WO2005025512A3 - Cobalamin conjugates for anti-tumor therapy - Google Patents

Cobalamin conjugates for anti-tumor therapy Download PDF

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Publication number
WO2005025512A3
WO2005025512A3 PCT/US2004/029879 US2004029879W WO2005025512A3 WO 2005025512 A3 WO2005025512 A3 WO 2005025512A3 US 2004029879 W US2004029879 W US 2004029879W WO 2005025512 A3 WO2005025512 A3 WO 2005025512A3
Authority
WO
WIPO (PCT)
Prior art keywords
conjugate
drug
cobalamin
cleavable linker
cell
Prior art date
Application number
PCT/US2004/029879
Other languages
French (fr)
Other versions
WO2005025512A2 (en
Inventor
Ned M Weinshenker
Frederick G West
Barbara A Araneo
Weiping Li
Original Assignee
Manticore Pharmaceuticals Inc
Ned M Weinshenker
Frederick G West
Barbara A Araneo
Weiping Li
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 Manticore Pharmaceuticals Inc, Ned M Weinshenker, Frederick G West, Barbara A Araneo, Weiping Li filed Critical Manticore Pharmaceuticals Inc
Priority to JP2006526379A priority Critical patent/JP2007505144A/en
Priority to EP04783919A priority patent/EP1672978A4/en
Priority to CA2538748A priority patent/CA2538748C/en
Priority to AU2004272105A priority patent/AU2004272105B2/en
Publication of WO2005025512A2 publication Critical patent/WO2005025512A2/en
Publication of WO2005025512A3 publication Critical patent/WO2005025512A3/en

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—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
    • A61K47/50—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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—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
    • A61K47/50—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
    • A61K47/51—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
    • A61K47/54—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 organic compound
    • A61K47/55—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 organic compound the modifying agent being also a pharmacologically or therapeutically active agent, i.e. the entire conjugate being a codrug, i.e. a dimer, oligomer or polymer of pharmacologically or therapeutically active compounds
    • A61K47/551—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 organic compound the modifying agent being also a pharmacologically or therapeutically active agent, i.e. the entire conjugate being a codrug, i.e. a dimer, oligomer or polymer of pharmacologically or therapeutically active compounds one of the codrug's components being a vitamin, e.g. niacinamide, vitamin B3, cobalamin, vitamin B12, folate, vitamin A or retinoic acid
    • 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
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents

Abstract

The present invention provides a cobalamin-drug conjugate suitable for the treatment of tumor related diseases. Cobalamin is indirectly covalently bound to an antitumor drug via a cleavable linker and one or more optional spacers. Cobalanin is covalently bound to a first spacer or the cleavable linker via the 5'-OH of the cobalamin ribose ring. The drug is bound to a second spacer of the cleavable linker via an existing or added functional group on the drug. After administration, the conjugate forms a complex with transcobalamin (any of its isoforms). The complex then binds to a receptor on a cell membrane and is taken up into the cell. Once in the cell, an intracellular enzyme cleaves the conjugate thereby releasing the drug. Depending upon the structure of the conjugate, a particular class or type of intracellular enzyme affects the cleavage. Due to the high demand for cobalamin in growing cells, tumor cells typically take up a higher percentage of the conjugate than do normal non-growing cells. The conjugate of the invention advantageously provides a reduced systemic toxicity and enhanced efficacy as compared to a corresponding free drug.
PCT/US2004/029879 2003-09-10 2004-09-10 Cobalamin conjugates for anti-tumor therapy WO2005025512A2 (en)

Priority Applications (4)

Application Number Priority Date Filing Date Title
JP2006526379A JP2007505144A (en) 2003-09-10 2004-09-10 Cobalamin conjugates for antitumor therapy
EP04783919A EP1672978A4 (en) 2003-09-10 2004-09-10 Cobalamin conjugates for anti-tumor therapy
CA2538748A CA2538748C (en) 2003-09-10 2004-09-10 Cobalamin conjugates for anti-tumor therapy
AU2004272105A AU2004272105B2 (en) 2003-09-10 2004-09-10 Cobalamin conjugates for anti-tumor therapy

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US10/659,501 US7232805B2 (en) 2003-09-10 2003-09-10 Cobalamin conjugates for anti-tumor therapy
US10/659,501 2003-09-10

Publications (2)

Publication Number Publication Date
WO2005025512A2 WO2005025512A2 (en) 2005-03-24
WO2005025512A3 true WO2005025512A3 (en) 2005-07-28

Family

ID=34226964

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2004/029879 WO2005025512A2 (en) 2003-09-10 2004-09-10 Cobalamin conjugates for anti-tumor therapy

Country Status (7)

Country Link
US (1) US7232805B2 (en)
EP (1) EP1672978A4 (en)
JP (1) JP2007505144A (en)
KR (1) KR20070019942A (en)
AU (1) AU2004272105B2 (en)
CA (1) CA2538748C (en)
WO (1) WO2005025512A2 (en)

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US20100113328A1 (en) * 2003-05-29 2010-05-06 The Scripps Research Institute Targeted delivery to legumain-expressing cells
JP2009509918A (en) * 2005-08-05 2009-03-12 シンタルガ・ビーブイ Triazole-containing releasable linkers, their conjugates, and production methods
WO2007064759A2 (en) * 2005-11-29 2007-06-07 The Scripps Research Institute Inhibiting tumour cell invasion, metastasis and angiogenesis through targetting legumain
EP1979487A4 (en) * 2006-01-26 2010-05-05 Bebaas Inc Cobalamin compositions for the treatment of cancer
TW200745163A (en) * 2006-02-17 2007-12-16 Syntonix Pharmaceuticals Inc Peptides that block the binding of IgG to FcRn
EP2139469A4 (en) * 2007-03-19 2011-09-07 Inflabloc Pharmaceuticals Inc Cobalamin taxane bioconjugates
BRPI0814763A2 (en) * 2007-08-09 2015-03-03 Syntonix Pharmaceuticals Inc IMMUNOMODULATING PEPTIDES
DK2187965T3 (en) 2007-08-17 2020-01-20 Purdue Research Foundation PSMA BINDING LIGAND LINKER CONJUGATES AND PROCEDURES FOR USE
US20100016256A1 (en) * 2008-07-21 2010-01-21 Gebhard John R Taxane Compounds for Treating Eye Disease
US20100048488A1 (en) * 2008-08-01 2010-02-25 Syntonix Pharmaceuticals, Inc. Immunomodulatory peptides
CN103432566A (en) 2008-12-16 2013-12-11 建新公司 Oligosaccharide-protein conjugates
EP2445518A1 (en) * 2009-01-27 2012-05-02 Osiris Therapeutics, Inc. Cobalamin taxane bioconjugates for treating eye disease
US9951324B2 (en) 2010-02-25 2018-04-24 Purdue Research Foundation PSMA binding ligand-linker conjugates and methods for using
CN102199180B (en) * 2011-04-12 2014-07-09 连云港杰瑞药业有限公司 Preparation method of capectabine
US20150335761A1 (en) * 2012-02-16 2015-11-26 Raymond Firestone Compositions and methods for contraception
EA201890915A1 (en) 2012-11-15 2018-09-28 Эндосайт, Инк. CONJUGATES FOR DELIVERY OF MEDICINES AND METHODS OF TREATMENT OF DISEASES CAUSED BY CELLS EXPRESSING PSMA
WO2014106208A1 (en) * 2012-12-28 2014-07-03 Blend Therapeutics, Inc. Targeted conjugates encapsulated in particles and formulations thereof
EP3495355A1 (en) 2013-10-18 2019-06-12 Deutsches Krebsforschungszentrum Labeled inhibitors of prostate specific membrane antigen (psma), their use as imaging agents and pharmaceutical agents for the treatment of prostate cancer
US10188759B2 (en) 2015-01-07 2019-01-29 Endocyte, Inc. Conjugates for imaging
CN108371709A (en) * 2018-03-29 2018-08-07 苟春虎 Lycium ruthenicum tumor recovering gene enzyme
US11155821B2 (en) 2018-07-31 2021-10-26 The Regents Of The University Of Colorado, A Body Corporate Compositions and methods for tagging ribonucleic acids

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Also Published As

Publication number Publication date
AU2004272105B2 (en) 2011-03-10
EP1672978A2 (en) 2006-06-28
EP1672978A4 (en) 2006-12-20
AU2004272105A1 (en) 2005-03-24
US20050054607A1 (en) 2005-03-10
CA2538748A1 (en) 2005-03-24
US7232805B2 (en) 2007-06-19
WO2005025512A2 (en) 2005-03-24
JP2007505144A (en) 2007-03-08
KR20070019942A (en) 2007-02-16
CA2538748C (en) 2011-12-06

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