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NZ740707B2 - Methods and materials for galgt2 gene therapy - Google Patents
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NZ740707B2 - Methods and materials for galgt2 gene therapy - Google Patents

Methods and materials for galgt2 gene therapy

Info

Publication number
NZ740707B2
NZ740707B2 NZ740707A NZ74070716A NZ740707B2 NZ 740707 B2 NZ740707 B2 NZ 740707B2 NZ 740707 A NZ740707 A NZ 740707A NZ 74070716 A NZ74070716 A NZ 74070716A NZ 740707 B2 NZ740707 B2 NZ 740707B2
Authority
NZ
New Zealand
Prior art keywords
raav
aav
muscular dystrophy
medicament
seq
Prior art date
Application number
NZ740707A
Other versions
NZ740707A (en
Inventor
Paul Taylor Martin
Original Assignee
Research Institute At Nationwide Children's Hospital
Filing date
Publication date
Application filed by Research Institute At Nationwide Children's Hospital filed Critical Research Institute At Nationwide Children's Hospital
Priority to NZ780253A priority Critical patent/NZ780253B2/en
Priority claimed from PCT/US2016/052051 external-priority patent/WO2017049031A1/en
Publication of NZ740707A publication Critical patent/NZ740707A/en
Publication of NZ740707B2 publication Critical patent/NZ740707B2/en

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/43—Enzymes; Proenzymes; Derivatives thereof
    • A61K38/45—Transferases (2)
    • 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
    • A61K48/005—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy characterised by an aspect of the 'active' part of the composition delivered, i.e. the nucleic acid delivered
    • A61K48/0058—Nucleic acids adapted for tissue specific expression, e.g. having tissue specific promoters as part of a contruct
    • 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
    • A61K48/0075—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy characterised by an aspect of the delivery route, e.g. oral, subcutaneous
    • 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
    • C07—ORGANIC CHEMISTRY
    • C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
    • C07H21/00—Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids
    • C07H21/04—Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids with deoxyribosyl as saccharide radical
    • 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
    • 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
    • C12N15/864—Parvoviral vectors, e.g. parvovirus, densovirus
    • C12N15/8645—Adeno-associated virus
    • 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
    • C12N2830/00—Vector systems having a special element relevant for transcription
    • C12N2830/008—Vector systems having a special element relevant for transcription cell type or tissue specific enhancer/promoter combination
    • 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
    • C12N2830/00—Vector systems having a special element relevant for transcription
    • C12N2830/42—Vector systems having a special element relevant for transcription being an intron or intervening sequence for splicing and/or stability of RNA
    • 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
    • C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
    • C12N9/10—Transferases (2.)
    • C12N9/1048—Glycosyltransferases (2.4)
    • 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
    • C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
    • C12N9/10—Transferases (2.)
    • C12N9/1048—Glycosyltransferases (2.4)
    • C12N9/1051—Hexosyltransferases (2.4.1)
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
    • C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Y—ENZYMES
    • C12Y204/00—Glycosyltransferases (2.4)
    • C12Y204/01—Hexosyltransferases (2.4.1)
    • C12Y204/01165—N-Acetylneuraminylgalactosylglucosylceramide beta-1,4-N-acetylgalactosaminyltransferase (2.4.1.165)

Abstract

The present disclosure relates to recombinant adeno-associated virus (rAAV) delivery of a GALGT2 polynucleotide. The rAAV comprises a nucleic acid comprising a first AAV2 inverted terminal repeat sequence (ITR), a muscle creatine kinase core promoter sequence, a nucleo-tide sequence encoding a human GALGT2 polypeptide and a second AAV2 ITR sequence. The disclosure provides rAAV and methods of using the rAAV for GALGT2 gene therapy of neuro-muscular disorders. Exemplary neuromuscular disorders include, but are not limited to, mus-cular dystrophies such as Duchenne muscular dystrophy, Congenital Muscular Dystrophy 1A and Limb Girdle Muscular Dystrophy 2D.

Claims (24)

We claim:
1. A nucleic acid comprising nucleotides 53 to 2762 of SEQ ID NO: 2.
2. A recombinant associated virus particle (rAAV) comprising the nucleic acid of claim 1, wherein the rAAV is infectious.
3. The rAAV of claim 2, wherein the rAAV is serotype AAV-1, AAV-2, AAV-3, AAV-4, AAV-5, AAV-6, AAV-7, AAV-8, AAV-9, AAV-10, AAV-11, or 74.
4. The rAAV of claim 2 or 3, wherein the AAV DNA in the rAAV genome is from AAV rh.74.
5. The rAAV of any one of claims 2-4, wherein the polynucleotide sequence of the AAV rh.74 genome is set out in SEQ ID NO: 1.
6. A composition comprising the rAAV of any one of claims 2-5 and a pharmaceutically acceptable carrier.
7. Use of the composition of claim 6 in the manufacture of a medicament to treat or prevent a neuromuscular disorder in a subject suffering therefrom.
8. The use of claim 7, wherein the neuromuscular disorder is Duchenne Muscular Dystrophy (DMD); Becker Muscular Dystrophy; Congenital ar Dystrophy (MDC) 1A, 1B, 1C and 1D; Limb Girdle Muscular Dystrophy (LGMD) 1A, 1B, 1C, 1D, 1E, 1F, 1G, 1H, 2A, 2B, 2C, 2D, 2E, 2F, 2G 2H, 2I, 2J, 2K, 2L, 2M, 2N, 2O and 2Q; Bethlem Myopathy; h Congenital Muscular Dystrophy; Muscle Eye Brain e; Fukuyama Congenital Muscular Dystrophy; Walker Warburg Syndrome; Myotonic Dystrophy; Myasthenic syndromes; Congenital Myasthenias; ion Body Myopathy; Inclusion Body Myositis; Emery Dreifuss Muscular Dystrophy; Distal Muscular Dystrophy; Dermatomyositis; Centronuclear Myopathy; Faciosacpulohumeral Muscular Dystrophy; Myoshi Myopathy; Mitochondrial Myopathy; Nemaline hy; Nonaka Myopathy; Myasthenia Gravis; or Polymyositis.
9. The use of claim 7 or 8 wherein the neuromuscular disorder is a muscular dystrophy.
10. The use of claim 9 wherein the muscular dystrophy is Duchenne Muscular Dystrophy.
11. The use of claim 9 wherein the muscular dystrophy is Congenital ar Dystrophy 1A.
12. The use of claim 9 wherein the ar dystrophy is Limb Girdle Muscular Dystrophy 2D.
13. The use of any one of claims 7-12, wherein the medicament is formulated for intramuscular (IM), ed limb infusion or perfusion (ILP), or intravenous (IV) administration.
14. The use of claim 13 wherein the medicament is formulated for IM administration.
15. The use of claim 13 or 14, wherein the medicament comprises a dose of the rAAV from about 3x1011 to at least about 5x1012 vg/injection.
16. The use of claim 13 wherein the medicament is ated for on or ILP administration.
17. The use of claim 13 or 16 wherein the medicament comprises a dose of the rAAV from about 2x1012 to at least about 4.8x1013 vg/kg/limb, or a total dose of from about 4x1012 to at least about 9.6x1013 .
18. The use of claim 13 wherein the medicament is formulated for IV administration.
19. The use of claim 13 wherein the medicament comprises a dose of the rAAV from about 2x1014 to at least about 6x1015 vg/kg.
20. The use of claim 13 wherein the medicament comprises a dose of the rAAV from about 5x1013 vg/kg to about 5x1015 vg/kg.
21. Use of a composition comprising an rAAV comprising a nucleic acid comprising, in order from 5’ to 3’: (i) a first AAV2 inverted terminal repeat sequence (ITR); (ii) a muscle creatine kinase core promoter sequence set out in nucleotides 443-793 of SEQ ID NO: 2; (iii) a nucleotide sequence encoding a human GALGT2 ptide; and (iv) a second AAV2 ITR sequence; wherein the human GALGT2 polypeptide has an amino acid sequence that is at least 90% identical to SEQ ID NO:3 or is 100% identical to SEQ ID NO:3, or is encoded by a nucleotide sequence 90% cal to tides 1002-2522 of SEQ ID NO: 2 or 100% identical to tides 1002-2522 of SEQ ID NO: 2 in the manufacture of a medicament to treat or prevent a neuromuscular disorder in a subject ing therefrom.
22. The use of claim 21, where in the nucleic acid further comprises 5’ to said core promoter, an MCK enhancer set out in nucleotides 236-442 of SEQ ID NO: 2.
23. The nucleic acid of claim 1, substantially as herein bed with reference to any one of the examples thereof.
24. The use of claim 21, substantially as herein described with reference to any one of the examples thereof. 49985PCT_Seqlisting
NZ740707A 2016-09-16 Methods and materials for galgt2 gene therapy NZ740707B2 (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
NZ780253A NZ780253B2 (en) 2016-09-16 Methods and materials for GALGT2 gene therapy

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
US201562220107P 2015-09-17 2015-09-17
US201562221068P 2015-09-20 2015-09-20
US201662301260P 2016-02-29 2016-02-29
PCT/US2016/052051 WO2017049031A1 (en) 2015-09-17 2016-09-16 Methods and materials for galgt2 gene therapy

Publications (2)

Publication Number Publication Date
NZ740707A NZ740707A (en) 2025-06-27
NZ740707B2 true NZ740707B2 (en) 2025-09-30

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