RU2019124676A - СЛИТЫЙ БЕЛОК SIPRα-41BBL И СПОСОБЫ ЕГО ПРИМЕНЕНИЯ - Google Patents
СЛИТЫЙ БЕЛОК SIPRα-41BBL И СПОСОБЫ ЕГО ПРИМЕНЕНИЯ Download PDFInfo
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- RU2019124676A RU2019124676A RU2019124676A RU2019124676A RU2019124676A RU 2019124676 A RU2019124676 A RU 2019124676A RU 2019124676 A RU2019124676 A RU 2019124676A RU 2019124676 A RU2019124676 A RU 2019124676A RU 2019124676 A RU2019124676 A RU 2019124676A
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- fusion protein
- sirpα
- 41bbl
- polynucleotide
- host cell
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- 108020001507 fusion proteins Proteins 0.000 title claims 27
- 238000000034 method Methods 0.000 title claims 8
- 102000037865 fusion proteins Human genes 0.000 claims 26
- 210000004027 cell Anatomy 0.000 claims 21
- 102000040430 polynucleotide Human genes 0.000 claims 16
- 108091033319 polynucleotide Proteins 0.000 claims 16
- 239000002157 polynucleotide Substances 0.000 claims 16
- 102000039446 nucleic acids Human genes 0.000 claims 13
- 108020004707 nucleic acids Proteins 0.000 claims 13
- 150000007523 nucleic acids Chemical class 0.000 claims 13
- 201000010099 disease Diseases 0.000 claims 7
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims 7
- 101000868279 Homo sapiens Leukocyte surface antigen CD47 Proteins 0.000 claims 6
- 102100032913 Leukocyte surface antigen CD47 Human genes 0.000 claims 6
- 210000002865 immune cell Anatomy 0.000 claims 5
- 230000004913 activation Effects 0.000 claims 4
- 239000002246 antineoplastic agent Substances 0.000 claims 4
- 230000003213 activating effect Effects 0.000 claims 3
- 206010062016 Immunosuppression Diseases 0.000 claims 2
- 206010028980 Neoplasm Diseases 0.000 claims 2
- 230000002159 abnormal effect Effects 0.000 claims 2
- 125000003275 alpha amino acid group Chemical group 0.000 claims 2
- 201000011510 cancer Diseases 0.000 claims 2
- 239000003814 drug Substances 0.000 claims 2
- 230000003463 hyperproliferative effect Effects 0.000 claims 2
- 230000001506 immunosuppresive effect Effects 0.000 claims 2
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Natural products NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 claims 1
- 239000004471 Glycine Substances 0.000 claims 1
- 101000863873 Homo sapiens Tyrosine-protein phosphatase non-receptor type substrate 1 Proteins 0.000 claims 1
- 206010057249 Phagocytosis Diseases 0.000 claims 1
- 102100029948 Tyrosine-protein phosphatase non-receptor type substrate 1 Human genes 0.000 claims 1
- 230000009286 beneficial effect Effects 0.000 claims 1
- 229940079593 drug Drugs 0.000 claims 1
- 238000001962 electrophoresis Methods 0.000 claims 1
- 230000002708 enhancing effect Effects 0.000 claims 1
- 125000003630 glycyl group Chemical group [H]N([H])C([H])([H])C(*)=O 0.000 claims 1
- 238000000338 in vitro Methods 0.000 claims 1
- 208000015181 infectious disease Diseases 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 claims 1
- 239000005022 packaging material Substances 0.000 claims 1
- 238000004806 packaging method and process Methods 0.000 claims 1
- 230000001575 pathological effect Effects 0.000 claims 1
- 210000001539 phagocyte Anatomy 0.000 claims 1
- 230000008782 phagocytosis Effects 0.000 claims 1
- 230000001105 regulatory effect Effects 0.000 claims 1
- 230000019491 signal transduction Effects 0.000 claims 1
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 claims 1
- 229940124597 therapeutic agent Drugs 0.000 claims 1
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- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
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- A61K39/4643—Vertebrate antigens
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- A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
- A61K47/62—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being a protein, peptide or polyamino acid
- A61K47/65—Peptidic linkers, binders or spacers, e.g. peptidic enzyme-labile linkers
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
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- C07K14/70503—Immunoglobulin superfamily
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- 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
- C07K14/70575—NGF/TNF-superfamily, e.g. CD70, CD95L, CD153, CD154
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- 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
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- 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
- C07K14/70596—Molecules with a "CD"-designation not provided for elsewhere
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- 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
- C07K16/2863—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against receptors for growth factors, growth regulators
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- 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
- C07K16/2887—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against CD20
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- 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
- C07K16/2893—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against CD52
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- C07K2319/00—Fusion polypeptide
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- C07K2319/21—Fusion polypeptide containing a tag with affinity for a non-protein ligand containing a His-tag
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Claims (31)
1. Слитый белок SIRPα-41BBL, характеризующийся линкером из одной аминокислоты между указанным SIRPα и указанным 41BBL и/или находящийся в форме по меньшей мере гомотримера.
2. Слитый белок SIRPα-41BBL по п. 1, причем указанный по меньшей мере гомотример характеризуется молекулярной массой по меньшей мере 140 кДа, как определено с помощью ДСН-ПААГ-электрофореза.
3. Слитый белок SIRPα-41BBL по п. 1, в котором линкер представляет собой глицин.
4. Слитый белок SIRPα-41BBL по любому из пп. 1-3, являющийся растворимым.
5. Слитый белок SIRPα-41BBL по любому из пп. 1-3, причем указанный слитый белок способен по меньшей мере к одному из следующего:
(i) связывание CD47 и 41ВВ;
(ii) активация указанного сигнального пути 41ВВ в клетке, экспрессирующей указанный 41ВВ;
(iii) костимуляция иммунных клеток, экспрессирующих указанный 41ВВ; и/или
(iv) усиление фагоцитоза патологических клеток, экспрессирующих указанный
CD47, фагоцитами, по сравнению с таковым в отсутствие указанного слитого белка
SIRPα-41BBL.
6. Слитый белок SIRPα-41BBL по любому из пп. 1-3, причем указанная аминокислотная последовательность слитого белка SIRPα-41BBL содержит SEQ ID NO: 1.
7. Слитый белок SIRPα-41BBL по любому из пп. 1-3, причем указанная аминокислотная последовательность слитого белка SIRPα-41BBL состоит из SEQ ID NO: 1.
8. Полинуклеотид, кодирующий слитый белок SIRPα-41BBL по п. 1.
9. Конструкция нуклеиновой кислоты, содержащая полинуклеотид по п. 8 и регуляторный элемент для направления экспрессии указанного полинуклеотида в клетке-хозяине.
10. Клетка-хозяин, содержащая слитый белок SIRPα-41BBL по п. 1.
11. Клетка-хозяин, содержащая полинуклеотид по п. 8.
12. Способ получения слитого белка SIRPα-41BBL, предусматривающий экспрессию в клетке-хозяине полинуклеотида или конструкции нуклеиновой кислоты по любому из пп. 8-9.
13. Способ по п. 12, предусматривающий выделение слитого белка.
14. Слитый белок SIRPα-41BBL по любому из пп. 1-3, полинуклеотид или конструкция нуклеиновой кислоты по любому из пп. 8-9 или клетка-хозяин по любому из пп. 10-11 для применения при лечении заболевания, для которого может быть выгодна активация иммунных клеток.
15. Изделие, идентифицированное для лечения заболевания, для которого может быть выгодна активация иммунных клеток, содержащее упаковочный материал, упаковывающий терапевтическое средство для лечения указанного заболевания и слитый белок SIRPα-41BBL, кодирующий его полинуклеотид, кодирующую его конструкцию нуклеиновой кислоты или экспрессирующую его клетку-хозяина.
16. Слитый белок SIRPα-41BBL, полинуклеотид, конструкция нуклеиновой кислоты или клетка-хозяин для применения по п. 14, причем указанное заболевание включает в себя гиперпролиферативное заболевание, заболевание, связанное с иммуносупрессией или медикаментозно-индуцированной иммуносупрессией или инфекцией.
17. Слитый белок SIRPα-41BBL, полинуклеотид, конструкция нуклеиновой кислоты или клетка-хозяин для применения по п. 16, причем указанное гиперпролиферативное заболевание включает в себя рак.
18. Противораковое средство и слитый белок SIRPα-41BBL, кодирующий его полинуклеотид, кодирующая его конструкция нуклеиновой кислоты или экспрессирующая его клетка-хозяин для применения в лечении рака.
19. Слитый белок SIRPα-41BBL, полинуклеотид, конструкция нуклеиновой кислоты или клетка-хозяин для применения по п. 14, причем патологические клетки указанного субъекта экспрессируют CD47.
20. Способ активации иммунных клеток, предусматривающий активацию иммунных клеток in vitro в присутствии слитого белка SIRPα-41BBL, кодирующего его полинуклеотида, кодирующей его конструкции нуклеиновой кислоты или экспрессирующей его клетки-хозяина.
21. Способ по п. 20, при котором указанная активация происходит в присутствии клеток, экспрессирующих CD47 или экзогенный CD47.
22. Способ по п. 21, при котором указанные клетки, экспрессирующие указанный CD47, включают в себя патологические клетки.
23. Способ по п. 20, при котором указанная активация происходит в присутствии противоракового средства.
24. Изделие по п. 15, противораковое средство и слитый белок SIRPα-41BBL, полинуклеотид, конструкция нуклеиновой кислоты или клетка-хозяин для применения по п. 18 или способ по п. 23, причем указанное противораковое средство включает в себя антитело.
25. Слитый белок SIRPα-41BBL, полинуклеотид, конструкция нуклеиновой кислоты или клетка-хозяин для применения по п. 14, причем указанный слитый белок SIRPα-41BBL включает в себя слитый белок SIRPα-41BBL по любому из пп. 1-3, полинуклеотид или конструкция нуклеиновой кислоты включает в себя полинуклеотид или конструкцию нуклеиновой кислоты по любому из пп. 8-9, и клетка-хозяин включает в себя клетку-хозяина по любому из пп. 10 и 11.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201762442469P | 2017-01-05 | 2017-01-05 | |
| US62/442,469 | 2017-01-05 | ||
| PCT/IL2018/050017 WO2018127919A1 (en) | 2017-01-05 | 2018-01-04 | A SIRP1 alpha-41BBL FUSION PROTEIN AND METHODS OF USE THEREOF |
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| Publication Number | Publication Date |
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| RU2019124676A true RU2019124676A (ru) | 2021-02-06 |
| RU2019124676A3 RU2019124676A3 (ru) | 2021-04-09 |
| RU2769769C2 RU2769769C2 (ru) | 2022-04-05 |
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| RU2019124676A RU2769769C2 (ru) | 2017-01-05 | 2018-01-04 | СЛИТЫЙ БЕЛОК SIRPα-4-1BBL И СПОСОБЫ ЕГО ПРИМЕНЕНИЯ |
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| US (3) | US11130796B2 (ru) |
| EP (2) | EP3939993A1 (ru) |
| JP (1) | JP7194324B2 (ru) |
| KR (1) | KR102581439B1 (ru) |
| CN (1) | CN110573522B (ru) |
| AU (1) | AU2018205890B2 (ru) |
| CA (1) | CA3047708A1 (ru) |
| DK (1) | DK3565828T3 (ru) |
| ES (1) | ES2916217T3 (ru) |
| HR (1) | HRP20220230T1 (ru) |
| HU (1) | HUE057326T2 (ru) |
| IL (1) | IL267862B2 (ru) |
| PL (1) | PL3565828T3 (ru) |
| PT (1) | PT3565828T (ru) |
| RU (1) | RU2769769C2 (ru) |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| KR102597943B1 (ko) | 2017-01-05 | 2023-11-06 | 카 메디컬 리미티드 | Pd1-41bbl 융합 단백질 및 이의 이용 방법 |
| WO2018127916A1 (en) | 2017-01-05 | 2018-07-12 | Kahr Medical Ltd. | A pd1-cd70 fusion protein and methods of use thereof |
| IL267862B2 (en) | 2017-01-05 | 2024-05-01 | Kahr Medical Ltd | SIRPalpha-41BBL conjugate protein and methods of using it |
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