection in animals |
CA2757169A CA2757169A1 (en) | 2009-04-13 | 2010-04-12 | Milk oligosaccharide compositions and use thereof in treating infection in animals |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US16867409P | 2009-04-13 | 2009-04-13 | |
US61/168,674 | 2009-04-13 |
Publications (1)
Publication Number | Publication Date |
---|---|
WO2010120682A1 true WO2010120682A1 (en) | 2010-10-21 |
Family
ID=42982800
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/US2010/030728 WO2010120682A1 (en) | 2009-04-13 | 2010-04-12 | Milk oligosaccharide compositions and use thereof in treating infection in animals |
Country Status (5)
Country | Link |
---|---|
EP (1) | EP2418961B1 (en) |
AU (1) | AU2010236721B2 (en) |
CA (1) | CA2757169A1 (en) |
NZ (1) | NZ596099A (en) |
WO (1) | WO2010120682A1 (en) |
Cited By (9)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2012150504A1 (en) * | 2011-05-05 | 2012-11-08 | Life Science Nutrition As | Performance enhancing compositions and methods of use |
EP2769726A1 (en) * | 2013-02-21 | 2014-08-27 | Jennewein Biotechnologie GmbH | Synthetic or recombinant fucosylated Oligosaccarides for use in the treatment of infections |
EP2658548B1 (en) | 2010-12-31 | 2018-02-21 | Abbott Laboratories | Human milk oligosaccharides for modulating inflammation |
WO2018041803A1 (en) * | 2016-08-31 | 2018-03-08 | Prismagen Gmbh | Use of human milk oligosaccharides in calves fattening |
WO2019074387A2 (en) | 2017-10-12 | 2019-04-18 | Bojan Pavlovic | F-fucoidan, desulfated f-fucoidan, and its processed derivatives in terms of desulfated oligo-fucose as inhibitors of gastrointestinal infection |
US20190160082A1 (en) * | 2016-08-04 | 2019-05-30 | Nestec S.A. | Nutritional compositions with 2fl and lnnt for use in preventing and/or treating non-rotavirus diarrhea by acting on the gut microbiota dysbiosis |
RU2788854C2 (en) * | 2018-07-12 | 2023-01-25 | Н.В. Нютрисиа | Nutritional composition for increasing the integrity of the intestinal barrier, obtaining the composition and method for treatment |
WO2024003222A1 (en) * | 2022-06-29 | 2024-01-04 | Inbiose N.V. | Fucosylated saccharide for use in the prevention or treatment of bacterial disease |
WO2024003223A1 (en) * | 2022-06-29 | 2024-01-04 | Inbiose N.V. | Fucosylated saccharide for use in the prevention or treatment of parasitic disease |
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2010
- 2010-04-12 CA CA2757169A patent/CA2757169A1/en not_active Abandoned
- 2010-04-12 WO PCT/US2010/030728 patent/WO2010120682A1/en active Application Filing
- 2010-04-12 NZ NZ596099A patent/NZ596099A/en unknown
- 2010-04-12 AU AU2010236721A patent/AU2010236721B2/en active Active
- 2010-04-12 EP EP10764968.3A patent/EP2418961B1/en active Active
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CA2757169A1 (en) | 2010-10-21 |
EP2418961A1 (en) | 2012-02-22 |
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AU2010236721A1 (en) | 2011-11-17 |
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AU2010236721B2 (en) | 2015-03-12 |
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