JP7781085B2 - 抗原特異的ｔ細胞受容体及びキメラ抗原受容体、並びにがん免疫療法のための免疫シグナル伝達モジュレーションにおける使用方法 - Google Patents

抗原特異的ｔ細胞受容体及びキメラ抗原受容体、並びにがん免疫療法のための免疫シグナル伝達モジュレーションにおける使用方法

Info

Publication number
JP7781085B2
JP7781085B2 JP2022579946A JP2022579946A JP7781085B2 JP 7781085 B2 JP7781085 B2 JP 7781085B2 JP 2022579946 A JP2022579946 A JP 2022579946A JP 2022579946 A JP2022579946 A JP 2022579946A JP 7781085 B2 JP7781085 B2 JP 7781085B2
Authority
JP
Japan
Prior art keywords
tcr
cells
cell
eso
cancer
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Active
Application number
JP2022579946A
Other languages
English (en)
Japanese (ja)
Other versions
JP2023532278A5 (https=
JP2023532278A (ja
Inventor
ロンフー ワン，
イーチェン ワン，
ビンナン イン，
チェン チャン，
シン リウ，
Original Assignee
ザ・メソジスト・ホスピタル
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by ザ・メソジスト・ホスピタル filed Critical ザ・メソジスト・ホスピタル
Publication of JP2023532278A publication Critical patent/JP2023532278A/ja
Publication of JP2023532278A5 publication Critical patent/JP2023532278A5/ja
Priority to JP2025136019A priority Critical patent/JP2025166212A/ja
Application granted granted Critical
Publication of JP7781085B2 publication Critical patent/JP7781085B2/ja
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K40/00—Cellular immunotherapy
    • A61K40/10—Cellular immunotherapy characterised by the cell type used
    • A61K40/11—T-cells, e.g. tumour infiltrating lymphocytes [TIL] or regulatory T [Treg] cells; Lymphokine-activated killer [LAK] cells
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K40/00—Cellular immunotherapy
    • A61K40/30—Cellular immunotherapy characterised by the recombinant expression of specific molecules in the cells of the immune system
    • A61K40/31—Chimeric antigen receptors [CAR]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K40/00—Cellular immunotherapy
    • A61K40/30—Cellular immunotherapy characterised by the recombinant expression of specific molecules in the cells of the immune system
    • A61K40/32—T-cell receptors [TCR]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K40/00—Cellular immunotherapy
    • A61K40/40—Cellular immunotherapy characterised by antigens that are targeted or presented by cells of the immune system
    • A61K40/41—Vertebrate antigens
    • A61K40/42—Cancer antigens
    • A61K40/4202—Receptors, cell surface antigens or cell surface determinants
    • A61K40/421—Immunoglobulin superfamily
    • A61K40/4211—CD19 or B4
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K40/00—Cellular immunotherapy
    • A61K40/40—Cellular immunotherapy characterised by antigens that are targeted or presented by cells of the immune system
    • A61K40/41—Vertebrate antigens
    • A61K40/42—Cancer antigens
    • A61K40/4267—Cancer testis antigens, e.g. SSX, BAGE, GAGE or SAGE
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K40/00—Cellular immunotherapy
    • A61K40/40—Cellular immunotherapy characterised by antigens that are targeted or presented by cells of the immune system
    • A61K40/41—Vertebrate antigens
    • A61K40/42—Cancer antigens
    • A61K40/4267—Cancer testis antigens, e.g. SSX, BAGE, GAGE or SAGE
    • A61K40/4269—NY-ESO
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K40/00—Cellular immunotherapy
    • A61K40/40—Cellular immunotherapy characterised by antigens that are targeted or presented by cells of the immune system
    • A61K40/46—Viral antigens
    • 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
    • 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
    • C07K14/70539—MHC-molecules, e.g. HLA-molecules
    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2239/00—Indexing codes associated with cellular immunotherapy of group A61K40/00
    • A61K2239/31—Indexing codes associated with cellular immunotherapy of group A61K40/00 characterized by the route of administration
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2239/00—Indexing codes associated with cellular immunotherapy of group A61K40/00
    • A61K2239/38—Indexing codes associated with cellular immunotherapy of group A61K40/00 characterised by the dose, timing or administration schedule
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2239/00—Indexing codes associated with cellular immunotherapy of group A61K40/00
    • A61K2239/46—Indexing codes associated with cellular immunotherapy of group A61K40/00 characterised by the cancer treated
    • A61K2239/47—Brain; Nervous system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2239/00—Indexing codes associated with cellular immunotherapy of group A61K40/00
    • A61K2239/46—Indexing codes associated with cellular immunotherapy of group A61K40/00 characterised by the cancer treated
    • A61K2239/48—Blood cells, e.g. leukemia or lymphoma
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2239/00—Indexing codes associated with cellular immunotherapy of group A61K40/00
    • A61K2239/46—Indexing codes associated with cellular immunotherapy of group A61K40/00 characterised by the cancer treated
    • A61K2239/49—Breast
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/20—Immunoglobulins specific features characterized by taxonomic origin
    • C07K2317/24—Immunoglobulins specific features characterized by taxonomic origin containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
    • 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
    • C12N2740/00—Reverse transcribing RNA viruses
    • C12N2740/00011—Details
    • C12N2740/10011—Retroviridae
    • C12N2740/13011—Gammaretrovirus, e.g. murine leukeamia virus
    • C12N2740/13041—Use of virus, viral particle or viral elements as a vector
    • C12N2740/13043—Use of virus, viral particle or viral elements as a vector viral genome or elements thereof as genetic vector

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Epidemiology (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Immunology (AREA)
  • Genetics & Genomics (AREA)
  • Zoology (AREA)
  • Medicinal Chemistry (AREA)
  • Molecular Biology (AREA)
  • Biochemistry (AREA)
  • Biophysics (AREA)
  • Engineering & Computer Science (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Toxicology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Cell Biology (AREA)
  • Biomedical Technology (AREA)
  • Wood Science & Technology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • General Engineering & Computer Science (AREA)
  • Biotechnology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Physics & Mathematics (AREA)
  • Plant Pathology (AREA)
  • Microbiology (AREA)
  • Peptides Or Proteins (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)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
  • Preparation Of Compounds By Using Micro-Organisms (AREA)
JP2022579946A 2020-06-25 2021-06-25 抗原特異的ｔ細胞受容体及びキメラ抗原受容体、並びにがん免疫療法のための免疫シグナル伝達モジュレーションにおける使用方法 Active JP7781085B2 (ja)

Priority Applications (1)

Application Number Priority Date Filing Date Title
JP2025136019A JP2025166212A (ja) 2020-06-25 2025-08-18 抗原特異的ｔ細胞受容体及びキメラ抗原受容体、並びにがん免疫療法のための免疫シグナル伝達モジュレーションにおける使用方法

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US202063044150P 2020-06-25 2020-06-25
US63/044,150 2020-06-25
PCT/US2021/039262 WO2021263211A2 (en) 2020-06-25 2021-06-25 Antigen-specific t cell receptors and chimeric antigen receptors, and methods of use in immune signaling modulation for cancer immunotherapy

Related Child Applications (1)

Application Number Title Priority Date Filing Date
JP2025136019A Division JP2025166212A (ja) 2020-06-25 2025-08-18 抗原特異的ｔ細胞受容体及びキメラ抗原受容体、並びにがん免疫療法のための免疫シグナル伝達モジュレーションにおける使用方法

Publications (3)

Publication Number Publication Date
JP2023532278A JP2023532278A (ja) 2023-07-27
JP2023532278A5 JP2023532278A5 (https=) 2023-08-24
JP7781085B2 true JP7781085B2 (ja) 2025-12-05

Family

ID=79281973

Family Applications (2)

Application Number Title Priority Date Filing Date
JP2022579946A Active JP7781085B2 (ja) 2020-06-25 2021-06-25 抗原特異的ｔ細胞受容体及びキメラ抗原受容体、並びにがん免疫療法のための免疫シグナル伝達モジュレーションにおける使用方法
JP2025136019A Pending JP2025166212A (ja) 2020-06-25 2025-08-18 抗原特異的ｔ細胞受容体及びキメラ抗原受容体、並びにがん免疫療法のための免疫シグナル伝達モジュレーションにおける使用方法

Family Applications After (1)

Application Number Title Priority Date Filing Date
JP2025136019A Pending JP2025166212A (ja) 2020-06-25 2025-08-18 抗原特異的ｔ細胞受容体及びキメラ抗原受容体、並びにがん免疫療法のための免疫シグナル伝達モジュレーションにおける使用方法

Country Status (7)

Country Link
US (1) US20230250149A1 (https=)
EP (1) EP4171587A4 (https=)
JP (2) JP7781085B2 (https=)
CN (1) CN116322750A (https=)
AU (1) AU2021297458A1 (https=)
CA (1) CA3188143A1 (https=)
WO (1) WO2021263211A2 (https=)

Families Citing this family (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP4519675A4 (en) * 2022-05-03 2026-04-08 3T Biosciences Inc T-LYMPHOCYTE TARGET DISCOVERY
KR20250017213A (ko) * 2022-05-25 2025-02-04 고쿠리츠 다이가쿠 호우징 도우카이 고쿠리츠 다이가쿠 기코우 폴리뉴클레오티드
WO2024163292A1 (en) * 2023-01-30 2024-08-08 Board Of Regents, The University Of Texas System T-cell receptors targeting her2 and methods of use thereof
EP4731758A2 (en) * 2023-06-20 2026-04-29 The Methodist Hospital Antigen-specific t cell receptors and chimeric antigen receptors, and methods of use in immune signaling modulation for cancer immunotherapy
WO2024263818A2 (en) * 2023-06-20 2024-12-26 Immunova Therapeutics Llc Synthetic t cell receptors for enhancing memory (stem) t cells using new transmembranes and signaling domains
WO2025084880A1 (ko) * 2023-10-20 2025-04-24 주식회사 이온셀 Ct83 항원에 결합하는 car-t 세포 및 이의 용도

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2017531687A (ja) 2014-10-27 2017-10-26 フレッド ハッチンソン キャンサー リサーチ センター 養子細胞免疫療法の有効性を増強させるための組成物および方法
JP2018517410A (ja) 2015-06-01 2018-07-05 ユーシーエル ビジネス ピーエルシー 細胞
WO2019165116A1 (en) 2018-02-26 2019-08-29 Fred Hutchinson Cancer Research Center Compositions and methods for cellular immunotherapy

Family Cites Families (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CA2899679C (en) * 2013-01-29 2023-03-21 Max-Delbruck-Centrum Fur Molekulare Medizin (Mdc) Berlin-Buch High avidity antigen recognizing constructs
CA3051222C (en) * 2013-06-10 2023-01-24 Dana-Farber Cancer Institute, Inc. Methods and compositions for reducing immunosupression by tumor cells
US10934346B2 (en) * 2014-02-14 2021-03-02 Bellicum Pharmaceuticals, Inc. Modified T cell comprising a polynucleotide encoding an inducible stimulating molecule comprising MyD88, CD40 and FKBP12
US20170335331A1 (en) * 2014-10-31 2017-11-23 The Trustees Of The University Of Pennsylvania Altering Gene Expression in CART Cells and Uses Thereof
CA2996887A1 (en) * 2015-09-11 2017-03-16 Agenus Inc. Engineered host cells and methods of use thereof
JP2019515656A (ja) * 2016-03-15 2019-06-13 キャンサー・リサーチ・テクノロジー・リミテッドＣａｎｃｅｒ Ｒｅｓｅａｒｃｈ Ｔｅｃｈｎｏｌｏｇｙ Ｌｉｍｉｔｅｄ キメラ抗原受容体
EP3806857A4 (en) * 2018-06-14 2022-03-02 2seventy bio, Inc. CD79A CHIMERIC ANTIGEN RECEPTORS
WO2020086647A1 (en) * 2018-10-23 2020-04-30 Regeneron Pharmaceuticals, Inc. Ny-eso-1 t cell receptors and methods of use thereof

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2017531687A (ja) 2014-10-27 2017-10-26 フレッド ハッチンソン キャンサー リサーチ センター 養子細胞免疫療法の有効性を増強させるための組成物および方法
JP2018517410A (ja) 2015-06-01 2018-07-05 ユーシーエル ビジネス ピーエルシー 細胞
WO2019165116A1 (en) 2018-02-26 2019-08-29 Fred Hutchinson Cancer Research Center Compositions and methods for cellular immunotherapy

Non-Patent Citations (6)

* Cited by examiner, † Cited by third party
Title
J. Immunol.，1998年，Vol. 160, No. 1，pp. 145-154
J. Immunol.，2005年，Vol. 174, No. 7，pp. 4415-4423
J. Immunol.，2010年，vol. 184, No. 11，pp. 6223-6231
J. Immunother.，2006年，Vol. 29，pp. 398-406
J. Immunother.，2010年，Vol. 33，pp. 780-788
Journal of Hematology & Oncology，2020年，13:54

Also Published As

Publication number Publication date
WO2021263211A2 (en) 2021-12-30
AU2021297458A1 (en) 2023-02-02
US20230250149A1 (en) 2023-08-10
JP2025166212A (ja) 2025-11-05
CN116322750A (zh) 2023-06-23
WO2021263211A3 (en) 2022-03-10
JP2023532278A (ja) 2023-07-27
EP4171587A4 (en) 2024-07-24
CA3188143A1 (en) 2021-12-30
WO2021263211A9 (en) 2022-02-03
EP4171587A2 (en) 2023-05-03

Similar Documents

Publication Publication Date Title
JP7781085B2 (ja) 抗原特異的ｔ細胞受容体及びキメラ抗原受容体、並びにがん免疫療法のための免疫シグナル伝達モジュレーションにおける使用方法
Chandran et al. Immunogenicity and therapeutic targeting of a public neoantigen derived from mutated PIK3CA
CN112110995A (zh) 肿瘤新抗原多肽及其用途
US12565680B2 (en) Cancer neoantigens and their utilities in cancer vaccines and TCR-based cancer immunotherapy
EP2488548A1 (en) A low density lipoprotein-related protein 1 splice variant as cancer marker
US20220257735A1 (en) A peptide-based screening method to identify neoantigens for use with tumor infiltrating lymphocytes
US20240082304A1 (en) Antigen-specific t cell receptors and chimeric antigen receptors, and methods of use in immune signaling modulation for cancer immunotherapy
US20240218053A1 (en) Engineering biologics to hpv oncoproteins
AU2024311891A1 (en) Antigen-specific t cell receptors and chimeric antigen receptors, and methods of use in immune signaling modulation for cancer immunotherapy
US20160074428A1 (en) Compositions and methods for the treatment of human immunodeficiency virus infection
HK40092820A (zh) 抗原特异性t细胞受体和嵌合抗原受体以及用於癌症免疫疗法的免疫信号传导调节中的使用方法
CN117693521A (zh) 新的肽模拟物及其用途
WO2022105922A1 (zh) 源自于ssx2抗原的短肽
US20250304636A1 (en) Dap12 constructs and their use to enhance dc vaccines and immunotherapies
US12209137B2 (en) Antigen binding proteins specifically binding CT45
US20250282853A1 (en) Utilization of immortalized b cells to identify sdcbp as a novel therapeutic target in ovarian carcinoma
WO2025171250A1 (en) Nyeso1 tcr for t-cell therapy and methods of use
HK40111113A (zh) 肽筛选
WO2026076157A1 (en) Synthetic notch agonist constructs and methods of use
KR20170093806A (ko) 항원 제시의 검출 방법
HK40097893A (zh) Ras新抗原及其用途

Legal Events

Date Code Title Description
A521 Request for written amendment filed

Free format text: JAPANESE INTERMEDIATE CODE: A523

Effective date: 20230816

A621 Written request for application examination

Free format text: JAPANESE INTERMEDIATE CODE: A621

Effective date: 20230816

A131 Notification of reasons for refusal

Free format text: JAPANESE INTERMEDIATE CODE: A131

Effective date: 20240807

A601 Written request for extension of time

Free format text: JAPANESE INTERMEDIATE CODE: A601

Effective date: 20241106

A601 Written request for extension of time

Free format text: JAPANESE INTERMEDIATE CODE: A601

Effective date: 20250107

A521 Request for written amendment filed

Free format text: JAPANESE INTERMEDIATE CODE: A523

Effective date: 20250207

A02 Decision of refusal

Free format text: JAPANESE INTERMEDIATE CODE: A02

Effective date: 20250416

A521 Request for written amendment filed

Free format text: JAPANESE INTERMEDIATE CODE: A523

Effective date: 20250818

TRDD Decision of grant or rejection written
A01 Written decision to grant a patent or to grant a registration (utility model)

Free format text: JAPANESE INTERMEDIATE CODE: A01

Effective date: 20251118

A61 First payment of annual fees (during grant procedure)

Free format text: JAPANESE INTERMEDIATE CODE: A61

Effective date: 20251125

R150 Certificate of patent or registration of utility model

Ref document number: 7781085

Country of ref document: JP

Free format text: JAPANESE INTERMEDIATE CODE: R150