CN108440571B - Etp衍生物 - Google Patents

Etp衍生物 Download PDF

Info

Publication number
CN108440571B
CN108440571B CN201810252982.1A CN201810252982A CN108440571B CN 108440571 B CN108440571 B CN 108440571B CN 201810252982 A CN201810252982 A CN 201810252982A CN 108440571 B CN108440571 B CN 108440571B
Authority
CN
China
Prior art keywords
unsubstituted
substituted
membered
alkyl
independently
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
CN201810252982.1A
Other languages
English (en)
Chinese (zh)
Other versions
CN108440571A (zh
Inventor
L·E·奥弗曼
M·博伊曼
S·南
D·霍内
R·约韦
J·谢
C·科沃利克
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
University of California San Diego UCSD
City of Hope
Original Assignee
City of Hope
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 City of Hope filed Critical City of Hope
Publication of CN108440571A publication Critical patent/CN108440571A/zh
Application granted granted Critical
Publication of CN108440571B publication Critical patent/CN108440571B/zh
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Images

Classifications

    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D513/00Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00
    • C07D513/12Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00 in which the condensed system contains three hetero rings
    • C07D513/18Bridged systems
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44Non condensed pyridines; Hydrogenated derivatives thereof
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/54Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one sulfur as the ring hetero atoms, e.g. sulthiame
    • A61K31/548Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one sulfur as the ring hetero atoms, e.g. sulthiame having two or more sulfur atoms in the same ring
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/70Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7042Compounds having saccharide radicals and heterocyclic rings
    • A61K31/7052Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides
    • A61K31/706Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/70Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7042Compounds having saccharide radicals and heterocyclic rings
    • A61K31/7052Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides
    • A61K31/706Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom
    • A61K31/7064Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines
    • A61K31/7068Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines having oxo groups directly attached to the pyrimidine ring, e.g. cytidine, cytidylic acid
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00Antineoplastic agents
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00Antineoplastic agents
    • A61P35/02Antineoplastic agents specific for leukemia
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D487/00Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
    • C07D487/02Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
    • C07D487/04Ortho-condensed systems
    • YGENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02ATECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
    • Y02A50/00TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
    • Y02A50/30Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Organic Chemistry (AREA)
  • Public Health (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Medicinal Chemistry (AREA)
  • Epidemiology (AREA)
  • Molecular Biology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Hematology (AREA)
  • Oncology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Pyridine Compounds (AREA)
  • Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
  • Plural Heterocyclic Compounds (AREA)
CN201810252982.1A 2012-10-22 2013-10-22 Etp衍生物 Active CN108440571B (zh)

Applications Claiming Priority (6)

Application Number Priority Date Filing Date Title
US201261716803P 2012-10-22 2012-10-22
US61/716,803 2012-10-22
US201361799160P 2013-03-15 2013-03-15
US61/799,160 2013-03-15
PCT/US2013/066252 WO2014066435A1 (en) 2012-10-22 2013-10-22 Etp derivatives
CN201380065997.2A CN104870452B (zh) 2012-10-22 2013-10-22 Etp衍生物

Related Parent Applications (1)

Application Number Title Priority Date Filing Date
CN201380065997.2A Division CN104870452B (zh) 2012-10-22 2013-10-22 Etp衍生物

Publications (2)

Publication Number Publication Date
CN108440571A CN108440571A (zh) 2018-08-24
CN108440571B true CN108440571B (zh) 2022-11-04

Family

ID=50545193

Family Applications (2)

Application Number Title Priority Date Filing Date
CN201810252982.1A Active CN108440571B (zh) 2012-10-22 2013-10-22 Etp衍生物
CN201380065997.2A Active CN104870452B (zh) 2012-10-22 2013-10-22 Etp衍生物

Family Applications After (1)

Application Number Title Priority Date Filing Date
CN201380065997.2A Active CN104870452B (zh) 2012-10-22 2013-10-22 Etp衍生物

Country Status (7)

Country Link
US (3) US9527868B2 (enExample)
EP (1) EP2909214B1 (enExample)
JP (3) JP6465803B2 (enExample)
CN (2) CN108440571B (enExample)
AU (1) AU2013334707B2 (enExample)
CA (1) CA2900335C (enExample)
WO (1) WO2014066435A1 (enExample)

Families Citing this family (28)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2014517079A (ja) 2011-06-22 2014-07-17 バーテックス ファーマシューティカルズ インコーポレイテッド Atrキナーゼ阻害剤として有用な化合物
JP6465803B2 (ja) * 2012-10-22 2019-02-06 シティ・オブ・ホープCity of Hope Etp誘導体
SMT202000713T1 (it) 2012-12-07 2021-03-15 Vertex Pharma Pirazolo [1,5-a] pirimidine utili come inibitori dell'atr chinasi per il trattamento di malattie del cancro
US9663519B2 (en) 2013-03-15 2017-05-30 Vertex Pharmaceuticals Incorporated Compounds useful as inhibitors of ATR kinase
US8969360B2 (en) 2013-03-15 2015-03-03 Vertex Pharmaceuticals Incorporated Compounds useful as inhibitors of ATR kinase
EP2970289A1 (en) 2013-03-15 2016-01-20 Vertex Pharmaceuticals Inc. Compounds useful as inhibitors of atr kinase
CN105934246B (zh) 2013-11-18 2019-10-22 福马疗法公司 作为bet溴域抑制剂的四氢喹啉组成物
RU2720237C2 (ru) 2013-11-18 2020-04-28 Форма Терапеутикс, Инк. Композиции, содержащие бензопиперазин, в качестве ингибиторов бромодоменов вет
ES2768678T3 (es) 2013-12-06 2020-06-23 Vertex Pharma Compuesto de 2-amino-6-fluoro-N-[5-fluoro-piridin-3-il]pirazolo[1,5-a]pirimidin-3-carboxamida útil como inhibidor de la ATR quinasa, su preparación, diferentes formas sólidas y derivados radiomarcados de las mismas
SG10201902206QA (en) 2014-06-05 2019-04-29 Vertex Pharma Radiolabelled derivatives of a 2-amino-6-fluoro-n-[5-fluoro-pyridin-3-yl]- pyrazolo[1,5-a]pyrimidin-3-carboxamide compound useful as atr kinase inhibitor, the preparation of said compound and different solid forms thereof
AU2015277212B2 (en) 2014-06-17 2020-07-02 Vertex Pharmaceuticals Incorporated Method for treating cancer using a combination of Chk1 and ATR inhibitors
US10272093B2 (en) * 2015-06-08 2019-04-30 Regents Of The University Of California Use of H3K9me3 modulation for enhancing cognitive function
RU2768621C1 (ru) 2015-09-30 2022-03-24 Вертекс Фармасьютикалз Инкорпорейтед Способ лечения рака с использованием комбинации повреждающих днк средств и ингибиторов atr
EP3512520B1 (en) 2016-09-15 2023-06-21 City of Hope Dithio derivatives of epidithiodiketopiperazine (etp)
WO2018213634A1 (en) * 2017-05-17 2018-11-22 Denali Therapeutics Inc. Compounds, compositions and methods
US11766442B2 (en) 2017-06-16 2023-09-26 City Of Hope T-cell lymphoma treatments
PL3538645T3 (pl) 2017-06-20 2021-11-08 Institut Curie Komórki odpornościowe z defektem suv39h1
EP3641739A1 (en) 2017-06-20 2020-04-29 Institut Curie Inhibitor of suv39h1 histone methyltransferase for use in cancer combination therapy
SMT202400233T1 (it) 2018-04-18 2024-07-09 Constellation Pharmaceuticals Inc Modulatori di enzimi modificanti il metile, composizioni e usi degli stessi
EP3797108B1 (en) 2018-05-21 2022-07-20 Constellation Pharmaceuticals, Inc. Modulators of methyl modifying enzymes, compositions and uses thereof
CN111205308B (zh) * 2020-01-19 2022-03-15 中国科学院海洋研究所 一种硫代二酮哌嗪类化合物及其制备方法和应用
CN116096864A (zh) 2020-07-30 2023-05-09 居里研究所 Socs1缺陷的免疫细胞
JP2025501272A (ja) 2021-12-28 2025-01-17 ムネモ・セラピューティクス 不活性化されたsuv39h1及び改変tcrを有する免疫細胞
CN114751919B (zh) * 2022-03-18 2023-05-23 华南理工大学 一种环丁烷稠合螺环吲哚啉类化合物及其制备方法和应用
EP4279085A1 (en) 2022-05-20 2023-11-22 Mnemo Therapeutics Compositions and methods for treating a refractory or relapsed cancer or a chronic infectious disease
WO2024137659A1 (en) * 2022-12-20 2024-06-27 Cedars-Sinai Medical Center Methods and compositions for the treatment of parkinson's disease, huntington's disease, amyotrophic lateral sclerosis, and learning disorders
EP4520334A1 (en) 2023-09-07 2025-03-12 Mnemo Therapeutics Methods and compositions for improving immune response
WO2025052001A1 (en) 2023-09-07 2025-03-13 Mnemo Therapeutics Methods and compositions for improving immune response

Family Cites Families (26)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US1A (en) * 1836-07-13 John Ruggles Locomotive steam-engine for rail and other roads
DE2157783A1 (de) * 1971-11-22 1973-05-30 Licentia Gmbh Verfahren zur korrektur von daten
AR206504A1 (es) * 1972-11-03 1976-07-30 Lepetit Spa Un procedimiento para preparar 6,7,8,8a-tetrahidro-pirrol(1,2-a)pirazina-1(2h),4(3h)-dionas
NZ212051A (en) * 1984-05-18 1988-10-28 Univ Australian Immune response suppression; certain epipolythio- dioxopiperazine derivatives and their preparation
US4911920A (en) 1986-07-30 1990-03-27 Alcon Laboratories, Inc. Sustained release, comfort formulation for glaucoma therapy
FR2588189B1 (fr) 1985-10-03 1988-12-02 Merck Sharp & Dohme Composition pharmaceutique de type a transition de phase liquide-gel
JP2594486B2 (ja) 1991-01-15 1997-03-26 アルコン ラボラトリーズ インコーポレイテッド 局所的眼薬組成物
US5212162A (en) 1991-03-27 1993-05-18 Alcon Laboratories, Inc. Use of combinations gelling polysaccharides and finely divided drug carrier substrates in topical ophthalmic compositions
JP2801491B2 (ja) * 1993-01-26 1998-09-21 敦 沼田 エピポリチオジオキソピペラジン誘導体およびその製造法
AU3232597A (en) * 1996-06-18 1998-01-07 Warner-Lambert Company Pyrrolo{1,2-a}pyrazine-1,4-dione serine protease inhibitors
WO1998024926A1 (en) 1996-12-02 1998-06-11 Ajinomoto Co., Inc. Gliotoxin derivatives and anticancer agent comprising the same
US7202279B1 (en) * 1998-02-11 2007-04-10 Georgetown University Cyclic dipeptides and azetidinone compounds and their use in treating CNS injury and neurodegenerative disorders
US6906060B2 (en) * 2002-06-06 2005-06-14 Novo Nordisk A/S Substituted hexahydropyrrolo[1,2-a]pyrazines, octahydropyrido[1,2-a]-pyrazines and decahydropyrazino[1,2-a]azepines
JP4842817B2 (ja) * 2003-09-03 2011-12-21 ニューレン ファーマシューティカルズ リミテッド 神経保護二環式化合物およびその使用方法
US7253168B2 (en) * 2004-04-07 2007-08-07 Neurogen Corporation Substituted 1-benzyl-4-substituted piperazine analogues
TW200609219A (en) * 2004-06-17 2006-03-16 Neurogen Corp Aryl-substituted piperazine derivatives
ITMI20042477A1 (it) * 2004-12-23 2005-03-23 Cell Therapeutics Europe Srl Uso di antibiotici a strutura dichetoditiopiperazinica per la preparazione di composizioni farmaceutiche antiangiogeniche
US7642285B2 (en) * 2005-02-04 2010-01-05 Wisconsin Alumni Research Foundation Compounds and methods for modulating communication and virulence in quorum sensing bacteria
TW200800204A (en) 2005-08-15 2008-01-01 Astrazeneca Ab Bicyclic piperazines as metabotropic glutatmate receptor antagonists
RU2318818C1 (ru) * 2006-04-12 2008-03-10 Общество С Ограниченной Ответственностью "Исследовательский Институт Химического Разнообразия" Азагетероциклы, комбинаторная библиотека, фокусированная библиотека, фармацевтическая композиция и способ получения (варианты)
WO2008112014A1 (en) * 2006-10-05 2008-09-18 Mayo Foundation For Medical Education And Research Methods and compositions for treating cancer
EP2088205A1 (en) * 2008-02-11 2009-08-12 Institut National De La Sante Et De La Recherche Medicale (Inserm) PSMB10: A diagnosis marker and therapeutic target of chronic rejection.
US20120040916A1 (en) * 2008-12-22 2012-02-16 Massachusetts Institute Of Technology Molecular inhibitors of the wnt/beta-catenin pathway
CN103189063B (zh) * 2010-11-01 2016-10-19 宾夕法尼亚州研究基金会 治疗组合物和方法
JP6465803B2 (ja) * 2012-10-22 2019-02-06 シティ・オブ・ホープCity of Hope Etp誘導体
DK2958926T5 (da) * 2013-05-24 2024-06-10 Vasthera Co Ltd Epidithiodioxopiperazinforbindelse eller derivater deraf og anvendelse deraf

Also Published As

Publication number Publication date
US10246471B2 (en) 2019-04-02
US20150291622A1 (en) 2015-10-15
US9527868B2 (en) 2016-12-27
US20180155367A1 (en) 2018-06-07
EP2909214A4 (en) 2016-04-20
AU2013334707A1 (en) 2015-05-07
JP6465803B2 (ja) 2019-02-06
WO2014066435A1 (en) 2014-05-01
CA2900335A1 (en) 2014-05-01
CN108440571A (zh) 2018-08-24
JP2019070010A (ja) 2019-05-09
CN104870452B (zh) 2018-04-13
CA2900335C (en) 2021-10-26
US9856273B2 (en) 2018-01-02
EP2909214A1 (en) 2015-08-26
HK1214259A1 (en) 2016-07-22
US20170037058A1 (en) 2017-02-09
AU2013334707B2 (en) 2018-02-22
EP2909214B1 (en) 2020-07-22
JP2016500691A (ja) 2016-01-14
JP2020125342A (ja) 2020-08-20
CN104870452A (zh) 2015-08-26

Similar Documents

Publication Publication Date Title
CN108440571B (zh) Etp衍生物
RU2659786C2 (ru) 5-[[4-[[морфолин-2-ил]метиламино]-5-(трифторметил)-2-пиридил]амино]пиразин-2-карбонитрил, его терапевтические применения
TR201905647T4 (tr) Cdk inhibitörleri olarak pirazolo[1,5-a]pirimidin-5,7-diamin bileşikleri ve onların terapötik kullanımı.
JP2020125302A (ja) Hiv治療におけるアポトーシスタンパク質阻害剤(iap)のアンタゴニストの使用
US10730864B2 (en) RAD51 inhibitors and uses thereof
EP3395345A1 (en) Antitumor effect potentiator comprising pyrrolopyrimidine compound
FR2943058A1 (fr) Derives de pyrazolo°1,5-a!-1,3,5-triazines, leur preparation et leur application en therapeutique.
WO2016210289A1 (en) Chemical modulators of signaling pathways and therapeutic use
EP3632443B1 (en) Anti-tumor effect potentiator using a biphenyl compound
JP2022516685A (ja) ホスファターゼ結合化合物およびそれらを使用する方法
WO2016210247A1 (en) New methods of use for an anti-diarrhea agent
WO2021055936A1 (en) Small-molecule inhibitors for the β-catenin/b-cell lymphoma 9 protein−protein interaction
CA2946833A1 (en) Pyrrolopyrimidine compounds for prevention of tumors based on nae inhibitory effect
US11584760B2 (en) Dithio ETP derivatives
HK1214259B (en) Etp derivatives
WO2020247679A1 (en) Wdr5 inhibitors and modulators
HK1256535A1 (en) Pyrazolidine derivatives and their uses
HK1236948B (zh) 毗咯并嘧啶化合物或其盐、含有其的药物组合物及应用

Legal Events

Date Code Title Description
PB01 Publication
PB01 Publication
SE01 Entry into force of request for substantive examination
SE01 Entry into force of request for substantive examination
GR01 Patent grant
GR01 Patent grant
TR01 Transfer of patent right
TR01 Transfer of patent right

Effective date of registration: 20231226

Address after: California, USA

Patentee after: CITY OF HOPE

Patentee after: THE REGENTS OF THE University OF CALIFORNIA

Address before: California, USA

Patentee before: CITY OF HOPE