RU2019141647A - Векторы экспрессии фактора viii на основе аденоассоциированного вируса - Google Patents
Векторы экспрессии фактора viii на основе аденоассоциированного вируса Download PDFInfo
- Publication number
- RU2019141647A RU2019141647A RU2019141647A RU2019141647A RU2019141647A RU 2019141647 A RU2019141647 A RU 2019141647A RU 2019141647 A RU2019141647 A RU 2019141647A RU 2019141647 A RU2019141647 A RU 2019141647A RU 2019141647 A RU2019141647 A RU 2019141647A
- Authority
- RU
- Russia
- Prior art keywords
- sequence
- seq
- presented
- construct
- construction
- Prior art date
Links
- 229960000301 factor viii Drugs 0.000 title claims 13
- 241000702421 Dependoparvovirus Species 0.000 title claims 3
- 239000013598 vector Substances 0.000 title 1
- 108010054218 Factor VIII Proteins 0.000 claims 12
- 102000001690 Factor VIII Human genes 0.000 claims 12
- 238000010276 construction Methods 0.000 claims 12
- 238000012772 sequence design Methods 0.000 claims 8
- 239000013607 AAV vector Substances 0.000 claims 3
- 102100026735 Coagulation factor VIII Human genes 0.000 claims 3
- 201000003542 Factor VIII deficiency Diseases 0.000 claims 3
- 208000009292 Hemophilia A Diseases 0.000 claims 3
- 101000911390 Homo sapiens Coagulation factor VIII Proteins 0.000 claims 3
- 239000013604 expression vector Substances 0.000 claims 3
- 239000002245 particle Substances 0.000 claims 3
- 239000003623 enhancer Substances 0.000 claims 2
- 238000004519 manufacturing process Methods 0.000 claims 2
- 108020004707 nucleic acids Proteins 0.000 claims 2
- 150000007523 nucleic acids Chemical class 0.000 claims 2
- 102000039446 nucleic acids Human genes 0.000 claims 2
- 239000013603 viral vector Substances 0.000 claims 2
- FWMNVWWHGCHHJJ-SKKKGAJSSA-N 4-amino-1-[(2r)-6-amino-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]piperidine-4-carboxylic acid Chemical compound C([C@H](C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N1CCC(N)(CC1)C(O)=O)NC(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 FWMNVWWHGCHHJJ-SKKKGAJSSA-N 0.000 claims 1
- 241000702423 Adeno-associated virus - 2 Species 0.000 claims 1
- 108091092195 Intron Proteins 0.000 claims 1
- 238000012258 culturing Methods 0.000 claims 1
- 239000003814 drug Substances 0.000 claims 1
- 210000004185 liver Anatomy 0.000 claims 1
- 238000000034 method Methods 0.000 claims 1
- 239000002773 nucleotide Substances 0.000 claims 1
- 125000003729 nucleotide group Chemical group 0.000 claims 1
- 230000008488 polyadenylation Effects 0.000 claims 1
- 230000022532 regulation of transcription, DNA-dependent Effects 0.000 claims 1
- 239000006228 supernatant Substances 0.000 claims 1
- 230000003612 virological effect Effects 0.000 claims 1
Classifications
-
- 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
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/36—Blood coagulation or fibrinolysis factors
- A61K38/37—Factors VIII
-
- 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
- A61K48/005—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
- A61K48/0066—Manipulation of the nucleic acid to modify its expression pattern, e.g. enhance its duration of expression, achieved by the presence of particular introns in the delivered nucleic acid
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/04—Antihaemorrhagics; Procoagulants; Haemostatic agents; Antifibrinolytic agents
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/745—Blood coagulation or fibrinolysis factors
- C07K14/755—Factors VIII, e.g. factor VIII C (AHF), factor VIII Ag (VWF)
-
- 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
- C12N7/00—Viruses; Bacteriophages; Compositions thereof; Preparation or purification thereof
-
- 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
- C12N2750/14132—Use of virus as therapeutic agent, other than vaccine, e.g. as cytolytic agent
-
- 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
- C12N2750/14142—Use of virus, viral particle or viral elements as a vector virus or viral particle as vehicle, e.g. encapsulating small organic molecule
-
- 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
- C12N2750/14151—Methods of production or purification of viral material
-
- 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
- C12N2800/00—Nucleic acids vectors
- C12N2800/22—Vectors comprising a coding region that has been codon optimised for expression in a respective host
-
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Genetics & Genomics (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Zoology (AREA)
- Medicinal Chemistry (AREA)
- Biotechnology (AREA)
- Biochemistry (AREA)
- Wood Science & Technology (AREA)
- Biomedical Technology (AREA)
- Molecular Biology (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Hematology (AREA)
- General Engineering & Computer Science (AREA)
- Epidemiology (AREA)
- Biophysics (AREA)
- Virology (AREA)
- Microbiology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Gastroenterology & Hepatology (AREA)
- Immunology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Diabetes (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Plant Pathology (AREA)
- Physics & Mathematics (AREA)
- Toxicology (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Peptides Or Proteins (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Claims (53)
1. Вектор экспрессии фактора VIII (FVIII) на основе аденоассоциированного вируса (ААВ), содержащий нуклеиновую кислоту, содержащую 5’-инвертированный концевой повтор (ITR) ААВ2, специфическую для печени область регуляции транскрипции, кодон-оптимизированную область, кодирующую функционально активный FVIII, возможно один или более интронов, последовательность полиаденилирования и 3’-ITR ААВ2.
2. ААВ-вектор экспрессии FVIII по п. 1, отличающийся тем, что указанная нуклеиновая кислота включает последовательность нуклеотидов, выбранную из группы, состоящей из
i. последовательности Proto 1, представленной в SEQ ID NO: 1,
ii. последовательности Proto 1S, представленной в SEQ ID NO: 2,
iii. последовательности Proto 2S, представленной в SEQ ID NO: 3,
iv. последовательности Proto 3S, представленной в SEQ ID NO: 4,
v. последовательности Proto 4, представленной в SEQ ID NO: 5,
vi. последовательности Proto 5, представленной в SEQ ID NO: 6,
vii. последовательности Proto 6, представленной в SEQ ID NO: 7,
viii. последовательности Proto 7, представленной в SEQ ID NO: 8,
ix. последовательности конструкции 100ATG, представленной в SEQ ID NO: 9,
x. последовательности конструкции 100ATG bGH polyA, представленной в SEQ ID NO: 10,
xi. последовательности конструкции 100ATG short bGH polyA, представленной в SEQ ID NO: 11,
xii. последовательности конструкции 103ATG, представленной в SEQ ID NO: 12,
xiii. последовательности конструкции 103ATG short bGH polyA, представленной в SEQ ID NO: 13,
xiv. последовательности конструкции 105ATG bGH polyA, представленной в SEQ ID NO: 14,
xv. последовательности конструкции DC172ATG FVIII, представленной в SEQ ID NO: 15,
xvi. последовательности конструкции DC172 ATG FVIII hAAT, представленной в SEQ ID NO: 16,
xvii. последовательности конструкции DC172 2xHCR ATG FVIII, представленной в SEQ ID NO: 17,
xviii. последовательности конструкции DC172 2xHCR ATG FVIII hAAT, представленной в SEQ ID NO: 18,
xix. последовательности конструкции 2x SerpinA hAAT ATG FVIII, представленной в SEQ ID NO: 19,
xx. последовательности конструкции 2x SerpinA hAAT ATG FVIII 2x μ-globulin enhancer, представленной в SEQ ID NO: 20,
xxi. последовательности конструкции 100ATG short polyA 2x μ-globulin enhancer, представленной в SEQ ID NO: 21,
xxii. последовательности конструкции Factor VIII-BMN001, представленной в SEQ ID NO: 22,
xxiii. последовательности конструкции Factor VIII-BMN002, представленной в SEQ ID NO: 23,
xxiv. последовательности конструкции 99, представленной в SEQ ID NO: 24,
xxv. последовательности конструкции 100, представленной в SEQ ID NO: 25,
xxvi. последовательности конструкции 100 в обратной ориентации, представленной в SEQ ID NO: 26,
xxvii. последовательности конструкции 100AT, представленной в SEQ ID NO: 27,
xxviii. последовательности конструкции 100AT 2x MG, представленной в SEQ ID NO: 28,
xxix. последовательности конструкции 100AT 2x MG polyA, представленной в SEQ ID NO: 29,
xxx. последовательности конструкции 100AT 2x MG (reverse) bGH polyA, представленной в SEQ ID NO: 30,
xxxi. последовательности конструкции 100 bGH polyA, представленной в SEQ ID NO: 31,
xxxii. последовательности конструкции 100-400, представленной в SEQ ID NO: 32,
xxxiii. последовательности конструкции 101, представленной в SEQ ID NO: 33,
xxxiv. последовательности конструкции 102, представленной в SEQ ID NO: 34,
xxxv. последовательности конструкции 103, представленной в SEQ ID NO: 35,
xxxvi. последовательности конструкции 103 в обратной ориентации, представленной в SEQ ID NO: 36,
xxxvii. последовательности конструкции 103AT, представленной в SEQ ID NO: 37,
xxxviii. последовательности конструкции 103AT 2x MG, представленной в SEQ ID NO: 38,
xxxix. последовательности конструкции 103AT 2x MG polyA, представленной в SEQ ID NO: 39,
xl. последовательности конструкции 103 bGH polyA, представленной в SEQ ID NO: 40,
xli. последовательности конструкции 104, представленной в SEQ ID NO: 41,
xlii. последовательности конструкции 105, представленной в SEQ ID NO: 42,
xliii. последовательности конструкции 106, представленной в SEQ ID NO: 43,
xliv. последовательности конструкции 106AT, представленной в SEQ ID NO: 44, и
xlv. последовательности конструкции 2x Serpin A hAAT, представленной в SEQ ID NO: 45.
3. Способ получения частицы рекомбинантного аденоассоциированного вируса (ААВ), включающий A) культивирование клетки, которая была трансфицирована ААВ-вектором по п. 1 или 2; и B) получение частицы рекомбинантного ААВ из супернатанта трансфицированной клетки.
4. Вирусная частица, содержащая вирусный вектор по п. 1 или 2.
5. Клетка, содержащая вирусный вектор по п. 1 или 2.
6. Способ лечения пациента, страдающего гемофилией A, включающий введение пациенту эффективного количества ААВ-вектора экспрессии FVIII по п. 1 или 2.
7. Применение ААВ-вектора экспрессии FVIII по п. 1 или 2 для получения лекарственного средства для лечения гемофилии A.
8. Композиция, содержащая ААВ-вектор экспрессии FVIII по п. 1 или 2, для лечения гемофилии A.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201361877042P | 2013-09-12 | 2013-09-12 | |
| US61/877,042 | 2013-09-12 |
Related Parent Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| RU2016113702A Division RU2710307C2 (ru) | 2013-09-12 | 2014-09-10 | Векторы экспрессии фактора viii на основе аденоассоциированного вируса |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| RU2019141647A true RU2019141647A (ru) | 2020-01-27 |
| RU2019141647A3 RU2019141647A3 (ru) | 2020-05-18 |
| RU2777372C2 RU2777372C2 (ru) | 2022-08-02 |
Family
ID=
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| RU2016113702A (ru) | Векторы экспрессии фактора viii на основе аденоассоциированного вируса | |
| JP2016534739A5 (ru) | ||
| JP2020522269A5 (ru) | ||
| NZ600104A (en) | Novel viral vector construct for neuron specific optimized continuous DOPA synthesis in vivo | |
| JP2020514286A5 (ru) | ||
| JP2018537984A5 (ru) | ||
| US20200390866A1 (en) | Factor viii sequences | |
| FI3596222T3 (fi) | Lihasspesifisen mikrodystrofiinin adenoassosioitu virusvektori -kuljetus lihasdystrofian hoitamiseksi | |
| JP2013500726A5 (ru) | ||
| HRP20201544T1 (hr) | Pripravci korisni u liječenju nedostatka ornitinske transkarbamilaze (otc) | |
| JP2017532966A5 (ru) | ||
| JP2013518899A5 (ru) | ||
| JP2018520997A5 (ru) | ||
| JPWO2020069461A5 (ru) | ||
| JP2011101646A5 (ru) | ||
| CA2627200A1 (en) | Novel activin receptor and its uses in treating metabolic disorders | |
| EP2292779A3 (en) | Adeno-associated virus (AAV) clades, sequences, vectors containing same, and uses thereof | |
| RU2019139555A (ru) | Генная терапия нейрональных цероидных липофусцинозов | |
| CN100998939A (zh) | 具有抗SO2性能的MnOx/Z rO2－TiO2低温选择性催化还原NOx催化剂及其制备工艺 | |
| CN105431451B (zh) | 突变型因子viii组合物和方法 | |
| WO2003061582A3 (en) | Generation of recombinant adeno-associated viral vectors by a complete adenovirus-mediated approach | |
| JP2008508899A5 (ru) | ||
| JP2005508158A5 (ru) | ||
| FI3850089T3 (fi) | Polynukleotidejä | |
| JPWO2021181118A5 (ru) |