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AR134556A1 - COMPOSITIONS AND METHODS FOR THE TREATMENT OF DISORDERS RELATED TO THE PROTEIN KINASE OF MYOTONIC DYSTROPHY - Google Patents

COMPOSITIONS AND METHODS FOR THE TREATMENT OF DISORDERS RELATED TO THE PROTEIN KINASE OF MYOTONIC DYSTROPHY

Info

Publication number
AR134556A1
AR134556A1 ARP240103328A ARP240103328A AR134556A1 AR 134556 A1 AR134556 A1 AR 134556A1 AR P240103328 A ARP240103328 A AR P240103328A AR P240103328 A ARP240103328 A AR P240103328A AR 134556 A1 AR134556 A1 AR 134556A1
Authority
AR
Argentina
Prior art keywords
aav
cell
dmpk
capsid variant
viral genome
Prior art date
Application number
ARP240103328A
Other languages
Spanish (es)
Inventor
Mathieu Emmanuel Nonnenmacher
Jing Lin
Hongxing Wang
Jinzhao Hou
Wei Wang
Jiangyu Li
Original Assignee
Voyager 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 Voyager Therapeutics Inc filed Critical Voyager Therapeutics Inc
Publication of AR134556A1 publication Critical patent/AR134556A1/en

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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
    • C12N15/63—Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
    • C12N15/79—Vectors or expression systems specially adapted for eukaryotic hosts
    • C12N15/85—Vectors or expression systems specially adapted for eukaryotic hosts for animal cells
    • C12N15/86—Viral vectors
    • 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
    • A61K48/0091—Purification or manufacturing processes for gene therapy compositions
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/005—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from viruses
    • 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
    • C12N2750/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA ssDNA viruses
    • C12N2750/00011—Details
    • C12N2750/14011—Parvoviridae
    • C12N2750/14111—Dependovirus, e.g. adenoassociated viruses
    • C12N2750/14122—New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes
    • 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
    • C12N2750/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA ssDNA viruses
    • C12N2750/00011—Details
    • C12N2750/14011—Parvoviridae
    • C12N2750/14111—Dependovirus, e.g. adenoassociated viruses
    • C12N2750/14141—Use of virus, viral particle or viral elements as a vector
    • C12N2750/14143—Use of virus, viral particle or viral elements as a vector viral genome or elements thereof as genetic vector
    • 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
    • C12N2750/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA ssDNA viruses
    • C12N2750/00011—Details
    • C12N2750/14011—Parvoviridae
    • C12N2750/14111—Dependovirus, e.g. adenoassociated viruses
    • C12N2750/14141—Use of virus, viral particle or viral elements as a vector
    • C12N2750/14145—Special targeting system for viral vectors

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Genetics & Genomics (AREA)
  • Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Organic Chemistry (AREA)
  • Molecular Biology (AREA)
  • General Health & Medical Sciences (AREA)
  • Biotechnology (AREA)
  • Medicinal Chemistry (AREA)
  • Biophysics (AREA)
  • Wood Science & Technology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • General Engineering & Computer Science (AREA)
  • Biomedical Technology (AREA)
  • Virology (AREA)
  • Zoology (AREA)
  • Biochemistry (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Veterinary Medicine (AREA)
  • Physics & Mathematics (AREA)
  • Public Health (AREA)
  • Animal Behavior & Ethology (AREA)
  • Plant Pathology (AREA)
  • Epidemiology (AREA)
  • Microbiology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Manufacturing & Machinery (AREA)
  • Medicines Containing Material From Animals Or Micro-Organisms (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

Composiciones y métodos para modular, por ejemplo, reducir o eliminar, la expresión de DMPK mutado mediante la administración con el uso de una variante de cápside viral adenoasociada (AAV). Las composiciones y métodos son útiles en el tratamiento de sujetos a los que se les diagnosticó, se sospecha que tienen o que tienen distrofia miotónica tipo 1 u otro trastorno relacionado con DMPK o al menos un síntoma de este. Reivindicación 1: Una partícula de virus adenoasociado (AAV) caracterizada porque comprende una variante de cápside de AAV y un genoma viral, en donde el genoma viral comprende una secuencia de nucleótidos que codifica un polinucleótido modulador para reducir o eliminar la expresión de mARN mutado de proteína quinasa de distrofia miotónica (DMPK), opcionalmente en donde el polinucleótido modulador comprende un agente de ARNi dirigido a mARN de DMPK; y en donde la variante de cápside de AAV comprende una secuencia de aminoácidos que tiene la fórmula [N1]-[N2]-[N3] (SEQ ID Nº 4681) en el bucle VIII; en donde [N2] comprende la secuencia de aminoácidos de DWHR (SEQ ID Nº 4682); y en donde: (i) [N1] comprende los aminoácidos X₁, X₂, X₃ y X₄, en donde X₄ es Q, K, E, S, P, R, N o H; y/o (ii) [N3] comprende los aminoácidos X₅, X₆ y X₇, en donde X₅ es I, V, T, M, S, N, L o F. Reivindicación 47: Una célula caracterizada porque comprende la partícula de AAV de acuerdo con cualquiera de las reivindicaciones 1 - 46, opcionalmente en donde la célula es una célula de mamífero (por ejemplo, una célula HEK293), una célula de insecto (por ejemplo, una célula Sf9) o una célula bacteriana. Reivindicación 48: Un método para producir la partícula de AAV de acuerdo con cualquiera de las reivindicaciones 1 - 46, caracterizado porque el método comprende: (i) proporcionar una célula que comprende el genoma viral que comprende una secuencia de nucleótidos que codifica un polinucleótido modulador para reducir o eliminar la expresión de mARN de DMPK mutado y un ácido nucleico que codifica la variante de cápside de AAV; y (ii) incubar la célula en condiciones adecuadas para encapsular el genoma viral en la variante de cápside de AAV; lo que produce la partícula de AAV. Reivindicación 55: Una composición farmacéutica caracterizada porque comprende la partícula de AAV de acuerdo con cualquiera de las reivindicaciones 1 - 46 y un excipiente aceptable desde el punto de vista farmacéutico.Compositions and methods for modulating, for example, reducing or eliminating, the expression of mutated DMPK by administration using an adeno-associated viral (AAV) capsid variant. The compositions and methods are useful in the treatment of subjects diagnosed with, suspected of having, or who have myotonic dystrophy type 1 or another DMPK-related disorder or at least one symptom thereof. Claim 1: An adeno-associated virus (AAV) particle characterized in that it comprises an AAV capsid variant and a viral genome, wherein the viral genome comprises a nucleotide sequence encoding a modulating polynucleotide for reducing or eliminating the expression of mutated myotonic dystrophy protein kinase (DMPK) mRNA, optionally wherein the modulating polynucleotide comprises an RNAi agent targeting DMPK mRNA; and wherein the capsid variant of AAV comprises an amino acid sequence having the formula [N1]-[N2]-[N3] (SEQ ID No. 4681) in loop VIII; wherein [N2] comprises the amino acid sequence of DWHR (SEQ ID No. 4682); and wherein: (i) [N1] comprises the amino acids X₁, X₂, X₃ and X₄, wherein X₄ is Q, K, E, S, P, R, N or H; and/or (ii) [N3] comprises the amino acids X₅, X₆, and X₇, wherein X₅ is I, V, T, M, S, N, L, or F. Claim 47: A cell characterized in that it comprises the AAV particle according to any one of claims 1-46, optionally wherein the cell is a mammalian cell (e.g., an HEK293 cell), an insect cell (e.g., an Sf9 cell), or a bacterial cell. Claim 48: A method for producing the AAV particle according to any one of claims 1-46, characterized in that the method comprises: (i) providing a cell comprising the viral genome comprising a nucleotide sequence encoding a modulator polynucleotide for reducing or eliminating the expression of mutated DMPK mRNA and a nucleic acid encoding the AAV capsid variant; and (ii) incubating the cell under conditions suitable for encapsulating the viral genome in the AAV capsid variant; thereby producing the AAV particle. Claim 55: A pharmaceutical composition characterized in that it comprises the AAV particle according to any one of claims 1-46 and a pharmaceutically acceptable excipient.

ARP240103328A 2023-12-05 2024-12-04 COMPOSITIONS AND METHODS FOR THE TREATMENT OF DISORDERS RELATED TO THE PROTEIN KINASE OF MYOTONIC DYSTROPHY AR134556A1 (en)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
US202363606204P 2023-12-05 2023-12-05

Publications (1)

Publication Number Publication Date
AR134556A1 true AR134556A1 (en) 2026-01-28

Family

ID=94083351

Family Applications (1)

Application Number Title Priority Date Filing Date
ARP240103328A AR134556A1 (en) 2023-12-05 2024-12-04 COMPOSITIONS AND METHODS FOR THE TREATMENT OF DISORDERS RELATED TO THE PROTEIN KINASE OF MYOTONIC DYSTROPHY

Country Status (2)

Country Link
AR (1) AR134556A1 (en)
WO (1) WO2025122536A1 (en)

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