AR122644A1 - NEW CONJUGATED NUCLEIC ACID MOLECULES AND THEIR USES - Google Patents

NEW CONJUGATED NUCLEIC ACID MOLECULES AND THEIR USES

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Publication number
AR122644A1
AR122644A1 ARP210101648A ARP210101648A AR122644A1 AR 122644 A1 AR122644 A1 AR 122644A1 AR P210101648 A ARP210101648 A AR P210101648A AR P210101648 A ARP210101648 A AR P210101648A AR 122644 A1 AR122644 A1 AR 122644A1
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AR
Argentina
Prior art keywords
integer
nucleic acid
independently
molecule
double
Prior art date
Application number
ARP210101648A
Other languages
Spanish (es)
Inventor
Christelle Zandanel
Original Assignee
Onxeo
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Publication of AR122644A1 publication Critical patent/AR122644A1/en

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    • 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
    • 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
    • A61K47/54—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 compound
    • A61K47/554—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 compound the modifying agent being a steroid plant sterol, glycyrrhetic acid, enoxolone or bile acid
    • 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
    • C12N2310/13—Decoys
    • 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
    • C12N2310/18—Type of nucleic acid acting by a non-sequence specific mechanism
    • 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
    • C12N2310/31—Chemical structure of the backbone
    • C12N2310/315—Phosphorothioates
    • 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
    • C12N2310/31—Chemical structure of the backbone
    • C12N2310/318—Chemical structure of the backbone where the PO2 is completely replaced, e.g. MMI or formacetal
    • C12N2310/3183—Diol linkers, e.g. glycols or propanediols
    • 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
    • C12N2310/32—Chemical structure of the sugar
    • C12N2310/323—Chemical structure of the sugar modified ring structure
    • 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
    • C12N2310/3515—Lipophilic moiety, e.g. cholesterol
    • 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
    • C12N2310/50—Physical structure
    • C12N2310/53—Physical structure partially self-complementary or closed
    • C12N2310/531—Stem-loop; Hairpin
    • 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

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Genetics & Genomics (AREA)
  • Biomedical Technology (AREA)
  • Chemical & Material Sciences (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Organic Chemistry (AREA)
  • Biotechnology (AREA)
  • General Engineering & Computer Science (AREA)
  • General Health & Medical Sciences (AREA)
  • Zoology (AREA)
  • Molecular Biology (AREA)
  • Wood Science & Technology (AREA)
  • Biophysics (AREA)
  • Microbiology (AREA)
  • Biochemistry (AREA)
  • Plant Pathology (AREA)
  • Physics & Mathematics (AREA)
  • Botany (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

Abstract

La presente invención se refiere a nuevas moléculas de ácido nucleico de interés terapéutico, en particular para uso en el tratamiento del cáncer. Reivindicación 1: Una molécula de ácido nucleico conjugado que comprende un resto de ácido nucleico bicatenario de 16 pares de bases, estando el extremo 5’ de la primera hebra y el extremo 3’ de la hebra complementaria unidos por un bucle; teniendo el resto de ácido nucleico bicatenario la siguiente secuencia SEQ ID Nº 1 de fórmula (1) en donde los enlaces internucleotídicos “s” se refieren a enlaces internucleotídicos de fosforotioato, y en donde los nucleótidos subrayados son nucleótidos modificados en 2’; siendo el bucle -O-P(X)OH-O-{[(CH₂)₂-O]ᵍ-P(X)OH-O}ʳ-K-O-P(X)OH-O-{[(CH₂)₂-O]ₕ-P(X)OHO-}ₛ- (I) siendo r y s independientemente un número entero 0 ó 1; g y h son independientemente un número entero de 1 a 7 y la suma g + h es de 4 a 7; siendo X O ó S; siendo K un resto de fórmula (2) con y, j, k y l independientemente un número entero de 0 a 6, preferentemente de 1 a 3; o O-P(X)OH-O-[(CH₂)ᵈ-C(O)-NH]ᵇ-CHR-[C(O)-NH-(CH₂)ₑ]ᶜ-O-P(X)OH-O- (II) siendo b y c independientemente un número entero de 0 a 4, y la suma b + c es de 3 a 7; siendo d y e independientemente un número entero de 1 a 3, preferentemente de 1 a 2; y siendo R -Lᶠ-J, siendo X O ó S, siendo L un enlazador y siendo f un número entero que es 0 ó 1, y siendo J una molécula que facilita la endocitosis o que es H. Reivindicación 2: La molécula de ácido nucleico conjugado según la reivindicación 1, en donde la molécula que facilita la endocitosis se selecciona del grupo que consiste en un colesterol, ácidos grasos de cadena simple o doble, ligando que se dirige a un receptor celular que permite la endocitosis mediada por receptor, o una transferrina.The present invention relates to new nucleic acid molecules of therapeutic interest, in particular for use in the treatment of cancer. Claim 1: A conjugated nucleic acid molecule comprising a 16 base pair double-stranded nucleic acid moiety, the 5 end of the first strand and the 3 end of the complementary strand being joined by a loop; the double-stranded nucleic acid moiety having the following sequence SEQ ID NO: 1 of formula (1) wherein "s" internucleotide linkages refer to phosphorothioate internucleotide linkages, and wherein the underlined nucleotides are 2-modified nucleotides; the loop being -O-P(X)OH-O-{[(CH₂)₂-O]ᵍ-P(X)OH-O}ʳ-K-O-P(X)OH-O-{[(CH₂)₂-O] ₕ-P(X)OHO-}ₛ- (I) where r and s are independently an integer 0 or 1; g and h are independently an integer from 1 to 7 and the sum g + h is from 4 to 7; being X O or S; K being a moiety of formula (2) with y, j, k and l independently an integer from 0 to 6, preferably from 1 to 3; or O-P(X)OH-O-[(CH₂)ᵈ-C(O)-NH]ᵇ-CHR-[C(O)-NH-(CH₂)ₑ]ᶜ-O-P(X)OH-O- ( II) where b and c are independently an integer from 0 to 4, and the sum b + c is from 3 to 7; d and e being independently an integer from 1 to 3, preferably from 1 to 2; and R being -Lᶠ-J, X being O or S, L being a linker and f being an integer that is 0 or 1, and J being a molecule that facilitates endocytosis or that is H. Claim 2: The acid molecule conjugated nucleic according to claim 1, wherein the molecule that facilitates endocytosis is selected from the group consisting of cholesterol, single or double chain fatty acids, ligand that targets a cellular receptor that allows receptor-mediated endocytosis, or a transferrin.

ARP210101648A 2020-06-19 2021-06-17 NEW CONJUGATED NUCLEIC ACID MOLECULES AND THEIR USES AR122644A1 (en)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
EP20305669 2020-06-19

Publications (1)

Publication Number Publication Date
AR122644A1 true AR122644A1 (en) 2022-09-28

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ID=71728679

Family Applications (1)

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AR (1) AR122644A1 (en)
TW (1) TW202214857A (en)
WO (1) WO2021255223A1 (en)

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2023220744A2 (en) * 2022-05-13 2023-11-16 Alnylam Pharmaceuticals, Inc. Single-stranded loop oligonucleotides

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