WO2017214709A1 - Reagents, compositions and methods for improving viability and function of cells, tissues and organs - Google Patents

Reagents, compositions and methods for improving viability and function of cells, tissues and organs Download PDF

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Publication number
WO2017214709A1
WO2017214709A1 PCT/CA2017/000151 CA2017000151W WO2017214709A1 WO 2017214709 A1 WO2017214709 A1 WO 2017214709A1 CA 2017000151 W CA2017000151 W CA 2017000151W WO 2017214709 A1 WO2017214709 A1 WO 2017214709A1
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WO
WIPO (PCT)
Prior art keywords
group
carbon atoms
alkyl group
substituted
cells
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Ceased
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PCT/CA2017/000151
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English (en)
French (fr)
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WO2017214709A8 (en
Inventor
Shant DER SARKISSIAN
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Noiseux Nicolas
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Noiseux Nicolas
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
Priority to DK17812341.0T priority Critical patent/DK3471733T3/da
Priority to CN201780049693.5A priority patent/CN109803664A/zh
Priority to AU2017285486A priority patent/AU2017285486B2/en
Priority to JP2019518343A priority patent/JP7009463B2/ja
Priority to CA3027682A priority patent/CA3027682A1/en
Priority to ES17812341T priority patent/ES2992544T3/es
Priority to EP17812341.0A priority patent/EP3471733B1/en
Priority to CN202510670682.5A priority patent/CN121313845A/zh
Priority to US16/309,474 priority patent/US11446265B2/en
Application filed by Noiseux Nicolas filed Critical Noiseux Nicolas
Publication of WO2017214709A1 publication Critical patent/WO2017214709A1/en
Publication of WO2017214709A8 publication Critical patent/WO2017214709A8/en
Anticipated expiration legal-status Critical
Priority to JP2022003014A priority patent/JP2022062037A/ja
Priority to US17/870,476 priority patent/US12419849B2/en
Priority to JP2023208559A priority patent/JP2024019483A/ja
Ceased legal-status Critical Current

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N1/00—Preservation of bodies of humans or animals, or parts thereof
    • A01N1/10—Preservation of living parts
    • A01N1/12—Chemical aspects of preservation
    • A01N1/122—Preservation or perfusion media
    • A01N1/125—Freeze protecting agents, e.g. cryoprotectants or osmolarity regulators
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N1/00—Preservation of bodies of humans or animals, or parts thereof
    • A01N1/10—Preservation of living parts
    • A01N1/12—Chemical aspects of preservation
    • A01N1/122—Preservation or perfusion media
    • A01N1/126—Physiologically active agents, e.g. antioxidants or nutrients
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N1/00—Preservation of bodies of humans or animals, or parts thereof
    • A01N1/10—Preservation of living parts
    • A01N1/12—Chemical aspects of preservation
    • A01N1/128—Chemically defined matrices for immobilising, holding or storing living parts, e.g. alginate gels; Chemically altering living parts, e.g. by cross-linking
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/16—Amides, e.g. hydroxamic acids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/16—Amides, e.g. hydroxamic acids
    • A61K31/164—Amides, e.g. hydroxamic acids of a carboxylic acid with an aminoalcohol, e.g. ceramides
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid

Definitions

  • the present invention provides reagents, compositions and methods for modulating the state of a cell, a cell preparation, a tissue, a graft or an organ in vitro, ex vivo or in vivo.
  • the present invention also relates to reagents, compositions and methods for improving the viability and/or function of cells or for the in vitro, ex vivo or in vivo protection of cells, tissues, grafts or organs from various damages.
  • the reagents and composition may comprise an HSP90 co-factor inhibitor such as Celastrol or a Celastrol analog either alone or in combination with an adjunct agent (e.g., NRF-2 activator, antioxidant, etc.).
  • the method may more specifically comprise administering to a mammal in need thereof a) a composition comprising one or more compound of Formula I, Formula la, a pharmaceutically acceptable salt, a stereisomer, a tautomer or a pro-drug thereof, b) a stem cell preparation pre-conditioned with one or more compound of Formula I, Formula la, a pharmaceutically acceptable salt, a stereisomer, a tautomer or a pro-drug thereof or c) a secretome of a cell preparation conditioned with such composition.
  • the cellular preparation may be a cell suspension.
  • the cellular preparation may in the form of a three-dimensional scaffold.
  • cells may be cultured as cell aggregates, in the presence of microcarriers, on alginate microencapsulates, in hydrogels (e.g., thermoreversible hydrogels, chitosane based hydrogels etc.), in nanostructure scaffolds composed of self- assembling peptides (Meng, X. et al., SpringerPlus, 2014, 3:80).
  • the invention relates to the use of a combination of a) compound of Formula I, Formula la, a pharmaceutically acceptable salt, a stereisomer, a tautomer or a pro-drug thereof and b) an adjunct agent.
  • the cellular preparation may comprise stem cells such as those suitable for preventing or repairing damages due to ischemia.
  • the stem cells may be from a commercial source, isolated from the individual in need of treatment (i.e., autologous) or isolated from a compatible donor (i.e., allogeneic).
  • FIG. 25B is a table representing mRNA expression of selected genes measured by real-time PCR in human mesenchymal stem cells (hMSC) conditioned with selected Celastrol analogs alone or in combination with selected adjunct agents. Results are expressed as fold change versus Vehicle-treated cells.
  • hMSC human mesenchymal stem cells
  • Celastrol mechanism of action may further include 3) induction / amplification of protective signaling:
  • Celastrol by stimulating ROS production may activate above described mechanisms thereby leading to activation of protective signaling pathways.
  • a combination of compounds having improved (e.g., synergistic) activity relative to activity of the compounds used alone are used.
  • combinations of compounds include (i) (a) Celastrol or an analog thereof; and (b) EGCG or an analog thereof; (ii) (a) Celastrol or an analog thereof; and (b) tBHQ or an analog thereof; (iii) (a) Gedunin or an analog thereof; and (b) EGCG or an analog thereof; (iv) (a) Gedunin or an analog thereof; and (b) tBHQ or an analog thereof; (v) (a) Celastrol or an analog thereof; and (b) 2HBA or an analog thereof; (vi) (a) Celastrol or an analog thereof; and (b) Curcumin or an analog thereof; or (vii) a) Celastrol or an analog thereof; and (b) Carnosol or an analog thereof.
  • straight alkyl group of 1 to 6 carbon atoms i.e., C1 -C6 alkyl
  • C1 -C6 alkyl saturated monovalent hydrocarbon radicals having straight or branched moieties and containing from 1 to 6 carbon atoms.
  • branched alkyl group refers to alkyl group that include one or more tertiary or quaternary carbon atoms.
  • the alkyl group may be substituted (OH, NH2, I, F, CI, Br, CN) unsubstituted. Examples of such groups include, but are not limited to, methyl, ethyl, propyl, iso-propyl, n-butyl, iso- butyl, and tert-butyl.
  • Example 1 HSP90-cochaperone inhibitors as cell conditioning agents

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Engineering & Computer Science (AREA)
  • Epidemiology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Dentistry (AREA)
  • Wood Science & Technology (AREA)
  • Zoology (AREA)
  • Environmental Sciences (AREA)
  • Urology & Nephrology (AREA)
  • Vascular Medicine (AREA)
  • Cardiology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines Containing Material From Animals Or Micro-Organisms (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Dispersion Chemistry (AREA)
  • Biophysics (AREA)
  • Physiology (AREA)
  • Hydrogenated Pyridines (AREA)
  • Micro-Organisms Or Cultivation Processes Thereof (AREA)
PCT/CA2017/000151 2016-06-15 2017-06-15 Reagents, compositions and methods for improving viability and function of cells, tissues and organs Ceased WO2017214709A1 (en)

Priority Applications (12)

Application Number Priority Date Filing Date Title
US16/309,474 US11446265B2 (en) 2016-06-15 2017-06-15 Reagents, compositions and methods for improving viability and function of cells, tissues and organs
AU2017285486A AU2017285486B2 (en) 2016-06-15 2017-06-15 Reagents, compositions and methods for improving viability and function of cells, tissues and organs
JP2019518343A JP7009463B2 (ja) 2016-06-15 2017-06-15 細胞、組織、および器官の生存能および機能を向上させるための試薬、組成物、および方法
CA3027682A CA3027682A1 (en) 2016-06-15 2017-06-15 Reagents, compositions and methods for improving viability and function of cells, tissues and organs
ES17812341T ES2992544T3 (es) 2016-06-15 2017-06-15 Reactivos, composiciones y métodos para mejorar la viabilidad y función de células, tejidos y órganos
EP17812341.0A EP3471733B1 (en) 2016-06-15 2017-06-15 Reagents, compositions and methods for improving viability and function of cells, tissues and organs
CN202510670682.5A CN121313845A (zh) 2016-06-15 2017-06-15 用于改善细胞、组织和器官的活力和功能的试剂、组合物和方法
DK17812341.0T DK3471733T3 (da) 2016-06-15 2017-06-15 Reagenser, sammensætninger og fremgangsmåder til forbedring af cellers, vævs og organers levedygtighed og funktion
CN201780049693.5A CN109803664A (zh) 2016-06-15 2017-06-15 用于改善细胞、组织和器官的活力和功能的试剂、组合物和方法
JP2022003014A JP2022062037A (ja) 2016-06-15 2022-01-12 細胞、組織、および器官の生存能および機能を向上させるための試薬、組成物、および方法
US17/870,476 US12419849B2 (en) 2016-06-15 2022-07-21 Reagents, compositions and methods for improving viability and function of cells, tissues and organs
JP2023208559A JP2024019483A (ja) 2016-06-15 2023-12-11 細胞、組織、および器官の生存能および機能を向上させるための試薬、組成物、および方法

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US201662350258P 2016-06-15 2016-06-15
US62/350,258 2016-06-15

Related Child Applications (2)

Application Number Title Priority Date Filing Date
US16/309,474 A-371-Of-International US11446265B2 (en) 2016-06-15 2017-06-15 Reagents, compositions and methods for improving viability and function of cells, tissues and organs
US17/870,476 Continuation US12419849B2 (en) 2016-06-15 2022-07-21 Reagents, compositions and methods for improving viability and function of cells, tissues and organs

Publications (2)

Publication Number Publication Date
WO2017214709A1 true WO2017214709A1 (en) 2017-12-21
WO2017214709A8 WO2017214709A8 (en) 2018-12-13

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PCT/CA2017/000151 Ceased WO2017214709A1 (en) 2016-06-15 2017-06-15 Reagents, compositions and methods for improving viability and function of cells, tissues and organs

Country Status (9)

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US (2) US11446265B2 (https=)
EP (1) EP3471733B1 (https=)
JP (3) JP7009463B2 (https=)
CN (2) CN109803664A (https=)
AU (1) AU2017285486B2 (https=)
CA (1) CA3027682A1 (https=)
DK (1) DK3471733T3 (https=)
ES (1) ES2992544T3 (https=)
WO (1) WO2017214709A1 (https=)

Cited By (5)

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WO2019158359A1 (en) * 2018-02-14 2019-08-22 Societe Des Produits Nestle S.A. Compounds that modulate von willebrand factor levels and their use in the treatment of blood disorders
US10947252B2 (en) 2018-08-20 2021-03-16 Janssen Pharmaceutica Nv Inhibitors of KEAP1-Nrf2 protein-protein interaction
WO2021055985A1 (en) * 2019-09-22 2021-03-25 Cellerant Therapeutics, Inc. Ipsc-derived, hypoimmunogenic, myeloid progenitor cells
WO2022020200A1 (en) * 2020-07-22 2022-01-27 Caladrius Biosciences, Inc. Compositions comprising cd34+ cells and methods for repairing a lung injury after severe virus infection
WO2022212878A1 (en) * 2021-04-01 2022-10-06 The Regents Of The University Of California Human pluripotent stem cell-derived secretome as a biologic for prevention and treatment of neurodegenerative and apoptotic diseases

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WO2019055817A1 (en) * 2017-09-14 2019-03-21 The Regents Of The University Of California EX VIVO CONSERVATION AND EXPANSION OF STEM CELLS
CN111202737B (zh) * 2020-03-20 2022-08-05 中国药科大学 雷公藤红素酰胺衍生物在制备治疗自身性免疫疾病药物的应用
CN111704647B (zh) * 2020-06-15 2021-10-22 中国人民解放军海军军医大学 一类三萜类衍生物及其作为程序性细胞坏死抑制剂的用途
CN112375802A (zh) * 2020-11-06 2021-02-19 中国科学院城市环境研究所 评价白藜芦醇干预肺上皮细胞多环芳烃毒性效应的试剂或试剂盒及其应用和检测
CN113057957A (zh) * 2021-03-30 2021-07-02 福建中医药大学 葛杜宁及其衍生物在制备抗氧化药物和/或化妆品及治疗类风湿性关节炎药物中的用途
CN118634317B (zh) * 2024-08-16 2024-10-22 四川大学 乳铁蛋白联合麦角硫因在制备预防和/或治疗阿尔茨海默症的药物中的用途

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Cited By (12)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2019158359A1 (en) * 2018-02-14 2019-08-22 Societe Des Produits Nestle S.A. Compounds that modulate von willebrand factor levels and their use in the treatment of blood disorders
CN111655266A (zh) * 2018-02-14 2020-09-11 雀巢产品有限公司 调节血管性血友病因子水平的化合物及其在治疗血液疾病中的用途
JP2021513513A (ja) * 2018-02-14 2021-05-27 ソシエテ・デ・プロデュイ・ネスレ・エス・アー フォン・ヴィレブランド因子のレベルを調節する化合物、及び血液疾患の治療におけるそれらの使用
US11446312B2 (en) 2018-02-14 2022-09-20 Societe Des Produits Nestle S.A. Compounds that modulate von Willebrand factor levels and their use in the treatment of blood disorders
JP7404246B2 (ja) 2018-02-14 2023-12-25 ソシエテ・デ・プロデュイ・ネスレ・エス・アー フォン・ヴィレブランド因子のレベルを調節する化合物、及び血液疾患の治療におけるそれらの使用
CN111655266B (zh) * 2018-02-14 2024-04-12 雀巢产品有限公司 调节血管性血友病因子水平的化合物及其在治疗血液疾病中的用途
US10947252B2 (en) 2018-08-20 2021-03-16 Janssen Pharmaceutica Nv Inhibitors of KEAP1-Nrf2 protein-protein interaction
US11427601B1 (en) 2018-08-20 2022-08-30 Janssen Pharmaceutica Nv Inhibitors of KEAP1-Nrf2 protein-protein interaction
US11897900B2 (en) 2018-08-20 2024-02-13 Janssen Pharmaceutica Nv Inhibitors of KEAP1-Nrf2 protein-protein interaction
WO2021055985A1 (en) * 2019-09-22 2021-03-25 Cellerant Therapeutics, Inc. Ipsc-derived, hypoimmunogenic, myeloid progenitor cells
WO2022020200A1 (en) * 2020-07-22 2022-01-27 Caladrius Biosciences, Inc. Compositions comprising cd34+ cells and methods for repairing a lung injury after severe virus infection
WO2022212878A1 (en) * 2021-04-01 2022-10-06 The Regents Of The University Of California Human pluripotent stem cell-derived secretome as a biologic for prevention and treatment of neurodegenerative and apoptotic diseases

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US20210169830A1 (en) 2021-06-10
US11446265B2 (en) 2022-09-20
JP2022062037A (ja) 2022-04-19
CN121313845A (zh) 2026-01-13
EP3471733A4 (en) 2020-02-05
WO2017214709A8 (en) 2018-12-13
AU2017285486A1 (en) 2019-02-07
EP3471733B1 (en) 2024-08-07
CN109803664A (zh) 2019-05-24
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ES2992544T3 (es) 2024-12-13
JP7009463B2 (ja) 2022-01-25
EP3471733A1 (en) 2019-04-24
JP2019523784A (ja) 2019-08-29
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