RU2018111462A - Химерные антигенные рецепторы, нацеленные на антиген созревания b-клеток - Google Patents
Химерные антигенные рецепторы, нацеленные на антиген созревания b-клеток Download PDFInfo
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- 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
- C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
- C07K14/70503—Immunoglobulin superfamily
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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
- A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
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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
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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
- A61P35/00—Antineoplastic agents
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/02—Antineoplastic agents specific for leukemia
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
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- 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
- C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
- C07K14/70503—Immunoglobulin superfamily
- C07K14/7051—T-cell receptor (TcR)-CD3 complex
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- 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
- C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
- C07K14/70503—Immunoglobulin superfamily
- C07K14/70517—CD8
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- 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
- C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
- C07K14/70503—Immunoglobulin superfamily
- C07K14/70521—CD28, CD152
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- 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
- C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
- C07K14/70578—NGF-receptor/TNF-receptor superfamily, e.g. CD27, CD30, CD40, CD95
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
- C07K16/2878—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the NGF-receptor/TNF-receptor superfamily, e.g. CD27, CD30, CD40, CD95
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- 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
- C12N15/62—DNA sequences coding for fusion proteins
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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
- A61K2039/505—Medicinal preparations containing antigens or antibodies comprising antibodies
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/60—Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments
- C07K2317/62—Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments comprising only variable region components
- C07K2317/622—Single chain antibody (scFv)
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
- C07K2317/73—Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
- C07K2319/01—Fusion polypeptide containing a localisation/targetting motif
- C07K2319/03—Fusion polypeptide containing a localisation/targetting motif containing a transmembrane segment
Claims (30)
1. Химерный рецептор антигена (CAR), включающий:
(a) одноцепочечный вариабельный фрагмент (scFv), направленный против антигена созревания В-клеток (ВСМА), содержащий (i) определяющую комплементарность область (CDR) тяжелой цепи - CDR1, (ii) CDR2 тяжелой цепи, (iii) CDR3 тяжелой цепи, (iv) CDR1 легкой цепи, (v) CDR2 легкой цепи и (vi) CDR3 легкой цепи, имеющие аминокислотные последовательности, выбранные из группы, состоящей из: SEQ ID №4, SEQ ID №5, SEQ ID №6, SEQ ID №8, SEQ ID №9, SEQ ID №10, SEQ ID №11 и SEQ ID №12;
(b) трансмембранный домен CD28 или CD8α; и
(c) один или более внутриклеточных доменов сигналинга Т-клеток, выделенных из белка, выбранного из группы, состоящей из: CD28, CD3ζ, FcRγ, CD27, ОХ40 и белка 4-1ВВ.
2. CAR по п. 1, включающий трансмембранный домен CD28.
3. CAR по п. 1, включающий трансмембранный домен CD8α.
4. CAR по любому из пп. 1-3, включающий внутриклеточные домены сигналинга Т-клеток CD28 и CD3ζ.
5. CAR по любому из пп. 1-3, включающий внутриклеточные домены сигналинга Т-клеток ОХ40 и CD3ζ.
6. CAR по любому из пп. 1-3, включающий внутриклеточные домены сигналинга Т-клеток 4-1 ВВ и CD3ζ.
7. CAR по п. 1, включающий трансмембранный домен CD8α и внутриклеточные домены сигналинга Т-клеток 4-1ВВ и CD3ζ
8. Выделенная молекула нуклеиновой кислоты, кодирующая CAR по любому из пп. 1-7.
9. Экспрессионный вектор, содержащий выделенную молекулу нуклеиновой кислоты по п. 8.
10. Экспрессионный вектор по п. 9, где указанный вектор представляет собой ретровирусный вектор.
11. Экспрессионный вектор по п. 10, где указанный ретровирусный вектор представляет собой лентивирусный вектор.
12. Выделенная клетка, которая экспрессирует CAR по любому из пп. 1-7.
13. Выделенная клетка, содержащая выделенную молекулу нуклеиновой кислоты по п. 8.
14. Выделенная клетка, содержащая вектор по любому из пп. 9-11.
15. Выделенная клетка по любому из пп. 12-14, которая представляет собой Т-клетку.
16. Выделенная клетка по любому из пп. 12-14, которая является натуральным киллером (NK-клеткой).
17. Выделенная клетка по п. 12, где указанная клетка представляет собой CD8+ Т-клетку.
18. Композиция, содержащая выделенную клетку по любому из пп. 12-17 и фармацевтически приемлемый носитель или разбавитель.
19. Способ разрушения клеток множественной миеломы, который включает контактирование клеток множественной миеломы, экспрессирующих ВСМА, с одной или более чем одной из выделенных Т-клеток по п. 15, где CAR экспрессируется и связывается с ВСМА на клетках множественной миеломы, и клетки множественной миеломы разрушаются.
20. Способ разрушения клеток множественной миеломы, который включает контактирование клеток множественной миеломы, экспрессирующих ВСМА, с одной или более чем одной из выделенных NK-клеток по п. 16, где CAR экспрессируется и связывается с ВСМА на клетках множественной миеломы, и клетки множественной миеломы разрушаются
21. Способ по п. 19 или 20, где клетки множественной миеломы являются человеческими.
22. Применение CAR по любому из пп. 1-7 при производстве лекарственного средства для разрушения раковых клеток.
23. Применение выделенной нуклеиновой кислоты по п. 8 при производстве лекарственного средства для разрушения раковых клеток.
24. Применение экспрессионного вектора по любому из пп. 9-11 при производстве лекарственного средства для разрушения раковых клеток.
25. Применение выделенной клетки по любому из пп. 12-17 при производстве лекарственного средства для разрушения раковых клеток.
26. Применение композиции по п. 18 при производстве лекарственного средства для разрушения раковых клеток.
27. Применение по любому из пп. 21-25, где раковые клетки представляют собой клетки множественной миеломы или клетки лимфомы Ходжкина.
Applications Claiming Priority (2)
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US201261622600P | 2012-04-11 | 2012-04-11 | |
US61/622,600 | 2012-04-11 |
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RU2014144143A Division RU2650805C2 (ru) | 2012-04-11 | 2013-03-15 | Химерные антигенные рецепторы, нацеленные на антиген созревания в-клеток |
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RU2022102579A Division RU2022102579A (ru) | 2012-04-11 | 2022-02-03 | Химерные антигенные рецепторы, нацеленные на антиген созревания b-клеток |
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RU2018111462A true RU2018111462A (ru) | 2019-02-27 |
RU2018111462A3 RU2018111462A3 (ru) | 2021-07-27 |
RU2766608C2 RU2766608C2 (ru) | 2022-03-15 |
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RU2018111462A RU2766608C2 (ru) | 2012-04-11 | 2013-03-15 | Химерные антигенные рецепторы, нацеленные на антиген созревания b-клеток |
RU2014144143A RU2650805C2 (ru) | 2012-04-11 | 2013-03-15 | Химерные антигенные рецепторы, нацеленные на антиген созревания в-клеток |
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US (19) | US9765342B2 (ru) |
EP (2) | EP2836239A1 (ru) |
JP (5) | JP6359520B2 (ru) |
KR (4) | KR20220029757A (ru) |
CN (3) | CN110331154A (ru) |
AU (4) | AU2013246443B2 (ru) |
BR (1) | BR112014024893B8 (ru) |
CA (1) | CA2869562C (ru) |
EA (2) | EA201990959A1 (ru) |
HK (1) | HK1203393A1 (ru) |
IL (4) | IL234870B (ru) |
IS (1) | IS9056A (ru) |
MX (3) | MX2018008352A (ru) |
NZ (1) | NZ700362A (ru) |
RU (2) | RU2766608C2 (ru) |
SG (1) | SG11201406414WA (ru) |
WO (1) | WO2013154760A1 (ru) |
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