AR110537A1 - OLIGOMERIC CONJUGATES FOR EXON LEAP FOR MUSCLE DYSTROPHY - Google Patents

OLIGOMERIC CONJUGATES FOR EXON LEAP FOR MUSCLE DYSTROPHY

Info

Publication number
AR110537A1
AR110537A1 ARP170103552A ARP170103552A AR110537A1 AR 110537 A1 AR110537 A1 AR 110537A1 AR P170103552 A ARP170103552 A AR P170103552A AR P170103552 A ARP170103552 A AR P170103552A AR 110537 A1 AR110537 A1 AR 110537A1
Authority
AR
Argentina
Prior art keywords
subject
exon
dystrophin
antisense oligomer
oligomer conjugate
Prior art date
Application number
ARP170103552A
Other languages
Spanish (es)
Inventor
Gunnar J Hanson
Marco A Passini
Original Assignee
Sarepta Therapeutics 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 Sarepta Therapeutics Inc filed Critical Sarepta Therapeutics Inc
Publication of AR110537A1 publication Critical patent/AR110537A1/en

Links

Classifications

    • 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
    • A61K47/549—Sugars, nucleosides, nucleotides or nucleic acids
    • 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
    • A61K31/7088—Compounds having three or more nucleosides or nucleotides
    • 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
    • A61K47/62—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 a protein, peptide or polyamino acid
    • A61K47/64—Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent
    • A61K47/645—Polycationic or polyanionic oligopeptides, polypeptides or polyamino acids, e.g. polylysine, polyarginine, polyglutamic acid or peptide TAT
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P21/00—Drugs for disorders of the muscular or neuromuscular system
    • 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
    • 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
    • C12N2310/11—Antisense
    • 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
    • C12N2310/3233—Morpholino-type ring
    • 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
    • C12N2320/35—Special therapeutic applications based on a specific dosage / administration regimen

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Chemical & Material Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Medicinal Chemistry (AREA)
  • Molecular Biology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Epidemiology (AREA)
  • Organic Chemistry (AREA)
  • Genetics & Genomics (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Biomedical Technology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Neurology (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Physical Education & Sports Medicine (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Biotechnology (AREA)
  • Biochemistry (AREA)
  • Zoology (AREA)
  • Wood Science & Technology (AREA)
  • General Engineering & Computer Science (AREA)
  • Microbiology (AREA)
  • Plant Pathology (AREA)
  • Biophysics (AREA)
  • Physics & Mathematics (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

Abstract

Reivindicación 1: Un conjugado de oligómero antisentido caracterizado porque es de fórmula (1), o una sal farmacéuticamente aceptable del mismo, en donde: cada Nu es una nucleobase las cuales tomadas en conjunto forman una secuencia de direccionamiento; y T es una unidad seleccionada entre los compuestos de fórmula (2), (3) y (4); donde R¹ es C₁₋₆ alquilo, en donde la secuencia de direccionamiento es complementaria con un sitio de apareamiento del exón 45 en el pre-ARNm de la distrofina designado como H45A(-03+19). Reivindicación 12: Una composición farmacéutica caracterizada porque comprende un conjugado de oligómero antisentido de cualquiera de las reivindicaciones 1 a 11, o una sal farmacéuticamente aceptable del mismo, y un vehículo farmacéuticamente aceptable. Reivindicación 13: Un método para tratar distrofia muscular de Duchenne (DMD) en un sujeto que lo requiere en donde el sujeto tiene una mutación del gen de la distrofina que es susceptible al salto del exón 45, caracterizado porque el método comprende administrar al sujeto el conjugado de oligómero antisentido de cualquiera de las reivindicaciones 1 a 11. Reivindicación 18: Un método para restaurar un marco de lectura de ARNm para inducir la producción de distrofina en un sujeto que tiene una mutación del gen de la distrofina que es susceptible al salto del exón 45, caracterizado porque comprende administrar al sujeto el conjugado de oligómero antisentido de cualquiera de las reivindicaciones 1 a 11. Reivindicación 25: Un método para excluir el exón 45 del pre-ARNm de la distrofina durante el procesamiento del ARNm en un sujeto que tiene una mutación del gen de la distrofina que es susceptible al salto del exón 45, caracterizado porque comprende administrar al sujeto la composición farmacéutica de la reivindicación 11.Claim 1: An antisense oligomer conjugate characterized in that it is of formula (1), or a pharmaceutically acceptable salt thereof, wherein: each Nu is a nucleobase which taken together form a targeting sequence; and T is a unit selected from the compounds of formula (2), (3) and (4); where R¹ is C₁₋₆ alkyl, where the targeting sequence is complementary to a mating site of exon 45 in the pre-mRNA of the dystrophin designated as H45A (-03 + 19). Claim 12: A pharmaceutical composition characterized in that it comprises an antisense oligomer conjugate of any one of claims 1 to 11, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier. Claim 13: A method for treating Duchenne muscular dystrophy (DMD) in a subject that requires it where the subject has a dystrophin gene mutation that is susceptible to exon 45 skipping, characterized in that the method comprises administering to the subject the antisense oligomer conjugate of any one of claims 1 to 11. Claim 18: A method of restoring an mRNA reading frame to induce dystrophin production in a subject that has a dystrophin gene mutation that is susceptible to the jump of the exon 45, characterized in that it comprises administering to the subject the antisense oligomer conjugate of any one of claims 1 to 11. Claim 25: A method of excluding exon 45 from the dystrophin pre-mRNA during mRNA processing in a subject having a mutation of the dystrophin gene that is susceptible to exon 45 skipping, characterized in that it comprises administering to subject l a pharmaceutical composition of claim 11.

ARP170103552A 2016-12-19 2017-12-18 OLIGOMERIC CONJUGATES FOR EXON LEAP FOR MUSCLE DYSTROPHY AR110537A1 (en)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
US201662436199P 2016-12-19 2016-12-19

Publications (1)

Publication Number Publication Date
AR110537A1 true AR110537A1 (en) 2019-04-10

Family

ID=66326249

Family Applications (1)

Application Number Title Priority Date Filing Date
ARP170103552A AR110537A1 (en) 2016-12-19 2017-12-18 OLIGOMERIC CONJUGATES FOR EXON LEAP FOR MUSCLE DYSTROPHY

Country Status (2)

Country Link
AR (1) AR110537A1 (en)
MA (1) MA47015B1 (en)

Also Published As

Publication number Publication date
MA47015A (en) 2019-10-23
MA47015B1 (en) 2022-11-30

Similar Documents

Publication Publication Date Title
NI201700020A (en) AMINOPYRIMIDINYL COMPOUNDS AS JAK INHIBITORS
PH12017500828A1 (en) Bile acid analogs as fxr/tgr5 agonists and methods of use thereof
EA202090486A3 (en) COMPOUNDS FOR THE TREATMENT OF SPINAL MUSCLE ATROPHY
MX2016013689A (en) 4-amino-imidazoquinoline compounds.
MX2021004492A (en) Compositions and methods for treating cns disorders.
PH12016502378A1 (en) Substituted dihydroisoquinolinone compounds
EA201790476A1 (en) AMINOPIRIDYLOXYPYRAZOLIC COMPOUNDS
UY36212A (en) TOLL TYPE RECEIVER MODULATORS FOR HIV TREATMENT
EA201790764A1 (en) NEW CARBON ACID CONNECTIONS SUITABLE FOR INHIBITING MICROSOMAL PROSTAGLANDIN-E2-SYNTHASE 1
EA201590693A1 (en) INHIBITORS GDF-8
UY34888A (en) HEPATITIS C VIRUS INHIBITORS
PH12017501539A1 (en) Disacetoxytubulysin h and analogs thereof
EA202090744A1 (en) OLIGOMER CONJUGATES FOR EXONE PASSING IN MUSCULAR DYSTROPHY
EA201490544A1 (en) PREPARATIONS AND MEDICATION FORMS BASED ON OXIDIZED PHOSPHOLIPIDS
GEP20207108B (en) Substituted 2,4 diamino-quinoline as new anticancer agents
CU20170007A7 (en) IMIDAZOPIRIDAZINE COMPOUNDS
BR112017008103A2 (en) compound, pharmaceutical composition, methods for treating a disease and condition, and use of a compound or pharmaceutically acceptable salt thereof and a second active agent.
EA201791804A1 (en) COMPOUNDS 1-HETEROCYCLYL ISOHROMANIL AND ANALOGUES FOR THE TREATMENT OF CNS DISORDERS
DOP2014000178A (en) NEW BENCIL SULFONAMIDE DERIVATIVES USEFUL AS MOGAT-2 INHIBITORS
MX2018000239A (en) Hbed-bisphosphonates, radiometal conjugates thereof and their use as theranostic agents.
EA201890898A1 (en) NEW CONNECTIONS AND CRYPTOPHICINE CONJUGATES, THEIR RECOVERY AND THEIR THERAPEUTIC APPLICATION
NZ721780A (en) Heterocyclic modulators of lipid synthesis for use against cancer and viral infections
CU24434B1 (en) COMPOUNDS DERIVED FROM N- (1,5-DIMETHYL-3-OXO-2,3-DIHYDRO-1H-PIRAZOL-4-IL) -4-METHYL-5-ISOXAZOLE-3-CARBOXAMIDE ACTIVE AS SELECTIVE INHIBITORS OF SMURF-1
EA201891319A1 (en) COMPOUNDS OF ALKYDYDYDROCHINOLINSULPHONAMIDE
CO2018013828A2 (en) Pharmaceutical compositions of morpholino phosphorodiamidate oligomer