JP7576816B2 - ポリグルタミン酸化抗葉酸剤およびその使用 - Google Patents

ポリグルタミン酸化抗葉酸剤およびその使用 Download PDF

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Publication number
JP7576816B2
JP7576816B2 JP2019529465A JP2019529465A JP7576816B2 JP 7576816 B2 JP7576816 B2 JP 7576816B2 JP 2019529465 A JP2019529465 A JP 2019529465A JP 2019529465 A JP2019529465 A JP 2019529465A JP 7576816 B2 JP7576816 B2 JP 7576816B2
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polyglutamated
antifolate
liposome
pentaglutamated
hexaglutamated
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Japanese (ja)
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JP2019524885A5 (https=
JP2019524885A (ja
Inventor
ニイェキザ，クレト
モヨ，ヴィクター，マンドラ
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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/US2017/046667 external-priority patent/WO2018031980A1/en
Publication of JP2019524885A publication Critical patent/JP2019524885A/ja
Publication of JP2019524885A5 publication Critical patent/JP2019524885A5/ja
Priority to JP2022100445A priority Critical patent/JP7733390B2/ja
Application granted granted Critical
Publication of JP7576816B2 publication Critical patent/JP7576816B2/ja
Priority to JP2025001190A priority patent/JP2025072362A/ja
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • 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
    • A61K31/517—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine
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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
    • A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
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    • A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
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    • 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
    • A61K47/6849—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 receptor, a cell surface antigen or a cell surface determinant
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    • A61K47/6905—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 conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit the form being a colloid or an emulsion
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    • A61K47/6905—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 conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit the form being a colloid or an emulsion
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    • C07K16/00—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans
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    • B82—NANOTECHNOLOGY
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    • B82Y5/00—Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery
    • C—CHEMISTRY; METALLURGY
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    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
    • C07K2317/73—Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation
    • C—CHEMISTRY; METALLURGY
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    • Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

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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)
  • Epidemiology (AREA)
  • 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)
  • Biophysics (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Rheumatology (AREA)
  • Genetics & Genomics (AREA)
  • Physical Education & Sports Medicine (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)
  • Polymers With Sulfur, Phosphorus Or Metals In The Main Chain (AREA)
  • Communicable Diseases (AREA)
  • Oncology (AREA)
  • Immobilizing And Processing Of Enzymes And Microorganisms (AREA)
  • Preparation Of Compounds By Using Micro-Organisms (AREA)
  • External Artificial Organs (AREA)
JP2019529465A 2016-08-12 2017-08-12 ポリグルタミン酸化抗葉酸剤およびその使用 Active JP7576816B2 (ja)

Priority Applications (2)

Application Number Priority Date Filing Date Title
JP2022100445A JP7733390B2 (ja) 2016-08-12 2022-06-22 ポリグルタミン酸化抗葉酸剤およびその使用
JP2025001190A JP2025072362A (ja) 2016-08-12 2025-01-06 ポリグルタミン酸化抗葉酸剤およびその使用

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
US15/675,701 US20180236098A1 (en) 2016-08-12 2017-08-11 Alpha and gamma-d polyglutamated antifolates and uses thereof
US15/675,701 2017-08-11
US15/675,695 2017-08-11
PCT/US2017/046667 WO2018031980A1 (en) 2016-08-12 2017-08-12 Polyglutamated antifolates and uses thereof

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JP2019524885A JP2019524885A (ja) 2019-09-05
JP2019524885A5 JP2019524885A5 (https=) 2020-10-01
JP7576816B2 true JP7576816B2 (ja) 2024-11-01

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JP2019529465A Active JP7576816B2 (ja) 2016-08-12 2017-08-12 ポリグルタミン酸化抗葉酸剤およびその使用
JP2019507107A Active JP7227123B2 (ja) 2016-08-12 2017-08-12 αおよびγ－Ｄポリグルタミン酸化抗葉酸剤およびその使用
JP2022100445A Active JP7733390B2 (ja) 2016-08-12 2022-06-22 ポリグルタミン酸化抗葉酸剤およびその使用
JP2023018363A Active JP7538268B2 (ja) 2016-08-12 2023-02-09 αおよびγ－Ｄポリグルタミン酸化抗葉酸剤およびその使用
JP2024131755A Pending JP2024160315A (ja) 2016-08-12 2024-08-08 αおよびγ－Ｄポリグルタミン酸化抗葉酸剤およびその使用
JP2025001190A Pending JP2025072362A (ja) 2016-08-12 2025-01-06 ポリグルタミン酸化抗葉酸剤およびその使用

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JP2022100445A Active JP7733390B2 (ja) 2016-08-12 2022-06-22 ポリグルタミン酸化抗葉酸剤およびその使用
JP2023018363A Active JP7538268B2 (ja) 2016-08-12 2023-02-09 αおよびγ－Ｄポリグルタミン酸化抗葉酸剤およびその使用
JP2024131755A Pending JP2024160315A (ja) 2016-08-12 2024-08-08 αおよびγ－Ｄポリグルタミン酸化抗葉酸剤およびその使用
JP2025001190A Pending JP2025072362A (ja) 2016-08-12 2025-01-06 ポリグルタミン酸化抗葉酸剤およびその使用

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US (11) US11344628B2 (https=)
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Families Citing this family (25)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN120939250A (zh) 2016-08-12 2025-11-14 L.E.A.F.控股集团公司 聚谷氨酸化抗叶酸剂及其用途
WO2018031968A1 (en) * 2016-08-12 2018-02-15 L.E.A.F. Holdings Group Llc Alpha and gamma-d polyglutamated antifolates and uses thereof
WO2019157129A1 (en) 2018-02-07 2019-08-15 L.E.A.F. Holdings Group Llc Alpha polyglutamated pralatrexate and uses thereof
WO2019157123A1 (en) * 2018-02-07 2019-08-15 L.E.A.F. Holdings Group Llc Alpha polyglutamated aminopterin and uses thereof
EP3749319A4 (en) * 2018-02-07 2022-06-22 L.E.A.F Holdings Group LLC TETRAHYDROFOLATES ALPHA POLYGLUTAMATE AND THEIR USES
EP3749321A4 (en) * 2018-02-07 2022-03-09 L.E.A.F Holdings Group LLC Gamma 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
WO2019157121A1 (en) * 2018-02-07 2019-08-15 L.E.A.F. Holdings Group Llc Alpha polyglutamated lometrexol and uses thereof
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
US12239734B2 (en) 2018-02-07 2025-03-04 L.E.A.F. Holdings Group Llc Gamma polyglutamated raltitrexed and uses thereof
EP3749311A4 (en) * 2018-02-07 2022-07-06 L.E.A.F Holdings Group LLC PEMETREXED POLYGLUTAMATE GAMMA COMPOSITIONS AND THEIR USES
CA3090500A1 (en) * 2018-02-07 2019-08-15 L.E.A.F. Holdings Group Llc Alpha polyglutamated antifolates 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
WO2019160732A1 (en) 2018-02-14 2019-08-22 L.E.A.F. Holdings Group Llc Gamma polyglutamated aminopterin and uses thereof
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
EP3752156A4 (en) * 2018-02-14 2021-10-27 L.E.A.F Holdings Group LLC GAMMA-POLYGLUTAMIZED PRALATREXATE AND USES THEREOF
EP3752157A4 (en) 2018-02-14 2022-07-06 L.E.A.F Holdings Group LLC GAMMA-POLYGLUTAMATED LOMETREXOLE AND USES THEREOF
US12048766B2 (en) 2018-02-14 2024-07-30 L.E.A.F. Holdings Group Llc Gamma polyglutamated tetrahydrofolates and uses thereof
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
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
CA3260122A1 (en) * 2022-03-21 2023-09-28 Franz Paul Armbruster 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
WO2026018920A1 (ja) * 2024-07-18 2026-01-22 国立大学法人九州大学 凍結乾燥装置、および、凍結乾燥試料とその製造方法

Family Cites Families (99)

* 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
US6569432B1 (en) 1995-02-24 2003-05-27 Sloan-Kettering Institute For Cancer Research Prostate-specific membrane antigen and uses thereof
CN1122456C (zh) 1996-01-31 2003-10-01 南亚拉巴马医学科学基金会 含有天然的还原叶酸盐异构体的食品和维生素制品
US20020168761A1 (en) 2000-01-24 2002-11-14 Gour Barbara J. Peptidomimetic modulators of cell adhesion
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
AU5283099A (en) 1998-07-09 2000-02-01 Rhodia Chimie Water-soluble or water-dispersible grafted copolymers
WO2001005405A1 (en) * 1999-07-16 2001-01-25 The General Hospital Corporation Folylpolyglutamyl synthetase gene transfer to enhance antifolate drug sensitivity
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
EP1313508B1 (en) 2000-06-30 2007-04-18 Eli Lilly And Company Combination containing an antifolate and methylmalonic acid lowering agent
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
US20040265368A1 (en) 2003-04-02 2004-12-30 Lawrence Mayer Combination compositions of camptothecins and fluoropyrimidines
NZ548195A (en) * 2004-01-14 2011-01-28 Gilead Sciences Inc Lipid-based dispersions useful for drug delivery
CA2556027C (en) 2004-02-12 2015-11-24 Morphotek, Inc. Monoclonal antibodies that specifically block biological activity of a tumor antigen
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
CA2928387A1 (en) 2004-05-03 2005-11-17 Merrimack Pharmaceuticals, Inc. Drug delivery liposomes containing anionic polyols or anionic sugars
US7695908B2 (en) * 2004-06-15 2010-04-13 Prometheus Laboratories Inc. Methods for predicting methotrexate polyglutamate levels using pharmacogenetics
EP1791544A4 (en) 2004-09-08 2007-09-12 Chelsea Therapeutics Inc CHINAZOLINE DERIVATIVES AS METABOLIC INERT ANTIFOLATE
WO2006035876A1 (ja) 2004-09-29 2006-04-06 Kowa Co., Ltd. 関節リウマチの予防及び／又は治療薬
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
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
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
CA2619992A1 (en) 2005-08-24 2007-03-01 Protherics Medicines Development Limited Cleavage of antifolate compounds
US20090155345A1 (en) 2005-12-08 2009-06-18 Ben Gurion University Of The Negev Research And Development Authority Methods for affecting liposome composition ultrasound irradiation
WO2007098089A2 (en) * 2006-02-17 2007-08-30 Novacea, Inc. Treatment of hyperproliferative diseases with methotrexate n-oxide and analogs
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
KR101195366B1 (ko) * 2006-12-29 2012-11-21 트라콘 파마수티칼즈, 인코포레이티드 암치료에서의 항엽산제 조합물
RU2423114C2 (ru) * 2006-12-29 2011-07-10 Тракон Фармасьютикалз, Инк. Комбинации антифолатного агента в лечении рака
BRPI0806632A2 (pt) 2007-01-19 2011-09-06 Chelsea Therapeutics Inc composto, composição farmacêutica, método para o tratamento de uma condição selecionada a partir do grupo constituìdo de proliferação celular anormal, inflamação, asma e artrite
CN101977620B (zh) 2008-03-18 2014-05-07 英国技术集团国际有限公司 用于治疗类风湿性关节炎或急性骨髓性白血病的环戊二烯并[g]喹唑啉衍生物
GB0811360D0 (en) 2008-06-20 2008-07-30 Imp Innovations Ltd Methods
WO2010141711A1 (en) 2009-06-03 2010-12-09 Ex-Tek, Llc Skin treatment compositions
TW201118098A (en) 2009-08-13 2011-06-01 Reddy S Lab Liimited Dr Processes for preparing pemetrexed
CN103037900B (zh) 2010-02-24 2016-04-06 伊缪诺金公司 叶酸受体1抗体与免疫缀合物以及其用途
JP5686886B2 (ja) 2010-03-19 2015-03-18 マサチューセッツ インスチテュート オブ テクノロジーＭａｓｓａｃｈｕｓｅｔｔｓ Ｉｎｓｔｉｔｕｔｅ Ｏｆ Ｔｅｃｈｎｏｌｏｇｙ 脂質小胞組成物及び使用方法
US9770414B2 (en) 2010-05-13 2017-09-26 Pacira Pharmaceuticals, Inc. Sustained release formulation of methotrexate as a disease-modifying antirheumatic drug (DMARD) and an anti-cancer agent
EP2394640A1 (en) 2010-05-21 2011-12-14 MediGene AG Improved liposomal formulations of lipophilic compounds
CA2800693A1 (en) 2010-05-28 2011-12-01 Purdue Research Foundation Delivery of therapeutic agents to inflamed tissues using folate-targeted agents
WO2012033987A2 (en) 2010-09-09 2012-03-15 Purdue Research Foundation Anti-human folate receptor beta antibodies and methods of 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
AU2011323124C1 (en) 2010-11-05 2016-09-22 Eisai 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
US20140086939A1 (en) 2011-02-28 2014-03-27 Michael Karin Compositions and methods for detecting and treating cancer
WO2012121682A2 (en) 2011-03-10 2012-09-13 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
PT2731591T (pt) 2011-07-13 2020-09-18 Yissum Res Dev Co Of Hebrew Univ Jerusalem Ltd Lipossomas que coencapsulam um bisfosfonato e um agente anfipático
PL2731972T3 (pl) 2011-07-15 2018-06-29 Eisai R&D Management Co., Ltd. Przeciwciała skierowane przeciwko receptorowi folianowemu alfa i ich zastosowania
EP2591770B1 (en) 2011-11-14 2016-03-16 Silenseed Ltd Compositions for siRNA delivery and methods of manufacturing and using same
US20150239956A1 (en) 2012-06-27 2015-08-27 Asahi Kasei Medical Co., Ltd. High-affinity antibody and method for manufacturing the same
WO2014016740A2 (en) 2012-07-23 2014-01-30 Fresenius Kabi Oncology Ltd. Improved process for the preparation of pralatrexate
US20140120157A1 (en) * 2012-09-19 2014-05-01 Georgetown University Targeted liposomes
WO2014046630A1 (en) 2012-09-19 2014-03-27 Keskin, Dilek Tumor targeted liposomal drug delivery system
JP6224619B2 (ja) 2012-12-07 2017-11-01 協和発酵キリン株式会社 抗ｆｏｌｒ１抗体
CN103040748B (zh) * 2012-12-18 2014-07-02 海南圣欣医药科技有限公司 一种培美曲塞二钠脂质体注射剂
US9192609B2 (en) 2013-04-17 2015-11-24 Hedgepath Pharmaceuticals, Inc. Treatment and prognostic monitoring of proliferation disorders using hedgehog pathway inhibitors
CA2911499A1 (en) 2013-05-14 2014-11-20 Immunogen, Inc. Anti-folr1 immunoconjugate dosing regimens
MX386433B (es) * 2014-08-14 2025-03-18 L E A F Holdings Group Llc Fármaco de afinidad encapsulado en liposoma.
CN104546723B (zh) * 2015-02-11 2017-07-18 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
JOP20170004B1 (ar) 2016-01-15 2022-09-15 Lilly Co Eli الأجسام المضادة لببتيد بيتا النشوي مضاد N3pGlu واستخداماته
CN109069666B (zh) 2016-04-29 2023-04-04 纪念斯隆凯特琳癌症中心 使靶向颗粒穿透、分布和响应于恶性脑肿瘤中的组合物和方法
WO2018031979A1 (en) 2016-08-12 2018-02-15 L.E.A.F. Holdings Group Llc Alpha and gamma-d polyglutamated antifolates and uses thereof
WO2018031968A1 (en) 2016-08-12 2018-02-15 L.E.A.F. Holdings Group Llc Alpha and gamma-d polyglutamated antifolates and uses thereof
CN120939250A (zh) 2016-08-12 2025-11-14 L.E.A.F.控股集团公司 聚谷氨酸化抗叶酸剂及其用途
US20190231690A1 (en) 2017-11-08 2019-08-01 L.E.A.F. Holdings Group Llc Platinum complexes and uses thereof
WO2019157123A1 (en) 2018-02-07 2019-08-15 L.E.A.F. Holdings Group Llc Alpha polyglutamated aminopterin and uses thereof
EP3749319A4 (en) 2018-02-07 2022-06-22 L.E.A.F Holdings Group LLC TETRAHYDROFOLATES ALPHA POLYGLUTAMATE AND THEIR USES
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
EP3749321A4 (en) 2018-02-07 2022-03-09 L.E.A.F Holdings Group LLC Gamma polyglutamated antifolates and uses thereof
WO2019157121A1 (en) 2018-02-07 2019-08-15 L.E.A.F. Holdings Group Llc Alpha polyglutamated lometrexol and uses thereof
EP3749311A4 (en) 2018-02-07 2022-07-06 L.E.A.F Holdings Group LLC PEMETREXED POLYGLUTAMATE GAMMA COMPOSITIONS AND THEIR USES
CA3090500A1 (en) 2018-02-07 2019-08-15 L.E.A.F. Holdings Group Llc Alpha polyglutamated antifolates and uses thereof
US12239734B2 (en) 2018-02-07 2025-03-04 L.E.A.F. Holdings Group Llc Gamma polyglutamated raltitrexed and uses thereof
US12246015B2 (en) 2018-02-07 2025-03-11 L.E.A.F. Holdings Group Llc Alpha polyglutamated raltitrexed and uses thereof
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
WO2019157129A1 (en) 2018-02-07 2019-08-15 L.E.A.F. Holdings Group Llc Alpha polyglutamated pralatrexate and uses thereof
EP3752157A4 (en) 2018-02-14 2022-07-06 L.E.A.F Holdings Group LLC GAMMA-POLYGLUTAMATED LOMETREXOLE AND USES THEREOF
US12048766B2 (en) 2018-02-14 2024-07-30 L.E.A.F. Holdings Group Llc Gamma polyglutamated tetrahydrofolates and uses thereof
WO2019160732A1 (en) 2018-02-14 2019-08-22 L.E.A.F. Holdings Group Llc Gamma polyglutamated aminopterin and uses thereof
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
EP3752156A4 (en) 2018-02-14 2021-10-27 L.E.A.F Holdings Group LLC GAMMA-POLYGLUTAMIZED PRALATREXATE 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

Non-Patent Citations (4)

* Cited by examiner, † Cited by third party
Title
．Ｊｏｕｒｎａｌ ｏｆ Ｍｅｄｉｃｉｎａｌ Ｃｈｅｍｉｓｔｒｙ、（１９９０）、３３（２）、７１１－７１７
Ｄｒｕｇ Ｒｅｓｉｓｔａｎｃｅ Ｕｐｄａｔｅｓ、（２０１２）、１５、１８３－２１０
Ｊｏｕｒｎａｌ ｏｆ Ｃｏｎｔｒｏｌｌｅｄ Ｒｅｌｅａｓｅ、（２０１５）、２２０、２９－３６
Ｍｏｌｅｃｕｌａｒ Ｐｈａｒｍａｃｅｕｔｉｃｓ、（２０１４）、１１、２６３１－２６３９

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