RU2019104180A - ХИМЕРНЫЕ БЕЛКИ ДЛЯ НАЦЕЛИВАНИЯ дцРНК - Google Patents
ХИМЕРНЫЕ БЕЛКИ ДЛЯ НАЦЕЛИВАНИЯ дцРНК Download PDFInfo
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- RU2019104180A RU2019104180A RU2019104180A RU2019104180A RU2019104180A RU 2019104180 A RU2019104180 A RU 2019104180A RU 2019104180 A RU2019104180 A RU 2019104180A RU 2019104180 A RU2019104180 A RU 2019104180A RU 2019104180 A RU2019104180 A RU 2019104180A
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- recombinant protein
- chimeric recombinant
- dsrna
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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
- C07K14/46—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
- C07K14/47—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
- C07K14/4701—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals not used
- C07K14/4748—Tumour specific antigens; Tumour rejection antigen precursors [TRAP], e.g. MAGE
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—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
- A61K47/50—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
- 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
- A61K47/68—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 an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
- A61K47/6835—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 an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment the modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site
- A61K47/6851—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 an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment the modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site the antibody targeting a determinant of a tumour cell
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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
-
- 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
- C07K16/30—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants from tumour cells
- C07K16/3069—Reproductive system, e.g. ovaria, uterus, testes, prostate
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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
- C12N15/117—Nucleic acids having immunomodulatory properties, e.g. containing CpG-motifs
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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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—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
- A61K47/50—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
- 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
- A61K47/68—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 an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—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
- A61K47/50—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
- 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
- A61K47/68—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 an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
- A61K47/6835—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 an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment the modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site
- A61K47/6851—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 an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment the modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site the antibody targeting a determinant of a tumour cell
- A61K47/6869—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 an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment the modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site the antibody targeting a determinant of a tumour cell the tumour determinant being from a cell of the reproductive system: ovaria, uterus, testes, prostate
-
- 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
- C07K2317/77—Internalization into the cell
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
- C07K2319/60—Fusion polypeptide containing spectroscopic/fluorescent detection, e.g. green fluorescent protein [GFP]
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
- C07K2319/85—Fusion polypeptide containing an RNA binding domain
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- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
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- C12N2310/00—Structure or type of the nucleic acid
- C12N2310/10—Type of nucleic acid
- C12N2310/17—Immunomodulatory nucleic acids
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- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
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- C12N2320/00—Applications; Uses
- C12N2320/30—Special therapeutic applications
- C12N2320/32—Special delivery means, e.g. tissue-specific
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- Biomedical Technology (AREA)
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- Immunology (AREA)
- Bioinformatics & Cheminformatics (AREA)
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- Biophysics (AREA)
- General Engineering & Computer Science (AREA)
- Wood Science & Technology (AREA)
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- Proteomics, Peptides & Aminoacids (AREA)
- Physics & Mathematics (AREA)
- Microbiology (AREA)
- Plant Pathology (AREA)
- Cell Biology (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
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- Reproductive Health (AREA)
- Pregnancy & Childbirth (AREA)
- Gynecology & Obstetrics (AREA)
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- Chemical Kinetics & Catalysis (AREA)
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- Epidemiology (AREA)
- Peptides Or Proteins (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Claims (23)
1. Химерный рекомбинантный белок, содержащий:
- домен, связывающий двухцепочечную РНК (дцРНК); и
- фрагмент, связывающий мишень, который связывается с простатическим поверхностным мембранным антигеном (PSMA).
2. Химерный рекомбинантный белок по п. 1, дополнительно содержащий спейсерный пептид между доменом, связывающим дцРНК, и фрагментом, связывающим мишень.
3. Химерный рекомбинантный белок по п. 1 или 2, характеризующийся тем, что указанный домен, связывающий дцРНК, содержит по меньшей мере один мотив, связывающий двухцепочечную РНК (dsRBM).
4. Химерный рекомбинантный белок по п. 3, характеризующийся тем, что указанный по меньшей мере один dsRBM выбран из dsRBM-мотива дцРНК-зависимой протеинкиназы (PKR), TRBP, PACT, Staufen, NFAR1, NFAR2, SPNR, RHA и NREBP.
5. Химерный рекомбинантный белок по п. 3, характеризующийся тем, что указанный по меньшей мере один dsRBM содержит полипептидную последовательность, которая по меньшей мере на 70% идентична аминокислотам 1-197 PKR человека, представленным в SEQ ID NO: 18.
6. Химерный рекомбинантный белок по любому из пп. 1-5, характеризующийся тем, что указанный фрагмент, связывающий мишень, представляет собой полипептид, антитело, фрагмент антитела или миметик антитела.
7. Химерный рекомбинантный белок по п. 2, характеризующийся тем, что указанный спейсерный пептид выбран из группы, состоящей из олигопептида, содержащего последовательность распознавания протеазы; гомоолигопептида из положительно заряженной аминокислоты; и их комбинации.
8. Химерный рекомбинантный белок по п. 7, характеризующийся тем, что указанный спейсерный пептид представляет собой гомоолигопептид аргинина.
9. Химерный рекомбинантный белок по любому из пп. 2-8, характеризующийся тем, что указанный домен, связывающий двухцепочечную РНК (дцРНК), представляет собой по меньшей мере один домен, связывающий дцРНК, из PKR человека, представленный в SEQ ID NO: 18, или его функциональный вариант,
причем указанный спейсерный пептид представляет собой ARG9, представленный в SEQ ID NO: 5, или его функциональный вариант, и
при этом указанный фрагмент, связывающий мишень, представляет собой одноцепочечное антитело к PSMA, представленное в SEQ ID NO: 20, или его функциональный вариант.
10. Химерный рекомбинантный белок по п. 9, содержащий полипептид, который по меньшей мере на 70% идентичен последовательности, представленной в SEQ ID NO: 3.
11. Комплекс, содержащий химерный рекомбинантный белок по любому из пп. 1-10 и дцРНК.
12. Комплекс по п. 11, характеризующийся тем, что указанная дцРНК содержит цепь полиинозиновой кислоты и цепь полицитидиловой кислоты (полиIC).
13. Нуклеиновая кислота, содержащая последовательность нуклеиновой кислоты, кодирующую рекомбинантный белок по любому из пп. 1-10.
14. Нуклеиновая кислота по п. 13, характеризующаяся тем, что указанная последовательность нуклеиновой кислоты оптимизирована для экспрессии в бактериальной или растительной клетке-хозяине.
15. Химерный рекомбинантный белок по любому из пп. 1-10 или комплекс по п. 11 или 12 для применения в лечении рака предстательной железы или ингибировании роста новой сосудистой сети опухоли.
16. Способ лечения рака предстательной железы или ингибирования роста новой сосудистой сети опухоли, включающий:
введение субъекту, нуждающемуся в этом, терапевтически эффективного количества комплекса по п. 11 или 12, что обеспечивает лечение рака или ингибирование роста новой сосудистой сети опухоли.
17. Способ по п. 16, характеризующийся тем, что указанный комплекс вводят системно или локально.
18. Способ по п. 16 или 17, дополнительно включающий введение субъекту терапевтически эффективного количества мононуклеарных клеток периферической крови (МКПК).
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US201662383466P | 2016-09-04 | 2016-09-04 | |
US62/383,466 | 2016-09-04 | ||
PCT/IL2016/051341 WO2018042411A1 (en) | 2016-09-04 | 2016-12-15 | Chimeric proteins for targeting dsrna |
Publications (3)
Publication Number | Publication Date |
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RU2019104180A true RU2019104180A (ru) | 2020-10-05 |
RU2019104180A3 RU2019104180A3 (ru) | 2021-06-24 |
RU2806285C2 RU2806285C2 (ru) | 2023-10-30 |
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Publication number | Publication date |
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US20220213158A1 (en) | 2022-07-07 |
RU2019104180A3 (ru) | 2021-06-24 |
BR112019004017A2 (pt) | 2019-06-25 |
CA3034989A1 (en) | 2018-03-08 |
EP3507308A1 (en) | 2019-07-10 |
US20190194282A1 (en) | 2019-06-27 |
US20180346596A1 (en) | 2018-12-06 |
CN109790225A (zh) | 2019-05-21 |
AU2016421686A1 (en) | 2019-04-04 |
JP2019534037A (ja) | 2019-11-28 |
JP2022104932A (ja) | 2022-07-12 |
WO2018042411A1 (en) | 2018-03-08 |
JP7096249B2 (ja) | 2022-07-05 |
CN109790225B (zh) | 2022-09-09 |
US11230580B2 (en) | 2022-01-25 |
US11912747B2 (en) | 2024-02-27 |
EP3507308A4 (en) | 2020-03-18 |
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