RU2019126606A - Модификация b-клеток - Google Patents
Модификация b-клеток Download PDFInfo
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- RU2019126606A RU2019126606A RU2019126606A RU2019126606A RU2019126606A RU 2019126606 A RU2019126606 A RU 2019126606A RU 2019126606 A RU2019126606 A RU 2019126606A RU 2019126606 A RU2019126606 A RU 2019126606A RU 2019126606 A RU2019126606 A RU 2019126606A
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- 238000012986 modification Methods 0.000 title claims 3
- 230000004048 modification Effects 0.000 title claims 3
- 210000003719 b-lymphocyte Anatomy 0.000 claims 23
- 108090000623 proteins and genes Proteins 0.000 claims 13
- 102000004169 proteins and genes Human genes 0.000 claims 12
- 108700019146 Transgenes Proteins 0.000 claims 7
- 230000001225 therapeutic effect Effects 0.000 claims 6
- 239000003114 blood coagulation factor Substances 0.000 claims 4
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims 4
- 238000002641 enzyme replacement therapy Methods 0.000 claims 4
- 201000010099 disease Diseases 0.000 claims 3
- 208000023275 Autoimmune disease Diseases 0.000 claims 2
- 108010039209 Blood Coagulation Factors Proteins 0.000 claims 2
- 102000015081 Blood Coagulation Factors Human genes 0.000 claims 2
- 102100022641 Coagulation factor IX Human genes 0.000 claims 2
- 108010076282 Factor IX Proteins 0.000 claims 2
- 208000031220 Hemophilia Diseases 0.000 claims 2
- 208000009292 Hemophilia A Diseases 0.000 claims 2
- 238000009825 accumulation Methods 0.000 claims 2
- 230000002950 deficient Effects 0.000 claims 2
- 229960004222 factor ix Drugs 0.000 claims 2
- 230000002132 lysosomal effect Effects 0.000 claims 2
- 238000004519 manufacturing process Methods 0.000 claims 2
- 108010088751 Albumins Proteins 0.000 claims 1
- 102000009027 Albumins Human genes 0.000 claims 1
- 108091008875 B cell receptors Proteins 0.000 claims 1
- 102100035875 C-C chemokine receptor type 5 Human genes 0.000 claims 1
- 101710149870 C-C chemokine receptor type 5 Proteins 0.000 claims 1
- 101000634835 Homo sapiens M1-specific T cell receptor alpha chain Proteins 0.000 claims 1
- 101001000998 Homo sapiens Protein phosphatase 1 regulatory subunit 12C Proteins 0.000 claims 1
- 101000634836 Homo sapiens T cell receptor alpha chain MC.7.G5 Proteins 0.000 claims 1
- 102100029450 M1-specific T cell receptor alpha chain Human genes 0.000 claims 1
- 206010028980 Neoplasm Diseases 0.000 claims 1
- 102100035620 Protein phosphatase 1 regulatory subunit 12C Human genes 0.000 claims 1
- 230000001455 anti-clotting effect Effects 0.000 claims 1
- 230000006023 anti-tumor response Effects 0.000 claims 1
- 230000005875 antibody response Effects 0.000 claims 1
- 230000033228 biological regulation Effects 0.000 claims 1
- 230000008499 blood brain barrier function Effects 0.000 claims 1
- 229940019700 blood coagulation factors Drugs 0.000 claims 1
- 210000001218 blood-brain barrier Anatomy 0.000 claims 1
- 201000011510 cancer Diseases 0.000 claims 1
- 210000004027 cell Anatomy 0.000 claims 1
- 230000008614 cellular interaction Effects 0.000 claims 1
- 238000012217 deletion Methods 0.000 claims 1
- 230000037430 deletion Effects 0.000 claims 1
- 208000035475 disorder Diseases 0.000 claims 1
- 210000001280 germinal center Anatomy 0.000 claims 1
- 210000003958 hematopoietic stem cell Anatomy 0.000 claims 1
- 208000015181 infectious disease Diseases 0.000 claims 1
- 230000002401 inhibitory effect Effects 0.000 claims 1
- 238000003780 insertion Methods 0.000 claims 1
- 230000037431 insertion Effects 0.000 claims 1
- 238000000034 method Methods 0.000 claims 1
- 244000052769 pathogen Species 0.000 claims 1
- 230000001717 pathogenic effect Effects 0.000 claims 1
- 108090000765 processed proteins & peptides Proteins 0.000 claims 1
- 210000002707 regulatory b cell Anatomy 0.000 claims 1
- 210000000130 stem cell Anatomy 0.000 claims 1
- 230000001629 suppression Effects 0.000 claims 1
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- C—CHEMISTRY; METALLURGY
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- C12N5/00—Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
- C12N5/06—Animal cells or tissues; Human cells or tissues
- C12N5/0602—Vertebrate cells
- C12N5/0634—Cells from the blood or the immune system
- C12N5/0635—B lymphocytes
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- C—CHEMISTRY; METALLURGY
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- C12N5/00—Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
- C12N5/10—Cells modified by introduction of foreign genetic material
- C12N5/12—Fused cells, e.g. hybridomas
- C12N5/16—Animal cells
- C12N5/163—Animal cells one of the fusion partners being a B or a T lymphocyte
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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- A61K35/12—Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells
- A61K35/14—Blood; Artificial blood
- A61K35/17—Lymphocytes; B-cells; T-cells; Natural killer cells; Interferon-activated or cytokine-activated lymphocytes
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- A—HUMAN NECESSITIES
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- A61K35/12—Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells
- A61K35/28—Bone marrow; Haematopoietic stem cells; Mesenchymal stem cells of any origin, e.g. adipose-derived stem cells
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- 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
- A61K38/46—Hydrolases (3)
- A61K38/48—Hydrolases (3) acting on peptide bonds (3.4)
- A61K38/482—Serine endopeptidases (3.4.21)
- A61K38/4846—Factor VII (3.4.21.21); Factor IX (3.4.21.22); Factor Xa (3.4.21.6); Factor XI (3.4.21.27); Factor XII (3.4.21.38)
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/46—Cellular immunotherapy
- A61K39/461—Cellular immunotherapy characterised by the cell type used
- A61K39/4612—B-cells
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/46—Cellular immunotherapy
- A61K39/462—Cellular immunotherapy characterized by the effect or the function of the cells
- A61K39/4621—Cellular immunotherapy characterized by the effect or the function of the cells immunosuppressive or immunotolerising
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/46—Cellular immunotherapy
- A61K39/462—Cellular immunotherapy characterized by the effect or the function of the cells
- A61K39/4622—Antigen presenting cells
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/46—Cellular immunotherapy
- A61K39/464—Cellular immunotherapy characterised by the antigen targeted or presented
- A61K39/4643—Vertebrate antigens
- A61K39/46433—Antigens related to auto-immune diseases; Preparations to induce self-tolerance
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- 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
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- 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
- A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
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- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
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- 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
- C12N15/87—Introduction of foreign genetic material using processes not otherwise provided for, e.g. co-transformation
- C12N15/90—Stable introduction of foreign DNA into chromosome
- C12N15/902—Stable introduction of foreign DNA into chromosome using homologous recombination
- C12N15/907—Stable introduction of foreign DNA into chromosome using homologous recombination in mammalian cells
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- 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
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- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Cell Biology (AREA)
- General Health & Medical Sciences (AREA)
- Immunology (AREA)
- Genetics & Genomics (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Biomedical Technology (AREA)
- Biotechnology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Epidemiology (AREA)
- Zoology (AREA)
- Microbiology (AREA)
- Organic Chemistry (AREA)
- Wood Science & Technology (AREA)
- Mycology (AREA)
- General Engineering & Computer Science (AREA)
- Hematology (AREA)
- Molecular Biology (AREA)
- Developmental Biology & Embryology (AREA)
- Biochemistry (AREA)
- Virology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Gastroenterology & Hepatology (AREA)
- Physics & Mathematics (AREA)
- Plant Pathology (AREA)
- Biophysics (AREA)
- Diabetes (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Claims (21)
1. Генетически модифицированная B-клетка, содержащая одну или более модификаций, содержащих:
(a) один или более трансгенов, и/или
(b) вставки и/или делеции, модифицирующие (i) гены B-клеточного рецептора, и/или (ii) клеточные взаимодействия в зародышевых центрах, и/или
(c) модификации, ингибирующие супрессию какой-либо функции B-клетки, ассоциированную с инфекцией патогеном или регуляцией злокачественной опухоли.
2. Генетически модифицированная B-клетка по п.1, где один или более трансгенов интегрированы в эндогенный локус B-клетки.
3. Генетически модифицированная B-клетка по п.1 или 2, где трансген кодирует белок, отсутствующий или недостаточный у субъекта с гемофилией, с заболеванием с накоплением лизосом, терапевтическое антитело и/или пептид, облегчающий пересечение гематоэнцефалического барьера при слиянии с терапевтическим белком.
4. Генетически модифицированная B-клетка по п.3, где терапевтическое антитело является специфическим для B-клетки, которая образует ингибирующие антитела против белка, предоставленного посредством заместительной ферментной терапии (ERT), или принимает участие в аутоиммунном заболевании.
5. Генетически модифицированная B-клетка по п.3, где терапевтическое антитело является специфическим для регуляторной B-клетки (B-рег), способной ослаблять противоопухолевый ответ.
6. Генетически модифицированная B-клетка по п.4, где белок, предоставленный посредством ERT, представляет собой фактор свертывания крови.
7. Генетически модифицированная B-клетка по п.6, где фактор свертывания крови представляет собой фактор IX (F9).
8. Генетически модифицированная B-клетка по любому из пп. 1-7, где трансген дополнительно содержит промотор, управляющий экспрессией трансгена.
9. Генетически модифицированная B-клетка по п.8, где промотор представляет собой специфический для линии B-клеток промотор.
10. Генетически модифицированная B-клетка по любому из пп. 1-9, где трансген экспрессируется в клетке.
11. Генетически модифицированная B-клетка по п.10, где трансген интегрирован в локус области безопасности, выбранный из группы, состоящей из AAVS1, TCRA, CCR5 или альбумина.
12. Генетически модифицированная B-клетка по любому из пп. 1-11, происходящая из генетически модифицированной гематопоэтической стволовой клетки.
13. Способ продукции белка у нуждающегося в этом субъекта, включающий введение субъекту популяции B-клеток по любому из пп.1-12.
14. Способ по п.13, где белок модулирует ответ антител у субъекта.
15. Применение генетически модифицированных B-клеток по любому из пп. 1-12 в способе продукции белка у субъекта, включающем: введение субъекту B-клеток или их клеток-предшественников в таких условиях, что B-клетка продуцирует белок у субъекта.
16. Применение по п.15, где белок представляет собой белок, отсутствующий или недостаточный при заболевании или нарушении, таком как гемофилия или заболевание с накоплением лизосом, или аутоиммунное заболевание, или антитело, специфическое для B-клетки, продуцирующей антитела против терапевтического белка, поставляемого посредством ERT.
17. Применение по п.16, где терапевтический белок, поставляемый посредством ERT, представляет собой фактор свертывания крови, такой как фактор IX (F9), и антитело является специфическим для B-клеток, продуцирующих антитела против фактора свертывания крови (против F9).
18. Набор, содержащий одну или более B-клеток по любому из пп. 1-12.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201762450917P | 2017-01-26 | 2017-01-26 | |
| US62/450,917 | 2017-01-26 | ||
| PCT/US2018/015180 WO2018140573A1 (en) | 2017-01-26 | 2018-01-25 | B-cell engineering |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| RU2019126606A true RU2019126606A (ru) | 2021-02-26 |
| RU2019126606A3 RU2019126606A3 (ru) | 2021-06-11 |
| RU2783116C2 RU2783116C2 (ru) | 2022-11-09 |
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Also Published As
| Publication number | Publication date |
|---|---|
| JP2022191524A (ja) | 2022-12-27 |
| WO2018140573A1 (en) | 2018-08-02 |
| AU2018212652A1 (en) | 2019-08-01 |
| JP2020505044A (ja) | 2020-02-20 |
| KR20190111063A (ko) | 2019-10-01 |
| AU2018212652B2 (en) | 2024-03-28 |
| CA3051113A1 (en) | 2018-08-02 |
| US20190352614A1 (en) | 2019-11-21 |
| RU2019126606A3 (ru) | 2021-06-11 |
| MX2019008844A (es) | 2019-09-10 |
| IL268110B1 (en) | 2023-09-01 |
| EP3573464A4 (en) | 2020-12-30 |
| IL268110B2 (en) | 2024-01-01 |
| BR112019015355A2 (pt) | 2020-05-19 |
| CN110536963A (zh) | 2019-12-03 |
| EP3573464A1 (en) | 2019-12-04 |
| IL268110A (en) | 2019-09-26 |
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