CN109689104A - α和γ-D聚谷氨酸化抗叶酸剂及其用途 - Google Patents

α和γ-D聚谷氨酸化抗叶酸剂及其用途 Download PDF

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Publication number
CN109689104A
CN109689104A CN201780052159.XA CN201780052159A CN109689104A CN 109689104 A CN109689104 A CN 109689104A CN 201780052159 A CN201780052159 A CN 201780052159A CN 109689104 A CN109689104 A CN 109689104A
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China
Prior art keywords
polyglutamic
liposome
acidification
antifol
cancer
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Pending
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CN201780052159.XA
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English (en)
Chinese (zh)
Inventor
C·尼基萨
V·M·莫约
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LEAF Holdings Group LLC
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LEAF Holdings Group LLC
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Priority claimed from US15/675,701 external-priority patent/US20180236098A1/en
Application filed by LEAF Holdings Group LLC filed Critical LEAF Holdings Group LLC
Priority claimed from PCT/US2017/046666 external-priority patent/WO2018031979A1/en
Publication of CN109689104A publication Critical patent/CN109689104A/zh
Pending legal-status Critical Current

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    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
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    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Pharmacology & Pharmacy (AREA)
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  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Immunology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Organic Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Dispersion Chemistry (AREA)
  • Molecular Biology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Biochemistry (AREA)
  • Cell Biology (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Rheumatology (AREA)
  • Genetics & Genomics (AREA)
  • Physical Education & Sports Medicine (AREA)
  • Biophysics (AREA)
  • Oil, Petroleum & Natural Gas (AREA)
  • Medicinal Preparation (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
  • Communicable Diseases (AREA)
  • Polymers With Sulfur, Phosphorus Or Metals In The Main Chain (AREA)
  • Oncology (AREA)
  • Preparation Of Compounds By Using Micro-Organisms (AREA)
  • Immobilizing And Processing Of Enzymes And Microorganisms (AREA)
  • External Artificial Organs (AREA)
CN201780052159.XA 2016-08-12 2017-08-12 α和γ-D聚谷氨酸化抗叶酸剂及其用途 Pending CN109689104A (zh)

Applications Claiming Priority (7)

Application Number Priority Date Filing Date Title
US201662374458P 2016-08-12 2016-08-12
US62/374,458 2016-08-12
US201715675695A 2017-08-11 2017-08-11
US15/675,695 2017-08-11
US15/675,701 2017-08-11
US15/675,701 US20180236098A1 (en) 2016-08-12 2017-08-11 Alpha and gamma-d polyglutamated antifolates and uses thereof
PCT/US2017/046666 WO2018031979A1 (en) 2016-08-12 2017-08-12 Alpha and gamma-d polyglutamated antifolates and uses thereof

Related Child Applications (1)

Application Number Title Priority Date Filing Date
CN202511400940.4A Division CN121177507A (zh) 2016-08-12 2017-08-12 α和γ-D聚谷氨酸化抗叶酸剂及其用途

Publications (1)

Publication Number Publication Date
CN109689104A true CN109689104A (zh) 2019-04-26

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CN201780052159.XA Pending CN109689104A (zh) 2016-08-12 2017-08-12 α和γ-D聚谷氨酸化抗叶酸剂及其用途
CN202511392165.2A Pending CN120939250A (zh) 2016-08-12 2017-08-12 聚谷氨酸化抗叶酸剂及其用途
CN201780062078.8A Pending CN109789212A (zh) 2016-08-12 2017-08-12 聚谷氨酸化抗叶酸剂及其用途

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CN202511392165.2A Pending CN120939250A (zh) 2016-08-12 2017-08-12 聚谷氨酸化抗叶酸剂及其用途
CN201780062078.8A Pending CN109789212A (zh) 2016-08-12 2017-08-12 聚谷氨酸化抗叶酸剂及其用途

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US (11) US11344628B2 (enExample)
EP (3) EP3496757A4 (enExample)
JP (6) JP7227123B2 (enExample)
KR (6) KR102708209B1 (enExample)
CN (3) CN109689104A (enExample)
AU (4) AU2017308159B2 (enExample)
CA (3) CA3033077C (enExample)
EA (1) EA201990473A1 (enExample)
MX (5) MX2019001755A (enExample)

Cited By (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN111867593A (zh) * 2018-02-07 2020-10-30 L.E.A.F.控股集团公司 α聚谷氨酸化抗叶酸剂及其用途
CN111936145A (zh) * 2018-02-14 2020-11-13 L.E.A.F.控股集团公司 γ聚谷氨酸化氨甲蝶呤及其用途
CN111954530A (zh) * 2018-02-07 2020-11-17 L.E.A.F.控股集团公司 γ聚谷氨酸化培美曲塞及其用途
CN111954531A (zh) * 2018-02-07 2020-11-17 L.E.A.F.控股集团公司 α聚谷氨酸化培美曲塞及其用途
CN111954529A (zh) * 2018-02-07 2020-11-17 L.E.A.F.控股集团公司 α聚谷氨酸化氨甲蝶呤及其用途
CN114555127A (zh) * 2019-08-06 2022-05-27 L.E.A.F.控股集团公司 制备聚谷氨酸化抗叶酸剂的方法以及它们的组合物的用途

Families Citing this family (18)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP3496757A4 (en) 2016-08-12 2020-04-15 L.E.A.F Holdings Group LLC POLYGLUTAMATE ANTIFOLATES AND USES THEREOF.
US20180236098A1 (en) 2016-08-12 2018-08-23 L.E.A.F. Holdings Group Llc Alpha and gamma-d polyglutamated antifolates and uses thereof
US12220431B2 (en) 2018-02-07 2025-02-11 L.E.A.F. Holdings Group Llc Gamma polyglutamated antifolates and uses thereof
CA3090506A1 (en) 2018-02-07 2019-08-15 L.E.A.F. Holdings Group Llc Alpha polyglutamated tetrahydrofolates and uses thereof
EP3749318A4 (en) 2018-02-07 2022-07-06 L.E.A.F Holdings Group LLC GAMMA-POLYGLUTAMATED RALTITREXED AND ITS USES
US12246015B2 (en) 2018-02-07 2025-03-11 L.E.A.F. Holdings Group Llc Alpha polyglutamated raltitrexed and uses thereof
US12310966B2 (en) 2018-02-07 2025-05-27 L.E.A.F. Holdings Group Llc Alpha polyglutamated aminopterin and uses thereof
US12246019B2 (en) 2018-02-07 2025-03-11 L.E.A.F. Holdings Group Llc Alpha polyglutamated lometrexol and uses thereof
US11730738B2 (en) 2018-02-07 2023-08-22 L.E.A.F. Holdings Group Llc Alpha polyglutamated pralatrexate and uses thereof
EP3749321A4 (en) * 2018-02-07 2022-03-09 L.E.A.F Holdings Group LLC Gamma polyglutamated antifolates and uses thereof
CA3090753A1 (en) 2018-02-14 2019-08-22 L.E.A.F. Holdings Group Llc Gamma polyglutamated pralatrexate and uses thereof
WO2019160734A1 (en) 2018-02-14 2019-08-22 L.E.A.F. Holdings Group Llc Gamma polyglutamated lometrexol and uses thereof
EP3752158A4 (en) 2018-02-14 2022-03-09 L.E.A.F Holdings Group LLC GAMMA-POLYGLUTAMATED AMINOPTERINE AND USES THEREOF
WO2019160735A1 (en) * 2018-02-14 2019-08-22 L.E.A.F. Holdings Group Llc Gamma polyglutamated tetrahydrofolates and uses thereof
CN112010862B (zh) * 2020-10-23 2021-03-30 南京诺源医疗器械有限公司 一种主动靶向叶酸受体近红外荧光分子及其制备方法
EP4497004A1 (en) * 2022-03-21 2025-01-29 Immundiagnostik AG Kit of parts and microbiological method for assessment of the folate status in serum and red blood cells
CN115626928B (zh) * 2022-10-13 2023-11-17 南京诺源医疗器械有限公司 一种靶向α型叶酸受体的培美近红外荧光分子作为荧光示踪剂的用途
JP2024060824A (ja) * 2022-10-20 2024-05-07 プレミアアンチエイジング株式会社 経口製剤及びその製造方法

Citations (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2001005405A1 (en) * 1999-07-16 2001-01-25 The General Hospital Corporation Folylpolyglutamyl synthetase gene transfer to enhance antifolate drug sensitivity
US6569432B1 (en) * 1995-02-24 2003-05-27 Sloan-Kettering Institute For Cancer Research Prostate-specific membrane antigen and uses thereof
WO2005070465A2 (en) * 2004-01-14 2005-08-04 Gilead Sciences, Inc. Lipid-based dispersions useful for drug delivery
WO2006002049A2 (en) * 2004-06-15 2006-01-05 Prometheus Laboratories Inc. Methods for predicting methotrexate polyglutamate levels using pharmacogenetics
WO2006074416A1 (en) * 2005-01-07 2006-07-13 Health Research Inc. 5-amino-4-imidazolecarboxamide riboside and its nucleobase as potentiators of antifolate transport and metabolism
WO2007098089A2 (en) * 2006-02-17 2007-08-30 Novacea, Inc. Treatment of hyperproliferative diseases with methotrexate n-oxide and analogs
CN103002877A (zh) * 2010-05-13 2013-03-27 帕西拉制药有限公司 作为缓解疾病的抗风湿性药（dmard）和抗癌药剂的甲氨蝶呤的持续释放制剂
CN103040748A (zh) * 2012-12-18 2013-04-17 海南百思特医药科技有限公司 一种培美曲塞二钠脂质体注射剂
US20140120157A1 (en) * 2012-09-19 2014-05-01 Georgetown University Targeted liposomes
CN104546723A (zh) * 2015-02-11 2015-04-29 上海交通大学医学院附属新华医院 一种培美曲塞脂质体及其制备方法

Family Cites Families (89)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR2564319A1 (fr) 1984-05-21 1985-11-22 Inst Nat Sante Rech Med Nouvelles compositions de liposomes dotees d'une action specifique vis-a-vis de la proliferation de cellules donnees
US4584375A (en) * 1984-08-21 1986-04-22 Rensselaer Polytechnic Institute Fluorine-containing antifolates incapable of polyglutamate formation
US5225539A (en) 1986-03-27 1993-07-06 Medical Research Council Recombinant altered antibodies and methods of making altered antibodies
EP0492316A1 (en) 1990-12-14 1992-07-01 Takeda Chemical Industries, Ltd. Condensed heterocyclic oligoglutamate derivatives, their production and pharmaceutical compositions containing them
US5646253A (en) 1994-03-08 1997-07-08 Memorial Sloan-Kettering Cancer Center Recombinant human anti-LK26 antibodies
US5639641A (en) 1992-09-09 1997-06-17 Immunogen Inc. Resurfacing of rodent antibodies
US5997915A (en) 1996-01-31 1999-12-07 South Alabama Medical Science Foundation Compositions for human and animal consumption containing reduced folates and methods for making and using same
US5912251A (en) 1998-01-17 1999-06-15 Nair; Madhavan G. Metabolically inert anti-inflammatory and anti-tumor antifolates
US20050031679A1 (en) 1998-03-27 2005-02-10 Clemens Unger Method for producing liposomal formulations of active ingredients
JP2002520431A (ja) 1998-07-09 2002-07-09 ロディア・シミ 水溶性又は水分散性グラフト共重合体
WO2001053331A2 (en) 2000-01-24 2001-07-26 Adherex Technologies, Inc. Peptidomimetic modulators of cell adhesion
CN1095472C (zh) 2000-04-17 2002-12-04 上海复康医药科技发展有限公司 叶酸－多聚糖复合物，其制备方法和以该复合物为活性成分的药物组合物
AU7526901A (en) 2000-06-09 2001-12-24 Gilead Sciences Inc Liposomal benzoquinazoline thymidylate synthase inhibitor formulations
DE60127970T2 (de) 2000-06-30 2007-12-20 Eli Lilly And Co., Indianapolis Zusammensetzung, welche ein antifolate und ein methylmalonsäuresenkendes mittel enthält
US20050163832A1 (en) 2002-02-13 2005-07-28 Vladimir Torchilin Intracellular delivery of therapeutic agents
CH696628A5 (de) 2002-02-26 2007-08-31 Eprova Ag Verwendung von Folaten zur Herstellung einer Zubereitung geeignet zur Vorbeugung und Behandlung von Entzündungen und entzündungsassoziierter Krankheiten, im Speziellen zur Beeinflussung der
US7563590B2 (en) 2002-08-30 2009-07-21 Cypress Bioscience Inc. Methods of quantifying methotrexate metabolites
US6921667B2 (en) * 2003-03-07 2005-07-26 Prometheus Laboratories, Inc. Methods for direct detection of individual methotrexate metabolites
US20060240090A1 (en) 2003-04-02 2006-10-26 Lawrence Mayer Combination compositions of camptothecins and fluoropyrimidines
AU2005214331B2 (en) 2004-02-12 2011-09-15 Eisai, Inc. Monoclonal antibodies that specifically bind to folate receptor alpha
US7612071B2 (en) 2004-03-12 2009-11-03 Syntrix Biosystems, Inc. Compositions and methods employing aminopterin
WO2005103250A1 (ja) 2004-04-26 2005-11-03 Takami Matsuyama 葉酸リセプターベータ（FR-β）に対する単クローン抗体を含有する治療薬
RU2424792C2 (ru) 2004-05-03 2011-07-27 Хермес Байесайенсиз, Инк. Липосомы, используемые для доставки лекарственных средств
AU2005282241B2 (en) 2004-09-08 2011-03-03 Chelsea Therapeutics, Inc. Quinazoline derivatives as metabolically inert antifolate compounds.
EP1797882A4 (en) 2004-09-29 2009-11-18 Kowa Co PREVENTIVE AND / OR THERAPEUTIC MEDICAMENT FOR RHEUMATOID ARTHRITIS
US8126089B2 (en) 2004-09-30 2012-02-28 Alcatel Lucent Method and apparatus for providing frame synchronization in a digital communication system that supports multiple modulation formats
US20100266709A1 (en) 2004-12-16 2010-10-21 Hicks Terry Lee Compositions and Methods for Treating Burns
JP2006248978A (ja) 2005-03-10 2006-09-21 Mebiopharm Co Ltd 新規なリポソーム製剤
GB2424837B (en) 2005-04-06 2010-10-06 Cilag Ag Int Injection device
WO2007023243A2 (en) 2005-08-24 2007-03-01 Protherics Medicines Development Limited Cleavage of antifolate compounds
CN101365424A (zh) 2005-12-08 2009-02-11 耶路撒冷希伯来大学伊森姆研究发展公司 通过超声辐射改变脂质体组成的方法
US9265746B2 (en) 2006-05-31 2016-02-23 Merck & Cie Method for cell-specific targeting
WO2008030818A2 (en) 2006-09-05 2008-03-13 Mebiopharm Co., Ltd. Novel liposome compositions
EP1900752A1 (en) 2006-09-15 2008-03-19 DOMPE' pha.r.ma s.p.a. Human anti-folate receptor alpha antibodies and antibody fragments for the radioimmunotherapy of ovarian carcinoma
RU2423114C2 (ru) * 2006-12-29 2011-07-10 Тракон Фармасьютикалз, Инк. Комбинации антифолатного агента в лечении рака
BRPI0722053A2 (pt) * 2006-12-29 2018-04-17 Tracon Pharmaceuticals Inc método para o tratamento de câncer, formulação anticâncer, método de uso da formulação, e, uso de metoxiamina
KR20090113295A (ko) 2007-01-19 2009-10-29 첼시 쎄라퓨틱스, 인코포레이티드 새로운 유형의 항엽산제
WO2009115776A1 (en) 2008-03-18 2009-09-24 Btg International Limited Cyclopenta[g]quinazoline derivatives for the treatment of rheumatoid arthritis or acute myeloid leukaemia
GB0811360D0 (en) 2008-06-20 2008-07-30 Imp Innovations Ltd Methods
US8609642B2 (en) 2009-06-03 2013-12-17 Ex-Tek, Llc Skin treatment compositions
TW201118098A (en) 2009-08-13 2011-06-01 Reddy S Lab Liimited Dr Processes for preparing pemetrexed
SG10201501342UA (en) 2010-02-24 2015-04-29 Immunogen Inc Folate receptor 1 antibodies and immunoconjugates and uses thereof
US8747869B2 (en) 2010-03-19 2014-06-10 Massachusetts Institute Of Technology Lipid vesicle compositions and methods of use
EP2394640A1 (en) 2010-05-21 2011-12-14 MediGene AG Improved liposomal formulations of lipophilic compounds
WO2011150392A1 (en) 2010-05-28 2011-12-01 Purdue Research Foundation Delivery of therapeutic agents to inflamed tissues using folate-targeted agents
EP2614084A4 (en) 2010-09-09 2014-02-19 Purdue Research Foundation HUMANE FOLAT RECEPTOR BETA ANTIBODIES AND METHOD FOR THEIR USE
WO2012037068A1 (en) * 2010-09-13 2012-03-22 De Novo Diagnostics, Inc. Methods for monitoring methotrexate therapy
WO2012061469A2 (en) 2010-11-02 2012-05-10 Sicor Inc. Crystalline forms of pralatrexate
SG189957A1 (en) 2010-11-05 2013-06-28 Morphotek Inc Folate receptor alpha as a diagnostic and prognostic marker for folate receptor alpha-expressing cancers
WO2012078708A1 (en) 2010-12-07 2012-06-14 Chelsea Therapeutics, Inc. Combination comprising methotrexate and an antifolate compound
WO2012118806A2 (en) 2011-02-28 2012-09-07 The Regents Of The University Of California Compositions and methods for detecting and treating cancer
US9000003B2 (en) 2011-03-10 2015-04-07 National Science And Technology Development Agency Anti-folate antimalarials with dual-binding modes and their preparation
US8673914B2 (en) 2011-03-28 2014-03-18 St. John's University Use of phosphodiesterase inhibitors for treating multidrug resistance
EP2508894A1 (en) 2011-04-05 2012-10-10 Receptomon LLC Method for monitoring gene expression of translation and Integral/Secretory protein synthesis by magnetic resonance spectroscopy (MRS)
US8183227B1 (en) 2011-07-07 2012-05-22 Chemo S. A. France Compositions, kits and methods for nutrition supplementation
HRP20201465T1 (hr) 2011-07-13 2021-02-19 Yissum Research Development Company Of The Hebrew University Of Jerusalem Ltd. Liposomi koji ko-inkapsuliraju bisfosfonat i amfipatsko sredstvo
SI2731972T1 (en) 2011-07-15 2018-04-30 Eisai R&D Management Co., Ltd. Anti-folate receptor alpha antibodies and uses thereof
US20130122096A1 (en) 2011-11-14 2013-05-16 Silenseed Ltd. Compositions for drug delivery and methods of manufacturing and using same
JPWO2014003137A1 (ja) 2012-06-27 2016-06-02 旭化成メディカル株式会社 高アフィニティー抗体、及びその製造方法
WO2014016740A2 (en) 2012-07-23 2014-01-30 Fresenius Kabi Oncology Ltd. Improved process for the preparation of pralatrexate
WO2014046630A1 (en) 2012-09-19 2014-03-27 Keskin, Dilek Tumor targeted liposomal drug delivery system
CN104884617B (zh) 2012-12-07 2019-02-19 协和发酵麒麟株式会社 抗folr1抗体
US9192609B2 (en) 2013-04-17 2015-11-24 Hedgepath Pharmaceuticals, Inc. Treatment and prognostic monitoring of proliferation disorders using hedgehog pathway inhibitors
US20140363451A1 (en) 2013-05-14 2014-12-11 Immunogen, Inc. Anti-FOLR1 Immunoconjugate Dosing Regimens
WO2016025882A2 (en) 2014-08-14 2016-02-18 L.E.A.F Holdings Group Llc. Liposome encapsulated affinity drug
JOP20170004B1 (ar) 2016-01-15 2022-09-15 Lilly Co Eli الأجسام المضادة لببتيد بيتا النشوي مضاد N3pGlu واستخداماته
KR20190003630A (ko) 2016-04-29 2019-01-09 메모리얼 슬로안 케터링 캔서 센터 악성 뇌 종양에서의 표적화된 입자 침투, 분포, 및 반응을 위한 조성물 및 방법
US20180236098A1 (en) 2016-08-12 2018-08-23 L.E.A.F. Holdings Group Llc Alpha and gamma-d polyglutamated antifolates and uses thereof
EP3496757A4 (en) 2016-08-12 2020-04-15 L.E.A.F Holdings Group LLC POLYGLUTAMATE ANTIFOLATES AND USES THEREOF.
WO2018031980A1 (en) 2016-08-12 2018-02-15 L.E.A.F. Holdings Group Llc Polyglutamated antifolates and uses thereof
WO2019094648A1 (en) 2017-11-08 2019-05-16 L.E.A.F. Holdings Group Llc Platinum complexes and uses thereof
US12076402B2 (en) 2018-02-07 2024-09-03 L.E.A.F. Holdings Group Llc Alpha polyglutamated antifolates and uses thereof
US11730738B2 (en) 2018-02-07 2023-08-22 L.E.A.F. Holdings Group Llc Alpha polyglutamated pralatrexate and uses thereof
CA3090506A1 (en) 2018-02-07 2019-08-15 L.E.A.F. Holdings Group Llc Alpha polyglutamated tetrahydrofolates and uses thereof
US12246019B2 (en) 2018-02-07 2025-03-11 L.E.A.F. Holdings Group Llc Alpha polyglutamated lometrexol and uses thereof
EP3749321A4 (en) 2018-02-07 2022-03-09 L.E.A.F Holdings Group LLC Gamma polyglutamated antifolates and uses thereof
WO2019157145A1 (en) 2018-02-07 2019-08-15 L.E.A.F. Holdings Group Llc Gamma polyglutamated pemetrexed and uses thereof
EP3749317A4 (en) 2018-02-07 2022-06-22 L.E.A.F Holdings Group LLC PEMETREXED ALPHA-POLYGLUTAMATE AND ASSOCIATED USES
US12310966B2 (en) 2018-02-07 2025-05-27 L.E.A.F. Holdings Group Llc Alpha polyglutamated aminopterin and uses thereof
JP7491573B2 (ja) 2018-02-07 2024-05-28 エル．イー．エー．エフ． ホールディングス グループ エルエルシー アルファポリグルタミン酸化メトトレキセートおよびその使用
US12246015B2 (en) 2018-02-07 2025-03-11 L.E.A.F. Holdings Group Llc Alpha polyglutamated raltitrexed and uses thereof
EP3749318A4 (en) 2018-02-07 2022-07-06 L.E.A.F Holdings Group LLC GAMMA-POLYGLUTAMATED RALTITREXED AND ITS USES
CA3090753A1 (en) 2018-02-14 2019-08-22 L.E.A.F. Holdings Group Llc Gamma polyglutamated pralatrexate and uses thereof
CA3090989A1 (en) 2018-02-14 2019-08-22 L.E.A.F. Holdings Group Llc Gamma polyglutamated methotrexate and uses thereof
WO2019160734A1 (en) 2018-02-14 2019-08-22 L.E.A.F. Holdings Group Llc Gamma polyglutamated lometrexol and uses thereof
EP3752158A4 (en) 2018-02-14 2022-03-09 L.E.A.F Holdings Group LLC GAMMA-POLYGLUTAMATED AMINOPTERINE AND USES THEREOF
WO2019160735A1 (en) 2018-02-14 2019-08-22 L.E.A.F. Holdings Group Llc Gamma polyglutamated tetrahydrofolates and uses thereof
KR102765012B1 (ko) 2019-05-27 2025-02-07 삼성디스플레이 주식회사 표시 장치
CA3149914A1 (en) 2019-08-06 2021-02-11 L.E.A.F. Holdings Group Llc Processes of preparing polyglutamated antifolates and uses of their compositions

Patent Citations (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6569432B1 (en) * 1995-02-24 2003-05-27 Sloan-Kettering Institute For Cancer Research Prostate-specific membrane antigen and uses thereof
WO2001005405A1 (en) * 1999-07-16 2001-01-25 The General Hospital Corporation Folylpolyglutamyl synthetase gene transfer to enhance antifolate drug sensitivity
WO2005070465A2 (en) * 2004-01-14 2005-08-04 Gilead Sciences, Inc. Lipid-based dispersions useful for drug delivery
WO2006002049A2 (en) * 2004-06-15 2006-01-05 Prometheus Laboratories Inc. Methods for predicting methotrexate polyglutamate levels using pharmacogenetics
WO2006074416A1 (en) * 2005-01-07 2006-07-13 Health Research Inc. 5-amino-4-imidazolecarboxamide riboside and its nucleobase as potentiators of antifolate transport and metabolism
WO2007098089A2 (en) * 2006-02-17 2007-08-30 Novacea, Inc. Treatment of hyperproliferative diseases with methotrexate n-oxide and analogs
CN103002877A (zh) * 2010-05-13 2013-03-27 帕西拉制药有限公司 作为缓解疾病的抗风湿性药（dmard）和抗癌药剂的甲氨蝶呤的持续释放制剂
US20140120157A1 (en) * 2012-09-19 2014-05-01 Georgetown University Targeted liposomes
CN103040748A (zh) * 2012-12-18 2013-04-17 海南百思特医药科技有限公司 一种培美曲塞二钠脂质体注射剂
CN104546723A (zh) * 2015-02-11 2015-04-29 上海交通大学医学院附属新华医院 一种培美曲塞脂质体及其制备方法

Non-Patent Citations (10)

* Cited by examiner, † Cited by third party
Title
CHUAN SHIH ET AL: "LY231514, a Pyrrolo[2,3-d]pyrimidine-based Antifolate That Inhibits Multiple Folate-requiring Enzymes", 《CANCER RESEARCH》 *
CONRAD PITTS ET AL: "INTERACTION ENERGY ANALYSES OF FOLATE ANALOG BINDING TO HUMAN DIHYDROFOLATE", 《INTERACTION ENERGY ANALYSES OF FOLATE ANALOG BINDING》 *
KA-YUN NG ET AL: "Liposome-dependent delivery of pteridine antifolates:a two-compartment growth inhibition assay for evaluating drug leakage and metaoolism", 《BIOCHIMICA ET BIOPLRYSIRA ACTA》 *
NITZAN GONEN ET AL: "Antifolates in cancer therapy: Structure, activity and mechanisms of drug resistance", 《DRUG RESISTANCE UPDATES》 *
ROLAND J.W.MEESTERS ET AL: "Assessment of intracellular methotrexate and methotrexate-polyglutamate metabolite concentrations in erythrocytes by ultrafast matrix-assisted laser desorption/ionization triple quadrupole tandem mass spectrometry", 《RAPID COMMUNICATION MASS SPECTROMETRY》 *
SHRIKANTA CHATTOPADHYAY ET AL: "Pemetrexed:biochemical and cellular pharmacology,mechanisms,and clinical applications", 《MOLECULAR CANCER THERAPEUTICS》 *
潘卫三主编: "《工业药剂学》", 30 August 2015, 中国医药科技出版社 *
赵霞等: "多聚谷氨酸化甲氨蝶吟：甲氨蝶吟细胞内代谢物研究进展", 《中国医院药学杂志》 *
陈吉生主编: "《新编临床药物学》", 30 August 2013, 中国中医药出版社 *
马英主编: "《药物化学》", 30 August 2012 *

Cited By (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN111867593A (zh) * 2018-02-07 2020-10-30 L.E.A.F.控股集团公司 α聚谷氨酸化抗叶酸剂及其用途
CN111954530A (zh) * 2018-02-07 2020-11-17 L.E.A.F.控股集团公司 γ聚谷氨酸化培美曲塞及其用途
CN111954531A (zh) * 2018-02-07 2020-11-17 L.E.A.F.控股集团公司 α聚谷氨酸化培美曲塞及其用途
CN111954529A (zh) * 2018-02-07 2020-11-17 L.E.A.F.控股集团公司 α聚谷氨酸化氨甲蝶呤及其用途
CN111936145A (zh) * 2018-02-14 2020-11-13 L.E.A.F.控股集团公司 γ聚谷氨酸化氨甲蝶呤及其用途
CN114555127A (zh) * 2019-08-06 2022-05-27 L.E.A.F.控股集团公司 制备聚谷氨酸化抗叶酸剂的方法以及它们的组合物的用途

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MX2019001756A (es) 2019-05-09
KR20190038851A (ko) 2019-04-09
CA3033077A1 (en) 2018-02-15
JP2023058619A (ja) 2023-04-25
CN109789212A (zh) 2019-05-21
BR112019002495A2 (pt) 2019-05-14
AU2017308158B2 (en) 2023-08-10
KR20230145501A (ko) 2023-10-17
AU2017308159A1 (en) 2019-02-07
KR20240141854A (ko) 2024-09-27

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