WO2023034849A3 - HIGH MOLECULAR WEIGHT MODIFIED dsRNA COMPOSITIONS - Google Patents

HIGH MOLECULAR WEIGHT MODIFIED dsRNA COMPOSITIONS Download PDF

Info

Publication number
WO2023034849A3
WO2023034849A3 PCT/US2022/075740 US2022075740W WO2023034849A3 WO 2023034849 A3 WO2023034849 A3 WO 2023034849A3 US 2022075740 W US2022075740 W US 2022075740W WO 2023034849 A3 WO2023034849 A3 WO 2023034849A3
Authority
WO
WIPO (PCT)
Prior art keywords
mdsrnas
molecular weight
high molecular
weight modified
modified dsrna
Prior art date
Application number
PCT/US2022/075740
Other languages
French (fr)
Other versions
WO2023034849A2 (en
WO2023034849A8 (en
Inventor
Darren H. Wakefield
Grace B. Arhancet
Vladimir Trubetskoy
Juan P. Arhancet
Jason Klein
Original Assignee
nanoSUR LLC
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 nanoSUR LLC filed Critical nanoSUR LLC
Priority to MX2024002299A priority Critical patent/MX2024002299A/en
Priority to CN202280059222.3A priority patent/CN118302524A/en
Priority to CA3228823A priority patent/CA3228823A1/en
Priority to EP22783223.5A priority patent/EP4396348A2/en
Publication of WO2023034849A2 publication Critical patent/WO2023034849A2/en
Publication of WO2023034849A3 publication Critical patent/WO2023034849A3/en
Publication of WO2023034849A8 publication Critical patent/WO2023034849A8/en

Links

Classifications

    • 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
    • C12N15/113—Non-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
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N63/00—Biocides, pest repellants or attractants, or plant growth regulators containing microorganisms, viruses, microbial fungi, animals or substances produced by, or obtained from, microorganisms, viruses, microbial fungi or animals, e.g. enzymes or fermentates
    • A01N63/60—Isolated nucleic acids
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01P—BIOCIDAL, PEST REPELLANT, PEST ATTRACTANT OR PLANT GROWTH REGULATORY ACTIVITY OF CHEMICAL COMPOUNDS OR PREPARATIONS
    • A01P23/00—Chemosterilants
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01P—BIOCIDAL, PEST REPELLANT, PEST ATTRACTANT OR PLANT GROWTH REGULATORY ACTIVITY OF CHEMICAL COMPOUNDS OR PREPARATIONS
    • A01P7/00—Arthropodicides
    • A01P7/02—Acaricides
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01P—BIOCIDAL, PEST REPELLANT, PEST ATTRACTANT OR PLANT GROWTH REGULATORY ACTIVITY OF CHEMICAL COMPOUNDS OR PREPARATIONS
    • A01P7/00—Arthropodicides
    • A01P7/04—Insecticides
    • 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
    • C12N2330/00—Production
    • C12N2330/30—Production chemically synthesised

Landscapes

  • Life Sciences & Earth Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Health & Medical Sciences (AREA)
  • Zoology (AREA)
  • Chemical & Material Sciences (AREA)
  • Wood Science & Technology (AREA)
  • Plant Pathology (AREA)
  • Genetics & Genomics (AREA)
  • Pest Control & Pesticides (AREA)
  • Environmental Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Biomedical Technology (AREA)
  • Molecular Biology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Biotechnology (AREA)
  • General Engineering & Computer Science (AREA)
  • Microbiology (AREA)
  • Organic Chemistry (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Biochemistry (AREA)
  • Insects & Arthropods (AREA)
  • Agronomy & Crop Science (AREA)
  • Physics & Mathematics (AREA)
  • Biophysics (AREA)
  • Dentistry (AREA)
  • Virology (AREA)
  • Saccharide Compounds (AREA)
  • Enzymes And Modification Thereof (AREA)
  • Preparation Of Compounds By Using Micro-Organisms (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Agricultural Chemicals And Associated Chemicals (AREA)

Abstract

Post-transcriptionally chemically modified double strand RNAs (MdsRNAs) having a high molecular weight polyalkyloxy modification at the 2'-OH position are described. This modification allows for greater bioavailability of the compound, better stability of the compound, and allows for greater stability against nucleases. The MdsRNAs can be economically produced in a readily scalable manner. Compositions of MdsRNAs having chemically modified nucleotides are described, such that the MdsRNAs are modified to contain high molecular weight polyalkyloxy polymers. Synthetic methods for efficiently making these MdsRNAs and methods of using MdsRNAs are described.
PCT/US2022/075740 2021-08-31 2022-08-31 HIGH MOLECULAR WEIGHT MODIFIED dsRNA COMPOSITIONS WO2023034849A2 (en)

Priority Applications (4)

Application Number Priority Date Filing Date Title
MX2024002299A MX2024002299A (en) 2021-08-31 2022-08-31 HIGH MOLECULAR WEIGHT MODIFIED dsRNA COMPOSITIONS.
CN202280059222.3A CN118302524A (en) 2021-08-31 2022-08-31 High molecular weight modified dsRNA compositions
CA3228823A CA3228823A1 (en) 2021-08-31 2022-08-31 High molecular weight modified dsrna compositions
EP22783223.5A EP4396348A2 (en) 2021-08-31 2022-08-31 High molecular weight modified dsrna compositions

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US202163239165P 2021-08-31 2021-08-31
US63/239,165 2021-08-31

Publications (3)

Publication Number Publication Date
WO2023034849A2 WO2023034849A2 (en) 2023-03-09
WO2023034849A3 true WO2023034849A3 (en) 2023-05-19
WO2023034849A8 WO2023034849A8 (en) 2024-03-07

Family

ID=83508899

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2022/075740 WO2023034849A2 (en) 2021-08-31 2022-08-31 HIGH MOLECULAR WEIGHT MODIFIED dsRNA COMPOSITIONS

Country Status (6)

Country Link
EP (1) EP4396348A2 (en)
CN (1) CN118302524A (en)
AR (1) AR126939A1 (en)
CA (1) CA3228823A1 (en)
MX (1) MX2024002299A (en)
WO (1) WO2023034849A2 (en)

Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2000066605A2 (en) * 1999-04-30 2000-11-09 Cyclops Genome Sciences Limited Polynucleotides
WO2004076630A2 (en) * 2003-02-21 2004-09-10 Mirus Corporation Covalent modification of rna for in vitro and in vivo delivery
WO2008070477A2 (en) * 2006-11-27 2008-06-12 Enzon Pharmaceuticals, Inc. Polymeric short interfering rna conjugates
US20140154673A1 (en) * 2012-08-14 2014-06-05 The Board Of Trustees Of The Leland Stanford Junior University Probes of rna structure and methods for using the same
US20190264205A1 (en) * 2018-01-29 2019-08-29 The Board Of Trustees Of The Leland Stanford Junior University Photoreversible Acylation Reagents
WO2020257194A1 (en) * 2019-06-17 2020-12-24 Alnylam Pharmaceuticals, Inc. Delivery of oligonucleotides to the striatum

Family Cites Families (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
PL1732379T3 (en) 2004-04-09 2014-04-30 Monsanto Technology Llc Compositions and methods for control of insect infestations in plants
EA029482B1 (en) 2010-03-08 2018-04-30 Монсанто Текнолоджи Ллс Polynucleotide molecules for gene regulation in plants
WO2014204667A1 (en) 2013-06-19 2014-12-24 Apse, Llc Compositions and methods using capsids resistant to hydrolases
EP3431601B1 (en) 2013-07-10 2022-09-07 Basf Se Rnai for the control of phytopathogenic fungi and oomycetes by inhibiting the expression of cyp51 genes
CA2959402A1 (en) 2014-09-17 2016-03-24 Pioneer Hi-Bred International, Inc. Compositions and methods to control insect pests
MX2019005149A (en) 2016-11-07 2019-06-24 nanoSUR LLC Post-transcriptionally chemically modified double strand rnas.
AU2018261075A1 (en) 2017-05-01 2019-12-12 Donald Danforth Plant Science Center RNAi approach for crop pest protection
CN111033816B (en) 2017-08-28 2022-09-13 株式会社村田制作所 Nonaqueous electrolyte battery and communication device
WO2020036747A1 (en) 2018-08-13 2020-02-20 Pioneer Hi-Bred International, Inc. Novel insecticidal toxin receptors and methods of use
DE102019212345B4 (en) 2019-08-19 2024-02-08 Robert Bosch Gmbh Electromechanically driven brake pressure generator

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2000066605A2 (en) * 1999-04-30 2000-11-09 Cyclops Genome Sciences Limited Polynucleotides
WO2004076630A2 (en) * 2003-02-21 2004-09-10 Mirus Corporation Covalent modification of rna for in vitro and in vivo delivery
WO2008070477A2 (en) * 2006-11-27 2008-06-12 Enzon Pharmaceuticals, Inc. Polymeric short interfering rna conjugates
US20140154673A1 (en) * 2012-08-14 2014-06-05 The Board Of Trustees Of The Leland Stanford Junior University Probes of rna structure and methods for using the same
US20190264205A1 (en) * 2018-01-29 2019-08-29 The Board Of Trustees Of The Leland Stanford Junior University Photoreversible Acylation Reagents
WO2020257194A1 (en) * 2019-06-17 2020-12-24 Alnylam Pharmaceuticals, Inc. Delivery of oligonucleotides to the striatum

Non-Patent Citations (19)

* Cited by examiner, † Cited by third party
Title
ALTMANN K-H ET AL: "Second generation antisense oligonucleotides: Inhibition of PKC-alpha and c-RAF kinase expression by chimeric oligonucleotides incorporating 6'-substituted carbocyclic nucleosides and 2'-O-ethylene glycol substituted ribonucleosides", NUCLEOSIDES AND NUCLEOTIDES, TAYLOR & FRANCIS, US, vol. 16, no. 7-9, July 1997 (1997-07-01), pages 917 - 926, XP008089270, ISSN: 0732-8311 *
ANONYMOUS: "JENKEM TECHNOLOGY USA - INNOVATIVE MANUFACTURER DEDICATED TO THE DEVELOPMENT AND MANUFACTURE OF HIGH-QUALITY PEG PRODUCTS", 2020, New York, XP093009441, Retrieved from the Internet <URL:https://www.namiki-s.co.jp/upload/news/293JTH6-news_file.pdf> [retrieved on 20221219] *
BAI-ZHONG ZHANG ET AL: "Silencing of Cytochrome P450 in Spodoptera frugiperda (Lepidoptera: Noctuidae) by RNA Interference Enhances Susceptibility to Chlorantraniliprole", JOURNAL OF INSECT SCIENCE, vol. 20, no. 3, 2 June 2020 (2020-06-02), XP093011587, Retrieved from the Internet <URL:https://academic.oup.com/jinsectscience/article-pdf/20/3/12/33337182/ieaa047.pdf> DOI: 10.1093/jisesa/ieaa047 *
CAGLIARI DEISE ET AL: "Management of Pest Insects and Plant Diseases by Non-Transformative RNAi", FRONTIERS IN PLANT SCIENCE, vol. 10, 25 October 2019 (2019-10-25), XP093011563, DOI: 10.3389/fpls.2019.01319 *
GAUTHIER FLORIAN ET AL: "Conjugation of Small Molecules to RNA Using a Reducible Disulfide Linker Attached at the 2'-OH Position through a Carbamate Function", EUROPEAN JOURNAL OF ORGANIC CHEMISTRY, vol. 2019, no. 33, 19 August 2019 (2019-08-19), DE, pages 5636 - 5645, XP093007935, ISSN: 1434-193X, Retrieved from the Internet <URL:https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1002%2Fejoc.201900740> DOI: 10.1002/ejoc.201900740 *
HABIBIAN MARYAM ET AL: "Polyacetate and Polycarbonate RNA: Acylating Reagents and Properties", ORGANIC LETTERS, vol. 21, no. 14, 3 July 2019 (2019-07-03), US, pages 5413 - 5416, XP093009469, ISSN: 1523-7060, Retrieved from the Internet <URL:https://pubs.acs.org/doi/pdf/10.1021/acs.orglett.9b01526> DOI: 10.1021/acs.orglett.9b01526 *
JAESCHKE ANDRES ET AL: "Synthesis and analytical characterization of RNA-polyethylene glycol conjugates", NUCLEOSIDES AND NUCLEOTIDES, TAYLOR & FRANCIS, US, vol. 15, no. 9, 1996, pages 1519 - 1529, XP008126329, ISSN: 0732-8311, DOI: 10.1080/07328319608002451 *
JAVIER F. GUASTAVINO ET AL: "Simple Synthesis of Aldehyde and Carboxylic Acid Terminated Methoxypoly(ethylene glycol)", MACROMOLECULAR CHEMISTRY AND PHYSICS, vol. 217, no. 15, 9 June 2016 (2016-06-09), DE, pages 1745 - 1751, XP055477766, ISSN: 1022-1352, DOI: 10.1002/macp.201600094 *
KRASHENININA OLGA A. ET AL: "Postsynthetic On-Column 2' Functionalization of RNA by Convenient Versatile Method", INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, vol. 21, no. 14, 20 July 2020 (2020-07-20), pages 5127, XP093009893, Retrieved from the Internet <URL:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7404181/pdf/ijms-21-05127.pdf> DOI: 10.3390/ijms21145127 *
KRASHENININA OLGA A. ET AL: "Supplementary materials - Postsynthetic On-Column 2' Functionalization of RNA by Convenient Versatile Method", INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 20 July 2020 (2020-07-20), XP093011573, Retrieved from the Internet <URL:https://www.mdpi.com/1422-0067/21/14/5127/s1> [retrieved on 20230104], DOI: 10.3390/ijms21145127 *
MARINUS TYCHO ET AL: "A novel SHAPE reagent enables the analysis of RNA structure in living cells with unprecedented accuracy", NUCLEIC ACIDS RESEARCH, vol. 49, no. 6, 4 January 2021 (2021-01-04), GB, pages e34 - e34, XP093029753, ISSN: 0305-1048, Retrieved from the Internet <URL:https://watermark.silverchair.com/gkaa1255.pdf?token=AQECAHi208BE49Ooan9kkhW_Ercy7Dm3ZL_9Cf3qfKAc485ysgAAAtYwggLSBgkqhkiG9w0BBwagggLDMIICvwIBADCCArgGCSqGSIb3DQEHATAeBglghkgBZQMEAS4wEQQMBjmhqhQ_YgWe2b2YAgEQgIICieiE_-dWfeyFuYqO9IXE2F9LuZPZwygSUy7L-d1QZpd8wFM-jYO8FYWcD5zy9a2lhzwyKDCotCZ6lD4H1Igyppryoq0> DOI: 10.1093/nar/gkaa1255 *
MARINUS TYCHO ET AL: "Supplementary Information for A novel SHAPE reagent enables the analysis of RNA structure in living cells with unprecedented accuracy", NUCLEIC ACIDS RESEARCH, 4 January 2021 (2021-01-04), XP093029870, Retrieved from the Internet <URL:https://oup.silverchair-cdn.com/oup/backfile/Content_public/Journal/nar/49/6/10.1093_nar_gkaa1255/2/gkaa1255_supplemental_file.pdf?Expires=1681293819&Signature=4W7iq-UtGUKj7u7DlCDoeuU-yg74Mvtbck2t8~jXE~z7Q7GpBW5D2fM3RtzJENlVX0Uob5dvdkMv0QZgDr~5dm~2bnC8W7SfeIaoTUX8vEZ6~PpPaAkKP-a9n3DgLoEJ8vWZVEoAxZAU> [retrieved on 20230308] *
NODIN LAURA ET AL: "RNA SHAPE chemistry with aromatic acylating reagents", BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, ELSEVIER, AMSTERDAM NL, vol. 25, no. 3, 15 December 2014 (2014-12-15), pages 566 - 570, XP029131278, ISSN: 0960-894X, DOI: 10.1016/J.BMCL.2014.12.020 *
PARTHASARATHY RAMASESHADRI ET AL: "Physiological and Cellular Responses Caused by RNAi-Mediated Suppression of Snf7 Orthologue in Western Corn Rootworm (Diabrotica virgifera virgifera) Larvae", PLOS ONE, vol. 8, no. 1, 18 January 2013 (2013-01-18), pages e54270, XP055478240, DOI: 10.1371/journal.pone.0054270 *
SPITALE ROBERT C ET AL: "RNA SHAPE analysis in living cells", NATURE CHEMICAL BIOLOGY, NATURE PUBLISHING GROUP US, NEW YORK, vol. 9, no. 1, 25 November 2012 (2012-11-25), pages 18 - 20, XP037548208, ISSN: 1552-4450, [retrieved on 20121125], DOI: 10.1038/NCHEMBIO.1131 *
SPITALE ROBERT C ET AL: "Supplementary Information - RNA SHAPE analysis in living cells", NATURE CHEMICAL BIOLOGY, 25 November 2012 (2012-11-25), XP093029894, Retrieved from the Internet <URL:https://static-content.springer.com/esm/art%3A10.1038%2Fnchembio.1131/MediaObjects/41589_2013_BFnchembio1131_MOESM294_ESM.pdf> [retrieved on 20230308], DOI: 10.1038/nchembio.1131 *
VELEMA WILLEM A ET AL: "Supporting Information - RNA Control by Photoreversible Acylation", J. AM. CHEM. SOC., 23 February 2018 (2018-02-23), XP093029770, Retrieved from the Internet <URL:https://pubs.acs.org/doi/suppl/10.1021/jacs.7b12408/suppl_file/ja7b12408_si_001.pdf> [retrieved on 20230307] *
VELEMA WILLEM A ET AL: "The chemistry and applications of RNA 2'-OH acylation", NATURE REVIEWS CHEMISTRY, NATURE PUBLISHING GROUP UK, LONDON, vol. 4, no. 1, 19 November 2019 (2019-11-19), pages 22 - 37, XP036984688, DOI: 10.1038/S41570-019-0147-6 *
VELEMA WILLEM A. ET AL: "RNA Control by Photoreversible Acylation", JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, vol. 140, no. 10, 23 February 2018 (2018-02-23), pages 3491 - 3495, XP093029667, ISSN: 0002-7863, DOI: 10.1021/jacs.7b12408 *

Also Published As

Publication number Publication date
CN118302524A (en) 2024-07-05
CA3228823A1 (en) 2023-03-09
WO2023034849A2 (en) 2023-03-09
WO2023034849A8 (en) 2024-03-07
AR126939A1 (en) 2023-11-29
EP4396348A2 (en) 2024-07-10
MX2024002299A (en) 2024-03-07

Similar Documents

Publication Publication Date Title
WO2007056326A3 (en) Compositions and methods for inhibiting expression of nav1.8 gene
WO2007051045A3 (en) Compositions and methods for inhibiting expression of huntingtin gene
WO2008109105A3 (en) Methods and compositions for improved therapeutic effects with sirna
WO2009129465A3 (en) Compositions and methods for inhibiting expression of xbp-1 gene
SG170780A1 (en) Compositions and methods for inhibiting expression of eg5 gene
WO2008008719A3 (en) Compositions and methods for inhibiting expression of the myc gene
MX2012001581A (en) Improved polypropylene for use in bopp applications.
WO2006032041A3 (en) Compositions and methods for inhibiting expression of anti-apoptotic genes
EA200702341A1 (en) PROPYLENE POLYMER WITH A HIGH DEGREE OF CRYSTALLITY
WO2009029688A3 (en) Compositions of asymmetric interfering rna and uses thereof
UA101806C2 (en) Single-stranded circular rna and process for its production
BRPI0515328A (en) flexible hydraulic compositions
WO2006008028A8 (en) Novel 6-formyltetrahydropteridines method for production and use thereof as medicament against cancer amongst other things
MX2010004452A (en) Lipid-modified double-stranded rna having potent rna interference effect.
EA200970736A1 (en) MATERIALS BASED ON POLYOLEPHINES, EXTENDED EXTRACT, PRODUCTS OBTAINED FROM THEM
WO2019147308A3 (en) Rna nanostructures and methods of making and using rna nanostructures
WO2010056690A3 (en) Polymeric compositions and method of making and articles thereof
WO2010016907A3 (en) Methods for sorting nanotubes by wall number
WO2022084331A3 (en) Novel ligands for asialoglycoprotein receptor
EP2157182A3 (en) Modified short interfering RNA
WO2008112277A3 (en) Compositions and methods for treating cancer
CY1115938T1 (en) NEW COMPOSITION FOR INCREASING NEURTURIN BIO-AVAILABILITY
WO2023034849A3 (en) HIGH MOLECULAR WEIGHT MODIFIED dsRNA COMPOSITIONS
WO2007115929A8 (en) Thiazolyl-dihydroquinazolines
MXPA05009109A (en) Modification of paper coating rheology.

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 22783223

Country of ref document: EP

Kind code of ref document: A2

WWE Wipo information: entry into national phase

Ref document number: 3228823

Country of ref document: CA

WWE Wipo information: entry into national phase

Ref document number: 202417013408

Country of ref document: IN

WWE Wipo information: entry into national phase

Ref document number: 2024513327

Country of ref document: JP

WWE Wipo information: entry into national phase

Ref document number: 202280059222.3

Country of ref document: CN

REG Reference to national code

Ref country code: BR

Ref legal event code: B01A

Ref document number: 112024003831

Country of ref document: BR

WWE Wipo information: entry into national phase

Ref document number: 2022783223

Country of ref document: EP

NENP Non-entry into the national phase

Ref country code: DE

ENP Entry into the national phase

Ref document number: 2022783223

Country of ref document: EP

Effective date: 20240402

ENP Entry into the national phase

Ref document number: 112024003831

Country of ref document: BR

Kind code of ref document: A2

Effective date: 20240227