CL2015003580A1 - In vivo polynucleotide delivery conjugates that have enzyme sensitive couplings. - Google Patents

In vivo polynucleotide delivery conjugates that have enzyme sensitive couplings.

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Publication number
CL2015003580A1
CL2015003580A1 CL2015003580A CL2015003580A CL2015003580A1 CL 2015003580 A1 CL2015003580 A1 CL 2015003580A1 CL 2015003580 A CL2015003580 A CL 2015003580A CL 2015003580 A CL2015003580 A CL 2015003580A CL 2015003580 A1 CL2015003580 A1 CL 2015003580A1
Authority
CL
Chile
Prior art keywords
polynucleotide delivery
delivery conjugates
enzyme sensitive
vivo polynucleotide
couplings
Prior art date
Application number
CL2015003580A
Other languages
Spanish (es)
Inventor
David B Rozema
Jeffrey C Carlson
Darren H Wakefield
Eric A Kitas
Philipp Hadwiger
David L Lewis
Jon A Wolff
Ingo Roehl
Peter Mohr
Torsten Hoffmann
Kerstin Jahn-Hofmann
Hans Martin Mueller
Guenther Ott
Andrei V Blokhin
Jonathan D Benson
Original Assignee
Arrowhead Res Corp
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
Priority claimed from US13/336,028 external-priority patent/US8426554B2/en
Application filed by Arrowhead Res Corp filed Critical Arrowhead Res Corp
Priority to CL2015003580A priority Critical patent/CL2015003580A1/en
Publication of CL2015003580A1 publication Critical patent/CL2015003580A1/en

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C233/00—Carboxylic acid amides
    • C07C233/01—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms
    • C07C233/02—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having nitrogen atoms of carboxamide groups bound to hydrogen atoms or to carbon atoms of unsubstituted hydrocarbon radicals
    • C07C233/04—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having nitrogen atoms of carboxamide groups bound to hydrogen atoms or to carbon atoms of unsubstituted hydrocarbon radicals with carbon atoms of carboxamide groups bound to acyclic carbon atoms of an acyclic saturated carbon skeleton
    • C07C233/05—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having nitrogen atoms of carboxamide groups bound to hydrogen atoms or to carbon atoms of unsubstituted hydrocarbon radicals with carbon atoms of carboxamide groups bound to acyclic carbon atoms of an acyclic saturated carbon skeleton having the nitrogen atoms of the carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
    • C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
    • C07K5/06—Dipeptides
    • C07K5/06008—Dipeptides with the first amino acid being neutral
    • C07K5/06017—Dipeptides with the first amino acid being neutral and aliphatic
    • C07K5/06034—Dipeptides with the first amino acid being neutral and aliphatic the side chain containing 2 to 4 carbon atoms
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50—Medicinal 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
    • A61K47/51—Medicinal 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
    • A61K47/56—Medicinal 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
    • A61K47/58—Medicinal 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 obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. poly[meth]acrylate, polyacrylamide, polystyrene, polyvinylpyrrolidone, polyvinylalcohol or polystyrene sulfonic acid resin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50—Medicinal 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
    • A61K47/51—Medicinal 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
    • A61K47/56—Medicinal 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
    • A61K47/59—Medicinal 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 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes
    • A61K47/60—Medicinal 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 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes the organic macromolecular compound being a polyoxyalkylene oligomer, polymer or dendrimer, e.g. PEG, PPG, PEO or polyglycerol
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K48/00—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C69/00—Esters of carboxylic acids; Esters of carbonic or haloformic acids
    • C07C69/96—Esters of carbonic or haloformic acids
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
    • C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
    • C07K5/06—Dipeptides
    • C07K5/06104—Dipeptides with the first amino acid being acidic
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
    • C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
    • C07K5/06—Dipeptides
    • C07K5/06104—Dipeptides with the first amino acid being acidic
    • C07K5/06113—Asp- or Asn-amino acid
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
    • C08G63/00—Macromolecular compounds obtained by reactions forming a carboxylic ester link in the main chain of the macromolecule
    • C08G63/91—Polymers modified by chemical after-treatment
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09—Recombinant DNA-technology
    • C12N15/87—Introduction of foreign genetic material using processes not otherwise provided for, e.g. co-transformation
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
    • C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
    • C07K5/06—Dipeptides
    • C07K5/06008—Dipeptides with the first amino acid being neutral
    • C07K5/06078—Dipeptides with the first amino acid being neutral and aromatic or cycloaliphatic
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09—Recombinant DNA-technology
    • C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
    • C12N15/111—General methods applicable to biologically active non-coding nucleic acids
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/10—Type of nucleic acid
    • C12N2310/14—Type of nucleic acid interfering N.A.
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/30—Chemical structure
    • C12N2310/35—Nature of the modification
    • C12N2310/351—Conjugate
    • C12N2310/3513—Protein; Peptide
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2320/00—Applications; Uses
    • C12N2320/30—Special therapeutic applications
    • C12N2320/32—Special delivery means, e.g. tissue-specific
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2800/00—Nucleic acids vectors
    • C12N2800/95—Protection of vectors from inactivation by agents such as antibodies or enzymes, e.g. using polymers
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2810/00—Vectors comprising a targeting moiety
    • C12N2810/10—Vectors comprising a non-peptidic targeting moiety

Abstract

COMPUESTO PARA LA MODIFICACIÓN REVERSIBLE DE UNA POLIAMINA ACTIVA EN MEMBRANA ANFIFÁTICA, EL CUAL PERMITE LA ADMINISTRACIÓN DE POLINUCLEÓTIDOS DE INTERFERENCIA (iARN) A CÉLULAS IN VIVO.COMPOSITE FOR THE REVERSIBLE MODIFICATION OF AN ACTIVE AMPHIPATH MEMBRANE POLYAMINE, WHICH ALLOWS THE ADMINISTRATION OF INTERFERENCE POLINUCLEOTIDES (iRNA) TO IN VIVO CELLS.

CL2015003580A 2010-12-29 2015-12-10 In vivo polynucleotide delivery conjugates that have enzyme sensitive couplings. CL2015003580A1 (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CL2015003580A CL2015003580A1 (en) 2010-12-29 2015-12-10 In vivo polynucleotide delivery conjugates that have enzyme sensitive couplings.

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
US201061427936P 2010-12-29 2010-12-29
US13/336,028 US8426554B2 (en) 2010-12-29 2011-12-23 In vivo polynucleotide delivery conjugates having enzyme sensitive linkages
CL2013001876A CL2013001876A1 (en) 2010-12-29 2013-06-25 Compound for the reversible modification of an active amphipathic membrane polyamine; supply polymer for delivering an arn interference polynucleotide (iarn) to a cell in vivo; use of an iarn with a supply polymer.
CL2015003580A CL2015003580A1 (en) 2010-12-29 2015-12-10 In vivo polynucleotide delivery conjugates that have enzyme sensitive couplings.

Publications (1)

Publication Number Publication Date
CL2015003580A1 true CL2015003580A1 (en) 2016-07-15

Family

ID=46383848

Family Applications (2)

Application Number Title Priority Date Filing Date
CL2013001876A CL2013001876A1 (en) 2010-12-29 2013-06-25 Compound for the reversible modification of an active amphipathic membrane polyamine; supply polymer for delivering an arn interference polynucleotide (iarn) to a cell in vivo; use of an iarn with a supply polymer.
CL2015003580A CL2015003580A1 (en) 2010-12-29 2015-12-10 In vivo polynucleotide delivery conjugates that have enzyme sensitive couplings.

Family Applications Before (1)

Application Number Title Priority Date Filing Date
CL2013001876A CL2013001876A1 (en) 2010-12-29 2013-06-25 Compound for the reversible modification of an active amphipathic membrane polyamine; supply polymer for delivering an arn interference polynucleotide (iarn) to a cell in vivo; use of an iarn with a supply polymer.

Country Status (15)

Country Link
EP (1) EP2658579A4 (en)
JP (1) JP5941926B2 (en)
KR (1) KR20130136494A (en)
CN (1) CN103491982B (en)
AU (1) AU2011352204B2 (en)
BR (1) BR112013014115A2 (en)
CA (1) CA2816041C (en)
CL (2) CL2013001876A1 (en)
MX (2) MX341118B (en)
NZ (1) NZ611656A (en)
PE (1) PE20140198A1 (en)
RU (1) RU2619453C2 (en)
SG (1) SG189942A1 (en)
WO (1) WO2012092373A2 (en)
ZA (1) ZA201302896B (en)

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US20150291958A1 (en) 2012-11-15 2015-10-15 Roche Innovation Center Copenhagen A/S Anti apob antisense conjugate compounds
SG11201600379TA (en) * 2013-08-07 2016-02-26 Arrowhead Res Corp Polyconjugates for delivery of rnai triggers to tumor cells in vivo
JOP20210043A1 (en) 2015-10-01 2017-06-16 Arrowhead Pharmaceuticals Inc Compositions and Methods for Inhibiting Gene Expression of LPA
MA45328A (en) * 2016-04-01 2019-02-06 Avidity Biosciences Llc NUCLEIC ACID-POLYPEPTIDE COMPOSITIONS AND USES THEREOF
US20200277647A1 (en) 2017-05-24 2020-09-03 Ramot At Tel-Aviv University Ltd. Chemiluminescent probes for imaging/detection of proteases
MX2020005860A (en) 2017-12-06 2020-09-09 Avidity Biosciences Inc Compositions and methods of treating muscle atrophy and myotonic dystrophy.
AU2019416109A1 (en) * 2018-12-28 2021-07-22 Sirnaomics, Inc. Targeted delivery of therapeutic molecules
JP2023537798A (en) 2020-03-19 2023-09-06 アビディティー バイオサイエンシーズ，インク． Compositions and methods for treating facioscapulohumeral muscular dystrophy
CA3198230A1 (en) * 2021-01-28 2022-08-04 Jian Chen Conjugate and use thereof
JPWO2022270607A1 (en) * 2021-06-24 2022-12-29
KR20230016999A (en) * 2021-07-27 2023-02-03 안동대학교 산학협력단 Pharmaceutical composition comprising the extract from vespa velutina nigrithorax as an effective component for prevention or treatment of thrombosis and health functional food comprising the same
CN113621003B (en) * 2021-09-10 2023-02-03 国科温州研究院(温州生物材料与工程研究所) Method for preparing organic molecule covalent modification functionalized nucleic acid material and application thereof
AU2022345098A1 (en) 2021-09-16 2024-04-04 Avidity Biosciences, Inc. Compositions and methods of treating facioscapulohumeral muscular dystrophy

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US6214345B1 (en) * 1993-05-14 2001-04-10 Bristol-Myers Squibb Co. Lysosomal enzyme-cleavable antitumor drug conjugates
US6180095B1 (en) * 1997-12-17 2001-01-30 Enzon, Inc. Polymeric prodrugs of amino- and hydroxyl-containing bioactive agents
CN1433478A (en) * 1999-12-30 2003-07-30 诺瓦提斯公司 Novel colloid synthetic vectors for gene therapy
BR0108930A (en) * 2000-02-24 2002-12-10 Genentech Inc Method of delivering an active agent to a cell type of interest, pharmaceutical composition, caspase-activated prodrug, kit, method of treating mammals, using a caspase conjugate and using a pro-agent
EP1243276A1 (en) * 2001-03-23 2002-09-25 Franciscus Marinus Hendrikus De Groot Elongated and multiple spacers containing activatible prodrugs
US7091186B2 (en) * 2001-09-24 2006-08-15 Seattle Genetics, Inc. p-Amidobenzylethers in drug delivery agents
US7541330B2 (en) * 2004-06-15 2009-06-02 Kosan Biosciences Incorporated Conjugates with reduced adverse systemic effects
WO2007059404A2 (en) * 2005-11-10 2007-05-24 Medarex, Inc. Duocarmycin derivatives as novel cytotoxic compounds and conjugates
RU2430740C2 (en) * 2006-08-18 2011-10-10 Ф.Хоффманн-Ля Рош Аг Polyconjugates for polynucleotide introduction in vivo
CN102614528B (en) * 2006-08-18 2014-02-26 箭头研究公司 Polyconjugates for in vivo delivery of polynucleotides
CA2916671C (en) * 2007-01-17 2018-01-09 Immunomedics, Inc. Polymeric carriers of therapeutic agents and recognition moieties for antibody-based targeting of disease sites
TW201004647A (en) * 2008-05-20 2010-02-01 Sigma Tau Ind Farmaceuti Novel dual targeting antitumoural conjugates
US8501930B2 (en) * 2010-12-17 2013-08-06 Arrowhead Madison Inc. Peptide-based in vivo siRNA delivery system

Also Published As

Publication number Publication date
EP2658579A4 (en) 2015-07-22
MX2013007316A (en) 2013-07-29
NZ611656A (en) 2014-10-31
JP2014505685A (en) 2014-03-06
RU2013117286A (en) 2015-03-10
ZA201302896B (en) 2014-07-25
CN103491982A (en) 2014-01-01
WO2012092373A3 (en) 2013-10-24
AU2011352204A1 (en) 2013-05-02
RU2619453C2 (en) 2017-05-16
AU2011352204B2 (en) 2015-05-21
CN103491982B (en) 2017-09-12
KR20130136494A (en) 2013-12-12
BR112013014115A2 (en) 2019-09-24
WO2012092373A2 (en) 2012-07-05
MX347298B (en) 2017-04-21
CA2816041C (en) 2019-01-08
PE20140198A1 (en) 2014-02-21
CL2013001876A1 (en) 2014-04-11
JP5941926B2 (en) 2016-06-29
MX341118B (en) 2016-08-09
SG189942A1 (en) 2013-06-28
CA2816041A1 (en) 2012-07-05
EP2658579A2 (en) 2013-11-06

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