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SG11201405902PA - Dually derivatized chitosan nanoparticles and methods of making and using the same for gene transfer in vivo - Google Patents

Dually derivatized chitosan nanoparticles and methods of making and using the same for gene transfer in vivo

Info

Publication number
SG11201405902PA
SG11201405902PA SG11201405902PA SG11201405902PA SG11201405902PA SG 11201405902P A SG11201405902P A SG 11201405902PA SG 11201405902P A SG11201405902P A SG 11201405902PA SG 11201405902P A SG11201405902P A SG 11201405902PA SG 11201405902P A SG11201405902P A SG 11201405902PA
Authority
SG
Singapore
Prior art keywords
vivo
making
methods
same
gene transfer
Prior art date
Application number
SG11201405902PA
Inventor
Jun Gao
Eric Hsu
Anthony Cheung
Original Assignee
Engene Inc
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Engene Inc filed Critical Engene Inc
Publication of SG11201405902PA publication Critical patent/SG11201405902PA/en

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Classifications

    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/51Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
    • A61K47/56Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule
    • A61K47/61Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule the organic macromolecular compound being a polysaccharide or a derivative thereof
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/70Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7088Compounds having three or more nucleosides or nucleotides
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/69Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit
    • A61K47/6921Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit the form being a particulate, a powder, an adsorbate, a bead or a sphere
    • A61K47/6927Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit the form being a particulate, a powder, an adsorbate, a bead or a sphere the form being a solid microparticle having no hollow or gas-filled cores
    • A61K47/6929Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit the form being a particulate, a powder, an adsorbate, a bead or a sphere the form being a solid microparticle having no hollow or gas-filled cores the form being a nanoparticle, e.g. an immuno-nanoparticle
    • A61K47/6931Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit the form being a particulate, a powder, an adsorbate, a bead or a sphere the form being a solid microparticle having no hollow or gas-filled cores the form being a nanoparticle, e.g. an immuno-nanoparticle the material constituting the nanoparticle being a polymer
    • A61K47/6939Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit the form being a particulate, a powder, an adsorbate, a bead or a sphere the form being a solid microparticle having no hollow or gas-filled cores the form being a nanoparticle, e.g. an immuno-nanoparticle the material constituting the nanoparticle being a polymer the polymer being a polysaccharide, e.g. starch, chitosan, chitin, cellulose or pectin
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/04Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00Drugs for disorders of the metabolism
    • A61P3/04Anorexiants; Antiobesity agents
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00Drugs for disorders of the metabolism
    • A61P3/08Drugs for disorders of the metabolism for glucose homeostasis
    • A61P3/10Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07HSUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
    • C07H13/00Compounds containing saccharide radicals esterified by carbonic acid or derivatives thereof, or by organic acids, e.g. phosphonic acids
    • C07H13/02Compounds containing saccharide radicals esterified by carbonic acid or derivatives thereof, or by organic acids, e.g. phosphonic acids by carboxylic acids
    • C07H13/04Compounds containing saccharide radicals esterified by carbonic acid or derivatives thereof, or by organic acids, e.g. phosphonic acids by carboxylic acids having the esterifying carboxyl radicals attached to acyclic carbon atoms
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07HSUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
    • C07H5/00Compounds containing saccharide radicals in which the hetero bonds to oxygen have been replaced by the same number of hetero bonds to halogen, nitrogen, sulfur, selenium, or tellurium
    • C07H5/04Compounds containing saccharide radicals in which the hetero bonds to oxygen have been replaced by the same number of hetero bonds to halogen, nitrogen, sulfur, selenium, or tellurium to nitrogen
    • C07H5/06Aminosugars
    • CCHEMISTRY; METALLURGY
    • C08ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08BPOLYSACCHARIDES; DERIVATIVES THEREOF
    • C08B37/00Preparation of polysaccharides not provided for in groups C08B1/00 - C08B35/00; Derivatives thereof
    • C08B37/0006Homoglycans, i.e. polysaccharides having a main chain consisting of one single sugar, e.g. colominic acid
    • C08B37/0024Homoglycans, i.e. polysaccharides having a main chain consisting of one single sugar, e.g. colominic acid beta-D-Glucans; (beta-1,3)-D-Glucans, e.g. paramylon, coriolan, sclerotan, pachyman, callose, scleroglucan, schizophyllan, laminaran, lentinan or curdlan; (beta-1,6)-D-Glucans, e.g. pustulan; (beta-1,4)-D-Glucans; (beta-1,3)(beta-1,4)-D-Glucans, e.g. lichenan; Derivatives thereof
    • C08B37/00272-Acetamido-2-deoxy-beta-glucans; Derivatives thereof
    • C08B37/003Chitin, i.e. 2-acetamido-2-deoxy-(beta-1,4)-D-glucan or N-acetyl-beta-1,4-D-glucosamine; Chitosan, i.e. deacetylated product of chitin or (beta-1,4)-D-glucosamine; Derivatives thereof
    • CCHEMISTRY; METALLURGY
    • C08ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08LCOMPOSITIONS OF MACROMOLECULAR COMPOUNDS
    • C08L5/00Compositions of polysaccharides or of their derivatives not provided for in groups C08L1/00 or C08L3/00
    • C08L5/08Chitin; Chondroitin sulfate; Hyaluronic acid; Derivatives thereof
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N15/00Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09Recombinant DNA-technology
    • C12N15/11DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
    • C12N15/111General methods applicable to biologically active non-coding nucleic acids
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N15/00Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09Recombinant DNA-technology
    • C12N15/11DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
    • C12N15/113Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N15/00Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09Recombinant DNA-technology
    • C12N15/87Introduction of foreign genetic material using processes not otherwise provided for, e.g. co-transformation
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/48Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/50Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
    • A61K9/51Nanocapsules; Nanoparticles
    • A61K9/5107Excipients; Inactive ingredients
    • A61K9/513Organic macromolecular compounds; Dendrimers
    • A61K9/5161Polysaccharides, e.g. alginate, chitosan, cellulose derivatives; Cyclodextrin
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
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    • C12N2310/00Structure or type of the nucleic acid
    • C12N2310/10Type of nucleic acid
    • C12N2310/14Type of nucleic acid interfering N.A.
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
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    • C12N2320/00Applications; Uses
    • C12N2320/30Special therapeutic applications
    • C12N2320/32Special delivery means, e.g. tissue-specific
    • YGENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10TECHNICAL SUBJECTS COVERED BY FORMER USPC
    • Y10STECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10S424/00Drug, bio-affecting and body treating compositions
    • Y10S424/13Burn treatment

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  • Chemical & Material Sciences (AREA)
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  • Genetics & Genomics (AREA)
  • General Health & Medical Sciences (AREA)
  • Bioinformatics & Cheminformatics (AREA)
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  • Biochemistry (AREA)
  • General Engineering & Computer Science (AREA)
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  • Wood Science & Technology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Animal Behavior & Ethology (AREA)
  • Polymers & Plastics (AREA)
  • Biophysics (AREA)
  • Plant Pathology (AREA)
  • Microbiology (AREA)
  • Physics & Mathematics (AREA)
  • Epidemiology (AREA)
  • Nanotechnology (AREA)
  • Materials Engineering (AREA)
  • Diabetes (AREA)
  • Immunology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Obesity (AREA)
  • Hematology (AREA)
  • Child & Adolescent Psychology (AREA)
  • Endocrinology (AREA)
  • Emergency Medicine (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
SG11201405902PA 2012-03-21 2013-03-15 Dually derivatized chitosan nanoparticles and methods of making and using the same for gene transfer in vivo SG11201405902PA (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US201261613885P 2012-03-21 2012-03-21
PCT/CA2013/050218 WO2013138930A1 (en) 2012-03-21 2013-03-15 Dually derivatized chitosan nanoparticles and methods of making and using the same for gene transfer in vivo

Publications (1)

Publication Number Publication Date
SG11201405902PA true SG11201405902PA (en) 2014-10-30

Family

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Family Applications (1)

Application Number Title Priority Date Filing Date
SG11201405902PA SG11201405902PA (en) 2012-03-21 2013-03-15 Dually derivatized chitosan nanoparticles and methods of making and using the same for gene transfer in vivo

Country Status (20)

Country Link
US (4) US9623112B2 (en)
EP (1) EP2828332B1 (en)
JP (1) JP6247276B2 (en)
KR (2) KR102064142B1 (en)
CN (1) CN104395391B (en)
AU (1) AU2013234795B2 (en)
BR (1) BR112014023405B1 (en)
CA (1) CA2867888C (en)
DK (1) DK2828332T3 (en)
EA (1) EA032034B1 (en)
ES (1) ES2635990T3 (en)
HK (1) HK1206378A1 (en)
IL (1) IL234682A (en)
MX (1) MX353705B (en)
PL (1) PL2828332T3 (en)
PT (1) PT2828332T (en)
SG (1) SG11201405902PA (en)
SI (1) SI2828332T1 (en)
WO (1) WO2013138930A1 (en)
ZA (1) ZA201407600B (en)

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CN104395391B (en) 2012-03-21 2017-09-01 恩根尼公司 The chitin nanometer of double derivative and manufacture and it is used for the method for vivo gene transfer using it
AU2014280796A1 (en) * 2013-06-10 2016-01-28 Polyvalor, Societe En Commandite Freeze-dried polyelectrolyte complexes that maintain size and biological activity
AU2014328439B2 (en) * 2013-09-25 2018-06-28 Engene, Inc. Dually derivatized chitosan nanoparticles and methods of making and using the same for gene transfer in vivo
US10786527B2 (en) * 2015-03-19 2020-09-29 University Of Massachusetts Nanoparticle-stabilized nanocapsules and methods of preparation and use for nucleic acid delivery
WO2017073767A1 (en) 2015-10-30 2017-05-04 株式会社ボナック COMPOSITION STABLY CONTAINING SINGLE-STRANDED NUCLEIC ACID MOLECULE THAT SUPPRESSES EXPRESSION OF TGF-β1 GENE
KR101741977B1 (en) 2016-04-26 2017-05-31 한국교통대학교산학협력단 Nanoparticles for oral gene delivery system and pharmaceutical composition containing the same as an active ingredient
US11603398B2 (en) * 2016-11-09 2023-03-14 Engene, Inc. Intestinal expression of programmed death ligand 1
US20200069594A1 (en) * 2016-12-09 2020-03-05 Board Of Regents, The University Of Texas System Hybrid exosomal-polymeric (hexpo) nano-platform for delivery of rnai therapeutics
WO2019055594A1 (en) 2017-09-13 2019-03-21 North Carolina State University Locally-induced adipose tissue browning by microneedle patch for obesity treatment
CA3090278A1 (en) * 2018-02-02 2019-08-08 John Mansell Compositions and methods for treatment of obesity and obesity-related disorders
EP3543325A1 (en) * 2018-03-19 2019-09-25 Green Impact Holding AG Organic disinfecting agent
CN108773831B (en) * 2018-06-11 2019-07-02 南京师范大学 L-arginine nanoparticle and nitric oxide are the degradable nano-motor and preparation method thereof of power source
EP3822292A4 (en) * 2018-07-11 2022-04-06 Josho Gakuen Educational Foundation Polymer compound and promoter for introducing compound into cells using same
WO2020102166A1 (en) * 2018-11-12 2020-05-22 Massachusetts Institute Of Technology Organelle-selective gene delivery and expression in the chloroplast in planta using chitosan-complexed single-walled carbon nanotube carriers
CN109358191B (en) * 2018-12-07 2021-07-09 上海荣盛生物药业有限公司 Composition for immunoreagent and preparation method thereof
BR112021018186A2 (en) * 2019-03-14 2021-11-30 Engene Inc Chitosan polyplex-based localized expression of IL-12 alone or in combination with ifn type-I inducers for treatment of mucosal cancers
GB202116867D0 (en) * 2021-11-23 2022-01-05 Highersteaks Ltd Methods and compositions for protein expression and cell differentiation
KR20240087488A (en) 2022-11-30 2024-06-19 한양대학교 산학협력단 Gold nanozyme containing glycol chitosan and gold particles, and pharmaceutical composition containing the same for preventing or treating inflammatory bowel disease
WO2024167803A2 (en) * 2023-02-07 2024-08-15 Merck Sharp & Dohme Llc Adjuvant formulations including low viscosity chitosan or chitosan derivatives
CN116693708B (en) * 2023-04-28 2024-08-30 百珍堂生物科技(浙江)有限公司 High-activity abalone visceral polysaccharide and eutectic solvent extraction method thereof

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CN104395391B (en) 2012-03-21 2017-09-01 恩根尼公司 The chitin nanometer of double derivative and manufacture and it is used for the method for vivo gene transfer using it

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EP2828332B1 (en) 2017-05-10
WO2013138930A1 (en) 2013-09-26
DK2828332T3 (en) 2017-08-28
CA2867888A1 (en) 2013-09-26
US11623011B2 (en) 2023-04-11
BR112014023405A2 (en) 2017-06-20
EA201401041A1 (en) 2015-03-31
IL234682A (en) 2017-06-29
EP2828332A4 (en) 2015-12-09
HK1206378A1 (en) 2016-01-08
AU2013234795B2 (en) 2016-12-22
EA032034B1 (en) 2019-03-29
KR102223224B1 (en) 2021-03-08
ES2635990T3 (en) 2017-10-05
KR102064142B1 (en) 2020-01-09
CA2867888C (en) 2021-06-01
MX2014011216A (en) 2015-03-10
KR20150021022A (en) 2015-02-27
US9623112B2 (en) 2017-04-18
JP6247276B2 (en) 2017-12-13
MX353705B (en) 2018-01-24
AU2013234795A1 (en) 2014-11-06
US20230414769A1 (en) 2023-12-28
PL2828332T3 (en) 2017-10-31
EP2828332A1 (en) 2015-01-28
SI2828332T1 (en) 2017-09-29
CN104395391B (en) 2017-09-01
US10456478B2 (en) 2019-10-29
ZA201407600B (en) 2017-04-26
US20200054759A1 (en) 2020-02-20
BR112014023405B1 (en) 2021-08-24
KR20200004468A (en) 2020-01-13
CN104395391A (en) 2015-03-04
PT2828332T (en) 2017-08-10
US20150051265A1 (en) 2015-02-19
JP2015512372A (en) 2015-04-27
US20180008720A1 (en) 2018-01-11

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